Category: Hepatitis C

Rationale

Diseases are abnormal conditions that affect living organisms and occur when cells in the body are damaged as a result of infection and signs of an illness appear (National Academy of Sciences, 2019). They fall under four main categories; infectious, deficiency, hereditary and physiological diseases, all of which have harmful effects on the human body. However, through vaccines many diseases have been successfully controlled. Since 1796, when Edward Jenner discovered the smallpox vaccination, mass vaccination programs have been used to combat many other diseases. Mass vaccinations programs involve immunizing a large group of people in one or more locations in a short period of time (Grabenstein, 20016). These programs provide long-term protection and in some cases immunity to several diseases. For highly contagious diseases including measles, vaccines are effective in preventing transmission through immunity. Two doses of the MMR vaccine at 12-15 months and 4-6 years of age are 97% effective at preventing measles (Centres for Disease Control and Prevention, 2019). Mass vaccination programs have also been effective in combatting Hepatitis B with an effective rate of over 98% (World Health Organisation, 2019). Therefore, this essay proposes the following research question.

Has Taiwan’s program of universal hepatitis B vaccination reduced the number of acute and chronic liver diseases in infants?

Background

Hepatitis B is a viral infection that attacks the liver which can cause both acute and chronic (long lasting) liver disease (World Health Organisation, 2019). It is spread when infectious body fluids come into contact with body tissue underneath the skin. Mother-to-baby transmission during pregnancy and child-to-child contact generally through contact of open wounds are the most common ways to become infected in Australia (SA health, 2019). The world’s first nation-wide hepatitis B vaccination program was launched in Taiwan, July 1984. Following this, after 2 decades the program was found to provide long term protection for up to 20 years against hepatitis B.

Evidence

A study conducted in 2010 reported that all infants in the study received three to four doses of the Hepatitis B vaccination (HBV). Infants of Hepatitis B positive mothers were also given 0.5ml of hepatitis B within 24hours after birth. This particular vaccination coverage rate was as high as 97% (Cross, 2006). The level of pathogen in Taipei City of hepatitis B surface antigen also declined from 9.8% to 0.6% in children after 20 years of mass vaccination (Cross, 2006). As well as the decrease of chronic HBV infection, the cases of hepatocellular carcinoma in Taiwanese children also decreased. This suggests, that Taiwan’s program of hepatitis B vaccination reduced the number of liver disease in infants.

References

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321493/
2. https://www.nejm.org/doi/full/10.1056/NEJM199706263362602
3. https://www.sciencedirect.com/science/article/abs/pii/S1473309902003158
4. https://academic.oup.com/epirev/article/28/1/126/570747
5. https://www.ncbi.nlm.nih.gov/pubmed/20116181

Hepatitis C:

HCV is a viral contamination causing aggravation of the liver. It is transmitted from individual to individual through unscreened blood transfusions just as debased needles and instruments utilized for inking and body penetrating. Sharing sullied individual consideration things, for example, razors and having unprotected sex are less normal methods of getting the infection.

Hepatitis C infection causes both intense and constant contamination. New HCV contaminations are typically asymptomatic. A few people get intense hepatitis which doesn’t prompt a perilous ailment. Around 30% (15–45%) of tainted people precipitously away from infection inside a half year of contamination with no treatment.

The staying 70% (55–85%) of people will create constant HCV disease. Of those with interminable HCV disease, the danger of cirrhosis goes somewhere in the range of 15% and 30% inside 20 years.

How hepatitis C harms the liver:

Hepatitis C makes harm the liver primarily as irritation, which at that point prompts scarring or fibrosis.

Hepatitis C brings about the demise of liver cells. It is unsure whether the infection slaughters the cells or in the event that it is the safe framework’s reaction to intrusion by the infection. At present it is imagined that it is likely a mix of the two, yet that the invulnerable framework’s reaction is the thing that causes the most harm. The passing of liver cells triggers the dispatching of fiery cells to the influenced territory. Irritation prompts the extension of the liver (hepatomegaly) in over 60% of individuals tainted with hepatitis C and can cause the fibro versatile sheath (Glisson’s container) encompassing the liver to extend, which might be the reason for torment in the liver region.

Irritation starts the procedures that lead to fibrosis. Fibrosis isn’t a sickness yet is a condition brought about by the body’s reaction to liver harm. Aggravation triggers a response by a gathering of cells in the liver called stellate (actually star-formed) or fat cells. At the point when the liver is working ordinarily stellate cells store fat and nutrient An in the liver. They likewise help manage the progression of blood through the liver. Be that as it may, when the liver is aroused by the nearness of hepatitis C, a response happens among various liver cells. This leads stellate cells to get rid of nutrient A, modifying their capacity.

Contaminated and aroused liver cells discharge compound signs called ‘cytokines’. These actuate leukocytes (white platelets) from outside the liver which travel to the zone of contamination. On appearance they collaborate with Kupffer cells (specific white platelets that kill and evacuate microscopic organisms, infections, parasites and tumor cells from the liver) and produce further compound signs. These signs cause stellate cells to start delivering and setting down collagen filaments in the extra cell lattice, which is the zone between the phones.

Collagen is a stringy protein which is crucial to the arrangement of scar tissue. The body’s utilization of collagen in a territory of injury is an endeavor to restrict the spread of contamination to different cells. As a contamination or injury settle, the collagen network encasing the injury is ordinarily broken down. The enacted stellate cells at that point cease to exist, permitting the tissue to come back to ordinary.

In a constant disease, for example, hepatitis C the collagen lattice becomes excessively quick and can’t be appropriately broken up. This outcomes in a development of scar tissue around cells. Liver cells lose essential access to the blood conveying supplements and oxygen thus pass on. An endless loop brings about which irritation and fibrogenic cells invigorate each other prompting expanded fibrosis.

Free Radicals and Fibrosis

A further conceivable reason for fibrosis is because of harm by free radicals. Free radicals are exceptionally receptive concoction substances. They are the result of a cell’s ordinary responses, for example, vitality age and the breakdown of fats. During these responses oxygen is changed into the free extreme superoxide. Typically cells have systems for shielding themselves from the threats of free radicals. When too many are produced, or in the event that they are not controlled appropriately, there is a peril that they will cause cell and tissue harm.

Free radicals are of worry for individuals with hepatitis C for various reasons:

• Chronic liver aggravation may prompt over-creation of free radicals inside the liver.
• There is proof that free radicals assume a job in liver fibrosis. Free radicals can synthetically change fat in the body. This is called lipid peroxidation. The free radicals assault the cell film and can harm and in the long run execute cells. In the event that this happens to liver cells, this will prompt fibrosis.

In the event that the liver capacity is now hindered and this has prompted an over-burden of iron, the free radicals may communicate with the iron bringing on additional harm.

The liver is celebrated for its capacity to recover, so for what reason doesn’t liver recovery forestall liver harm in hepatitis?

Hepatitis C is typically described by a degeneration of the liver through moderate yet dynamic scarring. The liver has two reactions to hurtful specialists which are equipped for harming its cell structure. Either there is recovery with complete rebuilding of the liver structure and capacity or there is supported scarring of liver tissue prompting harm. At the point when the liver is harmed by a solitary solid physical issue, recovery is almost certain regardless of whether an enormous zone is influenced. In any case, if the injury is tedious similar to the case with hepatitis C disease – the liver can’t successfully adapt. It doesn’t have the opportunity and space to recuperate and recover.

Transmission

Hepatitis C infection is a blood borne infection and it is most normally transmitted through:

• Injecting drug use through the sharing of infusion hardware.
• The reuse or lacking sanitization of clinical gear, particularly syringes and needles in medicinal services settings.
• The transfusion of unscreened blood and blood items.
• Sexual rehearses that lead to introduction to blood (for instance, among men who have intercourse with men, especially those with HIV contamination or those taking pre-presentation prophylaxis against HIV disease).
• HCV can likewise be transmitted explicitly and can be passed from a contaminated mother to her infant; in any case, these methods of transmission are less normal.

Hepatitis C isn’t spread through bosom milk, food, water or easygoing contact, for example, embracing, kissing and offering food or beverages to a tainted individual.

Manifestations:

The brooding time frame for hepatitis C ranges from about fourteen days to a half year. Following starting disease, roughly 80% of individuals don’t display any indications. The individuals who are intensely indicative may display fever, weakness, diminished craving, queasiness, spewing, stomach torment, dim pee, dark shaded defecation, joint torment and jaundice (yellowing of skin and the whites of the eyes).

Avoidance

Essential Prevention:

There is no viable immunization against hepatitis C, along these lines anticipation of HCV disease relies on lessening the danger of introduction to the infection in human services settings and in higher hazard populaces, for instance, individuals who infuse medications and men who have intercourse with men, especially those tainted with HIV or the individuals who are taking pre-presentation prophylaxis against HIV.

The following are instances of essential counteraction mediations.

• Safe and fitting utilization of social insurance infusions.
• Safe dealing with and removal of sharps and waste.
• Provision of far reaching hurt decrease administrations to individuals who infuse drugs including sterile infusing hardware and viable treatment of reliance.
• Testing of gave blood for HBV and HCV (just as HIV and syphilis).
• Training of wellbeing work force.
• Prevention of presentation to blood during sex.
• Hand cleanliness, including careful hand readiness, hand washing and utilization of gloves.
• Promotion of right and steady utilization of condoms.
• Know the dangers of the exercises you will be occupied with during your excursion to forestall any wounds.
• Avoid getting new piercings or tattoos on your excursion.
• Do not share needles or disposable cutters.

Optional avoidance:

The optional avoidance is for individuals tainted with the hepatitis C infection and these mediations must be kept up:

• Education and directing on alternatives for care and treatment.
• Immunization with the hepatitis An and B immunizations to forestall co-contamination from these hepatitis infections and to ensure their liver.
• Early and fitting clinical administration including antiviral treatment.
• Regular checking for early analysis of ceaseless liver malady.

Pathology of Hepatitis C

Intense Hepatitis C

Intense HCV hepatitis in immunocompetent people is to a great extent asymptomatic and, thus, it is once in a while biopsied. In any case, in indicative patients with unsettled liver capacity tests, a liver biopsy assumes a vital job in clinical and research facility work-up to decide the etiology. The clinical picture, in this setting, might be absolutely hepatitic, or a blended hepatitic and cholestatic type. The clinical differential conclusion is wide and incorporates immune system hepatitis, steatohepatitis, Wilson infection, biliary disarranges including essential biliary cirrhosis, essential sclerosing cholangitis, or a medication impact. Liver biopsy helps in showing up at an authoritative determination in a larger part of cases.

Since this is an unprecedented situation for liver biopsy, there is restricted writing on liver histology in intense period of HCV contamination. The histological range is wide and incorporates both bile pipe and lobular hepatocytic injury. Early period of ailment may show a cholestatic picture portrayed by blended entryway irritation made out of lymphocytes and neutrophils, cholangiolar expansion, cholestasis, canalicular or hepatocellular, and mellow to direct lobular aggravation (Figure1). The biopsies done in the later piece of the intense stage show mellow vague entry and lobular aggravation. Other histologic highlights incorporate an unmistakable bile conduit sore ‘Poulsen-Christoffersen sore’ that shows pipe driven lymphoid totals related with lymphocytic aggravation and injury to the bile channel legitimate (Figure2), blended entryway irritation, lobular necroinflammation with disorder, steatosis and conspicuous sinusoidal incendiary invade.

Figure 1

Liver biopsy with cholestasis, gentle entry and lobular irritation, and apoptotic bodies. Hematoxylin and eosin stain, amplification × 100.

Figure 2

Lymphocyte transcendent entry irritation and a harmed bile channel (Poulsen Christofferson injury). Periportal hepatocytes show expanding/padded degeneration. Hematoxylin and eosin stain, amplification × 200.

Intense hepatitis C in immunocompromised host, explicitly in the setting of simultaneous human immunodeficiency infection (HIV) disease, shows lymphoplasmacytic gateway irritation, interface hepatitis, and necroinflammatory lobular changes, highlights of ceaseless viral hepatitis. Moreover, liver biopsies from these patients show modestly propelled fibrosis at presentation[17] (Figure (Figure3)3) or fast movement to fibrosis over a time of time[18,19].

Figure 3

Entry and periportal fibrosis in a patient with simultaneous human immunodeficiency infection and intense hepatitis C contamination. Hematoxylin and eosin stain, amplification × 100.

Constant Hepatitis C:

The constant hepatitis is characterized as determination of disease for in any event 6 mo after the beginning of contamination. Histologically, it is portrayed by necroinflammation joined by factor level of fibrosis. The pathologic highlights of constant viral hepatitis, as a rule, have been very much described. These highlights are not explicit to interminable hepatitis C but rather can likewise be seen in constant hepatitis because of hepatitis B infection with or without hepatitis D infection, and medication incited hepatitis.

Entrance aggravation

The unmistakable element of constant hepatitis is entry based irritation with or without lobular aggravation. The inconsistent entrance extension by interminable lymphoplasmacytic aggravation is promptly obvious under low amplification as ‘blue entryway tracts’. The entrance aggravation is made overwhelmingly out of lymphocytes admixed with scarcely any plasma cells and uncommon eosinophil, the alleged lymphoid follicles or lymphoid totals (Figure (Figure4).4). The aggravation is of variable force, and changes among various entryway tracts in a single biopsy, among sequential biopsies from one patient, and fluctuates from patient to quiet. Now and again, plasma cells might be noticeable and these can be depicted as having immune system highlights. On the off chance that clinical and serological highlights of immune system hepatitis are available, this can speak to a cover disorder of immune system hepatitis and hepatitis C (Figure (Figure5).5). Entry and lobular macrophages can be available and may contain overwhelmed flotsam and jetsam as shade or PAS positive-diastase safe material and is viewed as a proof of late movement (Figure (Figure6).6). Entrance as well as remarkably focal endothelialitis can be seen.

Figure 4

Stringy septa with lymphocyte overwhelming incendiary invades and different lymphoid totals, in a patient with cirrhosis auxiliary to hepatitis C. Hematoxylin and eosin stain, amplification × 40.

Figure 5

Entry lymphoid total and lymphoplasmacytic aggravation with serious interface hepatitis, demonstrative of a cover disorder of immune system hepatitis and hepatitis C. Hematoxylin and eosin stain, amplification × 100.

Figure 6

Little groups of lobular macrophages containing intermittent corrosive Schiff positive-diastase safe cytoplasmic flotsam and jetsam. Intermittent corrosive Schiff with diastase stain, amplification × 200.

Entry lymphoid totals, bile conduit harm, steatosis

The lymphoid totals happen in nearness to bile conduits and are here and there related with harm to bile pipe epithelium that was initially depicted by Poulsen and Christoffersen. The bile channel harm is gentle and non-dangerous, and is portrayed by cell vacuolation, cytoplasmic eosinophilia, atomic covering and atomic dropout.

The bile conduit sores are visit and have been accounted for in as high as 91% of cases, and are increasingly predominant in hepatitis C genotype 3a.

Steatosis, macrovesicular or blended macrovesicular and microvesicular type, is a viral cytopathic impact, that when present is a trademark highlight of ceaseless hepatitis C and is generally found in relationship with hepatitis C genotype 3a. The steatosis in this setting is normally mellow and is periportal or azonal in appropriation. The steatosis is proposed to be auxiliary to free radical intervened peroxidation that is inspired by expanded infection incited iron stockpiling. Nearness of moderate to stamped steatosis in a liver biopsy, particularly in a centrilobular/perivenular appropriation, from a patient with hepatitis C should raise a clinical thought for attendant greasy liver malady auxiliary to heftiness, liquor, hyperlipidemia or diabetes. Such cases may, likewise, show neutrophilic penetration, expanding degeneration, and Mallory-Denk-hyaline and pericellular/perisinusoidal fibrosis.

Iron affidavit

Different highlights of interminable hepatitis C incorporate iron statement. Gentle iron testimony happens in both hepatocytes and sinusoidal coating Kupffer cells in constant viral hepatitis. Appraisal of iron in liver biopsy is relevant, as hepatocellular iron affidavit has been demonstrated to be an opposite indicator of reaction to interferon treatment. Perls stain is the most normally utilized stain for surveying hemosiderosis in liver as a result of high affectability. The iron statement in hepatocytes is evaluated and normally reviewed utilizing the Searle’ adjustment of Scheuer scoring framework for iron testimony. Inherited hemochromatosis is consistently a clinical thought in nearness of hepatocellular iron in liver biopsies, even in limited quantities, on account of variable penetrance of the ailment.

Fibrosis

Fibrosis is a unique reparative procedure and is an outcome of incessant aggravation, hepatocyte misfortune and recovery in viral hepatitis. Fibrosis as a rule begins in the entryway tracts bringing about extension, and afterward stretches out to periportal tissue as dainty sinewy septa that represent the unpredictable forms of the gateway tracts. As the ailment advances after some time (typically 10-20 years), the sinewy septa connection to adjoining gateway tracts or focal veins and advances into crossing over fibrosis. This joined with hepatocytic recovery prompts engineering mutilation, development of knobs and inevitable cirrhosis (Figure (Figure10).10). Cholestasis isn’t a component of hepatitis C, however can be seen in cirrhotic livers with decompensation. The phase of fibrosis is best surveyed on connective tissue stains, for example, Masson’s trichrome stain.

Figure 10

Cirrhosis described by crossing over fibrosis with knob development. Masson’s trichrome stain, amplification × 40.

Fibrosis has by and large been viewed as an irreversible procedure. A few examinations have detailed reduction in fibrosis scores following treatment of the etiological procedure in an assortment of ailments, for example, steatohepatitis, hemochromatosis, Wilson malady, Indian youth cirrhosis, biliary hindrance, immune system hepatitis, ceaseless viral hepatitis. In liver tissue of patients with interminable viral hepatitis, the fibrosis has been believed to relapse with antiviral treatment and supported viral reaction and annihilation. The relapse is restricted to diminish or vanishing of sinewy septa on histological assessment, be that as it may, the sequelae of cirrhosis, for example, an arteriovenous shunt may persevere.

Introduction

Hepatitis B and hepatitis C are highly infectious diseases and occur due to being infected by the hepatitis B virus (HBV) and the hepatitis C virus (HCV) respectively. Millions of people worldwide are infected with these viruses and the infected population can suffer from long term complications such as liver cirrhosis or hepatocellular carcinomas (Busch & Thimme, 2015). A contrast and comparison of both HBV and HCV will be presented in this report. The viruses’ morphology, epidemiological features, pathophysiology, clinical presentation and immune system responses will be examined and measured. Legislative requirements will also be highlighted alongside infection prevention and control measures.

Etiology, Morphology, Incidence and Prevalence

The HBV antigen, originally named the Australia antigen, was first recognised in 1967 by Dr Blumberg (Saeed, Waheed, & Ashraf, 2014). This virus spreads through mucosal and percutaneous exposure to infected blood or other bodily fluids, including salvia, seminal, and vaginal fluids. Infection can also occur through perinatal, and horizontal transmission (Hyun, Lee, Ventura, & McMenamin, 2017; Orlando et al., 2015). Similarly, HCV is likewise transmitted through percutaneous blood exposure. This exposure is generally a result of unsafe intravenous drug administration, perinatal exposure, high risk sexual activity, use of unsterilized medical equipment and administration of blood products not tested for HCV (Manns et al., 2017).

HBV is a double-stranded Deoxyribonucleic acid (DNA) virus and is a part of the hepadnaviruses family, while the HCV is a single stranded spherical ribonucleic acid (RNA) virus from the Flavivirus family. The HBV virion, commonly known as the Dane particle, is a double shelled particle. The outer envelope encloses the surface antigen known as the (HBsAg), while the inner envelope contains the viral nucleocapsid element of HBV core antigen (HBcAg). It is the HBcAg-derived peptides which stimulate the infected person’s cellular immune response against HBV (Doo & Ghany, 2010; World Health Organization, 2015). HCV is an enveloped virus that has an inner core of RNA which is encased in a protective protein shell, which is surrounded by a lipid envelope (Dubuisson & Cosset, 2014). Embedded within the lipid envelope are E2 and E1, which are glycoproteins required for the virus to viral attachment and cellular fusion (Dubuisson & Cosset, 2014; Freedman, Logan, Law, & Houghton, 2016). It is the HCV core protein that is a key factor in the development of liver disease; it affects the cell cycle regulation, cell growth promotion, cell proliferation, lipid metabolism and apoptosis (Mahmoudvand, Shokri, Taherkhani, & Farshadpour, 2019). There are seven different HCV genotypes, and they are classified accordingly (1-7). Genotype 1 being the most common. Genome 1 accounts for 46.2 percent of cases of HCV (Mohamed, 2015).

A systematic review performed by Ott, Stevens, Groeger & Wiersma (2012) reviewed the prevalence of HBsAg globally over a 27-year period. From their review, it was determined that the global prevalence of HBV in 2005 was 3.7 percent, with an estimated 240 million people infected. The region with the highest HBV incidence was the western sub-saharan of Africa. (Ott et al., 2012). HBV has an estimated 786,000 deaths each year (Lozano et al., 2012). A report by Petruzziello, Marigliano, Loquercio, Cozzolino & Cacciapuoti (2016) showed that the worldwide prevalence of HCV infection was an estimated 177.5 million people. HBV is more commonly reported in developing countries in Asia and Africa, with lower prevalence rates in industrial nations (Mohamed, 2015). HCV has been considered one of the world’s leading causes of morbidity and mortality, however overall HBV has a higher incidence.

Pathophysiology and Clinical Presentation

The HBV has an incubation period of 12 weeks on average, this is the acute infection phase (Baker, 2017). During the acute infection phase, clinical manifestations include fatigue, jaundice, vomiting, nausea, and pain (abdominal, arthralgia, and myalgia) (Busch & Thimme, 2015). Between 60 and 95 percent of infected individuals are asymptomatic (Mantzoukis et al., 2017). However, the clinical manifestations cannot distinguish an acute HBV infection from the other forms of acute viral hepatitis (Busch & Thimme, 2015). The constantly proliferating hepatocytes cause the virus to continue to shed into the blood stream, this contributes to the acute infection developing into a chronic HBV infection (McMahon, 2008). This signifies that the immune system has been unsuccessful at eradicating the virus. HBV infection becomes chronic in five to ten percent of adults (Zuckerman & Zuckerman, 2010). Spontaneous conversion to HBsAG negativity occurs in roughly one to two per cent of chronic carriers, however in 20 percent of HBsAG-positive carriers’ spontaneous reactivation of HBV occurs (Torresi, 2010). Chronic HBV infection can have long term complications, this includes cirrhosis, liver fibrosis, and hepatocellular carcinoma (Baker, 2017). 80 percent of all hepatocellular carcinomas are a result of chronic HBV (Torresi, 2010).

The initial period where a person becomes infected with HCV is known as an acute infection. This incubation period lasts 15 to 150 days, with people mainly presenting with fatigue, weakness, or malaise (Westbrook & Dusheiko, 2014). During this period the infection can be cleared spontaneously by the host immune system, through cell medicated response (Terilli & Cox, 2012). However, 75 to 85 percent of patients fail to clear the disease, and if the HCV virus remains for more than six months it is considered a chronic HCV infection, and progressive liver damage is likely to occur (Cobo, 2014). The development of liver cirrhosis and further hepatic complications occurs in 15 to 30 percent of patients with chronic hepatitis C, and this occurs over the course of 20 to 30 years (Centre of Disease Control and Prevention, 2018). This progression is hypothesised to occur due to locally driven immune responses, which can lead to hepatic decompensation with clinical manifestations such as upper gastrointestinal bleeding, ascites, hepatic encephalopathy. Further progression can result in the development of hepatocellular carcinoma (Ismail & Cabrera, 2013).

The Role of the Immune System

The immune system is critical in HBV and HCV infections for determining the outcome of the infection. Innate and adaptive immunity is the first line of defence to protect the body against the virus, as it provides recognition of viral proteins and fights the production of interferons (Tan, Koh, & Bertoletti, 2015). Activation of acquired immunity is an essential component of adaptive responses, this is through the production of antigens and their specific responses.

The innate immune response has a weak activation in HBV infections, this is a result of a lack of induction of interferons α and β (Tan et al., 2015). This is hypothesised to be caused by the HBV escaping innate recognition, and inhibiting the virus’s replication (Chisari, Isogawa, & Wieland, 2010). In an acute infection, the adaptive immune responses have been recognised as important in the resolution of the HBV. This response includes different effector cell types including Cluster of Differentiation (CD) 4 T cells and CD8 cytotoxic T lymphocytes and B cell antibody production (Tan et al., 2015). These are required to eradicate HBV infected hepatocytes by noncytokine and cytokine mechanisms, and therefore they can reduce the overall circulating viral levels (Cheng et al., 2017). It is the B cell antibody production which assists in preventing reinfection by neutralising free viral particles. The adaptive anti-viral immune response is only induced after an acute infection has occurred. The CD8 T-cell responses are important in an acute infection but cannot clear the virus in chronic carriers (Chisari et al., 2010; Mackie, 2011). It is these processes that cause alanine aminotransferase (ALT) to be released and can result in the development of cirrhosis due to the production of liver fibrosis (Trépo, Chan, & Lok, 2014). This immune response being so vigorous and aggressive can be the cause for such a fulminant HB infection, and therefore improving antiviral immunity can assist in controlling the HBV (Tan et al., 2015; Trépo et al., 2014)

Similar to HBV, the innate and adaptive immune responses are a key factor in the viral clearance of HCV, however these responses are often mild and facilitate the development of chronic infection but can prevent liver damage (Manns et al., 2017; Spengler, Nischalke, Natterman, & Strassburg, 2013). Natural killer cells are considered to be involved in the innate immune response to clear the HCV infection (Dustin, 2017). The adaptive immune response, similar to HBV, relies on T cell and antibody responses to control the infection. However, these antibodies have been shown to have limited activity against the HCV (Dustin, 2017). Comparable to HBV, spontaneous viral clearance is a consequence of CD4 and CD8 T cell responses. The HCV maintains persistent and this has been attributed to early loss of or inadequate T cell responsiveness (Spengler et al., 2013). Interferon stimulating genes are produced during the acute phase of HCV, but similarly to HBV this causes a poor response, and is ineffective at clearing the virus (Dustin, 2017). Chronic HCV infection evolves most commonly due to an alteration of immune responses or rapid exhaustion. The effect of immune system is apparent in the clearance of HBV and HCV; these responses are both positive and negative shows that there is the possibility of development to become a chronic carriage with liver protection mechanisms. However, more research is required to fully understand the immune response in all viral hepatitis diseases.

Diagnosis

Australian health professionals need to follow the National Hepatitis B Testing Policy when diagnosing HB (National Hepatitis B Virus (HBV) Testing Policy Expert Reference Committee, 2015). This policy helps guide health professionals and insures that current testing practices are upheld. As previously mentioned, the HBV is impossible to differentiate from other hepatitis viruses, and therefore proper laboratory diagnosis is critical for confirmation of the disease (World Health Organisation, 2018a). There are multiple tests that can diagnose and monitor people infected with HBV and can distinguish between an acute or chronic infection (World Health Organisation, 2018a). Tests to detect HBsAg and HBeA called serologic protein antigen tests, and antiHBs, anti-HBe, IgM anti-HBc, and total anti-HBC, are detected through serologic antibody assays (Baker, 2017). These tests can determine if a person has a HBV infection, if it is acute or chronic, how long they may have had the infection, what phase of chronic infection they are in, if a person has cleared the infection, or is immunised against the HBV (Hepatitis Victoria, 2019). Other tests such as the polymerase chain reaction assay, and nucleic acid amplification testing are recommended by Baker (2017) within the “Red Book” and they can detect and enumerate HBV DNA in serum or plasma. However, this is from an American text and some of these tests are not frequently used in Australia for just a diagnosis of HBV, but more so for reference testing.

HCV is commonly asymptomatic, and therefore diagnostic testing is rarely done during an acute infection phase and are mostly performed on people who have developed a chronic HCV infection, but usually only once secondary conditions develop (World Health Organisation, 2018b). Currently in Australia a person is first screened for HCV through a serology test also known as an antibody test, this test indicates if the person has had exposure to HCV, this can either be a past or current infection (Burke, 2014). The method for confirmation of diagnosis for a current HCV infection is through a polymerase chain reaction assay to look for HCV RNA. This test can indicate the presence of the HCV virus, and the viral load. As a result, this test is important to perform as a person with a positive serology test can be positive for multiple repeated serology tests but has no detectable HCV RNA in the assay (Holmes, Thompson, & Bell, 2013). This can be a result of a past HCV infection which has spontaneously cleared or been cleared through treatment. The National Hepatitis C Testing Policy released by the Australian Government Department of Health recommends that a person be subjected to at least two serology tests if deemed reactive before being subjected to supplemental testing to confirm a true positive result (National Hepatitis B Virus (HBV) Testing Policy Expert Reference Committee, 2015). Once a true positive result is confirmed, further testing should be done to determine the degree of liver damage as a result of the HCV infection. This should include a liver functioning profile, liver imaging, and/or liver biopsy (Holmes et al., 2013).

Infection Prevention and Control Considerations

HBV and HCV infections are considered to be a principal public health concern, this is due to its commonality, long lasting health impact, and that infected persons are often unaware that they have the infectious disease (Centres for Disease Control and Prevention, 2019). People who identify as indigenous Australians, people who participate in high risk sexual activity, and intravenous drug users are considered the be at high risk of being infected with HBV (Communicable Diseases Network Australia (CDNA), 2018). Likewise, HCV is most prevalent in intravenous drug users, but also through unsterile medical procedures such as blood transfusions, or unsterile vaccinations, this is more common in developing countries (Holmes, Thompson, & Bell, 2013). Therefore, education to the general public and health professionals is essential to reduce prevalence, and also ensure early diagnosis to ameliorate overall outcomes (Ditah et al., 2014).

As mentioned, intravenous drug users are at the most risk from transmission of HBC and HCV, thus implementing safe infection sites with medical supervision has been shown to reduce the risk of blood borne infections in intravenous drug users (Gastroenterological Society of Australia, 2018). These sites aid in providing sterile needles, reducing needle sharing, and by providing education on harm minimisation strategies.

Within a health care setting the prevention and control of HBV and HCV infections revolves around adherence to standard precautions (Gastroenterological Society of Australia, 2018). Through standard precautions health professionals treat all patients with the assumption that their body fluid or blood is potentially infectious. Isolation of patients with either virus is not required (Gastroenterological Society of Australia, 2018). However, ensuring that all health care workers and at-risk individuals are vaccinated against HBV is paramount in reducing the potential for the infection to spread. As health care workers can be more exposed to the HBV and HCV infected population, as well as other blood borne infectious diseases education of safe needle handling and phlebotomy is critical to reduce the prevalence of needle stick injuries, which can result in the health care worker seroconversion depending on if it is a HBV or HCV infection, and the viral proteins present, can be of low to high risk (Holmes et al., 2013).

Within areas of high prevalence of hepatitis b and c, including correctional facilities and haemodialysis units, increased screening has been identified has a way to control the infection risk, and provide early treat treatment for patients, while also minimising the risk to the overall population in these areas (MacArthur et al., 2014).

Legislative reporting requirements and Drug Resistance

Within Australia both HBV and HCV are notifiable diseases in every state and territory. Specifically, in Victoria, there is a statutory requirement where notification to the Department of Health, in writing, is required within five days of a diagnosis of hepatitis b or c. This is under the under the Public Health and Wellbeing Regulations 2009 (Communicable Diseases Network Australia (CDNA), 2018).

For a patient receiving treatment for hepatitis b or c one way is through antiviral medication. The main aim for antivirals is to reduce the virus from replicating and further damaging the liver, thereby making it possible for the liver to somewhat repair its self, but it is unlikely to provide much in the way of a cure (Kim, Han, & Ahn, 2016). However, these antivirals can cause the HBV to mutate, causing the antivirals to become less effective at targeting the HBV (Keeffe et al., 2006). This drug resistance is a nationwide concern, as more and more viruses and bacterium are mutating and causing our current forms of treatment to become redundant (Kim et al., 2016). Therefore, it is important for the patient to be closely monitored during treatment to monitor for signs of resistance.

Conclusion

In conclusion, an overview and comparison of HBV and HCV was delivered in this report with focus on the viruses’ morphology, epidemiology, aetiology, clinical presentations, pathophysiology, diagnosis, immune response, and implications for infection prevention and control, and legislative requirements. Overall, it shows that it is prevention, early diagnosis, monitoring, and early treatment which are pivotal in reducing the incidence, long term complications, and recognising resistance to treatment.

References

1. Baker, C. (2017). Red book. Elk Grove Village, IL: American Academy of Pediatrics.
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Context

Hepatitis C is a contagious disease caused by the HCV virus. It is one of the main causes of chronic liver disease and cirrhosis worldwide, resulting in a large proportion of all liver transplants in the United States, Australia & most of Europe. Hepatitis C was first isolated from non-A, non-B Hepatitis in 1989 and accounts for 90% of such cases (Chen & Morgan, 2006). An estimated 180 million people are infected with Hepatitis C globally with highest concentrations in Sub-Saharan Africa and East Asia (Strader & Seeff, 2009). In Ireland, around 700-800 new cases are identified each year. However, as the symptoms are similar to that of the flu, many cases go unidentified. It’s prevalence rate is estimated at 2.2% globally and between 0.5% and 1.2% in Ireland (Thornton et al, 2011). Hepatitis C is divided into two types depending on duration of illness, Acute Hepatitis C and Chronic Hepatitis C. Acute Hepatitis is generally diagnosed as a short-term illness that develops within the first 6 months of exposure to the virus. Approximately 75%-85% of those with Acute Hepatitis C will develop Chronic Hepatitis C (where the infected person’s body cannot get rid of the virus). Depending on the presence of cofactors (such as heavy alcohol consumption and older age when HCV is acquired), between 10% and 40% of patients with chronic Hepatitis C infection will develop cirrhosis (European Association for the Study of the Liver 2011 EASL Clinical Practice Guidelines Management of hepatitis C virus infection, 2011). Unlike Hepatitis A and B, there is no Hepatitis C vaccine.

Hepatitis C can be split into at least six genotypes (with genotypes 1 and 3 being the most prevalent in Ireland) and consequently, in this study, we are dealing with genotypes 1, 2 and 3. Each genotype can be further classified according to its subtype (which is denoted by a lower-case letter). The classification of genotypes and subtypes is important in order to determine the most suitable treatment method for an infected patient.

The Hepatitis C virus is carried in the blood, and most commonly infects a person if blood from someone who is already infected enters their body. The most common way this occurs is via the sharing of needles between a person who is infected and a person who is not, as a means of injecting drugs. Therefore, drug users are more likely to be infected with Hepatitis C.

It is also possible for Hepatitis C to spread as a result of sexual transmission, getting tattooed or being born to someone infected, although this is rare. Only 6% of infants born to mothers infected with Hepatitis C will, themselves, get infected (Centres for Disease Control and Prevention, 2015).

Of those with acute Hepatitis C, approximately 10-15% experience flu-like symptoms including fever, nausea and jaundice. The majority of acute cases don’t exhibit symptoms, so many are unaware that they have become infected. Most chronic cases of Hepatitis C are also asymptomatic, hence the virus usually only becomes noticeable after several years after infection, when the liver is sufficiently damaged. These patients can develop serious issues such as cirrhosis, fibrosis and liver cancer in approximately 6-8% of cases infected for over twenty years (Keating, 2003).

Motivation/Rationale

Chronic Hepatitis C is diagnosed using viral load tests and hence, it is important to be able to identify a 95% hit rate and a 95% confidence interval for the LOD for each genotype as we are doing in this study. Viral Load tests are blood tests in which the genetic material of the HCV virus, or its ribonucleic acid (RNA) is measured. Viral load tests have two main categories: qualitative tests, which determine whether or not HCV RNA is present in the blood, and have either a positive or a target not detected test result; and quantitative tests, which measure the amount of HCV RNA in one millilitre of blood. Viral load is typically measured in International Units per mL (IU/mL). A viral load test result is interpreted as low for a measurement of less than 800,000 IU/mL (5.90 log10 IU/mL) and high if a measurement greater than this is obtained, though it is disputed whether or not this is a feasible cut-off point (Franciscus & Highleyman, 2012). Log10 IU/mL units are commonly used to represent the viral load due to a tendency for transcription errors to occur when dealing with large figures of IU/mL.

Viral Load tests are used to track the progression in the treatment of HCV patients. When the virus can no longer be detected (ie. the Viral Load is below the LLOD), a virologic response (VR) is said to have taken place, which gives an indication that this method of treatment is effective on the patient. The patient’s Viral Load then continues to be monitored over time and if it remains below the LLOD (ie. result of Target Not Obtained, TND), a sustained virological response (SVR) is said to have occurred. However, it is pertinent to mention that due to the high cost of testing, the patient is generally tested at commencement of treatment, after 4 weeks and again usually after 3 months. It is very rare for a patient who achieves a SVR to ever become infected with HCV again. In a study on the “Risk of Late Relapse or Reinfection With Hepatitis C Virus After Achieving a Sustained Virological Response” carried out B. Simmons in 2016 of “low-risk” patients (n = 7969),the 5-year recurrence rate was found to be 0.95%. (B. Simmons, 2016)

Safety issues and side effects of the treatment are a major concern for many treatment approaches. For example, a small sample-size study carried out by Ghany, Stradder, Thomas and Seeff in 2009 found that despite 90% of patients who were treated with the drugs peginterferon and ribavirin achieving a SVR, the majority of patients experience adverse events during the course of therapy. Influenza like side effects such as fatigue and headache occurred in greater than half of the patients and Neuropsychiatric side effects (including anxiety, depression, insomnia,, mood disorders,, suicidal ideation, actual suicide, and homicide) occurred in 22% to 31% of patients. (Ghany Strader Thomas & Seeff 2009) These side effects of the drug, coupled with the high rates of adverse events such as severe neutropenia and anemia, means that it is crucial for whoever is administering the test to know the 95% hit rate and a 95% confidence interval for the LLOD, to limit the occurrence of false diagnoses or incorrect interpretation of the treatment progression of a patient.

Research Questions

This study aims to identify the 95% hit rate known as the Lower Limit of Detection (LLOD), a 95% confidence interval for the Lower Limit of Detection samples and finally, relate this to the manufacturing standard. In other words, we are trying the find the values for the Viral Load in International Units per ml (IU/mL) which will result in a greater than 95% probability of a positive hit. The hit rate is the number of positive tests (ie. hits) divided by the total number of replicates performed at each Viral Load. The total number of replicates performed at each Viral Load can be thought of as the sample size at that Viral Load (VL). For example, the “COBAS® AmpliPrep/COBAS®TaqMan®HCVTest” (diluted in EDTA plasma matrix) has 95% confidence limits for the hit rate of 11–19.8 log10 IU/mL, while the same test diluted in serum matrix (instead of plasma matrix) has 95% confidence limits for the hit rate of 8.4–14.8 log10 IU/mL (Sizmann et al, 2007).

In addition, we want to ascertain whether or not this 95% Confidence Interval can be considered to be the same across the three genotypes which are dealt with in this study, namely Genotypes 1, 2, and 3. Each genotype has a separate set of data, which tells us the Viral Load of the sample, the number of hits and the total total number of replicates performed. We are not given data regarding what sub-genotype each sample belongs to and hence, do not check whether or not this 95% Confidence level is the same across sub-genotypes.

Finally, the study seeks to identify the level of the Lower Limit of Detection and to compare this level to the manufacturing standard. The Lower Limit of Detection (LLOD) is the lowest actual value for the Viral Load in a sample that can be detected with 95% probability. We want to compare these 95% hit rates for the three genotypes to manufacturing standards for the LLOD, given to us as a figure for the LLOD of 1.18 log10 IU/mL.

There are numerous possible reasons for differences between the value of the LLOD indicated by our samples and those given by the manufacturer. Firstly, the sample of blood we are testing might not have a uniform level of viral load. This could lead to us taking a sample that does not reflect the viral load of the blood as a whole. The blood is also frozen multiple times, which could have an effect on the viral load. Other factors such as the Assay Manufacture/Device used and whether the test was carried out on Blood Serum or Plasma also provide potential for our level for the LLOD to different from manufacturing standards. Hence, it is important to calculate this LLOD value (as is the purpose of this study) instead of assuming that the manufacturing standard holds.

Kentucky S.B. 250: An ACT Relating to Screening for Hepatitis C

Hepatitis C (HCV) is a chronic infection that attacks the liver and if not treated liver failure, cancer, and/or death can be the result. This infection is spread through contact with contaminated/infected blood and most individuals that are carriers of Hepatitis C have no symptoms. Typically, we know the most common spread of HCV is done through dirty needles, but what about spreading it inutero if an infected person was pregnant? According to the Centers for Disease Control and Prevention, “a mother can transmit Hepatitis C to her baby via pregnancy, during delivery, and/or up to a month after the baby is born.” On March 1, 2018 a bill was proposed in Kentucky to screen all pregnant women for HCV, where as previously only pregnant women who were high-risk were screened for HCV (Kentucky General Assembly, 2018). The bill also states that it is recommended babies get tested if their mother did in fact test positive for HCV. By testing every pregnant woman and the babies born to a positive tested mom for HCV we are able to help identify, treat, and slow down the spread of transmission. This bill, now a law, was passed in April of 2018. Kentucky is the first state to require HCV testing to all pregnant women and it will be done at their first prenatal appointment. As an advanced practice nurse (APN) this is something that is needed to be implemented in everyday practice. If you are an APN in an obstetric office you would need to screen every pregnant woman that you see, if it hasn’t already been ordered. HCV antibodies can cross the placenta and be passed from the pregnant woman to the baby, therefore the presence of antibodies in the baby’s blood right after delivery is not enough to make a diagnosis for neonatal infection of HCV (Hughes, Page, & Kuller. 2017). The American Academy of Pediatrics and the CDC recommend for screening to be completed after the baby is 18 months of age (Hughes et al., 2017). I will be working in a Neonatal Intensive Care Unit (NICU) as an APN and it will be very important to always review the mother’s HCV results and know whether follow-up testing for baby is needed. Education will need to be provided to the mother regarding possible transmission to baby, breastfeeding, the importance for follow up, and when and where the screening process for baby will take place.

Sociocultural Environment

There is a big opioid crisis happening right now in the United States. This epidemic is seeing a lot of individuals using drugs intravenously (IV) with a syringe and needle. When IV drug users share needles, they can spread HCV to other individuals. “Sharing or reusing needles and syringes increases the chance of spreading the Hepatitis C virus. Syringes with detachable needles increase this risk even more because they can retain more blood after they are used than syringes with fixed-needles,” (Centers for Disease Control and Prevention, n.d.). Because of the widespread opioid crisis where sharing needles is common the rates of HCV are increasing. According to the Centers for Disease Control and Prevention (CDC), HCV has increased by 400% from 2004-2014. While the onset of

Hepatitis C can last a few months, some people may not have any symptoms, thus mothers would not know they are infected and could pass it along to their baby. Originally, Kentucky’s law was to only test women at risk for HCV but now have decided to test every pregnant woman, regardless of risk factors, so that treatment can be an option, and baby can be monitored throughout life. This overall will help to decrease the spread of HCV, despite the opioid crisis happening.

Ethical Environment

Pregnant women are among a population of vulnerable individuals. Prior to screening every pregnant woman, it was only women who were at risk for HCV. Women of childbearing age, the most common risk factor would be drug use. If a provider wasn’t 100% sure the patient was an IV drug user and decided to test them for HCV, then that could make the patient feel stereotyped. The principle of justice comes into play by testing every single pregnant woman that seeks prenatal care. The principle of beneficence would be testing a pregnant woman who potentially could be infected with HCV in order to identify the infection and to provide treatment. Treatment decisions would be autonomous in the context of the doctor-patient relationship (Geppert, Arora, 2005).

Economic Environment

Screening every pregnant woman (universal screening) versus risk-based screening (only those who have risk factors) is more cost effective. “While universal screening cost $308 more per patient, the associated incremental cost-effectiveness ratio was $18,139 for each active infection that was identified, with a quality-adjusted life year gained of $4662, which is below the willingness-to-pay cost-effectiveness threshold,” (Dangi-Garimella, 2018). Dangi-Garimella explains that although there is an increase in cost with this screening the undiagnosed women will be able to be identified and able to receive care, thus offsetting the cost.

Political Environments

Amidst the major opioid crisis, we are experiencing in Kentucky, the rate of HCV births has drastically increased. We as a healthcare system have fallen short in attempting to prevent and control the disease. “Experts say as many as 46,000 U.S. children are living with hep C, and research shows Kentucky fares much worse than other states because drug use among young women is so widespread. One federal study showed the disease rose 213 percent in four years among Kentucky women of childbearing age – nearly 10 times the national rise of 22 percent,” (Ungar, 2018). This Senate Bill was passed without discussion, it was evident that more needed to be done.

Legislative Environment

Senate Bill 250 was introduced in March of 2018 by Republican Senator, Julie Adams.

Passage and Progression

36 bill sponsors from the senate supported SB 250 to screen all pregnant women for Hepatitis C. The sponsors include these legislators by last name: Alvarado, Bowen, Buford Carpenter, Carroll D, Carroll J, Embry, Girdler, Givens, Harper Angel, Harris, Higdon, Hornnback, Humphries, Jones, McDaniel, McGarvey, Meredith, Neal, Parrett, Raque Adams, Ridley, Robinson, Schickel, Schroder, Seum, Smith, Stivers, Thayer, Thomas, Turner, Webb, West, Westerfield, Wilson, and Wise. There were 0 nays, 0 passes, and 2 legislators that did not vote. In the house of representatives there were 97 yeas (35 Democrats, 62 Republican), 0 nays, 0 abstained, and 3 who did not vote (Kentucky Legislature, 2018).

Stakeholders consists of the House of Representative and the Senate (133 legislators) that were all in favor of SB 250. There wasn’t anyone who opposed the bill, although 5 legislators did not vote. It was said that there was no discussion for this bill because the outcome was unanimous therefore there weren’t any difficulties in the effort to pass the bill (Ungar, 2018). Healthcare consumers have seen a positive outcome resulting from this bill due to the opportunity for treatment and monitoring of their children for HCV. Healthcare providers benefit from screening each patient so that they can be properly treated and monitored (babies) all while being cost effective. I believe if this did not end up being cost effective albeit more testing, then difficulties would have been faced.

SB 250 was introduced by Senator Julie Adams in the Senate on March 1, 2018 and then to Health and Welfare on March 5. By the 14th the bill was reported favorably during its first reading and had its second reading the following day. On the 16th the bill passed the Senate 36-0 during its 3rd reading. On March 19 the bill moved along to be received by the House and then to Health and Family Services by March 21. On the 22nd the bill was reported favorably during its first reading. The second reading in the House was on the 27th and on March 29th the third reading took place, where it passed 97-0. The bill then went back to the Senate on the same day where it was signed by Bertram Robert Stivers II, President of the Senate, and David Osborne, Speaker of the House and then delivered to the Governor. On April 10, 2018 SB 250 was signed by the Governor, Matt Bevin (Legiscan, 2018; Kentucky, C.O, n.d.; Kentucky Senate Leadership, n.d.; Loftus, T. 2018).

Effects on Consumers and Providers

Overall there is mostly positive outcomes of this bill. Positive impacts this would have on consumers is early detection of HCV when pregnant, treatment plans, and testing for babies delivered to HCV positive mothers. Negative impacts would be cost of treatment, cost of screening your baby, cost of their treatment if positive, and the stigma of having such results. Positive effects for providers would be knowing if their patient is HCV positive so that they can adhere to proper precautions during examinations and delivery of the baby. Negative impacts on providers would be for more educational opportunities such as communication for the screening. Since testing is completed during the first antenatal visit it is important to provide the patient with effective communication in order to build a rapport (Oni, H., Buultjens, M., Abdel-Latif, M., Islam, M., 2018). Time constraints at the first antenatal appointment, the presence of family members during the visit, and a concern about anxiety and/or guilt of the patient are other negative impacts on providers (Oni, et al. 2018). Short-term negative effects would be getting into the habit of screening each and every pregnant patient. Long-term negative effects could possibly be the amount of treatment provided for HCV positive women depending on the cost for each patient. Short-term positive effects would be for patients to be able to seek treatment earlier and be knowledgeable about screening their baby at 18 months, if needed. Long term positive effects of SB 250 would be to decrease the overall number of persons infected with HCV and transmission rates.

Hepatitis Screening Among Pregnant Women in Egypt

Although Egypt is the world’s highest prevalence of HCV, it relies on risk-based screening instead of universal screening. A study was completed to determine how reliable the risk-based only screening is in Egypt. “Prevalence of HCV infection in pregnant women in the US is estimated to range from 1 to 2.4% and in Egypt 15.7%–19%,” (El Kamary, et al, 2015). Despite having the highest rates of contracting HCV Egypt only practices risk-based screening which is insufficient. All these women may have no idea that they are even infected, have no symptoms, and no history of risk factors (El Kamary, et al, 2015). Waiting for women to develop long term complications from HCV before being diagnosed is worrisome, states El Kamary, et al (2015). Directly Acting antiviral medication (DAAs) have been approved and are highly effective in treating HCV and preventing the progression of liver disease. Although DAAs are effective in treating HCV the more prevalent the disease the higher the cost could become (Spengler, 2018). The Egyptian government was able to drive down the price initially and then even more once a generic form of medication became available from $900 to $84 per patient (Halter, 2018). Egypt is a country of limited resources, unlike the United States were resources are plentiful, so it is important to maintain cost effectiveness within HCV treatment. “The HCV sustainable MOC in Egypt is considered a successful disease control programme serving up to 6 million patients. This model provides access to all HCV‐infected individuals and an action plan and strategy for prevention of new infections. This control programme aims at elimination of HCV in Egypt in accordance with the WHO and global targets,” (El-Akel, 2017). “In 2017, the Egyptian Ministry of health also initiated a nationwide screening program through which more than 260 teams of community health workers go village to village testing people for the virus. So far, they’ve screened more than 1,200 towns, cities and villages, targeting poor, rural communities. Meanwhile, less than 20 percent of those estimated to be living with chronic hepatitis C in the United States have received treatment,” (Halter, 2018). Egypt is taking great strides by using their model of care and screening programs to decrease transmission of HCV, something the United States doesn’t offer. According to the El-Kamary study (2015) All pregnant women accepted the universal screening instead of rosk-based. If risk-based screening was the screening of choice it would have missed 10% of pregnant women in the study with chronic HCV. With that being said I think it would be even beneficial for Egypt, the world’s highest level of HCV prevalence, to start implementing universal screening for pregnant women.

Options for Refinement and Change

Although there aren’t many ways to improve a great policy, the communication between the physicians and the consumers could be better. Communication about mandatory testing for HCV to the patients when making their first prenatal appointment to lessen any awkwardness, prepare for who would accompany you to the visit, and to overall just to be aware of the new law that has taken place would be helpful. Another improvement that can possibly be foreseen would be to go out into the community and target the population of women who typically do not seek prenatal care. I understand this could potentially be costly but having a representative of the delivering hospital reach out and test the women not seeking or has limited prenatal care. Although not everyone would be located this would help to somewhat fill in the gap for this population. “Many young women may consistently seek medical care only during pregnancy. As has been previously noted for HIV and anecdotally by many HCV experts, the compliance of pregnant women for testing and follow-up is higher as they consider the future of unborn children. Studies have shown that after delivery, this compliance wanes, and reengaging these women in care can be difficult,” (Jhaveri, 2018). There are several women that do not even seek medical treatment while pregnant until they come into the hospital to deliver the baby, so we would at least know the status of HCV in that patient so the opportunity is not missed.

References

1. KY SB250. Regular Session. (2018, April 10). LegiScan. Retrieved March 06, 2019, from https://legiscan.com/KY/bill/SB250/2018
2. Kentucky General Assembly. (n.d.). Retrieved from https://apps.legislature.ky.gov/lrcsearch#tabs-3
3. HCV, Challenges, Pregnancy, NCHHSTP, CDC. (n.d.). Retrieved from https://www.cdc.gov/nchhstp/pregnancy/challenges/hcv.html
4. Hughes, B., Page, C., Kuller, J. (2017). Hepatits C in pregnancy: screening, treatment, and management. American Journal of Obstetrics and Gynecology. 217(5). https://doi.org/10.1016/j.ajog.2017.07.039
5. 2017 Increase in hepatitis C infections linked to worsening opioid epidemic | CDC. (n.d.). Retrieved from https://www.cdc.gov/nchhstp/newsroom/2017/hepatitis-c-and-opioid-injection-press-release.html
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Abstract

Hepatitis C virus (HCV) is a key RNA virus that contributes in the progressive damage of the liver. HCV infections have been shown to progress and eventually initiate the onset of complications such as cirrhosis and liver cancer. It is projected that close to 100 million individuals worldwide suffer from HCV infections. Recent statistics have shown that HC is the major predisposing factor for liver transplantation in most countries worldwide. Following the detection of HCV in 1989, research activities have led to the identification of novel and improved diagnostic tools as well as management strategies. Over the past few years, targeted drugs referred to as direct-acting antiviral agents (DAA)-based regimens have been produced to aid in treating and managing HCV infection. As opposed to the use of the previous interferon (IFN)-based therapies, DAA therapy produces significant beneficial health effects including enhancing the quality of life of HC patients various DAA agents such as simeprevir and sofosbuvir have been authorized for pharmaceutical use in the treatment HCV GT4. However, there are very few studies that have investigated the effectiveness and safety of DAA agents in patients suffering from for HCV. This research paper has effectively discussed the various aspects of HCV including its incidence, modes of transmission, its life cycle, pathogenesis, and the current preventive measures for HCV. This research paper has also analysed the study conducted by El Raziky et al. (2017) in order to understand the contribution of simeprevir and sofosbuvir in managing HCV GT4. The outcomes of this study support previous findings which showed that simeprevir and sofosbuvir are highly effective and well-tolerated drug therapies for HCV GT4.

Key words: Hepatitis C virus, Simeprevir, Sofosbuvir, Genotype 4, Virions

Background

Hepatitis C infection is an illness that affects the liver. This illness is initiated by HCV occurring in the blood of individuals possessing the disease. HCV is a spherical enveloped and positive strand ribonucleic acid (RNA) virus. HCV infection has been shown to cause acute hepatitis C infection, with close to 60% of the affected people developing chronic hepatitis C (Manns et al., 2017). HCV is responsible for causing hepatitis C through two main ways. The first means is by infecting the cell. It then kills the cell or damages it. This method of disease infection is referred to as cytopathic damage. The second means of HCV infection is through provocation of the immune response. A misdirected or overactive immune response has the potential to damage the infected cells as well as the surrounding tissues. This method of HCV infection is referred to as immunopathic damage (Razavi et al., 2014).

There are various signs and symptoms associated with HCV infection with the generalized symptoms being pain of the joints, fatigue, fever, myalgia, weakness and sleep disturbances. The pain reported in the joints of individuals with HCV infection is referred to as arthralgia. The common joints that suffer pain include the hips, knees, spine and fingers. The joint pain associated with hepatitis C is migratory, with the discomfort moving from one part of the body to another. Individuals with hepatitis C are also reported to experience fatigue which may be mild or severe. Individuals with hepatitis C often experience fever. As the fever reduces, some of the patients may experience chills and night sweating. Apart from the pain of the joints, individuals suffering from hepatitis C can suffer from muscle pain, also referred to as myalgia. Myalgia symptom appear intermittently and do not last long. Patients suffering from hepatitis C can sometimes experience a general sense of weakness. Further, they may suffer sleep disturbances, and in most cases may stake awake during the night. All these are subjective evidences of hepatitis C (Yuen et al., 2018).

The objective evidences include; cognitive changes, depression, blood sugar abnormalities, and ascites. Some individuals with hepatitis C may experience changes in their cognitive ability with most of the individuals finding it difficult to concentrate for long periods of time. In addition, the though process tends to become slower. Hepatitis C is responsible for causing depression indirectly by bringing changes that lead to depression such as irritability, sleep disturbances, and a sense of hopelessness. Another key feature of hepatitis C is that it has the ability to induce blood sugar imbalance in the body. High levels of blood sugar causes individuals to experience symptoms such as fatigue, thirst, frequent urination, and weight loss. Low blood sugar on the other hand causes individuals to suffer nausea, dizziness, weakness and light-headedness (Pfaender et al., 2015).

There are various complications linked with HC including cirrhosis, liver failure, and liver cancer. Liver cirrhosis is the commonly occurring complication. In such a case, the liver develops a scarred tissue that replaces the healthy tissue and eventually prevents the liver form functioning effectively. As a result of liver cirrhosis, the liver may lose its functions completely causing the affected individuals to suffer end-stage liver disease or liver failure. Another complication of hepatitis that has been on the rise in the past few decades is liver cancer. It is estimated that approximately 1 in 20 people suffering from hepatitis associated with cirrhosis eventually develop liver cancer (Reig et al., 2016). Unfortunately, there has been no successful cure for liver cancer.

HCV is transmitted mainly through exposure of the blood or body fluids containing the virus to individuals who are not infected. Infection can occur following the sharing of items such as tooth brushes, razor blades, diabetic lancelets and needles. Transmission of HCV can also occur via sexual and mother-to-mother transmission. The incidence of chronic HCV infection is considered to be approximately 1.7% in the adult global population, indicating that more than 75 million individuals are affected by the illness. Based on a recent survey, it is projected that the prevalence of HCV infection was about 3.5 million in the US (Messina et al., 2015). The occurrence of HCV infection varies considerably across nations worldwide, with the highest rates of infection occurring in countries with a history of iatrogenic infections (infections associated with medical therapy). The infection was reported to occur mostly in Africa and the Middle East countries such as Egypt, Cameroon, Mongolia, Uzbekistan, and Nigeria. The population infected by HCV has a peak age of about 30-35 years, but a higher peak age of approximately 50 to 60 years has been reported in countries dominated by iatrogenic infections (Blach et al., 2017).

The RNA of HCV can be traced in the blood, saliva, seminal fluid, tears, and cerebrospinal fluid. For majority of the affected individuals in the US and Europe, the HCV infection is obtained through intravenous drug abuse. Studies have shown that there exist various HCV genotypes that are based on variability of the nucleotide in HCV sequences obtained from diverse geographical regions; genotype 1 has the highest dispersal globally. Approximately 70% of isolates obtained from the US are subtype 1a and 1b; genotype 2 has been shown to be widely distributed in central and west Africa; genotype 3 is diverse in Asia; genotype 4 on the other is prevalent in Africa and the Middle East; genotypes 5 and 7 occur in Africa while genotype 6 occurs predominantly in Southeast Asia (Mohd Hanafiah et al., 2013).

HCV belongs to the family Flaviviridae and genus Hepacivirus. The HCV virions have a diameter of approximately 50 to 60 nm and are covered by a lipid bilayer that anchors two gylycoproteins (E1 and E2). The genome is about 9.6 kb in length. Hepatitis C is considered to be a key public health concern in various parts of the world including the United States. The HCV RNA genome can interact with the primary protein resulting in the formation of viral nucleocapsid and cytosolic lipid droplets. The nucleocapsid is covered by a lipid-rich cover and contains E1 and E2 glycoprteins that facilitate the entry of the virus through receptor binding and fusion. The E1 and E2 glycoproteins have the ability to create non-covalent heterodimers with the infected cells. The HCV virion can associate with other types of lipoproteins including apoB, apoE, apoC1, apoC2 to generate a complex lipoviroparticle (LVP) that can influence the entry of HCV (Pybus & Thézé. 2016).

Stages of the HCV life cycle

The first stage of the HCV lifecycle involves virion attachment to the receptors on hepatocyctes. The cellular receptors that initiate the attachment step of HCV lifecycle include high-density lipoprotein receptor, scavenger receptor class B, occluding, tetraspanin CD81, and tight junction protein claudin-1. During this stage, the virus binds with the receptor complex and after internalization, the nucleocapsid moves out into the cytoplasm (Scheel & Rice, 2013).

The second stage involves uncoating where the genomic RNA is released into the cytosol as shown in the figure below, where is functions as mRNA for the production of HVC polyprotein.

Figure: Illustration of the stage of the HCV life cycle (Dustin, Bartolini, Capobianchi & Pistello, 2016)

The large polyprotein that is produced undergoes translation in the endoplasmic reticulum. This results in the formation of three structural and seven unstructured proteins. After processing, the proteins are still attached with the intracellular membranes.

The next stage is the replication which is catalyzed by the NS5B protein. During the virus replication phase, the NS5A protein and helicase-NTPase regions of the NS3 play a regulatory role. The NS5A protein serves as a dimer involved RNA binding. The two domains (I and II) found in the NS5A protein have some key roles in the HCV replication. The NS3 helicase is involved in enhancing the separation of original and template strands of RNA. The NTPase/helicase part of the NS3 protein has various roles that are necessary for replication such as RNA binding, RNS induced NTPase activity, and opening up of the RNA regions of the entire secondary structure. The NS4B induces the generation of the replication complex that facilitates replication of HCV. Additionally, the NS5A protein contributes in enhancing regulation of the virus replication. Following the replication process, new direct acting antivirals (DAAs) are made available (Afzal et al., 2015).

In the next two stages, the virions are aggregated in an endoplasmic reticulum-derived section and are subsequently released through exocytosis. Along the process, the virus becomes mature and is encircled by lipoproteins that facilitate immune escape (Li & Lo, 2015).

Pathogenesis of HCV infection

The HC RNA virus moves into the hepatocyte through endocytosis with the process being mediated by four co-receptor molecules. The HC RNA virus is internalized in the cytoplasm and thereafter, the positive-stranded RNA is uncoated and translated into 10 mature peptides. The peptides are cleaved by the host proteases as well as by the virally encoded proteases referred to as NS3-4a serine proteases. Following the cleavage process, the mature peptides move and reside on the ER. This results in the generation of a replication molecule that contains a critical enzyme known as the NS5B RNA dependent RNA polymerase which catalyzes the positive strand of the RNA to form an intermediate with a negative strand. The intermediate can be utilized as a template for the synthesis of a new positive strand. The RNAs are packaged with the essential envelope glycoprotein into mature virions. The virions subsequently the cell via exocytosis. Within one to four weeks of exposure, the virus can be identified in the plasma. Viremia has been shown to peak in approximately 8 to 12 weeks after infection. Thereafter if plateaus or declines to undetectable levels in a process known as viral clearance. Continued and sustained infection is associated with the weak CD4+ and CD8+ T cell responses that are not effective in controlling viral replication (Irshad, Mankotia & Irshad, 2013).

How the host’s body fights infection

Immediately after initiating infection in the hepatic centers, the HCV goes through replication to generate more viruses. However, the replication is slowed down abruptly when the liver cells express various IFN-stimulated genes (ISGs) that prevent the replication of HCV. Innate immunity acts as the first line of defense against the infection caused by HC virus. Innate immunity contributes in stimulating adaptive immunity (Honer & Gale Jr. 2013). The HCV RNA becomes attached to the retinoic acid-inducible gene I and in the process activate the mitochondrial antiviral signaling (MAVS) proteins. The RNA that is bound to the Toll-like receptor-3 stimulates the initiation of signaling through the TRIF. The two pathways activate the translocation of NFκB and IRF3 to the nucleus. In the process, they stimulate the expression of ISGs and IFNs to prevent further viral replication. They also stimulate the proinflammatory cytokines as well as chemokines to activate the immune cells. The NS3-4A protease of the HCV cleaves TRIF and MAVS so to limit the induction of IFN. Hepatocytes have also been shown to induce IFN-λ after HCV infection. In addition, Kupffer cells, dendritic cells and other non-parenchymal cells start to recognize the molecular patterns of viruses and contribute to the generation of IFN and cytokines without themselves being infected by the replicating HCV (Boljes et al., 2014).

Current preventive measures of HCV

According to the World Health Organization (WHO), the preventive measures for HCV infection can be categorized into primary and secondary prevention measures. The primary measures include screening and testing of blood, plasma and other biological samples (He et al., 2016). It also includes the inactivation of virus in plasma-derived products. Other important activities include the implementation of counselling services to reduce risk as well as the implementation and maintenance of practices that control HCV infection. Secondary prevention measures include the identification and provision of counselling and testing services to individuals at risk. Moreover, it involves the medical management of people infected with HCV.

Purpose of the study and hypothesis

This research was carried out to examine the safety and effectiveness of a combinational of simeprevir and sofosbuvir in treating individuals with or without cirrhosis.

The hypothesis was that a combination of simeprevir (150 mg) and sofosbuvir (400 mg) given to HCV genotype 4 patients with or without cirrhosis daily for a period of eight to 12 weeks was safe and effective in managing HCV.

Independent and dependent variables

Independent variables are the dosage of the two drugs (simeprevir (150 mg) and sofosbuvir (400 mg) and the frequency of administration of the drugs. The independent variable is one that is manipulated by the researcher.

The dependent variables in the study are efficacy, safety and tolerability. These are the outcome variables that were measured at the various time intervals. Efficacy, safety, and tolerability were the outcomes measured so as to determine the findings of the experiment.

The control variables were the Peg-IFN/RBV control rates. This was a positive control, and it was considered as the standard of care for the treatment of HCV during the period in which the study was designed. The controlled variables are a standard measure used to compare the results of an experiment. In this case the previous results obtained using Peg-IFN/RBV will be used to make comparisons with the results from this study.

Study design

Figure: A flow diagram showing the experimental design

The study was conducted in three different sites in Egypt. The inclusion required that participants be aged between 18 and 70 years. Participants with experience in Peg-IFN/RBV were included in the research. Patients with liver disease but no HCV aetiology were excluded from the study. Moreover, individuals co-infected or infected with non-GT4 HCV were not included in the study. After providing consent to participate in the study, the participants in groups A2 and B were tested at baseline for plasma HCV. Participants were allocated into two major groups; Group A comprised of patients without cirrhosis. They were randomized in a ratio of 1:1 and placed into an 8-week treatment group (Group A1) or a 12-week treatment group (Group 12). Participants with cirrhosis were placed in Group B where they received treatment for 12 weeks as illustrated in the figure above. Baseline data was also obtained at weeks 1, 2, 4, 8, and 12. The study evaluations conducted for each group at the end of the treatment process included efficacy assessments and safety evaluations.

Results

From the study, it was observed that the sustained response after 12 weeks of treatment was approximately 92% (95% CI) as observed in the table below. This value was significantly higher compared that of the historical control rate which was 42%. This demonstrated the effectiveness of the treatment regimen in comparison with the historical treatment.

Treatment group General SVR12 rate 95% CI Historical control (SVR rate)

• All patients 58/63 (92%) 82.4, 97 41
• Noncirrhotic patients (8 weeks) 15/20 (75%) 50.9, 91 50
• Noncirrhotic patients (12 weeks) 20/20 (100%) 83.2, 100 50
• Noncirrhotic patients (8&12 weeks) 35/40 (88%) 73.1, 96 50
• Cirrhotic patients (12 weeks) 23/23 (100%) 85.1, 100 26

Table: The comparison of SVR12 treatment rates with historical control rates (El Raziky et al., 2017)

Eight weeks of treatment produced an SVR12 rate of 75% while the participants in treatment Group A2 experienced an SVR12 rate of 100%.

Further, after eight weeks of treatment, 100% of the participants had undetectable HCV RNA. All the participants under treatment for the 12 weeks exhibited sustained virologic response. In addition, all the participants who managed to achieve SVR4 were observed to SVR12 and SVR24.

With regards to virologic failure, no patient was reported to experience on-treatment failure. Of the 81% of the participants who experienced treatment emergent adverse effects, only 30% reported adverse events that were considered to be associated with simeprevir and sofosbuvir. Most of the adverse events were categorized as Grade 1 or 2. Only 3% of the patients were reported to experience Grade 3 adverse events, with a similar trend reported in Grade 4 adverse events (only 3% of patients affected). The adverse events that were reported in more than 5% of the patients and which were indicated to be associated with simeprevir were headache (13%), pruritis (11%) and fatigue (8%) as shown in the table below.

Common adverse events associated with simeprivir

• Group A1 (n=20) Group A2 (n=20) Group B (n=23) All (n=63)
• Headache 2 (10) 1 (5) 5 (22) 8 (13)
• Pruritis 3 (15) 1 (5) 3 (13) 7 (11)
• fatigue 1 (5) 3 (15) 1 (4) 5 (8)

Occurrence of more than 1 adverse events 80% 65% 96% 81%

Table: adverse effects associated with simeprivir (El Raziky et al., 2017).

Major finding of the study

The key finding of this study was that the results were consistent with recent studies conducted in other parts of the world, particularly with regards to individuals infected with HCV GT4. In conclusion it was found that combination of simeprevir and sofosbuvir administered for 12 weeks was highly effective and well-tolerated by patients with HVC GY4.

Importance of the study findings

Given that only a few studies have been carried out to examine the use of simeprevir-based regimens in the treatment of HCV GT4, the findings from this study will be useful in providing more information about the safety and effectiveness of this therapy in the health care setting. This is beneficial to medical practitioners, because they have additional source of information that will help influence their choice of treatment.

Limitations

The participants used in the study was not relatively small and thus the outcome of this study may not be generalizable. The partly randomized design of the study was reported to be a limiting factor because it prevents the drawing of comparisons between cirrhotic and non-cirrhotic patients.

The study focused on the key aspects of drugs that inform the choice of medical practitioners whether to adopt or ban the use of specific drugs. Effectiveness and safety can shape the quality of life of individuals using the specific drugs.

Factor contributing to the impact of hepatitis C in the society

Key factors such as recipient, donor, or transplant-related factors have been reported to contribute to the impact of HC among individuals in the society. With regards to donor factor, the old age of a donor has been linked with progressive HCV illness and graft loss in some cases. According to Gambato et al. (2014), there exists a 65% higher likelihood of graft loss among old donors aged between 40-50 years old. However, the likelihood increases to about 86% for donors aged between 50 and 60 years. The rate is significantly higher (221%) for donors who are above 60 years old. Therefore, it is highly discouraged to use elderly donors. It can thus be noted that old age plays a significant role in the recurrence or progression of HCV infection in individuals receiving transplants (Younossi etal., 2014).

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During August 2002 in Oklahoma, USA in a pain remediation clinic, the Oklahoma State Department of Health (OSDH) received a report of six patients who tested positive for acute hepatitis C virus (HCV). Immediately after this incident was reported the OSDH conducted a study on the clinic patients, serologic survey, interviews, review of medical records, and staff infection control practices (Comstock, 2004). The occurrences founded in the clinic patients were either HCV or HBV (hepatitis B) which both can be contracted from the reuse of needles. Following, a conclusion was made after the study and it was established the mechanism for patient transmission of HCV and HBV in this large hospital-acquired outbreak was the reuse of needles-syringes. Due to these findings, the OSDH had closed the clinic and continued for further investigation. Moreover, it was established that a total of 798 patients out of 908 were tested positive (87.6%); 71 hepatitis C infected patients (8.9%) and 31 hepatitis B infected patients (3.9%). During the investigation, the OSDH examined and found out During medical sessions, a licensed registered nurse anesthetist (CRNA) regularly reused needles and syringes (Comstock, 2004). A single needle and syringe were used to treat up to 24 sequentially treated patients at each session with each of the 3 sedation medications (Center for Disease Control and Prevention, 2019). Treatment after a patient who was positive for anti-HCV during a medical session was a statistically significant risk factor for contracting the disease HCV infection (RR = 9.2; 95% CI = 3.7-22.5), the same was true for the treatment of patients with hepatitis B surface antigen-positive (RR = 8.5; 95% CI = 4.2-17.0). the final inference made after the initial complaint was filed was that the CRNA must cease the reuse of needles and the transmission of HCV and HBV had stopped and showed no evidence of reoccurrence.

Causative organism

The causative organism for the outbreak that occurred in that clinic largely was hepatitis C a member of the Hepaciviral C species of the family Flaviviridae (Stiles, 2008). Often known as HCV, it is a blood-borne virus with a positive RNA strand, a lipid envelope, and a nucleocapsid. The lipid envelope is a lipoprotein that allows the virus to penetrate the host cell by binding receptors to the cell membrane. Replication happens inside the host cell. Once inside the cytoplasm of the host cell, the infection loses its container to decipher a reciprocal negative-strand RNA.

Hepatitis C is caused by exposure to small quantities of blood from the sharing of needles or other equipment that are from injecting into the body, this virus can cause major liver complications. HCV displays short- and long-term problems, for a few people the disease is short term, and for the majority, it will become a long-term problem due to the fact that patients are not aware of the disease since it does not show clinically ill signs (Stiles, 2008).

HCV is divided into 2 forms based on how long the patient has had the condition: acute (less than 6 months) and chronic hepatitis C (more than 6 months), the symptoms can range from a mild illness that will last a few weeks to serious lifelong illness (ANON, 2019). In some cases, people can acquire acute hepatitis C and it will not lead to a life-threatening disease; 30% of infected persons spontaneously clear the virus within 6 months while the remaining 70% contract chronic hepatitis C.

The incubation period ranges from 2 weeks to 6 months and from initial infection symptoms are not shown in 80% of people (ANON, 2019). But symptoms of hepatitis C may exhibit fever, fatigue, decreased appetite, nausea, vomiting, abdominal pain, grey coloured feces, etc.

Although currently there is no vaccine for the disease, it can still be cured with proper treatment. Treatment consists first of correct diagnosis due to HCV being asymptomatic (showing no symptoms) so it can be undiagnosed till it is too late, the disease can be undetected for years and develop into chronic HCV infection (ANON, 2019). It can stay undiagnosed for decades until secondary to serious liver damage forms. There are 2 steps for diagnosis: first is testing for anti-HCV antibodies with a serological test to identify the infected people, then if the test is positive for the antibody, further tests are done to determine if the disease is still acute or progressed to chronic. Step two is done by a ribonucleic acid test checking for the HCV ribonucleic acid as confirmation. Once a diagnosis is made the liver should be assessed looking at fibrosis and cirrhosis, this is done by a liver by a biopsy or non-invasive techniques and once liver damage level is the standard for treatment and management. Treatment of newly infected cases does not always require treatment because the immune response in some patients can clear the infection, but ongoing treatment for HCV is required when the infection occurs. Recommended treatment includes therapy with direct-acting antivirals (DAA’s), this treatment plan has a high success rate and can cure most people, the treatment duration is from 12-24 weeks depending on if there is cirrhosis present. DAA used to be an expensive treatment option but now due to the formation of more generic versions the prices have dropped. Getting tested and treatment is an imperative part in reducing the risk of acquiring and transmitting the disease and those that are risk of infection absolutely should get tested; like people who inject drugs, people in prison, facilities with inadequate infection control practices, users of intranasal drugs, people who have had tattoos or piercings, etc.

Impact on the public health

When an outbreak arises, it is the public health’s responsibility to take measures and bring the outbreak under control. That is why, following the occurrence and completion of the purpose, the State Nursing Board revoked the CRNA license and imposed a fine of $99’000 (Center for Disease Control and Prevention, 2019). The CRNA investigations was resource-intensive, including alerts, screening, treatment for hundreds of patients, and the Center for Disease Control and Prevention (CDC) collaborated with professional organizations, advisory committees, and the state and local health department to discuss the training of health care workers, the supervision of the administrative surveillance system, and the writing of the surveillance process, and writing strategies and techniques to predict patient-to-patient transmission. Likewise, in light of this flare-up, the American association of nurse anesthetists (AANA) sent mailings to all AANA individuals and understudies, nurture anesthesia school program chiefs, and emergency clinic executives Recall that needles and syringes are things of single-use and ought not to be reused (Balter, 2003). Finally, general prevention is in place to reduce risks of Hepatitis C outbreaks, there is primary and secondary prevention. Primary prevention includes reducing the risk of infection and medical procedures, including safe and appropriate use of health care treatments, safe handling, and disposal of sharps and waste, blood donation screening for HBV and HCV, prevention of exposure to blood during pregnancy, and so on. (ANON, 2019). Secondary prevention is targeted at people who are infected, including hepatitis A and B vaccines so that coinfection from these viruses does not cause liver damage, early antiviral therapy, and regular monitoring of chronic liver disease. Moreover, all the links of the chain of transmission for this outbreak can be broken simply is done by proper use of needles and to dispose of the needles after use and absolutely no re-use of the needles/syringes.

Reflection and analysis

After, research and analysis of the Hepatitis C outbreak in a pain clinic I believe that the outbreak was handled and prevented in an appropriate approach. Initially, this outbreak cannot just be blamed on the clinic itself but mainly on the anesthetist nurse. Looking more into the nurse it has to be recognized he was licensed and had gone through proper training and education to be able to be qualified to acquire the job, but he still reused needles and didn’t comprehend what he was doing was immoral. This shows how easy it is to go wrong and contract a virus with just simple oversight with the procedure of infection prevention control. In summary, the health department handled the outbreak by closing the clinic, suspending the clinic’s license while investigating, revoking the nurse’s license and fining him for malpractice. Doing this permits the complete stop of transmission of the virus within the clinic, while the health department can deal with infected patients’ proper treatment and minimization of the outbreak. A very efficient and effective prevention method done after this outbreak was the AANA sending all forms of associated nurses a mailing report reminding them of proper uses of needles and syringes. This is a respectable prevention method because it acts as a reminder to the medical community the importance of following prevention procedures and sets this outbreak as an example of all the lives that can be affected due to lack of information and understanding.

In the medical field, a virus named Hepatitis was disclosed by Dr. Baruch Blumberg in 1965. Dr. Baruch Blumberg received a Nobel Prize for his significant discovery that impacted the medical field with its benefits of knowing about the disease. The primary name of Hepatitis was called the ‘Australia Antigen’. ‘Australia Antigen’ was found when scientists looked for an Australian aborigine’s blood sample. This sample was filled with an antibody in the serum of an American hemophilia case. In contemporary world, Hepatitis has a clear meaning, origin, and is divided into types such as Hepatitis A, B, C, and D.

First, Hepatitis is a disease that is described as an inflammation of the liver. Hepatitis has the potential to remain inside of the liver or progress to the extent of fibroids, liver cancer, or cirrhosis. In the old days, hepatitis as a virus was discovered by DNA fossils in bird genomes. According to a published study about genomic bird DNA, “In the beginning, Hepatitis B passed the infection to birds and ancient animals”. Hepatitis is produced by viruses such as hepatitis A, B, C, D, or E.

Hepatitis A is a kind of viral hepatitis. This type of liver disease may have a complication such as acute liver failure. Very often Hepatitis A is asymptomatic and gives signs of existence two to six weeks after the infection. Some popular causes of it are a food or liquid that contains this virus. For example, shellfish is popular seafood and a product is not cooked enough, it commonly causes Hepatitis A. Therefore, in order to discover this disease, a medical worker has to do the blood tests. Significantly, the scientists found a treatment for Hepatitis A that involves surgical intervention such as liver transplantation or supportive care.

Another type of liver inflammatory disease is Hepatitis B. This is an infectious disease that is caused by hepatitis B virus such as HBV. This disease impacts the lives and is also a type of viral hepatitis. Possibly, Hepatitis B may lead to acute or chronic infection. Multiple amounts of patients have no symptoms of this disease. Sometimes, Hepatitis B progresses to acute infection, and therefore, a patient experiences vomiting, the skin becomes yellow color, a person feels weak, the urine changes color and the density makes it very dark, and a person experience an abnormal pain in the abdominal cavity. Fortunately, in the medical experience, this condition does not have an increased scale of mortality. Blood tests are purposed to diagnose the disease and antiviral medication or liver transportation treats it. So, Hepatitis B can be treated or prevented by a vaccine.

One more kind of Hepatitis is Hepatitis C. Hepatitis C has the same causes as previous types. However, this disease can have mild symptoms or be asymptomatic and causes fever, dark urine, pain in the abdomen, or the skin changes color and becomes dark and yellowish. Some complications might occur such as cirrhosis, liver failure, liver cancer, or dilated blood vessels. This disease spread mostly through blood contact that is related to intravenous drug use, poor sterilization of instrumentations, needles inaccurate work, or transfusions. In addition, Hepatitis C can be treated with medications, liver transplant, and can be prevented with clean needles, or testing donates blood. So, this type of Hepatitis may cause some people to have symptoms and give rise to complications. However, the medical field has enough tools to treat or prevent the spread of this disease.

Hepatitis D is caused by the hepatitis delta virus and it has a view as a small spherical enveloped particle that has a similar appearance as previous types of Hepatitis and is considered to be a satellite a type of subviral. Hepatitis D is a virus that has symptoms such as a feeling of being tired, nausea, and vomiting. Unfortunately, the most complicated stage of Hepatitis D is liver cancer and chronic infections. For diagnostic purposes, medical professionals check for globulin G and treat this disease with antivirals, pegylated interferon-alpha. A medication that is used against the virus is called Bulevirtide.

Hepatitis is a disease that has been know since ancient times and is considered as an inflammation of the liver. Hepatitis has leading causes by a virus and creates an inflammation that affects the way how the liver works. Different types of Hepatitis have multiple ways of how the disease spreads. The most common type spreads through eating or drinking food that includes fecal matters, alcohol consumption, or other reasons. In present times science proposes a medication that treats this sickness or in case of a profound distraction, the liver has to be transplanted.