Hepatitis C Virus Analysis - Essay Example

Hepatitis C” Introduction Hepatitis as the suggests affects the hepatic system, the liver. It was claimed to be a disease in 1970s but established as a disease in 1989. It is an infectious disease caused by the virus called the hepatitis C virus (HCV) which affects human species. The human defense system powerless in the sense to completely eradicate the virus and therefore the virus reaches the chronic stage where the virus damages liver. It spreads by means of blood to blood contact. Endurance of infection is curable in initial stages but when it reaches the stage of cirrhosis or cancer, liver transplantation becomes essential. It is unfortunate that no definite cure could be established for Hepatitis C moreover when injected into chimpanzees, they show no signs of disease and therefore no vaccine could be formulated. Biology or HCV and its transmission Hepatitis C virus (HCV) is an enveloped virus with RNA (ss) as the genetic material. The envelope contains enzymes and proteins that enable the virus to penetrate and multiply in the host cells using cell machinery. It exists in six genotypes, of these genotype I is most prevalent form of HCV. Since the virus exists in different genotypes and sub-genotypes, it becomes very challenging for the development of its vaccines. HCV is not related to other hepatitis viz. hepatitis A or hepatitis B. It is grouped in the family Flaviviridae along with yellow fever virus and dengue virus. As soon as virus gains entry in the liver, it elicits immune response resulting in inflammation; protracted inflammation lays the foundation of scarring which further takes the form of cirrhosis and thus preventing liver to perform its normal functions. Such condition paves the way for liver cancer (Alter, 2000). Transmission of HCV It is transmitted through blood especially through blood transfusion, use of unsterile injections and rarely through sexual transmission (in cases where an individual is suffering with Sexually Transmitted Disease and has open sores). 1. Injections: Injections used either for drugs or for blood transfusions. 2. Blood transfusion and blood products or organ transplant, if no appropriate measures are taken during the process could result as a big source of HCV. 3. Iatrogenic transmission: when the physicians are careless in their pursuits and use inappropriately sterilized medical or dental apparatus it aids in transmission of HCV. 4. As an occupational hazard: catastrophe due to accidents when firefighting or in paramedics, officers in military, medical or dental physicians or technicians. 5. Recreational hazards: due to sports injuries. Tattoos may also become the source of HCV transmission. 6. Vertical transmission encompassing delivery and breastfeeding from mother to child. 7. Sporadic transmission: in this case the source of the infection cannot be found out, it results due to community-acquired infections where virus gets entry in body through cuts or injuries or an abrasion (Alter, 2000). Prevention of transmission Use of sterile needles, safe hygiene conditions and routine blood examination, taking complete history of the patient, thorough screening of the blood for HCV when blood is donated by a donor or when given to the patient, use of self-capped needles, no sharing of personal belongings like razor, towels, toothbrushes, Symptoms of Hepatitis C Hepatitis C comprises of two stages- acute and chronic. Acute: it is the initial 6 months when the patient contacts the infection of Hepatitis C. as the disease is asymptomatic no initial signs appear in majority of the population. Only 30-40% of the infected cases develop symptoms like reduced appetite, tiredness, aching abdomen, jaundice, itch, burning sensation and flu. When blood is examined through PCR, HCV can be seen in 1-3 weeks after getting the infection, moreover antibodies against the HCV could be detected in 3- 15 weeks. Viral clearance is observed in around 10-60% of the infected cases. This is due to the actions carried out by various liver enzymes like alanine and aspartate transaminase (ALT & AST) along with the plasma HCV-RNA clearance. Even though such defense mechanisms are prevalent the infection persists and if last for more than 6 months it takes the form of chronic hepatitis C. Chronic phase of infection: since hepatitis C is asymptomatic patient is diagnosed with the infection through checkup. Moreover every individual suffering from hepatitis C shows difference in their courses. When liver biopsy is performed, chronic stage shows inflammation and fibrosis of tissues, leading to cirrhosis in the period of as long as 20- 30 years. The progression of the disease is directly related to the age, as the age advances the progression is at much faster pace; gender, males are more prone to the diseases than females; alcohol consumption adds to the progression of the disease, if the individual has an HIV infection then it contributes to much rapid pace of hepatitis C progression. On the other hand if excess fat is present in liver, it relates to the rapid progression of the disease. As the disease progresses towards cirrhosis, symptoms like joint-aches, itch, upset sleep, loss of appetite, vomiting and a phase of depression is observed. All these are attributed to the diminished liver function resulting in enhanced pressure on circulation of liver called portal hypertension. As the disease progress, fluid accumulation in the abdominal region is initiated called as ascites, bleeding may result due to extended veins in esophagus and stomach causing esophagus varices and gastric varices respectively, ensuing in hepatic encephalopathy owing to accretion of ammonia. This condition could be fatal and leads to coma. It is observed that men suffering from HCV show breast enlargement. There is a loss of weight, rash on the palms and clotting time is either prolonged or blood clots with intricacies. Blood vessels show spider like pattern (Hepatitis C). The infection is asymptomatic and the virus is able to survive in majority of the individuals and gradually establish infection, leading to fibrosis and cirrhosis of liver tissues under chronic conditions. The condition becomes critical and causes liver failure, cancer of liver, cirrhosis, bleeding due to dilation of sub-mucosal veins especially in the lower part of esophagus ensuing esophageal varices, under similar conditions when the sub-mucosal veins of stomach are dilated it results in gastric varices. In later stages of cirrhosis jaundice develops as the liver is not capable enough to remove bilirubin (Hepatitis C). Under these conditions liver enzyme, ALT and AST are also elevated; on the other hand prothrombin and albumin are normal and gradually as the condition progress towards cirrhosis their values deviate from the normal values. However, these tests along with the viral tests notifying viral load are not enough to describe the condition and injury of liver. For the appropriate investigation liver biopsy displaying scarring, fibrosis and irritation and inflammation of liver. It is also unfortunate that even CT scan and USG cannot detect liver damage in initial stages. In recent years Fibro Test and Acti Test are prevalent for the diagnosis of hepatitis C (Ngo, 2006; Halfon, 2008). Chronic condition may find association with extrahepatic (outside liver) tissues causing glomerulonephritis (Johnson, 1993). In response to HCV body generates antibodies called cryoglobulins, they are capable of bringing inflammation, joint pain, arthritis, heaved purple irritation on the legs, the condition is known as cryoglobulinemia (Pascual, 1990). These patients are known to develop Raynaud’s phenomenon where toes and fingers, the digits change color from white to purple to red (Hepatitis C). Autoimmune disorders, thrombocytopenia, skin conditions called lichen planus and porphyria cutanea tarda are also associated with HCV along with diabetes mellitus, three times more common in patients with HCV (Hepatitis C) and other lymphatic system anomalies (Zignego, 2006). The patients in chronic conditions also display less platelet counts and gradually they tend to develop B cell lymphoma (Hepatitis C). Serological tests Enzyme Immunoassay: Presence of anti-HCV must be tested for the suspected individuals. This is done by EIA-3. PCR (Polymerase Chain Reaction) or TMA (Transcription Medicated Amplification): detects the presence of HCV- RNA and thus confirms the presence of HCV. It is most effective in immuno-compromised individuals who are unable to produce anti-HCV (Starder, 2004). Recombinant Immunoblot Assay: it is the kind of Western blot, where the viral proteins are detected on nitrocellulose strips. Recombinant viral proteins adhere the antibodies if present forming an Immunoblot. if ~>2 proteins respond then the individual is said to be positive for HCV. They are routine tests executed in blood banks (Starder, 2004). Direct Assay for HCV RNA: it is the most reliable tests carried out for HCV infection. This test is effective in case where aminotrasferase levels are normal or little raised and even when anti-HCV is not reported to be present and when any other cause of liver disease is probable (Starder, 2004). Biochemical indicators for HCV: Under chronic conditions the alanine and aspartate aminotrasferase vary between 0-20 times, ALT levels is elevated than AST but this is the condition where cirrhosis is not developed. Elevated alkaline phosphatase and gamma glutamyl transpeptidase indicate cirrhosis. Reduced platelet count along with diminished WBCs and elevated serum globulins is often seen in case of fibrosis and advancing cirrhosis (Starder, 2004). Quantification of HCV RNA in serum: Viral load must be quantified and therefore quantitative PCR and a branched DNA (bDNA) are performed. It is seen that correlation between HCV RNA and viral levels does not indicate the severity of Hepatitis C but relationship between viral load and antiviral therapy must be established (Hepaitis C). Liver Biopsy: it is not mandatory for diagnosis. It only provides a means to assess the condition of liver and severity of disease or indicates the degree of fibrosis. The amount of necrosis is estimated using Hematoxylin and eosin stains along with Masson’s trichrome stain. Along with HCV it is also done in case of cirrhosis due to excessive alcohol consumption (Hepaitis C). Changes in liver: Necrosis and inflammation at the periphery of portal areas- interface hepatitis. Damage or necrosis of liver cells or hepatocytes occur, or portal inflammation is documented, followed by fibrosis are the conditions implying the HCV infection. Non-invasive tests: comprise elastrography where liver stiffness is documented, this is an indirect means to find out fibrosis (Hepaitis C). Diagnosis The disease is extremely hard to diagnose in its acute phase as the disease is asymptomatic during this stage of infection. Only in chronic phase, symptoms start appearing. Medical history plays a very crucial role in the diagnosis of HCV. History encompasses tattoos, any kind of anomaly that was instituted during routine blood and liver function tests, any history of blood transfusion i.e. both donation and receiving blood or its products. It is observed that in almost 80% of the patients, anti-HCV antibodies can be traced in 15 weeks of contraction with the HCV. In the rarest of the cases some individuals do not produce antibodies against HCV and therefore, RNA testing must be performed (Starder, 2004). Diagnosis for Acute Hepatitis C- Person who reports jaundice, nausea along with elevated ALT in serum and presence of anti-HCV. 30-40% patients do not report anti-HCV until 2-8 weeks and in that case history must be taken into consideration. Chronic Hepatitis C- diagnosed with the presence of anti-HCV and raised levels of aminotrasferase. Further confirmation of the diagnosis is made through HCV RNA, through PCR (Starder, 2004). Treatment Alpha- interferon: produced in answer to viral infection. Various recombinant forms are produced for hepatitis C. recently pegylated interferon or peginterferon are used which is a chemically modified form of alpha interferon with an immobile molecule of polyethylene glycol. It has prolonged half-life and are better in properties as compared to alpha interferon in a sense that they are being present constantly and are known to be more active in restraining HCV. Ribavirin: it is an antiviral means that is given orally. When given alone it does not have any remarkable effect but when given along with interferon, it enhances the response against HCV. Combination therapy: chances of relapse are diminished when peginterferon is given along with Ribavirin Fried, 2002). Dose Peginterferon alfa-2a, subcutaneously 180 micrograms (mcg)/week. Peginterferon alfa-2b, subcutaneously once a week. 1.5 mcg/kilogram body weight/week. Ribavirin OD (oral dose) 2XDay, 200mg/dose. For 75Kg- Ribavirin, 1200 mg. Adverse Drug Reaction (ADR) of alpha interferon and peginterferon encompass: fatigue, muscle throbbing, headache, queasiness and vomiting, skin irritation at the site of interferon injection, elevated temperature, loss of weight, petulance, depression and loss or hair Fried, 2002). ADR or Ribavirin: loss of hemoglobin causing anemia, fatigue, irritation, rashes on skin, sinus, stiffness in nasal area and severe cough Fried, 2002). ADR of combination therapy: Autoimmune disease, enhanced susceptibility to microbial infections, thrombocytopenia, neutropenia, seizures, depression, retinopathy, tinnitus. Under rare conditions- heart failure, renal failure, loss of vision, pneumonitis and sepsis (Fried, 2002). Research Fundamental Research: encompassing tissue culture system to carryout research and scientific investigations and studies should be promoted. Diagnostic tests: the diagnostic tests for HCV are very expensive and every one cannot afford it. It is therefore essential to devise cost-effective diagnostic tools for quick diagnosis of HCV presence in the patient. Molecular research- deriving new anti-viral agents to promote rapid action on HCV, drug designing for better action and cost-effective drugs along with the development of vaccine compatible with the genotype of the virus are on the way and future is promising to come up with agents to combat Hepatitis C virus effectively. References Alter, H. J, Seeff, L. B. (2000). Recovery, persistence, and sequelae in hepatitis C virus infection: a perspective on long-term outcome. Seminars in Liver Disease, 20(1),17–35. Fried, M. W., Shiffman, M.L., Reddy, K. R., et al. (2002). Peginterferon alfa-2a plus ribavirin for chronic hepatitis C infection. New England Journal of Medicine,347, 972–982 Halfon, P., Munteanu, M., Poynard, T. (2008). FibroTest-ActiTest as a non-invasive marker of liver fibrosis. Gastroenterol Clin Biol, 32 (6), 22–39. Hepatitis C. Available at http://www.medicinenet.com/hepatitis_c/page5.htm. [Accessed on 15th February 2010] Johnson, R., Gretch, D., Yamabe, H., Hart, J., Bacchi, C., Hartwell, P., Couser, W., Corey, L., Wener, M., Alpers, C. (1993). Membranoproliferative glomerulonephritis associated with hepatitis C virus infection.. N Engl J Med, 328 (7), 465–70. Ngo, Y., Munteanu, M., Messous, D., Charlotte, F., Imbert-Bismut, F., Thabut, D., Lebray, P., Thibault, V., Benhamou, Y., Moussalli, J., Ratziu, V., Poynard, T. (2006). A prospective analysis of the prognostic value of biomarkers (FibroTest) in patients with chronic hepatitis C. Clin Chem, 52 (10),1887–96. Pascual, M., Perrin, L., Giostra, E., Schifferli, J. (1990). Hepatitis C virus in patients with cryoglobulinemia type II. J Infect Dis, 162 (2), 569–70. Ryan, K. J, Ray, C. G. (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. Strader, D. B., Wright, T., Thomas, D. L., Seeff, L. B. (2004). Diagnosis, management, and treatment of hepatitis C. Hepatology, 39, 1147–1171. Zignego, A. L, Ferri, C. (2006). Commission On Extrahepatic Manifestations Of Hcv Infection, for the Italian Association of the Study of Liver (A.I.S.F). Extrahepatic manifestations of Hepatitis C Virus infection: A general overview and guidelines for a clinical approach". Dig Liver Dis. 39 (1). Read More