Hepatitis C overview: Difference between revisions

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==Classification==
==Classification==
HCV can be classified based upon the isolated [[genotype]] and [[subtype]]. Six major genotypes are identified; several new genotypes and subtypes have been recently discovered.


==Epidemiology and Demographics==
==Epidemiology and Demographics==

Revision as of 20:48, 29 July 2014

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-In-Chief: Yazan Daaboul; Serge Korjian

Overview

Hepatitis C virus (HCV) is a single-stranded RNA virus that causes liver injury. Initially discovered in 1989, HCV was found to be a bloodborne infection that tends to persist into a chronic state in the majority of cases. Although the exact pathogenesis and life cycle of HCV are poorly understood, it has been demonstrated that impaired innate and adaptive immunity to acute HCV may contribute to the development of chronic infection. While the transfusion of blood and blood products along with injectable therapy were considered the most common risk factors for HCV in the past, the use of injectable illicit drugs is currently the most important risk factor. In the absence of treatment, chronic HCV leads to liver cirrhosis several years after the initial infection, a course complicated by decompensated liver failure or hepatocellular carcinoma. Other extra-hepatic manifestations are also common. Specific patient populations should be screened for HCV first using HCV serological testing, or rarely directly by measuring HCV RNA in patients who have had previous HCV exposure, treatment-induced clearance, or immunosuppression. The diagnosis is made when anti-HCV and HCV RNA both demonstrate positive results. Measures to slow the progression of liver disease, such as vaccines against other diseases and awareness against the use of alcohol or drugs that injure the liver should be taken following diagnosis. Classically, interferon (IFN) therapy was used to treat HCV, followed by the use of ribavirin. More recently, protease inhibitors emerged as effective drugs of choice for HCV infection.

Historical Perspective

The discovery of hepatitis C virus was made based on early findings of patients with signs and symptoms of viral hepatitis lacking positive serologies for hepatitis A or B. These patients were originally described in 1974-5 to have "non-A, non-B viral hepatitis" (NANBH). It was not until 1989 that hepatitis C virus (HCV) was truly discovered when Qui-Lim Choo and colleagues successfully isolated the first cDNA clone 5-1-1 derived from NANBH genome. The first interferon-alpha (INF-a) to treat HCV was developed in 1986 and approved in 1991. Approximately 10-15 years later, the global effort to reduce the burden of HCV was launched; worldwide campaigns were led by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC).

Pathophysiology

In isolated acute HCV infection, the host immune system leads to secretion of interferon-alpha and activation of natural killer cells, followed by the activation of adaptive immune system. Chronic HCV is characterized by the impairment of these mechanisms. Eventually, chronic HCV infection leads to local inflammation and fibrogenesis causing hepatic injury and cirrhosis. Hepatocellular carcinoma, a known complication of chronic HCV infection, arises in cases of cirrhosis; the role of oncogenic proteins of HCV in the pathogenesis of hepatocellular carcinoma is yet to be elucidated.

Causes

The hepatitis C virus (HCV) is the causative agent of hepatitis C. It is a member of the genus Hepacivirus that belongs to the Flaviviridae family. It is an enveloped, single-stranded RNA virus. The RNA genome acts as a template for viral replication and eventually, protein synthesis. Humans are considered the only natural hosts for HCV. The virus is primarily transmitted by exposure to contaminated blood.

Classification

HCV can be classified based upon the isolated genotype and subtype. Six major genotypes are identified; several new genotypes and subtypes have been recently discovered.

Epidemiology and Demographics

Hepatitis C is a major health problem affecting approximately 2 to 4 million people in the United States, 5 to 10 million people in Europe, and 12 million people in India. Approximtely 150 000 new cases occur annually in the US and in Western Europe although accurate incidence rates are difficult to estimate given the asymptomatic course early in the disease. While the disease appears to be declining, hepatitis C is still highly prevalent in specific areas of the world. Egypt is the country with the highest prevalence of HCV, HCV-associated cirrhosis, and hepatocellular carcinoma, and the prevalence tends to increase with age, suggesting ongoing new cases of HCV. Approximately one-fourth of all cases of cirrhosis and hepatocellular carcinoma are attributed to HCV worldwide. Hepatitis C affects males and females equally.

Risk Factors

Risk factors for hepatitis C include intravenous drug use (most important), multiple blood transfusions prior to 1992, therapeutic injections for hemophilia prior to 1987, and work in the healthcare field given that exposure to contaminated blood products in the most important mode of transmission.

Other less important risk factors are:

  • Occupational exposure to blood, such as contaminated needle sticks

Screening

Persons living in regions highly prevalent with HCV and who have engaged in high risk should be screened. Screening by serological testing, confirmed by nucleic acid amplification (NAT) for HCV RNA is required. Additionally, screening for other bloodborne infections, such as HBV and HIV, is required once diagnosis is made. The frequency of testing in these patients is unclear and should be individualized according to frequency of exposure to risk.

Differentiating Hepatitis C from other Diseases

Hepatitis C must be differentiated from other diseases that cause hepatic injury and abnormal liver function tests such as other viral hepatitides (Hepatitis A, Hepatitic B, and Hepatitis E), and non viral etiologies namely alcoholic liver disease, non alcoholic steatohepatitis, drug-induced liver injury, autoimmune hepatitis, and hepatocellular carcinoma.

Natural History and Prognosis

The majority of individuals infected with HCV will become chronic carriers. The most important complications of HCV are hepatic, namely liver cirrhosis years after the onset of infection and consequent development of hepatocellular carcinoma. Other classical extrahepatic manifestations, such as cryoglobulinemia, lichen planus, membranoproliferative glomerulonephritis, and porphyria cutanea tarda are also complications of chronic HCV infection. Treatment is necessary for patients with chronic stable HCV infection; otherwise prognosis is poor and progression of disease is potentially fatal.

Treatment

The treatment of hepatitis C has changed dramatically over the past decade. Whereas relatively new protease inhibitors telaprevir and boceprevir were added to the regular regimen of IFN and ribavirin in 2011 to treat patients with genotype 1 HCV, newer oral agents sofosbuvir and simeprevir have demonstrated greater efficacy in viral clearance along with a better safety profile. New guidelines from the AASLD and the IDSA have recommended the use of these oral agents (particularly sofosbuvir) as first line agents in the treatment of chronic HCV in both relapsers and treatment-naive patients.

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