Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus(HCV). The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years. In some cases, those with cirrhosis will go on to develop liver failure or other complications, including liver cancer or life-threatening esophageal varices and gastric varices.
The hepatitis C virus is spread by blood-to-blood contact. Most people have few, if any symptoms after the initial infection, yet the virus persists in the liver in about 85% of those infected. Persistent infection can be treated with medication; peginterferon and ribavirin are the current standard therapy. Overall, between 51-80% of treated patients are cured. Those who develop cirrhosis or liver cancer may require a liver transplant, and the virus universally recurs after transplantation.
An estimated 180 million people worldwide are infected with hepatitis C. Hepatitis C is not known to cause disease in other animals. No vaccine against hepatitis C is currently available. The existence of hepatitis C (originally "non-A non-B hepatitis") was postulated in the 1970s and proven in 1989.
Signs and symptoms
Acute infection
During the first 12 years after infection with HCV, most people suffer no symptoms. For those who do, the main manifestations of acute infection are generally mild and vague, and rarely point to a specific diagnosis of hepatitis C. Symptoms of acute hepatitis C infection include decreased appetite, fatigue, abdominal pain, jaundice, itching, and flu-like symptoms.
The hepatitis C virus is usually detectable in the blood by PCR within one to three weeks after infection, and antibodies to the virus are generally detectable within three to 15 weeks. Spontaneous viral clearance rates are highly variable; between 10 and 60% of persons infected with HCV clear the virus from their bodies during the acute phase, as shown by normalization of the liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST), and plasma HCV-RNA clearance (this is known as spontaneous viral clearance). However, persistent infections are common and most patients develop chronic hepatitis C, i.e., infection lasting more than 6 months.
Previous practice was to not treat acute infections to see if the person would spontaneously clear; recent studies have shown that treatment during the acute phase of genotype 1 infections has a greater than 90% success rate, with half the treatment time required for chronic infections.
Chronic infection
Chronic hepatitis C is defined as infection with the hepatitis C virus persisting for more than six months. Clinically, it is often asymptomatic, and it is mostly discovered accidentally (e.g., usual checkup).
The natural course of chronic hepatitis C varies considerably from one person to another. Although almost all people infected with HCV have evidence of inflammation on liver biopsy, the rate of progression of liver scarring (fibrosis) shows significant variability among individuals. Accurate estimates of the risk over time are difficult to establish because of the limited time that tests for this virus have been available.
Recent data suggest that among untreated patients, roughly one-third progress to liver cirrhosis in less than 20 years. Another third progress to cirrhosis within 30 years. The remainder of patients appear to progress so slowly that they are unlikely to develop cirrhosis within their lifetimes. In contrast, the NIH consensus guidelines state the risk of progression to cirrhosis over a 20-year period is 3-20 percent.
Factors that have been reported to influence the rate of HCV disease progression include age (increasing age associated with more rapid progression), gender (males have more rapid disease progression than females), alcohol consumption (associated with an increased rate of disease progression), HIV coinfection (associated with a markedly increased rate of disease progression), and fatty liver (the presence of fat in liver cells has been associated with an increased rate of disease progression).
Symptoms specifically suggestive of liver disease are typically absent until substantial scarring of the liver has occurred. However, hepatitis C is a systemic disease and patients may experience a wide spectrum of clinical manifestations ranging from an absence of symptoms to a more symptomatic illness prior to the development of advanced liver disease. Generalized signs and symptoms associated with chronic hepatitis C include fatigue, flu-like symptoms, joint pains, itching, sleep disturbances, appetite changes, nausea, and depression.
Once chronic hepatitis C has progressed to cirrhosis, signs and symptoms may appear that are generally caused by either decreased liver function or increased pressure in the liver circulation, a condition known as portal hypertension. Possible signs and symptoms of liver cirrhosis include ascites (accumulation of fluid in the abdomen), bruising and bleeding tendency, varices (enlarged veins, especially in the stomach and esophagus), jaundice, and a syndrome of cognitive impairment known as hepatic encephalopathy. Hepatic encephalopathy is due to the accumulation of ammonia and other substances normally cleared by a healthy liver.
Liver enzyme tests show variable elevation of ALT and AST. Periodically, they might show normal results. Usually prothrombin and albuminresults are normal, but may become abnormal, once cirrhosis has developed. The levels of elevation of liver tests do not correlate well with the amount of liver injury on biopsy. Viral genotype and viral load also do not correlate with the amount of liver injury. Liver biopsy is the best test to determine the amount of scarring and inflammation. Radiographic studies, such as ultrasound or CT scan, do not always show liver injury until it is fairly advanced. However, noninvasive tests (blood sample) are coming, with FibroTest and ActiTest, respectively estimating liver fibrosis and necrotic inflammation. These tests are validated and recommended in Europe (FDA procedures initiated in USA).
Chronic hepatitis C can be associated with signs and symptoms in organs besides the liver, such as porphyria cutanea tarda, cryoglobulinemia(a form of small-vessel vasculitis) and glomerulonephritis (inflammation of the kidney), specifically membranoproliferative glomerulonephritis(MPGN). Hepatitis C is also rarely associated with sicca syndrome (an autoimmune disorder), thrombocytopenia, lichen planus, diabetes mellitus and with B-cell lymphoproliferative disorders.
