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DISEASES
 HEPATITIS C Other Diseases:

Hepatitis C is an infectious disease affecting the liver, caused by the hepatitisC virus (HCV). The infection is often asymptomatic,but once established, chronic infection can progress to scarring of the liver (fibrosis), andadvanced scarring (cirrhosis) which is generally apparent after many years. Insome cases, those with cirrhosis will go on to develop liver failure or othercomplications of cirrhosis, including liver cancer or life threatening esophageal varices and gastricvarices.

The hepatitis C virus (HCV) is spread by blood-to-blood contact. Mostpeople have few, if any symptoms after the initial infection, yet the viruspersist in the liver in about 85% of those infected. Persistent infection canbe treated with medication, peginterferonand ribavirinbeing the standard-of-care therapy. 51% are cured overall. Those who developcirrhosis or liver cancer may require a livertransplant, and the virus universally recurs after transplantation.

An estimated 270-300 million people worldwide are infected with hepatitisC. Hepatitis C is a strictly human disease. It cannot be contracted from orgiven to any other animal. Chimpanzees can be infected with the virus in thelaboratory, but do not develop the disease, which has made research more difficult.No vaccine against hepatitis C is available. The existence of hepatitis C(originally "non-A non-B hepatitis") was postulated in the 1970s andproved conclusively in 1989. It is one of five known hepatitisviruses: A,B,C, D,and E

Signs and symptoms

Acute

Acute hepatitis C refers to the first 6 months after infection with HCV.60%to 70% of people infected develop no symptoms during the acute phase. In theminority of patients who experience acute phase symptoms, they are generallymild and nonspecific, and rarely lead to a specific diagnosis of hepatitis C.Symptoms of acute hepatitis C infection include decreased appetite, fatigue, abdominalpain, jaundice,itching, and flu-likesymptoms. Hepatitis C genotypes 2A & 3A have the highest cure rates at81% and 74% respectively.

The hepatitis C virus is usually detectable in the blood within one to threeweeks after infection by PCR,and antibodies to the virus are generally detectable within 3 to 15 weeks.Spontaneous viral clearance rates are highly variable and between 10–60%of persons infected with HCV clear the virus from their bodies during the acutephase as shown by normalization in liver enzymes (alanine transaminase (ALT) & aspartate transaminase (AST)), and plasmaHCV-RNA clearance (this is known as spontaneousviral clearance). However, persistent infections are common and mostpatients develop chronic hepatitis C, i.e., infection lastingmore than 6 months.

Previous practice was to not treat acute infections to see if the personwould spontaneously clear; recent studies have shown that treatment during theacute phase of genotype1 infections has a greater than 90% success rate with half the treatment timerequired for chronic infections.

Chronic

Chronic hepatitis C is defined as infection with the hepatitis C viruspersisting for more than six months. Clinically, it is often asymptomatic(without symptoms) and it is mostly discovered accidentally (eg. usualcheckup).

The natural course of chronic hepatitis C varies considerably from oneperson to another. Although almost all people infected with HCV have evidenceof inflammation on liver biopsy, the rate of progression of liverscarring (fibrosis) shows significant variability among individuals. Accurateestimates of the risk over time are difficult to establish because of thelimited time that tests for this virus have been available.

Recent data suggest that among untreated patients, roughly one-thirdprogress to liver cirrhosis in less than 20 years. Another third progress tocirrhosis within 30 years. The remainder of patients appears to progress soslowly that they are unlikely to develop cirrhosis within their lifetimes. Incontrast the NIH consensus guidelines state that the risk of progression tocirrhosis over a 20-year period is 3-20 percent.

Factors that have been reported to influence the rate of HCV diseaseprogression include age (increasing age associated with more rapidprogression), 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 diseaseprogression), and fatty liver (the presence of fat in liver cells has beenassociated with an increased rate of disease progression).

Symptoms specifically suggestive of liver disease are typically absentuntil substantial scarring of the liver has occurred. However, hepatitis C is asystemic disease and patients may experience a wide spectrum of clinicalmanifestations ranging from an absence of symptoms to a more symptomaticillness prior to the development of advanced liver disease. Generalized signsand symptoms associated with chronic hepatitis C include fatigue, flu-likesymptoms, 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 decreasedliver function or increased pressure in the liver circulation, a conditionknown as portal hypertension. Possible signs and symptoms of liver cirrhosisinclude ascites(accumulation of fluid in the abdomen), bruising and bleeding tendency, varices (enlargedveins, especially in the stomach and esophagus), jaundice, and asyndrome of cognitive impairment known as hepatic encephalopathy. Hepaticencephalopathy is due to the accumulation of ammonia and other substancesnormally cleared by a healthy liver.

Liver enzyme tests show variable elevation of ALT and AST. Periodically they might show normalresults. Usually prothrombin and albuminresults are normal, but may become abnormal, once cirrhosis has developed. The levelof elevation of liver tests does not correlate well with the amount of liverinjury on biopsy. Viral genotype and viral load also do not correlate with theamount of liver injury. Liver biopsy is the best test to determine the amountof scarring and inflammation. Radiographic studies such as ultrasound or CTscan do not always show liver injury until it is fairly advanced. However,non-invasive tests (blood sample) are coming, with Fibro Testand ActiTest, respectively estimatingliver fibrosis and necrotico-inflammatory. These tests are validated andrecommended in Europe

Chronic hepatitis C, more than other forms of hepatitis, can be associatedwith extrahepatic manifestations associated with the presence of HCV such as porphyria cutanea tarda, cryoglobulinemia(a form of small-vessel vasculitis) and glomerulonephritis (inflammation of the kidney),specifically membranoproliferativeglomerulonephritis (MPGN). Hepatitis C is also rarely associated with sicca syndrome (anautoimmune disorder), thrombocytopenia, lichenplanus, diabetes mellitus and with B-cell lymphoproliferative disorders.

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