Hepatitis C is caused by an RNA virus that has many features similar to the fla-viviruses (35—39). Hepatitis C represented 16% of the cases of acute hepatitis in the sentinel study from the CDC from 1982 to 1993. Despite this, hepatitis C represents more than half of all the cases of chronic viral hepatitis in the United States. The incubation of the infection is from 2 to 26 wk. Clinical illness occurs in 30-40% of the patients, but only 20-30% of all the patients will develop jaundice.
There are an estimated 20,000 new cases of hepatitis C infections in the United States every year. Of these, 8400 are clinically apparent and very few will develop fulminant hepatitis. The overall prevalence of this infection in the United States is 1.8% with a total of 3.9-4 million persons in the United States suffering from chronic hepatitis C that will result in 8000-10,000 deaths every year.
The acquisition of hepatitis C is most often via the parenteral route, most commonly related to injected drug abuse. Other patients may acquire infection by transfusion or transplanted organs. Hemodialysis and accidental injuries with infected needles are other sources of infection. Additional risk factors include sexual contact with an infected person, nonparenteral cocaine abuse, multiple sex partners, or birth from a hepatitis C infected mother. The rate of transmission from monogamous heterosexual relations is in the order of 1.1-5.4%. Perinatal transmission from an infected mother who is HIV negative is approx 4.5% and for the mother who has coinfection with HIV it is approx 18%. The risk of a health care worker acquiring infection after percutaneous exposure with an infected needle is estimated to be 1.8% (range 0-7%) and only one case has been described secondary to a conjunctival splash.
In the United States, 38% of cases of hepatitis C have been related to use of intravenous drugs and 44% occur in patients of low socioeconomic status. However, in the "low socioeconomic group," more than 60% of infected individuals have used nonparenteral drugs, mostly cocaine by inhalation, and a fifth of them also have a history of sexually transmitted diseases. Sexual or household contact with a person infected with hepatitis C is found in only 10% of the cases, history of transfusions in 4%, occupational risks in 2%, and hemodialysis in 1%. Currently, 40% of the patients who have chronic liver disease have hepatitis C as a single or contributing factor. Approximately 26% have hepatitis C as the only factor and 14% have concomitant hepatitis C and alcohol abuse.
Many patients who have chronic hepatitis C infection are asymptomatic at the time that the diagnosis is established. Later, fatigue is the most common symptom and is found in 60% of the patients. Itching (30% of the patients) and abdominal pain (nearly 30%) are also frequent.
The progression of the hepatitis C tends to be very slow and may take 20, 30, or 40 yr to evolve from the time of acquisition to the development of complications from advanced liver disease. Eighty-five percent of patients infected with hepatitis C will develop chronic infection. Of those with chronic infection, perhaps 20% will evolve to cirrhosis (17% of the total). Of the cirrhotic patients, most remain well compensated over many years, but a subgroup will worsen and die of the disease (25% of cirrhotics or 4% of all the infected patients). These patients die either from complications of the chronic liver disease such as variceal bleed or spontaneous bacterial peritonitis or from hepatocellular carcinoma.
Alcohol is a critical cofactor for the development of hepatic injury in hepatitis C virus infected patients and as little as 10 g of alcohol a day increases the viral load. Amounts of alcohol in excess of 10 g a day cause additional elevation of liver enzymes with more accelerated progression of liver disease.
There are two approved therapies for chronic hepatitis C. One is interferon alone (Intron A, Roferon A, Infergen) and the second is a combination of interferon plus ribavirin (Rebetron). Patients who are most likely to receive benefit from therapy are those who show evidence of progression of disease. Liver biopsies are important to identify patients who have more advanced disease and differentiate them from those who have disease that is mild enough that it is not likely to progress. In the absence of "interface hepatitis" (piecemeal necrosis), fewer than 7% of the patients will develop cirrhosis over time. On the other hand, if interface hepatitis is present, even in the absence of fibrosis, the long-term risk of developing cirrhosis is 20-30%. Patients with more advanced disease with fibrosis outside the portal area, bridging inflammation, or necrosis have a chance of progressing to cirrhosis in the order of 70%.
Predictors of treatment outcome include viral load, genotype, and depending on the type of therapy, the presence or absence of cirrhosis. Patients with hepatitis C viral loads less than two million copies per milliliter tend to respond to therapy better. Patients with infection with genotype 2 or 3 respond better. In contrast, patients with genotype 1 (1a or 1b) or 4 tend to respond poorly. Other genotypes have been less studied. In therapies with a single agent (Interferon), the presence of cirrhosis also predicts poor response. Patients who have consistently normal liver enzymes over a period of 6 mo respond very poorly to therapy and should be treated only as part of study protocols.
Standard therapy with interferon alone is 3 million units three times a week for 12 mo. With that regimen, sustained virological response (absence of hepatitis C virus RNA 6 mo after therapy) is 13-19% (9% for genotype 1 and 30% for genotype 2 or 3). Similarly, patients with viral loads more than 2 million copies per milliliter have a sustained viral response (SVR) of only 10% compared with those who have <2 million copies per milliliter, who have a SVR of 30%. The presence of bridging fibrosis or cirrhosis also has a negative effect, with a SVR of 12% compared with 18% in the absence of fibrosis.
Combination therapy with oral ribavirin 1000-1200 mL a day depending on weight, plus 3 million units of interferon three times a week is more effective. The SVR to 48 wk of combination therapy is from 38% to 43% with a 1-yr course of therapy. SVR is only 31-35% for 6-mo therapy. In combination therapy, patients with hepatitis C due to genotype 1 respond less well (17% SVR with 6-mo therapy vs 29% SVR for 1-yr therapy). Genotypes 2 and 3 respond equally well to 6 or 12 mo of therapy with a SVR of 66%; clearly, these patients do not need a full year of therapy. Viral load also has some degree of importance and patients with more than 2 million copies per milliliter (Quan-tiplex test, Chiron Diagnostics) have a sustained virologic response of 38% compared with 45% for those who have <2 million copies. Patients with bridging fibrosis or cirrhosis have an SVR of 36% after 1 yr of therapy as compared with 43% in those without meaningful fibrosis. Patients with genotype 1, but with low viral load (< 2 million copies) have an SVR that is the same at either 6 or 12 mo of therapy (32%). Patients infected with genotype 2 or 3 have the same SVR with 6 or 12 mo of therapy, regardless of the viral load. The group that has been shown to obtain benefit from a full year of combination therapy is patients who have infection with genotype 1 (a or b) and viral load of more than 2 million copies, with sustained virologic response extending from 10% with 6 mo of therapy to 27% after 12 mo.
Patients who responded to interferon therapy and then relapsed after discontinuation or by the end of follow-up can be treated with reasonable success. There are two good therapeutic options: (1) Interferon alfacon-1 (Infergen) at a dose of 15 ^g three times a week has been shown to give an SVR of 58% after 48 wk of therapy. (2) Rebetron (3 million units of interferon three times a week + 1000-1200 mg of ribavirin every day according to weight) gives an SVR of 46% after 24 wk of therapy. Here, there is also a difference in patients with genotype 1 who had an SVR rate of 29% as compared to the non-genotype 1 who had an SVR of 74%. Patients with high viral loads of more than 2 million copies per milliliter had an SVR of 42% as compared with those with lesser viral loads who had an SVR of 67%. In this case, the presence of cirrhosis did not make a difference in SVR (46 vs 49%).
Was this article helpful?