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January 8, 2009
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Hepatitis C (cont.)

What is the usual progression of chronic infection with hepatitis C virus?

Our understanding of the natural progression (history) of hepatitis C infection is still evolving. About 15% of patients with acute hepatitis C virus infection spontaneously recover (clear the virus). Eighty five percent, however, develop chronic liver disease. How many of these patients progress to cirrhosis of the liver? Is there a way to predict who will develop cirrhosis? And then, how many will develop liver failure, including the complications of cirrhosis, or liver cancer? Once a person has cirrhosis, how long is he/she expected to live? These are very pertinent questions for which there are no clear-cut answers, only reasonable estimates.

There are several ways to examine the natural history of chronic hepatitis C infection; retrospective (looking back in time), prospective (looking forward), or combined retrospective/prospective studies. A retrospective study involves identifying patients with established chronic hepatitis C infection and correlating their current stage of liver disease to the duration of their infection. Several such investigations have suggested that after acquiring hepatitis C virus, it takes about 10 to14 years for biopsy evidence of chronic hepatitis to appear, about 20 years to develop cirrhosis, and about 28 years to develop liver cancer.

There are problems with retrospective studies, however. For example, retrospective studies are inclined (biased) to select chronic hepatitis C patients who have symptoms, which is the reason the patients sought medical attention. Accordingly, information about the actual duration of infection in these patients may be inaccurate, that is, underestimated. Furthermore, retrospective studies do not tell what proportion of patients with chronic hepatitis C virus will develop cirrhosis, liver failure, or HCC.

In a prospective study, an entire group of hepatitis C patients are followed from the time they first become infected. These studies have necessarily involved patients who received contaminated blood, since in these individuals, the time of acquisition of hepatitis C virus can be accurately determined. However, the follow-up in most of these studies is relatively short. Furthermore, since some of these patients are being treated with antiviral therapy, the natural progression of the disease may be modified by the treatment. Anyway, these prospective studies suggest that about 10 to 25% of patients develop cirrhosis within a 10 to 15 year follow-up. Moreover, only about 10% of patients develop symptoms related to their liver disease.

Retrospective/prospective studies involve identifying a group of patients who were exposed to hepatitis C virus many years ago, accounting for almost all of these patients, and then following them prospectively. The advantage of these studies is that there is a head start to the follow-up as compared to a prospective study. These retrospective studies confirm that the natural progression of chronic hepatitis C virus is quite slow and in general, complications develop over decades, not years.

Again, these retrospective/prospective studies have involved patients who were exposed to contaminated blood or blood products (such as immunoglobulin). On average, these studies have looked at patients who were exposed over twenty years ago. In two studies involving women who acquired chronic hepatitis C virus after receiving contaminated immunoglobulin over 20 years ago, less than 3% of the patients developed cirrhosis. The vast majority of patients had only mild inflammation and no fibrosis (scarring) of the liver. About one third of patients had aminotransferase (liver enzyme) levels over 100 U/L (2 to 3 times normal) and one third had normal liver tests. However, one quarter of the patients reported fatigue.

According to these retrospective/prospective studies, once cirrhosis is established, the risk of developing liver failure, that is, the complications of cirrhosis, is about 10% per year. These complications include bleeding from varices (dilated veins, usually in the esophagus), ascites (fluid in the abdomen), encephalopathy (confusion), and jaundice. The risk of developing liver cancer in a cirrhotic patient with hepatitis C virus is 1.4% per year. However, patients who have cirrhosis without complications (compensated cirrhosis) have an 80% likelihood of surviving 10 years. On the other hand, patients who have cirrhosis with complications (referred to either as decompensated cirrhosis or liver failure) have a much lower likelihood of survival, less than 50% at 5 years.

It is unclear which factors promote the progression of chronic liver disease in hepatitis C virus infection. Earlier studies suggested that individuals infected with genotype 1b may develop more serious disease, but these findings could not be substantiated. Moreover, as previously mentioned, the level of virus in the blood does not correlate with disease severity. What is clear, however, is that the regular use of alcohol, even in moderation, is detrimental in hepatitis C virus chronic liver disease.



Next: Who is at high risk and should be tested for hepatitis C infection? »

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