November 12, 2001
The risk factors for acquiring hepatitis C infection (HCV) and HIV are similar, thus co-infection is not infrequent. Prior to the introduction of HAART therapy for HIV, most patients co-infected with HIV and hepatitis C died from HIV before the hepatitis C infection could cause significant damage to the liver. Now that patients infected with HIV live much longer, the number of persons infected with HIV who present with advanced disease secondary to hepatitis C infection is increasing.
Prior research has suggested that in patients with HIV and HCV co-infection, hepatitis C progresses more rapidly and is more likely to cause cirrhosis and severe liver damage compared to those with only HCV infection. Many of these studies, however, have been done at referral hospitals where the sickest patients are usually seen. Other investigators do not think that HCV in HIV co-infected patients progresses more rapidly than in HCV-only patients.
Dr. Richard Sterling and colleagues from the Medical College of Virginia designed a study to determine the true spectrum of liver disease in patients co-infected with hepatitis C and HIV. To avoid selecting only the sickest patients, they looked at every patient seen in the HIV clinic who was also infected with hepatitis C, and compared them to other patients who had hepatitis C but no HIV infection. All patients underwent extensive testing to exclude other types of liver disease, liver biopsy to assess their degree of liver damage and blood testing to assess the severity of their HIV infection. Because the study population consisted primarily of African-Americans, the investigators designed the control group (hepatitis C infection without HIV infection) so that it was also predominantly African-American.
The study group consisted of 51 patients with HIV and HCV co-infection, and a mean age of 40 years. Seventy-five percent were males and 84% were African-Americans. They found that co-infected patients had similar levels of enzyme elevations (ALT) and viral load as those with hepatitis C infection only. Liver biopsy also showed that the severity of liver disease was similar in both groups: 34% of those co-infected had advanced fibrosis compared to 29% of those with HCV only, a statistically non-significant difference. The investigators also noted that normal ALT levels were more common among co-infected patients (57%), but those with elevated ALT tended to have more advanced fibrosis. The investigators noted that among patients with more advanced HIV (CD4 count <200), the prevalence of advanced fibrosis and cirrhosis was lower than in those with higher CD4 counts.
Dr. Sterling and colleagues concluded that a high percentage of co-infected patients have normal ALT levels and less severe liver disease. These patients often do not get tested for HCV and may remain undiagnosed, skewing results toward those with higher ALT levels and more severe disease upon biopsy. When HCV and HIV co-infected patients are evaluated regardless of ALT levels, there is no difference in severity of liver disease. They also noted that since those patients with higher CD4 counts had more severe disease, it is possible that immune reconstitution with HAART therapy could theoretically lead to worsening liver disease.
This study raises some valid points, but contradicts many other studies that have looked at the natural history of HIV and HCV co-infected patients. It is possible that by including patients with normal ALT levels, they may have selected a population with less severe liver disease that previously had not been studied. Another possibility is that the high proportion of African-Americans may have altered the results. Some studies have found that as a group, African-Americans tend to have less severe liver disease associated with hepatitis C infection. Until other investigators corroborate this data, HCV infection in patients with HIV and CD4 counts >200 should be treated aggressively to prevent the progression of the disease, particularly those in whom baseline liver biopsy shows severe inflammation or advanced fibrosis.
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