Liver deaths and HAART - the truth. 18 July 2003
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Peter J Flegg,
Consultant Physician
Blackpool Victoria Hospital, UK, FY3 8NR

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Re: Liver deaths and HAART - the truth.

I welcome the opportunity to correct yet another instance of data misinterpretation by an HIV dissident, Christopher Tyler (15 July). At the Barcelona AIDS conference in 2002 a University of Pittsburg researcher, Amy Justice, described the liver abnormalities within 2 North American cohort studies, concluding that that liver failure had become one of the most common cause of death in HIV-infected patients. Dissidents worldwide have inferred incorrectly that antiretrovirals have been responsible for this phenomenon, and have persisted in claiming this, despite being corrected on many occasions.

In reality, there has been no "epidemic" of liver toxicity related to HAART. What escaped the dissidents’ notice, (perhaps intentionally?) was the fact that liver deaths overall had risen only very modestly, and the reason why they form such a large proportion of total deaths in these cohorts is because far fewer patients have died of AIDS since the introduction of HAART.

Also conveniently ignored by the dissidents is that the majority of liver deaths have nothing to do with HAART whatsoever. The commonest reasons for cases of end stage liver disease and hepatocellular carcinoma have been hepatitis C or B co-infections. In the presence of HIV, HCV progression to cirrhosis is more rapid. Alcohol is also implicated as a major factor.

Antiretroviral drugs are linked to hepato-toxicity in several ways. These include early hypersensitivity (nevirapine, abacavir), direct hepatotoxicity with some protease inhibitors, and hepatic steatosis with the mitochondrial dysfunction of reverse transcriptase inhibitors. If these drugs were a common cause of hepatic problems, then we would be witnessing thousands of cases, rather than the small contribution to the low absolute number of liver deaths that we are seeing.

Apart from the North American cohorts, there are many other studies to support the evidence for a modest rise in background liver deaths against a startling drop in overall HIV deaths from AIDS. A quick calculation of cases analysed within 4 other cohort studies (1-5) yields the following:

Liver deaths out of total HIV/AIDS mortality:

PreHAART (before 1995) = 64/1970 cases (3.2%)

Post HAART (after 1995) = 72/631 cases (11.4%)

Once again we see that selective misquotation and deliberate attempts to mislead are the order of the day as far as the dissidents are concerned.

1. Soriano V,Garcia-Samaniego J,Valencia E, et al. Impact of chronic liver disease due to hepatitis viruses as cause of hospital admission and death in HIV-infected drug users. Eur J Epidemiol 15:1–4, 1999.

2. Puoti M, Spinetti A, Ghezzi A. et al. Mortality for liver disease in patients with HIV infection: a cohort study. J Acquired Immune Defic Syndr 24:211-17, 2000.

3. Martín-Carbonero L, Soriano V, Valencia ME, et al. Impact of chronic viral hepatitis on hospital admission and mortality in HIV-infected patients. AIDS Res Hum Retroviruses 17:1467-71, 2001.

4. Cacoub P,Geffray L,Rosenthal E,et al. Mortality among HIV-infected patients with cirrhosis or hepatocellular carcinoma due to hepatitis C virus in French Departments of Internal Medicine/Infectious Diseases in 1995 and 1997. Clin Infect Dis 32:1207-1214, 2001.

5. Bica I, McGovern B,Dhar R, et al. Increasing mortality due to end-stage liver disease in patients with HIV infection. Clin Infect Dis 32:492-7, 2001.

Competing interests:   Attendance at drug company-sponsored meetings