By Michael Carter

The long-term outlook for HIV-positive individuals with hepatitis C coinfection may be much better than previously thought, according to information from a cohort of patients in Milan which was presented to the Fourth International Workshop on HIV and Hepatitis Coinfection in Madrid. The investigators found that over 20 years after infection with HIV, the vast majority of patients with hepatitis C-coinfection were still alive and that the probability of progressing to end-stage liver disease was 9%.

Doctors are now optimistic that successful treatment with potent anti-HIV treatment will mean that HIV-positive patients will be able to live a normal lifespan. But liver disease, often associated with hepatitis B or hepatitis C infection, is now a major cause of illness and death in HIV-positive patients, and ina recent prognostic model, individuals coinfected with HIV and hepatitis C had a significantly poorer prognosis than patients who were only infected with HIV.

Although it is accepted that infection with HIV speeds up the course of hepatitis C disease there is little information available on the long-term risk of progression to cirrhosis, liver failure and liver cancer (end-stage liver disease) in patients with HIV and hepatitis C coinfection who have not received treatment for their hepatitis C infection.

Investigators in Milan therefore looked at the medical records of patients in the city who were diagnosed with HIV before 1988 with confirmed infection with hepatitis C infection, but who had not received any anti-hepatitis C treatment. They defined end-stage liver disease as a diagnosis of oesophageal varices or decompensated cirrhosis.

The investigators identified 1223 patients who were diagnosed with HIV 20 or more years ago. Of these, 628 had confirmed infection with hepatitis C infection, and 528 had not received anti-hepatitis C treatment. The investigators did not provide any information on the duration of hepatitis C coinfection. However, 86% of patients had injecting drug use documented as their risk factor and given the high prevalence of hepatitis C infection amongst injecting drug users it is likely that both HIV and hepatitis C infection were acquired at approximately the same time.

Analysis of the medical records showed that end-stage liver disease had developed in 49 individuals (9%). Of these patients 22 (38%) had died, 15 (14%) were lost to follow-up, and twelve (3%) were still alive.

A diagnosis of type-2 diabetes was significantly associated with the development of end-stage liver disease (p = 0.008), further confirmation of the connection between insulin resistance and poorer outcome in HIV/hepatitis C coinfected patients. The investigators also found that patients with end-stage liver disease were significantly more likely to have been diagnosed with AIDS (p = 0.047).

No cases of end-stage liver disease developed within the first ten years of diagnosis with HIV. After 15 years of HIV infection, the probability of developing end-stage liver disease was 2%, increasing to 9% after 20 years and 18% after 25 years.

The investigators then looked more closely at the details of the patients who had died with a diagnosis of end-stage liver disease. They found that 25% of these patients had developed end-stage liver disease within 17 years of their diagnosis with HIV, 50% within 20 years and 75% within 25 years.

Cause of death was available for 48 patients (72%). In 14 (29%) of these individuals, death was attributed to cirrhosis.

The investigators found that the patients who progressed to end-stage liver disease received less treatment with potent combination antiretroviral therapy (median 5.5 years vs. 8.4 years, p = 0.0005) and had lower CD4 cell counts (median 173 cells/mm3 vs. 373 cells/mm3, p < 0.001). But in subsequent “multivariate” analysis, only shorter duration of potent antiretroviral therapy remained a significant predictor of progression to end-stage liver disease (p = 0.0001).

“In HIV/hepatitis C-positive patients infected before 1988, the overall probability of developing end-stage liver disease is 9%”, conclude the investigators, “suggesting that the natural history of hepatitis C virus disease in this population my be more benign than previously thought.”


Reference
De Bona A. et al. Probability to develop HCV-related ESDL in patients with long-term exposure to HIV infection. Fourth International Workshop on HIV and Hepatitis Coinfection, Madrid, abstract 29, 2008.