HIV, hepatitis C co-infection may be deadly

It leads to high rate of end-stage liver disease

A group of Boston-area infectious disease physicians began to notice a trend in recent years of a high number of deaths among HIV patients related to end-stage liver disease and a co-infection with hepatitis C.

They decided to conduct a retrospective study, looking at the years 1991, 1996, and 1998, to determine whether there was an increase in deaths from liver disease.

"We wanted to look at the causes of death in patients at the beginning of monotherapy like AZT, and then in 1996 with the advent of highly active antiretroviral therapies [HAART], and then in 1998, a couple of years into HAART," explains Barbara McGovern, MD, an assistant professor of medicine at Tufts University School of Medicine in Boston and an associate physician in the infectious disease division of Lemuel Shattuck Hospital of Jamaica Plains, MA, and the New England Medical Center in Boston. McGovern presented the study at the Infectious Diseases Society of America conference held in Philadelphia in November 1999.

The researchers found that in 1991, there were three deaths due to end-stage liver disease, about 11.5% of the 26 HIV-infected people who had died at the hospital. In 1996, there were 31 deaths among HIV-infected patients; five or 16.1% involved end-stage liver disease. By 1998, the deaths from end-stage liver disease rose to 50%, accounting for 11 out of the total 22 deaths among HIV-infected patients.1

"So our findings obviously were incredibly striking," McGovern says. "Also, we found that in 1998, 55% of the patients who died either had undetectable HIV viral loads or their CD4 cell counts were greater than 200 prior to their deaths."

Those statistics suggest the patients’ liver disease resulted in an early demise, because the patients still had not progressed to AIDS, she adds. "These clearly were not people who died of HIV, and that’s a worrisome statistic."

The study raises questions about the proper use of antiretroviral drugs among patients who have a co-infection of HIV and HCV, because some of those medications can cause hepatotoxicity and need proper monitoring, McGovern says. "Patients with underlying hepatitis C may be at increased risk."

Researchers found that about one-third of the patients included in the 1998 cohort had a history of stopping their antiretroviral medications because of liver toxicity problems.

"So when practitioners were trying to treat them for HIV, their No. 1 problem, in retrospect, wasn’t HIV," McGovern says.

The Boston researchers had no way of knowing how many HIV patients had hepatitis C in 1991 and 1996, when such tests were less commonly done. But all three groups, including the 1998 group, had injection drug use as the predominant risk factor for both HIV and hepatitis C, so it was believed the groups were equivalent with regard to risk for hepatitis C infection. There also was a greater percentage of patients reporting alcohol use in the 1998 cohort.

"Of the 11 patients who died in 1998 of end-stage liver disease, 10 were tested for hepatitis C, and they were all positive," McGovern notes. "IV drug use is a huge part of our patient population, and that’s the biggest hepatitis C risk factor."

HIV clinicians treating patients with an HCV co-infection should consult a gastrointestinal specialist about the possibility of a liver biopsy and to discuss treatment options.

Clinicians should evaluate HIV and HCV jointly

"Patients with hepatitis C and HIV need to have both of their diseases evaluated side by side, and we can’t emphasize that enough," she adds. "Just as we as infectious disease doctors get CD4 counts and HIV viral loads, we need to follow liver function tests very carefully and do very careful physical exams to look for stigmata of liver disease."

A recent study published in JAMA found that 88% of HIV patients with an HCV infection were able to tolerate their medications without serious toxic effects. But the study also showed that patients who were taking ritonavir had an increased risk for liver toxicity.2

"So when these patients are started on HAART, they need to be monitored very closely over time," McGovern says.

Within the next couple of years clinicians may have some new treatment options for HCV, which may help patients with co-infections. These include peginterferon alfa 2-b and pegylated interferon alfa-2a. Peginterferon is still being reviewed by the U.S. Food and Drug Administration, and pegylated interferon is still being studied in clinical trials.

Also, there are two ongoing studies that have some early encouraging results showing that it appears that interferon and ribavirin are safe to treat patients with co-infection of HIV and HCV, McGovern says.

Moreover, peginterferon alfa 2-b has been studied for use in treating HIV patients as a possible agent to boost viral suppression during antiretroviral therapy. The study, highlighted at the 7th Conference on Retroviruses and Opportunistic Infections, held recently in San Francisco, showed a decrease in HIV viremia at week eight of the study.3

McGovern also advises clinicians to follow the U.S. Public Health Service’s recommendations and routinely test all HIV patients for HCV infection, regardless of risk factors.

Whether or not clinicians test patients for HCV, they should screen them for hepatitis C risk factors, asking these questions:

• Have you ever, even once, used IV drugs?

• Do you drink alcohol or have you ever used cocaine?

• Did you ever receive a blood transfusion before 1992?

If a patient’s hepatitis C test is negative and the clinician still is concerned about the patient’s risk factors, then it might be prudent to do a hepatitis C RNA test, which would more accurately determine infection.

"There’s a phenomenon of seroconversion where hepatitis C patients can lose antibodies, and you can be under the impression the patient is negative, while the patient still has a hep-C viral load," McGovern explains.

Then physicians should counsel their HIV patients, whether or not they are infected with hepatitis C, about the risk behaviors for transmitting HCV. For example, they should avoid using injection drugs or intranasal cocaine. Also, they should never share razors or toothbrushes. And, while studies have not made a strong case for hepatitis C transmission through sexual activity, it still is possible, so patients always should use protection for that reason, as well as to prevent the spread of HIV, McGovern advises.

"And in terms of alcohol use, you do your patients a great disservice if you don’t have a frank conversation about the harm that alcohol can cause in patients with hepatitis C," she says. "I advise my patients to abstain."

Reference

1. McGovern BH, Bica I, Stone D, et al. Increasing mortality from end-stage liver disease secondary to hepatitis C in patients with HIV. Presented at the 37th Annual Meeting of the Infectious Diseases Society of America. Philadelphia; Nov. 19, 1999.

2. Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. JAMA 2000; 283:74-80.

3. Reynes J, Rouzier-Panis R, Laughlin M, et al. Antire troviral activity and tolerability of PEG-interferon a-2b in patients on stable background therapy: Results of a phase I/II study. Abstract 542. Presented at the 7th Conference on Retroviruses and Opportunistic Infections. San Francisco; Jan. 30-Feb. 2, 2000.