By Annette M. Boyle
PHILADELPHIA – Otherwise “non-hazardous” levels of drinking pose a real danger for patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus. Drinking, even moderately, dramatically increases the risk of liver fibrosis, according to a new study.
“Our research suggests that there may be no safe levels of alcohol consumption for co-infected patients,” said Vincent Lo Re III, MD, an infectious disease physician at the Philadelphia VAMC and assistant professor of medicine and epidemiology in the division of infectious disease at the University of Pennsylvania’s Perelman School of Medicine.
Between 20% and 30% of HIV patients also have HCV.
Lo Re was one of the researchers in a cross-sectional study among participants in the Veterans Aging Cohort Study who received care at one of eight VAMCs around the country and reported any current alcohol consumption at enrollment. Of those, 701 were HIV/HCV co-infected, 1,410 had only HIV, 296 had only HCV and 1,158 had neither virus. The researchers analyzed reported alcohol use and advanced hepatic fibrosis. The results were recently published in the journal Clinical Infectious Diseases.1
Researchers classified each participant into one of three mutually exclusive categories: an alcohol-related diagnosis (854 or 24%), hazardous or binge drinking (1,232 or 34.6%) and nonhazardous drinking (1,479 or 41.5%). Classification was based on clinical records and the results of the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire, which asks about frequency of alcohol use, quantity of alcohol typically consumed and consumption of six or more drinks on any one occasion in the previous 12 months. Patients were considered to have advanced liver fibrosis if their fibrosis 4 (FIB-4) score exceeded 3.25.
Among the heaviest drinkers, those co-infected with HIV and HCV had 25.2 times the risk of advanced liver fibrosis compared with non-infected nonhazardous drinking participants. Even among the lightest drinkers, the risk rose substantially; co-infected nonhazardous drinkers were 14.2 times more likely to have advanced liver fibrosis compared with non-infected light-drinking participants.
While co-infection was associated with the highest rates of advanced hepatic fibrosis at all levels of alcohol consumption, the researchers found advanced liver disease was independently associated with increased levels of drinking.
Both HCV mono-infected and HIV mono-infected participants had significantly increased risk of advanced hepatic fibrosis compared with uninfected participants at all levels of alcohol consumption. HCV mono-infected participants with alcohol dependence had 13.8 times the risk of advanced hepatic fibrosis, and HIV mono-infected participants had 7.8 times the risk compared to uninfected, nonhazardous drinking participants.
“The difference between co-infected and uninfected groups was stark. Given the prevalence of drinking in co-infected individuals, it is important to determine the patterns of alcohol use, such as nonhazardous drinking and even binge drinking, which are not traditionally thought to contribute to liver fibrosis,” Lo Re told U.S. Medicine.
The researchers noted that in vitro studies indicate that both HIV and HCV contribute to hepatocyte apoptosis and hypothesized that alcohol may speed this process. Alternatively, alcohol may exacerbate the hepatotoxicity of the drugs used to treat HIV and chronic HCV.
Regardless of the cause of the increased risk, “the safest level of alcohol consumption for someone with hepatitis C is none at all,” said Amy Justice, MD, PhD, another study author, section chief of general internal medicine at the VA Connecticut Healthcare System and professor of medicine and public health at the Yale School of Medicine. “There is no benefit to alcohol consumption in HCV patients and many harms. We have previously published data that showed even modest alcohol consumption negatively affects adherence as well as progression.”
Lo Re and Justice also collaborated with other researchers on a second study of HIV/HCV co-infected veterans which found that the rate of serious liver disease remained much higher in co-infected patients than in HCV mono-infected patients despite positive response to antiretroviral therapy (ART).
That study, published in the Annals of Internal Medicine, analyzed the medical records of 4,280 co-infected patients who were on ART and 6,079 HCV mono-infected patients in the Veterans Aging Cohort Study who received care at VA facilities from Jan. 1, 1997, to Sept. 30, 2010. None of the patients had initiated treatment for HCV. 2
Overall, co-infected patients had an 83% higher rate of decompensated cirrhosis than those with only HCV. Maintaining HIV RNA levels below 1000 copies/mL during follow-up had some benefit for co-infected patients, but they still had a rate of decompensation 65% higher than HCV mono-infected patients. The researchers found similar results among patients who maintained HIV RNA levels below 400 copies/mL throughout the study period.
The authors concluded that “HIV viral suppression below these thresholds with ART is not sufficient to reduce rates of end-stage liver disease to those of HCV mono-infected patients.”
The studies lend additional weight to recommendations for veterans with HIV and HCV to begin treatment. “Our research suggests that it is very important for people who are co-infected to treat their HIV as soon as possible and that they consider treatment for hepatitis C because they have a much greater risk for disease progression than other patients,” Justice told U.S. Medicine.
VA guidelines recommend that all co-infected patients receive ART, regardless of CD4 counts. For many years, however, clinicians refrained from recommending HCV treatment for co-infected patients because of the low rates of sustained virological response achieved and the frequency of serious side effects.
“There had been a concern that interferon-based therapies were so toxic that co-infected patients wouldn’t be able to stay on them, and the low rates of SVR hardly seemed to justify exposing them to that toxicity,” Justice said.
With newer and more effective therapies, the balance has changed. “Today, cure rates are much higher, regimens are more tolerable and shorter in duration,” Lo Re added. “However, the cost of these therapies is quite high, so our group and others have been exploring ways to identify which HIV/HCV patients need treatment urgently.”
1 Lim JK, Tate JP, Fultz SL, Goulet JL, Conigliaro J, Bryant KJ, Gordon AJ, Gibert C, Rimland D, Goetz MB, Klein MB, Fiellin DA, Justice AC, Lo Re V III. Relationship between alcohol use categories and noninvasive markers of advanced hepatic fibrosis in HIV-infected, chronic hepatitis C virus-infected, and uninfected patients. Clin Infect Dis. 2014 May;58(10):1449-58.
2 Lo Re V III, Kallan MJ, Tate JP, Locallo AR, Lim JK, et al. Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients. Ann Intern Med. 2014;160:369-379.