About a quarter of people in a New York City cohort who had HIV and hepatitis C virus (HCV) died over a ten-year period – a "strikingly low" survival rate – according to a poster presented at the Eighth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015) last month in Vancouver.
HIV/HCV co-infected individuals typically experience more aggressive liver disease progression than those with HIV or HCV alone, and they are more likely to develop liver steatosis (fat accumulation) and fibrosis (build-up of scar tissue). Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NAFLD and NASH) are growing causes of cirrhosis, liver cancer and the need for liver transplantation in Europe and the US.
Carrie Down and colleagues at the Weill Cornell Medical School liver disease unit at New York Presbyterian Hospital explored the impact of steatosis on fibrosis progression, cardiovascular disease and survival over time in HIV/HCV co-infected people.
This retrospective study analysed clinical outcomes among 105 co-infected patients attending Weill Cornell who initially received liver biopsies between 1998 and 2003 for HCV-related liver disease. The research team evaluated this group in 2005 and continued follow-up for ten years.
The earliest patients received biopsies during the first years after the advent of effective combination antiretroviral therapy (ART) for HIV, and follow-up ended just as interferon-free direct-acting antiviral therapy for hepatitis C started to become widely available.
Results
A majority of participants (70%) were men and the mean age was 45 years. Most (84%) had HCV genotype 1; 39% had absent or mild (grade 0-1) liver fibrosis, 38% had moderate fibrosis and 23% had advanced fibrosis or cirrhosis (grade 3-4). Most (88%) were on ART, 61% had an undetectable HIV viral load, the median CD4 T-cell count was 410 cells/mm3 and about 60% had had an AIDS diagnosis. Ten per cent had diabetes and 20% had hypertension (high blood pressure).
The researchers looked at clinical outcomes including cardiac events, liver function and survival over 10 years. Liver fibrosis was assessed using FIB-4 and APRI scores, calculated using common laboratory biomarkers (ALT and AST liver enzyme levels and platelet count).
A total of 59 participants (56%) showed evidence of steatosis; this was mostly mild (grade 1), but 7% had moderate (grade 2) and 2% had advanced (grade 3) steatosis.
People with steatosis were more likely to be male, overweight or obese (the mean body mass index was 26.3; 25 and 30 are the respective thresholds for overweight and obesity) and to drink alcohol, but were equally likely to have elevated blood lipids (8%).
Over the ten years of the study there were trends towards greater risk of several conditions in the steatosis group compared to patients without steatosis, but the differences did not reach statistical significance:
- diabetes: 22% vs 11%
- decompensated liver disease: 19% vs 15%
- coronary artery disease: 5% vs 4%
- peripheral vascular disease: 5% vs 4%
- myocardial infarction: 5% vs 2%.
Thirty people (29%) died during follow-up, with liver disease being the most common cause, accounting for ten deaths (eight people had an unknown cause of death). Survival analysis showed that people with steatosis had decreased survival compared to those without steatosis at five years (88% vs 93%) and at ten years (65% vs 73%), though these differences were also not significant.
People with steatosis had higher mean FIB-4 and APRI scores at the time of initial biopsy and at ten years of follow-up. Changes in FIB-4 and APRI over time were both significantly associated with increased mortality (unadjusted hazard ratio 1.08 and 1.15, respectively).
A multivariate analysis showed that diabetes, obesity, elevated blood lipids, alcohol use and HIV and HCV viral load were not significant predictors of survival.
"This retrospective cohort study did not detect a significant association of steatosis with overall survival or cardiovascular or diabetic events," the researchers concluded. "However, the data trended toward an increased rate of cardiovascular events, diabetes, and decreased survival in patients with steatosis."
"The overall survival in this HIV/HCV co-infected cohort studied was strikingly low (25% mortality), given [the] age and demographics at time of enrolment," they continued. "Low survival rate and association between liver disease markers and survival in this cohort underscore the importance of HCV treatment in HIV/HCV co-infected individuals."
Down C et al. The risk of cardiovascular disease and death over 10 years in HIV/HCV co-infected patients with and without steatosis. 8th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2015), Vancouver, abstract TUPEB246, 2015.
Click on this link for an electronic version of this poster.