Coinfection

Incidence of Liver Cancer Is Increasing Among People with HIV/HCV Coinfection

Incidence of liver cancer is increasing among people with HIV co-infection, an international team of investigators report in the June 15 online edition of Clinical Infectious Diseases. Researchers from Europe and Canada pooled data gathered between 2001 and 2014 from 6 prospective cohorts and found that incidence of hepatocellular carcinoma (HCC) increased, but the incidence of serious liver related events -- decompensated liver disease or liver-related death -- declined.

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"It seems paradoxical that improvements in liver-related morbidity in HIV/HCV coinfected patients, demonstrated by a lower incidence of other events, would simultaneously yield a higher incidence of HCC," commented the authors. "Perhaps an improved management of liver cirrhosis and HIV treatment can increase the threshold for liver decompensation in the cirrhotic HIV/HCV coinfected individuals, but thus increasing longevity such that viral hepatocarcinogenesis has enough time to manifest itself as HCC."

Overall, the investigators believe their results support additional surveillance of trends in HCC incidence.

Large numbers of people living with HIV are coinfected with hepatitis C virus (HCV). Chronic HCV infection can lead to serious liver disease, including cirrhosis and HCC. HIV/HCV coinfection is known to accelerate liver disease progression. However, the prognosis for people with coinfection has improved significantly in recent years. Some research suggests that the overall incidence of serious liver disease is declining, but rates of HCC are increasing in people with coinfection.

Investigators from EuroSIDA, the South Alberta Clinic Cohort, the Canadian Coinfection Cohort, and the Swiss HIV Cohort therefore designed a study to determine incidences of HCC and other liver events between 2001 and 2014 and to identify the risk factors for liver cancer and serious liver disease or death.

A total of 7229 people with HIV/HCV coinfection were included in the study. Approximately two-thirds (68%) were male, 90% were white, the median age was 38 years, 5% also had hepatitis B, and the main HIV risk group was people who inject drugs.

There were 72 cases of HCC and 375 other liver events. Overall incidence of HCC was 1.6 per 1000 person-years (PY) of follow-up, with other liver events having an incidence of 8.6 per 1000 PY.

Incidence of HCC increased by 11% each year, from 0.4 per 1000 PY in 2001-2002 to 2.3 cases per 1000 PY in 2013-2014. In contrast, incidence of other liver events decreased by 4% per year, from 9.9 cases per 1000 PY in 2003-2004 to 6.2 cases per 1000 PY in 2013-2014.

"Changes in the proportion of individuals with cirrhosis -- which increased by 8% per year -- most likely explained the increase in HCC per calendar year," suggested the researchers.

Among people with cirrhosis, incidence of HCC was 7.9 cases per 1000 PY versus 0.5 per 1000 PY among people without cirrhosis. For other liver events, incidence was 35.6 per 1000 PY for those with cirrhosis compared to 2.4 per 1000 PY for people without cirrhosis.

Regardless of cirrhosis status, incidence of both HCC and serious liver events was lower in people with a CD4 cell count above 350 cells/mm³.

The median age at the development of HCC was 50 years compared to 44 years for other liver events. A third of people with HCC and 18% of individuals with other serious liver events had ever received therapy for hepatitis C. Almost all people had received combination HIV therapy (99% HCC vs 91% other liver events), however recent CD4 cell counts were quite low, between 242 and 286 cells/mm³.

Risk factors for HCC and other liver events included older age, cirrhosis, and a low current CD4 cell count.

"We found a significant protective effect of a doubling of current CD4 count after adjustment for cirrhosis, corroborating the independent effect of current immunosuppression as a risk factor for HCC," observed the researchers, who concluded, "New HCV treatment with direct-acting antivirals and earlier HIV treatment will likely reduce the rates of HCC and other liver events, but as HCC can develop after achieving SVR [sustained virological response], or as a consequence of long-term alcohol abuse, non-alcoholic steatohepatitis, or other hepatotoxic exposures, continuous surveillance of incidence trends is needed."

7/14/16

Reference

LI Gjaerde, LShepherd, E Jablonowska, et al.  LI et al. Trends in Incidences and Risk Factors for Hepatocellular Carcinoma and Other Liver Events in HIV and Hepatitis C Virus-coinfected Individuals From 2001 to 2014: A Multicohort Study. Clinical Infectious Diseases. June 15, 2016 (online ahead of print).