Incidence of liver cancer is increasing among people with HIV co-infection, an international team of investigators report in the online edition of Clinical Infectious Diseases. Researchers from Europe and Canada pooled data gathered between 2001 and 2014 from six 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.
“It seems paradoxical that improvements in liver-related morbidity in HIV/HCV co-infected patients, demonstrated by a lower incidence of other events, would simultaneously yield a higher incidence of HCC,” comment the authors. “Perhaps an improved management of liver cirrhosis and HIV treatment can increase the threshold for liver decompensation in the cirrhotic HIV/HCV co-infected 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 have co-infection with hepatitis C virus (HCV). Chronic HCV infection can lead to serious liver disease, including HCC. HIV co-infection is known to accelerate disease progression. However, the prognosis for people with co-infection 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 co-infection.
Investigators from EuroSIDA, the South Alberta Clinic Cohort, the Canadian Co-infection Cohort and the Swiss HIV Cohort therefore designed a study to determine incidences of HCC and other liver events between 2001 and 2014 and identify the risk factors for liver cancer and serious liver disease/death.
A total of 7229 people with co-infection were included in the study. Approximately two-thirds (68%) were male, 90% were white, median age was 38 years, 5% also had hepatitis B virus infection 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 of follow-up with other liver events having an incidence of 8.6 per 1000 person-years.
Incidence of HCC increased by 11% each year, from 0.4 per 1000 person-years in 2001-2002 to 2.3 cases per 1000 person-years in 2013-2014. In contrast, incidence of other liver events decreased by 4% per year, from 9.9 cases per 1000 person-years in 2003-2004 to 6.2 cases per 1000 person-years 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,” suggest the researchers.
In people with cirrhosis, incidence of HCC was 7.9 cases per 1000 person-years versus 0.5 per 1000 person-years in people without cirrhosis. For other liver events, incidence was 35.6 per 1000 person-years for those with cirrhosis compared to 2.4 per 1000 person-years 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.
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 HCV. Almost all people had received combination HIV therapy (99% HCC vs. 91% other liver events), however recent CD4 cell counts were quite low and 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,” observe the researchers, who conclude: “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 virologic response], or as a consequence of long-term alcohol abuse, non-alcoholic steatohepatitis, or other hepatotoxic exposures, continuous surveillance of incidence trends is needed.”
Gjaerde LI et al. Trends in incidences and risk factors for hepatocellular carcinoma and other liver events in HIV and hepatitis C virus co-infected individuals from 2001 to 2014: a multi-cohort study. Clin Infect Dis, online edition, 2016.