Infection with HIV is associated with significantly worse survival for people with hepatocellular carcinoma (HCC, the most common type of primary liver cancer), according to findings from a large international cohort study published in the Journal of Clinical Oncology. As none of the patients received treatment for HCC, the study provides important evidence of the natural history of HCC in the context of HIV.
The average survival time for people with HIV was half that observed in HIV-negative individuals. Predictors of worse survival in people with HIV included cancer stage and alpha-fetoprotein level, a key tumour marker. Significantly, no HIV-related factors, such as CD4 cell count and viral load, were associated with poorer survival, showing that people with HIV are good candidates for appropriate HCC therapy.
“We demonstrate that HIV infection adversely influences the clinical course of HCC, leading to a 24% increase in the hazard of death in patients who did not receive any active anticancer treatment,” write the authors. “A precise estimate of the relationship between HIV and survival in patients with untreated HCC is essential to gain insight into the natural history of the disease and to gather basic information on patients’ prognosis that can be used as a point of reference for future mechanistic and clinical studies.”
HCC is an increasingly important cause of death among people with HIV. This is largely due to the high prevalence of co-infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV). Whether HIV has an independent effect on the prognosis of people with HCC is uncertain. The studies that have examined this have yielded mixed results, with some showing that HIV was indeed a factor in poorer survival and others concluding that HIV has no effect on prognosis. These conflicting findings can be explained by the low quality of previous research, which usually relied on retrospective data or involved patients recruited from a single treatment centre.
Dr David Pinato of Imperial College London and colleagues wanted to establish a clearer understanding of the independent effect of HIV infection on the prognosis of individuals with HCC. They therefore designed an international cohort study involving 1588 people diagnosed with HCC, none of whom received anti-cancer therapy. Participants were diagnosed with HCC between 1992 and 2016 and received care at 44 treatment centres in the Americas, Europe, Asia and Australia.
Data were collected on infection with HIV and viral hepatitis, demographics and key factors known to affect outcomes in people with HCC. A series of analyses were undertaken to see if HIV had an effect on mortality risk, independent of other factors.
A total of 132 patients were HIV-positive. On average, people with HIV were younger (53 vs 66 years, p < 0.001), were more likely to be male (95% vs 82%, p = 0.003) and had a higher prevalence of HCV co-infection (78% vs 37%, p < 0.001) than the HIV-negative individuals.
HCC stage using the Barcelona Clinic Liver Cancer (BCLC) and Child-Turcotte-Pugh (CTP) criteria did not differ between the HIV-positive and HIV-negative groups. However, people with HIV had lower albumin (31 vs 29g/l, p < 0.001), higher ALT (56 vs 47, p = 0.0014) and higher AST (128 vs 95, p = 0.005) levels, all markers of poorer liver function.
While 78% of people with HIV had co-infection with HCV, only three individuals received HCV therapy before the onset of HCC. In each case, this treatment was interferon-based and was unsuccessful. HBV co-infection was present in 25% of those with HIV, and 36% of these individuals had evidence of HBV replication at the time of HCC diagnosis.
At the time of liver cancer diagnosis, two-thirds of people with HIV were taking combination antiretroviral therapy (median duration, 8.3 years), half had an undetectable viral load and average CD4 cell count was 256 cells/mm3.
The median duration of survival between HCC diagnosis and death was 2.2 months for people with HIV compared to 4.1 months for HIV-negative individuals.
After taking into account other prognostic factors, infection with HIV was associated with an independent increase in mortality risk (HR = 1.24; 95% CI, 1.2-1.52, p = 0.033). Other independent risk factors included male sex, more advanced cancer stage and alpha-fetoprotein levels (AFP, a key tumour marker).
In people with HIV specifically, factors associated with poorer survival were AFP (HR = 1.18; 95% CI, 1.09-1.28, p < 0.001) and more advanced Child-Turcotte-Pugh cancer stage (C vs. A; HR = 2.78; 95% CI, 1.31-5.91, p = 0.0079).
There was no evidence of an association between survival and CD4 cell count and viral load. “We believe this finding to have important ramifications regarding the clinical management of patients with HIV-associated HCC,” comment the investigators. “Patients with HCC and well-controlled HIV should face no barriers in the provision of active anticancer treatment.”
However, the authors suggest that the poorer survival seen in people with HIV “deserves to be taken into account.” Studies are urgently needed to investigate the immunobiology of HIV-associated HCC, they conclude.
Pinato DJ et al. Influence of HIV infection on the natural history of hepatoceullar carcinoma: results from a global multicohort study. Journal of Clinical Oncology, https://doi.org/10.1200/jco.18.00885 (2018).