Infection with HIV
is associated with significantly worse survival for patients 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 hepatocellular carcinoma, the study provides important evidence of the natural history of HCC in the context of HIV.

The average survival
time for patients 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 patients 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.”

Hepatocellular carcinoma 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 patients 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 patients 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 patients 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,
patients 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, patients 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 patients with HIV were co-infected 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 patients 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 patients with HIV “deserves to be taken into account.” Studies are
urgently needed to investigate the immunobiology of HIV-associated HCC, they conclude.