Hepatocellular carcinoma is
frequently diagnosed at an advanced stage in HIV-positive people with hepatitis
B or C co-infection, contributing to a high mortality rate that has changed
little in recent years, according to a report at the recent 53rd Interscience
Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Denver.
Over years or decades, chronic hepatitis B virus (HBV) or
hepatitis C virus (HCV) infection can lead to severe liver disease including
cirrhosis and hepatocellular carcinoma (HCC), a type of primary liver cancer.
People co-infected with HIV and viral hepatitis tend
to experience more rapid liver disease progression and respond less well to treatment
than those with HBV or HCV alone. As antiretroviral therapy has reduced
mortality due to AIDS, liver disease including HCC has become a growing cause
of death among people with HIV.
Juan Berenguer from Hospital General Universitario Gregorio Marañón in Madrid presented
findings from an analysis of tumour characteristics and survival among HIV-positive
patients with HCC. The researchers looked at how these have been affected by
surveillance practices, comparing outcomes before and after publication of the
American Association for the Study of the Liver (AASLD) HCC
practice guideline in 2005.
Guidelines recommend that people at risk for HCC
should undergo screening every six months. Risk factors include older age, active
HBV replication or inflammatory activity, HCV infection, non-alcoholic
steatosis (fatty liver) and liver cirrhosis due to any cause. Although most
people develop HCC after they already have advanced fibrosis or cirrhosis, it sometimes
also occurs in people with less advanced liver disease. Screening should
include ultrasound imaging to detect tumours and may also include liver
biopsies and measurement of alpha fetoprotein (AFP), a blood biomarker linked
to HCC and other types of cancer.
Berenguer's group did a retrospective analysis
of medical records from all HIV-positive patients diagnosed with HCC at their
centre between October 1998 and April 2012. Surveillance was defined as having
undergone liver imaging within the twelve months prior to HCC diagnosis. HCC was
diagnosed using non-invasive methods or pathology and staged using the
Barcelona Clinic Liver Cancer (BCLC) classification system:
Attempts at curative therapy such as resection (tumour removal) are
generally recommended for BCLC stages 0 or A, palliative therapy for stages B
or C and management of symptoms only for stage D.
The researchers identified 53 HIV-positive patients with HCC during the
study period. Nineteen were diagnosed between 1998 and 2005 and 34 between 2006 and 2012.
All but six (89%) were men and 82% had a history of injecting drug use.
Most (87%) were on combination antiretroviral therapy. Patients
diagnosed with HCC during the years 1998 to 2005 were younger (44 vs 48 years), had a higher
MELD score (12 vs 10) and were more likely to have undetectable HIV viral load
(47 vs 79%) than those diagnosed between 2006 and 2012. The median CD4 T-cell count
was also lower (272 vs 357 cells/mm3), but not significantly so.
Looking at liver disease characteristics, all patients diagnosed with
HCC had HCV (77%), HBV (11%) or both (11%). Almost all (95%) had cirrhosis, 60%
had a Child-Pugh score of B or C and half experienced liver decompensation.
More people were treated for hepatitis C with pegylated interferon/ribavirin
during the second period (32 vs 47%), but the difference did not reach
statistical significance. Berenguer noted that none of the treated patients
achieved sustained virological response.
Fewer than half
of participants had HCC diagnosed through surveillance during either period
(42% during 1998 to 2005 and 41% during 2006 to 2012), indicating no change after the
AASLD guidelines were issued. Biopsy confirmation, however, was more common
during the first period (37 vs 15%).
during the first period were less likely to have single tumours (32 vs 41%),
more likely to have large tumours (larger than 5cm, 67 vs 44%), had more metastases (21
vs 12%) and were more likely to have BCLC stages C or D (68% vs 47%), but none of these differences
reached statistical significance.
People diagnosed between 1998 and 2005 were significantly less likely to
receive treatment for HCC than those diagnosed later (42 vs 71%). This
included potentially curative therapies such as radiofrequency or ethanol
ablation (8 vs 22%) and resection (2 vs 6%), as well as palliative therapies such as transarterial chemoembolisation (11 vs 17%) and sorafenib
(2 vs 9%). Patients in the latter period were more than twice as likely to
undergo multiple types of treatment (11 vs 24%).
Consistent with having less advanced disease characteristics and
receiving more treatment, survival was longer during the second period compared
with the first (median 2 vs 11 months). Proportions of people surviving were higher
during the second period for one-year survival (37 vs 62%), two-year survival
(26 vs 37%) and three-year survival (14 vs 28%). However, none of these
differences reached statistical significance, meaning they could be attributable
to chance (p=0.16).
In a univariate analysis, factors
significantly associated with higher mortality included detectable HIV viral
load, higher MELD score, BCLC stage C-D vs A-B and AFP level >200ng/dl.
Receiving any type of treatment was associated with a significant 75% lower
risk of death. But CD4 cell count, Child-Pugh score, alcohol consumption and
HCC screening had no significant impact.
"In people with HIV,
HCC was frequently diagnosed at an advanced stage and outside of surveillance
programs," the researchers concluded. "Mortality was very high, with
no significant changes in recent years."
that "probably all patients with cirrhosis" are at risk of developing
liver cancer, and further studies are needed to see if some people are
especially at risk. He recommended screening HIV-positive people with advanced
liver disease at least every six months.