Diabetes is a
strong risk factor for hepatocellular carcinoma (HCC) in people with hepatitis C virus (HCV) infection who have
received successful treatment for the infection, Swedish investigators report
in Clinical Infectious Diseases. The
risk of HCC, or liver cancer, was especially high in the first two years after
therapy achieved a sustained virological response (SVR), or cure. The risk then
diminished. In contrast, people with advanced fibrosis at the time of SVR had
a very low risk of liver cancer, and the investigators question whether they
need advanced surveillance for this complication.
[DM] is a major risk factor for the development of HCC after SVR has been
achieved,” comment the authors. “Patients with cirrhosis and DM had a seven
times higher risk to develop HCC than patients without DM, and the annual HCC
risk for this group was 7.9% during the first two years after SVR.”
It is well
recognised that people with HCV with cirrhosis and advanced fibrosis
(stage F3) are at high risk of liver cancer. Successful treatment for HCV
reduces the risk of development of HCC, but a small risk may remain for many
years after SVR. Guidelines therefore recommend continued follow-up for HCC for
people with cirrhosis or advanced fibrosis at the time of successful
A protein made in the liver, needed to maintain a balance of the fluids in the body. In a blood test, lower than normal levels of albumin and total protein may indicate liver damage or disease. If there is not enough albumin, fluid may accumulate in the abdomen (ascites).
- hepatocellular carcinoma (HCC)
Liver cancer. A long-term complication of chronic inflammation of the liver or cirrhosis.
Abnormal fat deposits in the liver.
- sustained virological response (SVR)
Undetectable hepatitis C RNA after treatment has come to an end. Usually SVR refers to RNA remaining undetectable for 24 weeks (six months) after ending treatment and is considered to be a cure. SVR4 and SVR12 refer to RNA remaining undetectable for 4 and 12 weeks respectively.
people of Asian origin have shown that older age, male sex, diabetes, fatty
liver disease and alcohol use are all risk factors for the development of HCC
after SVR. Little is known about risk factors in European countries.
the Karolinska University Hospital, Sweden, therefore designed a retrospective
study involving people with cirrhosis or F3 fibrosis who were successfully
treated for HCV between 1992 and 2013. All received interferon-based therapy
and were followed to determine the incidence of, and risk factors for, HCC
population consisted of 399 people, 45% of whom had cirrhosis.
HCC was diagnosed
in 20 people during follow-up. The longest follow-up between SVR and the
diagnosis of liver cancer was a little over 15 years.
rates of HCC were 0.95 per 100 person-years for people with cirrhosis and
0.15 per 100 person-years for those with F3 cirrhosis. The risk of HCC was
therefore six times higher for people with cirrhosis compared to those with
pre-treatment cirrhosis and baseline diabetes had a liver cancer incidence rate
of 3.6 per 100 person-years in the first two years after SVR; this subsequently
fell to 1.9 per 100 person-years. People without baseline diabetes had a much
lower incidence rate, 0.5 per 100 person-years.
factors for HCC were diabetes (HR, 6.3; 95% CI, 1.7-2.3) and albumin levels
(HR, 6.2; 95% CI, 1.6-2.5).
35 people died and HCC was the cause in nine cases.
“The mechanism for
the association between DM and HCC is not fully discerned,” note the
investigators, “but these diseases share common risk factors, such as obesity
believe their findings could help guide HCC surveillance strategies. “The
diminishing risk of HCC seen in our study indicates that there might be a
time-point after SVR, when surveillance for HCC is no longer needed. Further
studies and also cost-effective analyses are needed to determine this issue.”
They also note
that the low incidence of HCC observed in people with F3 fibrosis, “was below
the 1.5% HCC incidence threshold usually proposed for HCC surveillance to be
cost-effective in cirrhotic patients.” The authors therefore question the value
of monitoring people without cirrhosis for HCC after SVR, especially when health
resources are limited.