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Diabetes is a risk factor for the development of liver cancer for people with cirrhosis successfully treated for HCV

Michael Carter
04 July 2016

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.

“Diabetes mellitus [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 therapy.   



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. 

Studies involving 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.

Investigators from 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 post-SVR.

The study 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.

The incidence 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 severe fibrosis.

People 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.

Significant risk 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).

During follow-up, 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 and steatosis.”

The authors 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.


Hedenstierna M et al. Diabetes and cirrhosis are risk factors for hepatocellular carcinoma after successful treatment for hepatitis C. Clin Infect Dis, online edition, 2016.