Insulin Resistance and Diabetes Increase the Risk of Liver Fibrosis and Hepatocellular
Carcinoma in People with Chronic Hepatitis C By
Liz Highleyman
 Two
recent journal articles add to the accumulating evidence linking blood glucose
abnormalities with liver disease progression in people with chronic
hepatitis C virus (HCV) infection.
Liver
Fibrosis
In
the first study, reported in the May 2008 American Journal of Gastroenterology,
Italian researchers looked at the association between increasing degrees of insulin
resistance and liver steatosis
(fat accumulation) and fibrosis
in patients with genotype 1 HCV. 
The
201 participants underwent liver biopsy
(staged using the Scheuer system) and anthropometric and metabolic measurements.
About half had normal insulin response, 38% had insulin resistance short of diabetes
(HOMA-IR score > 2.7), and 14% had frank type 2 diabetes mellitus.
Results
•
In a multivariate
analysis, the following factors predicted advanced fibrosis (stage 3 or higher):
- High necroinflammatory activity (odds ratio [OR] 2.994);
- Insulin resistance
(OR 2.692);
- High ferritin (a form of iron) level (OR 1.002);
- Low platelet
count (OR 0.994);
- Low serum cholesterol level (OR 0.987).
•
Patients with
diabetes were twice as likely to have advanced fibrosis (60%) than those with
insulin resistance short of diabetes (60 vs 30%; P = 0.006).
•
The degree
of liver steatosis and fibrosis were weakly associated with each other (P = 0.42).
In
subjects with genotype 1 chronic hepatitis C, the study authors concluded, "Insulin
resistance and overt diabetes are major determinants of advanced fibrosis, regardless
of the degree of steatosis, mainly in the presence of severe necroinflammation."
Hepatocellular
Carcinoma
In
the second study, reported in the June 2008 issue of Hepatology, an international
team of researchers assessed the link between diabetes and hepatocellular
carcinoma (HCC), a form of liver cancer that can develop in people with advanced
liver fibrosis or cirrhosis. This
study included 541 chronic hepatitis C patients with advanced fibrosis, 85 of
whom (16%) had diabetes. The median age at enrollment was 50 years. Fibrosis was
staged using the Ishak system.
Results •
The prevalence
of diabetes rose in association with Ishak fibrosis score: •
Stage 4 fibrosis:
10.5%;
•
Stage 5 fibrosis:
12.5%;
•
Stage 6 fibrosis:
19.1%.
•
Multiple logistic
regression analysis showed that elevated body mass index was associated with increased
risk of diabetes (OR 1.05; P = 0.060).
•
Elevated serum
albumin level was associated with decreased risk of diabetes (OR 0.81; P = 0.095).
•
During a median
follow-up period of 4 years, 11 patients with diabetes developed HCC, compared
to 27 without diabetes (13.0% vs 5.9%).
•
The 5-year
HCC incidence rates were 11.4% and 5.0%, respectively (P = 0.013).
•
Male sex and
older age were significantly associated with greater HCC risk.
•
There was a
trend towards higher HCC risk with increasing fasting glucose levels.
•
In a multivariate
Cox regression analysis of patients with stage 6 cirrhosis, diabetes was independently
associated with the development of HCC (hazard ratio 3.28; P = 0.009).
Based
on these findings, the study investigators concluded, "For patients with
chronic hepatitis C and advanced cirrhosis, diabetes mellitus increases the risk
of developing HCC."
Fortunately, even as insulin resistance and diabetes
increase the risk of advanced liver disease, including severe fibrosis and HCC,
research also shows that sustained response to interferon-based
therapy improves blood glucose abnormalities. 6/24/08
References S
Petta, C Camma, VD Marco, and others. Insulin resistance and diabetes increase
fibrosis in the liver of patients with genotype 1 HCV infection. American Journal
of Gastroenterology 103(5): 1136-1144. May 2008. BJ
Veldt, W Chen, EJ Heathcote, and others. Increased risk of hepatocellular carcinoma
among patients with hepatitis C cirrhosis and diabetes mellitus. Hepatology
47(6): 1856-1862. June 2008.
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