Hepatitis C Virus Infection is a Risk Factor for Gallstone Disease: A Prospective Hospital-based Study of Patients with Chronic Viral C Hepatitis

M. Acalovschi; C. Buzas; C. Radu; M. Grigorescu


J Viral Hepat. 2009;16(12):860-6. 

In This Article

Abstract and Introduction


We evaluated the prevalence and the risk factors for gallstone disease in patients with chronic hepatitis C infection. We investigated 453 consecutively admitted patients with chronic infection with hepatitis C virus (HCV) (cirrhosis excluded) and 879 patients without liver disease (October 2006–April 2007). Gallstone disease was diagnosed if gallstones were present at ultrasonography or if there had been a previous cholecystectomy. Variables evaluated were age, gender, gallstone heredity, body mass index, waist circumference, parity, serum lipids, fatty liver, arterial hypertension, diabetes mellitus and metabolic syndrome (International Diabetes Federation criteria). Informed consent was obtained from all patients. We found that 88 of 453 (19%) patients with chronic HCV hepatitis (age 50.1 ± 11.7 years) and 153 of 879 (17%) controls (age 60.6 ± 12.6 years) had gallstone disease (GD). Abdominal obesity (OR = 2.108, 95% CI 1.287–3.452) and steatosis (OR = 3.699, 95% CI 2.277–6.008) were risk factors for GD in HCV patients. Gallstone heredity, dyslipidaemia, type 2 diabetes mellitus and metabolic syndrome increased the risk for GD in controls vs HCV patients. Our study shows that even HCV patients with chronic hepatitis but not cirrhosis have an increased prevalence of gallstones. Compared with controls, gallstones are present in HCV patients at a younger age and are associated with central obesity and liver steatosis, but not with gallstone heredity, dyslipidaemia, diabetes mellitus or metabolic syndrome. Although we could not establish a temporal relationship, the association between HCV infection and gall stone disease is real and appears to be causally linked, at least in predisposed individuals (obese and with liver steatosis).


The prevalence of cholesterol gallstone disease (GD) is rising in industrialized countries of Europe and North America.[1–7] Given the higher incidence at advanced ages, the longer life expectancy of the population and the high costs of a cholecystectomy, gallstones represent a significant burden for these societies. Sustained efforts are presently directed to elucidate the risk factors of this common disease, with the goal of identifying high-risk groups and preventing gallstone formation.

Age, female gender and heredity are the major constitutional (unmodifiable) risk factors for cholesterol GD. A number of other risk factors have been documented. Although supersaturation of bile in cholesterol is a prerequisite of cholesterol lithogenesis, and cholesterol and bile acids in bile are the only ways of eliminating cholesterol from the body, even the largest series did not find an association between serum cholesterol level and gallstones. However, most case–control studies confirmed the association of low serum HDL-cholesterol levels and hypertriglyceridaemia with cholesterol gallstones.[8,9] Many studies have also found an association of gallstone disease with obesity, type 2 diabetes mellitus and recently, with fatty liver and metabolic syndrome.[10–12]

Liver cirrhosis represents a well-documented risk factor for gallstones.[13–19] About 25–30% of cirrhotic patients have gallstones, mainly the pigment type. Gallstone disease in cirrhotic patients has been associated with advanced disease and viral aetiology.[15,20] The risk of gallstones being symptomatic seems to be higher in viral compared with alcoholic cirrhosis.[21] A recently published study derived from the National Health and Nutrition Examination Survey (NHANES) III population survey in the United States has found that GD occurs more frequently in males with chronic hepatitis C virus (HCV) infection, and more commonly in those with severe liver disease.[22] To date, few studies on this subject have been undertaken.[20,23]

Hepatitis C virus infection is the major risk factor for chronic liver disease in the United States (1.8% of the population, i.e. 2.7 million people have chronic HCV infection) (NHANES III data).[24] In Romania, the prevalence of HCV infection is 4.9%, i.e. 1.05 million people (http://www.afladec.ro). Gallstone disease is also common in Romania, the age-adjusted prevalence of gallstones being 7.6% in males and 16.9% in females.[3] We decided to investigate whether the gallstone risk in patients with chronic HCV infection was linked only to cirrhosis or also to the HCV infection per se. With this objective, we assessed gallstone prevalence and risk factors for GD in patients with chronic HCV hepatitis.


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