Gallstone Disease Is Associated with More Severe Liver Damage in Patients with Non-Alcoholic Fatty Liver Disease

Abstract

BackgroundNonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD) are both highly prevalent in the general population and associated with obesity and insulin resistance. We aimed to evaluate the prevalence of GD in a cross sectional study of NAFLD patients and to define whether the presence of GD is associated with diabetes and predicts more severe liver disease.Methodology/Principal FindingsWe merged databases of four Liver Units, comprising 524 consecutive biopsy-proven NAFLD (373 males) observed between January 2003 and June 2010. GD was diagnosed in 108 (20%), and 313 cases (60%) were classified by liver biopsy as nonalcoholic steatohepatitis (NASH). The GD subgroup was characterized by a significantly higher prevalence of females, prediabetes/diabetes, abdominal obesity and metabolic syndrome, older age, higher BMI, fasting glucose, HOMA-IR and lower ALT. The prevalence of GD progressively increased with advancing fibrosis and with the severity of necroinflammatory activity (p for trend = 0.0001 and = 0.01, respectively), without differences in the severity of steatosis. At multivariate analysis GD was associated with female gender (OR 1.37, 95% CI 1.04–1.8), age (OR 1.027, 95% CI1.003–1.05), fasting glucose (OR 1.21, 95% CI 1.10–1.33) and NASH (OR 1.40,95% CI 1.06–1.89), whereas ALT levels were associated with a lower GD risk (OR 0.98, 95% CI 0.97–0.99). When subjects with cirrhosis were excluded from analysis, the association between GD and fasting glucose, female gender, and NASH was maintained.ConclusionPatients with NAFLD have a high prevalence of GD, which characterizes subjects with altered glucose regulation and more advanced liver disease.

Promotional effect of nonalcoholic fatty liver disease on Gallstone disease: A systematic review and meta-analysis

“…Information of GD prevalence in the NAFLD group vs. control group (non-NAFLD) was reported in four studies (20,26,29,33). There was a statistically significant association between NAFLD and GD, and OR was 1.40 (95% CI: 1.23-1.59, p=0.000, fixedeffects model; Figure 4).…”

“…Liver biopsy was used to define NAFLD in three studies (26)(27)(28), ultrasonography in seven studies (19)(20)(21)(29)(30)(31)(32), biochemistry in one study (33), and all three methods were used in one study (34). Study origins included two from North America (USA) (21,34), five from Europe (Slovakia, Italy, and Hungary) (26,(30)(31)(32)(33), and five from Asia (China, Turkey, and Korea) (20,(27)(28)(29).…”

“…Ten studies (19,21,(26)(27)(28)(30)(31)(32)(33)(34) that involved a total of 39,602 patients discussed GD prevalence in NAFLD patients with a range of 8%-47%. The pooled result was 17% (95% CI: 0.12-0.23), as shown in Figure 2.…”

“…Four studies (20,26,27,32) analyzed the effect of the female sex on GD occurrence in NAFLD patients. The association between the female sex and GD is statistically significant.…”

“…Three studies (26,27,32) discussed the effects of advanced age and high TC level on the prevalence of GD in NAFLD patients. In these three studies, older NAFLD patients (WMD: 6.61, 95% CI: 3.80-9.42, p<0.000; random-effects model) had a higher chance of suffering from GD (Figure 6a).…”