Diagnostic Utility of Chromosome 17 and p16 Abnormalities in Fluorescence in Situ Hybridization Tests in Primary Sclerosing Cholangitis

Abstract

We read with great interest the article by Azzalini et al., 1 who demonstrated that cigarette smoking worsens the severity of nonalcoholic fatty liver disease (NAFLD) in obese Zucker rats. In a related letter, Xu and coworkers 2 showed that cigarette smoking may act as a cofactor but not as an independent factor for NAFLD in humans. However, currently it is uncertain whether there is a significant association between smoking patterns and the severity of liver histology among patients with NAFLD. Clarification of this aspect may help to explain the underlying mechanisms and may be of clinical importance in planning preventive and therapeutic strategies. We have therefore assessed whether there is a significant association between liver histology and smoking patterns among patients with biopsy-proven NAFLD. A total of 90 consecutive outpatients with NAFLD (43 males and 47 females, mean age, 47 6 8 years) were recruited from our clinics. All patients had chronically elevated liver enzymes and hepatic steatosis detected by ultrasonography. The NAFLD diagnosis was based on liver biopsy and exclusion of other known etiologic factors of chronic liver disease (alcohol abuse or intake !20 g/day, viral hepatitis, autoimmune hepatitis, and use of hepatotoxic drugs). An experienced pathologist blinded to clinical data scored the liver biopsies according to the National Institute of Diabetes and Digestive and Kidney Diseases NASH Clinical Research Network scoring system. 3 Pack-years of smoking were calculated as the product of the duration of smoking (in years) and the average number of cigarettes smoked per day. The protocol was approved by the local ethics committee, and all participants gave written informed consent. In multivariable-adjusted linear logistic regression models, each histological feature of NAFLD (i.e., steatosis grade, necroinflammatory grade, or fibrosis stage analyzed separately) was considered as the dependent variable. Sex, age, body mass index, smoking, low-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance (HOMA-IR) score, and metabolic syndrome (considered as a single clinical entity) were included as covariates. A total of 30 patients had ever smoked, 26 were past smokers, whereas 34 were current smokers. The distribution of nonsmokers, past smokers, and current smokers was not different in NAFLD patients classified according to liver histopathology (steatosis alone, borderline steatohepatitis, definite steatohepatitis). Notably, pack-years of smoking were not associated with degree of hepatic steatosis (P ¼ 0.67), necroinflammation (P ¼ 0.34), and fibrosis among patients with NAFLD (P ¼ 0.41). These results suggest that the severity of liver histopathology among patients with NAFLD is not associated with smoking patterns, after allowance for classical risk factors, insulin resistance, and the presence of the metabolic syndrome. This study has shown for the first time that the histological severity of NAFLD is not independently predicted by smoking patterns after ad...

Role of Fluorescent In Situ Hybridization, Cholangioscopic Biopsies, and EUS-FNA in the Evaluation of Biliary Strictures

“…Our cohort contained relatively few PSC patients, making significant analysis difficult. Prior studies focused on this population have shown FISH abnormalities detected in patients with pre-malignancy or inflammation harboring these aneuploidies [16,17].…”