The characteristics and natural history of Japanese patients with nonalcoholic fatty liver disease
ABSTRACT The aim of our study was to elucidate the characteristics and natural history of Japanese nonalcoholic fatty liver disease (NAFLD).
Two hundred and forty-seven patients were diagnosed as having biopsy-proven NAFLD at Tokyo Women's Medical University or an affiliated hospital from 1990 to June 2004. Biopsies were scored for the severity of steatosis, necro-inflammation, and fibrosis according to modified Brunt criteria. We assessed the clinicopathological features and natural history of NAFLD in patients stratified by the stage of their fibrosis. Univariate and multivariate logistic analyses were performed, and the diagnostic ability was assessed by the area under the receiver operating characteristic curve.
Clinicopathological features: The median age of the patients was 53 years, with a range from 10 to 89 years. There were 130 males and 117 females. Histologically, 46 patients were classified as F3 (bridging fibrosis), and 43 patients had F4 (cirrhosis). Females and older patients were more common in the F3-4 patients. Most of the F3-4 patients showed mild elevation of transaminases with significant deterioration of liver function tests compared with F0-2 patients. Ten patients were simultaneously diagnosed as having cirrhotic NASH and hepatocellular carcinoma (HCC). Natural history: During follow-up (median 44 months) of the F3-4 patients, 10 patients developed liver-related morbidity and five patients developed HCC. In the F3-4 patients, the 5-year cumulative incidence of HCC was 20%. Eight patients died (two of liver failure, four of HCC and two of other carcinomas). Serum markers for detecting F3-4: Serum hyaluronic acid levels can accurately evaluate NAFLD patients with F3-4.
The most important consequence of NAFLD patients with advanced fibrosis was HCC. Regular screening for this complication is extremely important.
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ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is one of the critical public health problems in China. The full spectrum of the disease ranges from simple steatosis and nonalcoholic steatohepatitis (NASH) to cirrhosis and hepatocellular carcinoma(HCC). The infiltration of inflammatory cells characterizes NASH. This characteristic contributes to the progression of hepatitis, fibrosis, cirrhosis, and HCC. Therefore, distinguishing NASH from NAFLD is crucial. Ninety-five patients with NAFLD, 44 with NASH, and 51 with non-NASH were included in the study to develop a new scoring system for differentiating NASH from NAFLD. Data on clinical and biological characteristics, as well as blood information, were obtained. Cytokeratin-18 (CK-18) fragments levels were measured using an enzyme-linked immunosorbant assay. Several indexes show significant differences between the two groups, which include body mass index (BMI), waist-on-hip ratio (WHR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), platelets, uric acid (UA), hs-C-reactive protein (hs-CRP), triglycerides (TG), albumin (ALB), and CK-18 fragments (all P < 0.05). The CK-18 fragment levels showed a significant positive correlation with steatosis severity, ballooning, lobular inflammation, and fibrosis stage (all P < 0.05). Therefore, a new model that combines ALT, platelets, CK-18 fragments, and TG was established by logistic regression among NAFLD patients. The AUROC curve in predicting NASH was 0.920 (95% CI: 0.866 - 0.974, cutoff value = 0.361, sensitivity = 89%, specificity = 86%, positive predictive value = 89%, negative predictive value = 89%). The novel scoring system may be considered as a useful model in predicting the presence of NASH in NAFLD patients.PLoS ONE 12/2013; 8(12):e82092. DOI:10.1371/journal.pone.0082092 · 3.53 Impact Factor
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ABSTRACT: Patients with non-alcoholic fatty liver diseases (NAFLD) are recommended to have periodic follow-up exams because these patients are at increased risk of the presence of non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis or hepatocellular carcinoma. We investigated the follow-up status of NAFLD patients after a liver biopsy examination. We compared the follow-up rates of NAFLD patients who had received an ultrasonography-guided liver biopsy and patients who had received a liver biopsy for chronic viral hepatitis (hepatitis B or C). The 1- and 3-year follow-up rates after the liver biopsy were 92.7% and 88.3% for patients with chronic HBV infection, and 93.4% and 88.2% for patients with chronic HCV infection, respectively. In contrast, the follow-up rates for NAFLD patients were 77.6% and 49.9%, respectively, which were significantly lower than those of patients with chronic viral hepatitis (p < 0.0001). Among NAFLD patients, the respective 1- and 3-year follow-up rates were 73.0% and 44.6% for patients with simple steatosis and 80.0% and 52.4% for patients with NASH based on a pathologic diagnosis, without significant difference between these two subgroups (p = 0.5202). The outpatient-based follow-up rate after a liver biopsy was significantly lower in NAFLD patients compared to patients with chronic viral hepatitis, regardless of the presence of NASH. It is important to determine how to maintain regular hospital visits for NAFLD patients, preventing patient attrition.BMC Research Notes 09/2011; 4:341. DOI:10.1186/1756-0500-4-341
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ABSTRACT: Aim: Non-alcoholic steatohepatitis (NASH) may progress to liver cirrhosis, and NASH patients with liver cirrhosis are at risk of developing hepatocellular carcinoma. Statins, 3-hydroxy-3-methyglutaryl-coenzyme A reductase inhibitors, are well known to reduce low-density lipoprotein cholesterol and reduce the incidence of coronary heart disease and other major vascular events by anti-inflammatory and antifibrotic effects, and antiproliferative properties in colorectal cancers have also been reported. Recently, statins have been reported to improve hepatic steatosis; however, the effect on fibrosis is controversial. Methods: The effects of pitavastatin (one of the strongest statins) were examined using a choline-deficient L-amino acid-defined (CDAA) diet liver fibrosis model. Results: Pitavastatin significantly attenuated increases in serum aspartate aminotransferase, alanine aminotransferase, hepatic steatosis, oxidative stress, pre-neoplastic lesions (glutathione S-transferase placental form-positive lesions), expression of cytokines, such as tumor necrosis factor-α and transforming growth factor-β1, and the expression of tissue inhibitor of metalloproteinase-1, tissue inhibitor of metalloproteinase-2 and type I procollagen genes followed by attenuating fibrosis of the liver of CDAA-fed rats. Conclusion: These results indicate that pitavastatin may inhibit steatosis, hepatic fibrosis and carcinogenesis in rat model of NASH.Hepatology Research 04/2011; 41(4):375-85. DOI:10.1111/j.1872-034X.2010.00769.x · 2.22 Impact Factor