Disease progression of nonalcoholic steatohepatitis in Taiwanese patients: a longitudinal study of paired liver biopsies

Objectives Nonalcoholic steatohepatitis (NASH) might progress to fibrosis, cirrhosis, and hepatocellular carcinoma. However, the natural history of NASH has not been fully clarified. This study aimed to investigate the disease progression in NASH patients receiving paired liver biopsies. We also aimed to examine the factors associated with NASH progression. Patients and methods Ten NASH patients who had received liver biopsies during June 2001 and February 2010 were consecutively enrolled. The histopathological changes were examined retrospectively, including nonalcoholic fatty liver disease activity score (NAS) and fibrosis stage. The associated clinical profiles were also analyzed. Results The median duration between paired biopsies was 20.5 months (range: 12–106 months). According to NAS and fibrosis stage, disease progression, stable disease, and disease regression were observed in seven patients, two patients, and one patient, respectively. Six (60%) patients had increased NAS on second biopsy, and two were lean NASH patients. The only patient with an improvement in NAS had achieved body weight reduction (13.3%) between paired biopsies. None of the 10 patients experienced an improvement in fibrosis. Five (50%) patients showed progression of fibrosis on second biopsy and the annual fibrosis progression rate was 0.32/year. Two of the five patients who showed progression of fibrosis were of the nonobese phenotype, whereas three patients were nondiabetic. Conclusion NASH is a progressive disease in Taiwanese patients. The disease progression should be further clarified in lean and nondiabetic NASH patients.

[1]  N. Giama,et al.  More advanced disease and worse survival in cryptogenic compared to viral hepatocellular carcinoma , 2018, Liver international : official journal of the International Association for the Study of the Liver.

[2]  F. Foufelle,et al.  Steatosis and NASH in type 2 diabetes. , 2017, Biochimie.

[3]  Ramesh Kumar,et al.  Non-alcoholic Fatty Liver Disease in Lean Subjects: Characteristics and Implications , 2017, Journal of clinical and translational hepatology.

[4]  Ming‐Lung Yu,et al.  Cytokeratin-18 and uric acid predicts disease severity in Taiwanese nonalcoholic steatohepatitis patients , 2017, PloS one.

[5]  L. Adams,et al.  International Journal of Molecular Sciences the Natural Course of Non-alcoholic Fatty Liver Disease , 2022 .

[6]  L. Henry,et al.  Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009 , 2015, Hepatology.

[7]  Shyi-Jang Shin,et al.  Hyperuricemia Inversely Correlates with Disease Severity in Taiwanese Nonalcoholic Steatohepatitis Patients , 2015, PloS one.

[8]  E. Bjornsson,et al.  Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease. , 2015, Gastroenterology.

[9]  A. Burt,et al.  Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. , 2015, Journal of hepatology.

[10]  Mats Fredrikson,et al.  Fibrosis stage is the strongest predictor for disease‐specific mortality in NAFLD after up to 33 years of follow‐up , 2015, Hepatology.

[11]  Zhen Wang,et al.  Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. , 2015, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[12]  Aijaz Ahmed,et al.  Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S. , 2014, Hepatology.

[13]  Aijaz Ahmed,et al.  Obesity and non-alcoholic fatty liver disease: Disparate associations among Asian populations. , 2014, World journal of hepatology.

[14]  T. Tung,et al.  Relationship between obesity, metabolic syndrome, and nonalcoholic fatty liver disease in the elderly agricultural and fishing population of Taiwan , 2014, Clinical interventions in aging.

[15]  R. DeFronzo,et al.  Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Connection with Insulin Resistance, Dyslipidemia, Atherosclerosis and Coronary Heart Disease , 2013, Nutrients.

[16]  K. Cusi,et al.  Corrigendum:The Diagnosis and Management of Non-alcoholic Fatty Liver Disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association , 2012, The American Journal of Gastroenterology.

[17]  A. Baranova,et al.  Systematic review: the epidemiology and natural history of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis in adults , 2011, Alimentary pharmacology & therapeutics.

[18]  H. Makhlouf,et al.  Pathologic criteria for nonalcoholic steatohepatitis: Interprotocol agreement and ability to predict liver‐related mortality , 2011, Hepatology.

[19]  Vincent Wai-Sun Wong,et al.  Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years , 2010, Gut.

[20]  Greger Lindberg,et al.  Decreased survival of subjects with elevated liver function tests during a 28‐year follow‐up , 2010, Hepatology.

[21]  J. Girard,et al.  Role of ChREBP in hepatic steatosis and insulin resistance , 2008, FEBS letters.

[22]  G. Targher,et al.  Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. , 2007, Atherosclerosis.

[23]  Chien-Hua Chen,et al.  Prevalence and Risk Factors of Nonalcoholic Fatty Liver Disease in an Adult Population of Taiwan: Metabolic Significance of Nonalcoholic Fatty Liver Disease in Nonobese Adults , 2006, Journal of clinical gastroenterology.

[24]  E. Bugianesi,et al.  Steatosis and hepatocellular carcinoma risk. , 2005, European review for medical and pharmacological sciences.

[25]  O. Cummings,et al.  Design and validation of a histological scoring system for nonalcoholic fatty liver disease , 2005, Hepatology.

[26]  C. Nishida,et al.  Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies , 2004, The Lancet.

[27]  G. Marchesini,et al.  Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome , 2003, Hepatology.

[28]  P. Thuluvath,et al.  Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: A case‐control study , 2000, Hepatology.

[29]  B. Neuschwander‐Tetri,et al.  Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions , 1999, American Journal of Gastroenterology.

[30]  S. Caldwell,et al.  Cryptogenic cirrhosis: Clinical characterization and risk factors for underlying disease , 1999, Hepatology.