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Nonalcoholic fatty liver disease and alcohol-related liver disease: From clinical aspects to pathophysiological insights

Clinical and Molecular Hepatology 2020년 26권 4호 p.728 ~ 735
Ikejima Kenichi, Kon Kazuyoshi, Yamashina Shunhei,
소속 상세정보
 ( Ikejima Kenichi ) - Juntendo University Graduate School of Medicine Department of Gastroenterology
 ( Kon Kazuyoshi ) - Juntendo University Graduate School of Medicine Department of Gastroenterology
 ( Yamashina Shunhei ) - Juntendo University Graduate School of Medicine Department of Gastroenterology

Abstract


Two major causes of steatohepatitis are alcohol and metabolic syndrome. Although the underlying causes of alcoholrelated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) differ, there are certain similarities in terms of the mode of disease progression and underlying pathophysiological mechanisms. Further, excessive alcohol consumption is often seen in patients with metabolic syndrome, and alcoholic hepatitis exacerbation by comorbidity with metabolic syndrome is an emerging clinical problem. There are certain ethnic differences in the development of both NAFLD and ALD. Especially, Asian populations tend to be more susceptible to NAFLD, and genetic polymorphisms in patatin-like phospholipase domain-containing 3 (PNPLA3) play a key role in both NAFLD and ALD. From the viewpoint of pathophysiology, cellular stress responses, including autophagy and endoplasmic reticulum (ER) stress, are involved in the development of cellular injury in steatohepatitis. Further, gutderived bacterial products and innate immune responses in the liver most likely play a profound role in the pathogenesis of both ALD and NASH. Though the recent progress in the treatment of viral hepatitis has reduced the prevalence of viral-related development of hepatocellular carcinoma (HCC), non-viral HCC is increasing. Alcohol and metabolic syndrome synergistically exacerbate progression of steatohepatitis, resulting in carcinogenesis. The gut-liver axis is a potential therapeutic and prophylactic target for steatohepatitis and subsequent carcinogenesis.

키워드

Alcohol-related liver disease; Non-alcoholic fatty liver disease; Stress responses; Immunity, Innate; Gut microbiota

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