Nonalcoholic fatty liver disease (NAFLD) is classified as nonalcoholic steatohepatitis (NASH) or simple steatosis (SS) according to histological findings. It is well recognized that NASH may develop into cirrhosis and hepatocellular carcinoma (HCC), both with unfavorable prognoses. Although the outlook of SS is reported to be better than that of NASH, the long-term prognosis of SS remains unclear. Here, we report the case of a patient who was diagnosed as having SS by a first liver biopsy, and later developed into cirrhosis and HCC over a period of 27 years. In 1980, a 42-year-old Japanese man was admitted because of abnormal liver function tests. He had no history of alcohol intake and was negative for hepatitis virus markers and autoantibodies. A liver biopsy specimen showed macrovesicular steatosis without ballooned hepatocytes, Mallory hyaline, lobular inflammation, or perisinusoidal/perivenular fibrosis, confirming the diagnosis of SS. The patient’s serum aminotransferase levels did not normalize despite repeated dietary instruction, and in 2001, liver histology demonstrated cirrhosis with mild steatosis and hepatocyte ballooning, leading to the diagnosis of NASH-related cirrhosis. HCC appeared in 2007. Overall, this patient progressed to cirrhosis and HCC in 20 and 27 years, respectively, following initial diagnosis. Platelet counts and degree of steatosis, as assessed by periodic ultrasonography, were seen to gradually reduce with progression of fibrosis. This case demonstrates that even a diagnosis of SS does not guarantee non-progression to cirrhosis and HCC, and careful follow-up is needed not only in patients with NASH, but also in those with SS.
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We thank Mr. Trevor Ralph for his editorial assistance.
Ono M, Saibara T. Clinical features of nonalcoholic steatohepatitis in Japan: evidence from the literature. J Gastroenterol. 2006;41:725–32.CrossRefPubMedGoogle Scholar
Brunt EM, Janney CG, DiBisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94:2467–74.CrossRefPubMedGoogle Scholar
Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21.CrossRefPubMedGoogle Scholar
Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116:1413–9.CrossRefPubMedGoogle Scholar
Ekstedt M, Franzén LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44:865–73.CrossRefPubMedGoogle Scholar
Harrison SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease: a clinical and histopathological study. Am J Gastroenterol. 2003;98:2042–7.CrossRefPubMedGoogle Scholar
Fassio E, Alvarez E, Domínguez N, Landeira G, Longo C. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology. 2004;40:820–6.PubMedGoogle Scholar
Adams LA, Sanderson S, Lindor KD, Angulo P. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol. 2005;42:132–8.CrossRefPubMedGoogle Scholar
Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005;128:1898–906.CrossRefPubMedGoogle Scholar
Tanaka N, Ichijo T, Okiyama W, Mutou H, Misawa N, Matsumoto A, et al. Laparoscopic findings in patients with nonalcoholic steatohepatitis. Liver Int. 2006;26:32–8.CrossRefPubMedGoogle Scholar
Tanaka N, Tanaka E, Sheena Y, Komatsu M, Okiyama W, Misawa N, et al. Useful parameters for distinguishing nonalcoholic steatohepatitis with mild steatosis from cryptogenic chronic hepatitis in the Japanese population. Liver Int. 2006;26:956–63.CrossRefPubMedGoogle Scholar
Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology. 2007;132:2169–80.CrossRefPubMedGoogle Scholar
Kaneda H, Hashimoto E, Yatsuji S, Tokushige K, Shiratori K. Hyaluronic acid levels can predict severe fibrosis and platelet counts can predict cirrhosis in patients with nonalcoholic fatty liver disease. J Gastroenterol Hepatol. 2006;21:1459–65.PubMedGoogle Scholar
Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006;43:S99–S112.CrossRefPubMedGoogle Scholar
Tanaka N, Sano K, Horiuchi A, Tanaka E, Kiyosawa K, Aoyama T. Highly-purified eicosapentaenoic acid treatment improves nonalcoholic steatohepatitis. J Clin Gastroenterol. 2008;42:314–8.Google Scholar
Yokohama S, Yoneda M, Haneda M, Okamoto S, Okada M, Aso K, et al. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology. 2004;40:1222–5.CrossRefPubMedGoogle Scholar
Hirose A, Ono M, Saibara T, Nozaki Y, Masuda K, Yoshioka A, et al. Angiotensin II type 1 receptor blocker inhibits fibrosis in rat nonalcoholic steatohepatitis. Hepatology. 2007;45:1375–81.CrossRefPubMedGoogle Scholar
Seki S, Kitada T, Yamada T, Sakaguchi H, Nakatani K, Wakasa K. In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases. J Hepatol. 2002;37:56–62.CrossRefPubMedGoogle Scholar
Saito K, Inoue S, Saito T, Kiso S, Ito N, Tamura S, et al. Augmentation effect of postprandial hyperinsulinaemia on growth of human hepatocellular carcinoma. Gut. 2002;51:100–4.CrossRefPubMedPubMedCentralGoogle Scholar
Tanaka N, Moriya K, Kiyosawa K, Koike K, Aoyama T. Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor α in transgenic mice: implications for HCV-associated hepatocarcinogenesis. Int J Cancer. 2008;122:124–31.CrossRefPubMedGoogle Scholar
Tanaka N, Moriya K, Kiyosawa K, Koike K, Gonzalez FJ, Aoyama T. PPARα activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice. J Clin Invest. 2008;118:683–94.PubMedPubMedCentralGoogle Scholar