Skip to main content
Top
Published in: Journal of Gastroenterology 6/2011

01-06-2011 | Original Article—Liver, Pancreas, and Biliary Tract

Clinical characteristics of de novo nonalcoholic fatty liver disease following pancreaticoduodenectomy

Authors: Naoki Tanaka, Akira Horiuchi, Takahide Yokoyama, Gengo Kaneko, Naoto Horigome, Takahiro Yamaura, Tadanobu Nagaya, Michiharu Komatsu, Kenji Sano, Shin-ichi Miyagawa, Toshifumi Aoyama, Eiji Tanaka

Published in: Journal of Gastroenterology | Issue 6/2011

Login to get access

Abstract

Background

Hepatic steatosis may develop after pancreatic resection, but its clinicopathological features remain unclear. We explored the clinical characteristics of newly appearing nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD), designated as de novo NAFLD after PD.

Methods

Of 83 patients who underwent PD between 2001 and 2006, the patients with regular alcohol consumption after PD (n = 3), those who were unavailable for regular abdominal computed tomography follow-up (n = 12), and those who died within 6 months of PD (n = 8) were excluded from the study. In the remaining 60 patients, the prevalence and clinical features of de novo NAFLD after PD were examined.

Results

NAFLD developed after PD in 14 (23%) patients in our cohort. Liver biopsy was performed in 8 patients and all showed typical steatohepatitis. Compared with the patients who had conventional nonalcoholic steatohepatitis (NASH), patients with post-PD de novo NASH demonstrated significant decreases in body mass index and lower levels of serum albumin, cholesterol, apolipoprotein B, and homeostasis model assessment for insulin resistance. Multivariate logistic regression analysis revealed that pancreatic head cancer was associated with an increased risk of developing NAFLD after PD (odds ratio 12.0, 95% confidence interval 2.0–71.4, P = 0.006). Increased dosage of oral pancreatic enzymes significantly ameliorated the steatosis, as well as leading to the recovery of body weight loss and resolution of the biochemical abnormalities.

Conclusions

De novo NAFLD/NASH after PD is characterized by non-obesity and lack of hyperlipidemia and insulin resistance and is associated with pancreatic exocrine insufficiency. In such patients, intensifying pancreatic enzyme supplementation may be useful.
Literature
1.
go back to reference de Alwis NM, Day CP. Non-alcoholic fatty liver disease: the mist gradually clears. J Hepatol. 2008;48:S104–12.PubMed de Alwis NM, Day CP. Non-alcoholic fatty liver disease: the mist gradually clears. J Hepatol. 2008;48:S104–12.PubMed
2.
go back to reference Ono M, Saibara T. Clinical features of nonalcoholic steatohepatitis in Japan: evidence from the literature. J Gastroenterol. 2006;41:725–32.PubMedCrossRef Ono M, Saibara T. Clinical features of nonalcoholic steatohepatitis in Japan: evidence from the literature. J Gastroenterol. 2006;41:725–32.PubMedCrossRef
3.
go back to reference Shimada M, Hashimoto E, Taniai M, Hasegawa K, Okuda H, Hayashi N, et al. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis. J Hepatol. 2002;37:154–60.PubMedCrossRef Shimada M, Hashimoto E, Taniai M, Hasegawa K, Okuda H, Hayashi N, et al. Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis. J Hepatol. 2002;37:154–60.PubMedCrossRef
4.
go back to reference Nagaya T, Tanaka N, Komatsu M, Ichijo T, Sano K, Horiuchi A, et al. Development from simple steatosis to liver cirrhosis and hepatocellular carcinoma: a 27-year follow-up case. Clin J Gastroenterol. 2008;1:116–21.CrossRef Nagaya T, Tanaka N, Komatsu M, Ichijo T, Sano K, Horiuchi A, et al. Development from simple steatosis to liver cirrhosis and hepatocellular carcinoma: a 27-year follow-up case. Clin J Gastroenterol. 2008;1:116–21.CrossRef
5.
go back to reference Dresler CM, Fortner JG, McDermott K, Bajorunas DR. Metabolic consequences of (regional) total pancreatectomy. Ann Surg. 1991;214:131–40.PubMedCrossRef Dresler CM, Fortner JG, McDermott K, Bajorunas DR. Metabolic consequences of (regional) total pancreatectomy. Ann Surg. 1991;214:131–40.PubMedCrossRef
6.
go back to reference Nomura R, Ishizaki Y, Suzuki K, Kawasaki S. Development of hepatic steatosis after pancreatoduodenectomy. AJR Am J Roentgenol. 2007;189:1484–8.PubMedCrossRef Nomura R, Ishizaki Y, Suzuki K, Kawasaki S. Development of hepatic steatosis after pancreatoduodenectomy. AJR Am J Roentgenol. 2007;189:1484–8.PubMedCrossRef
7.
go back to reference Miyagawa S, Makuuchi M, Kawasaki S, Ogiwara M. Second-stage pancreatojejunostomy following pancreatoduodenectomy in high-risk patients. Am J Surg. 1994;168:66–8.PubMedCrossRef Miyagawa S, Makuuchi M, Kawasaki S, Ogiwara M. Second-stage pancreatojejunostomy following pancreatoduodenectomy in high-risk patients. Am J Surg. 1994;168:66–8.PubMedCrossRef
8.
go back to reference Ricci C, Longo R, Gioulis E, Bosco M, Pollesello P, Masutti F, et al. Noninvasive in vivo quantitative assessment of fat content in human liver. J Hepatol. 1997;27:108–13.PubMedCrossRef Ricci C, Longo R, Gioulis E, Bosco M, Pollesello P, Masutti F, et al. Noninvasive in vivo quantitative assessment of fat content in human liver. J Hepatol. 1997;27:108–13.PubMedCrossRef
9.
go back to reference Komatsu M, Yazaki M, Tanaka N, Sano K, Hashimoto E, Takei Y, et al. Citrin deficiency as a cause of chronic liver disorder mimicking non-alcoholic fatty liver disease. J Hepatol. 2008;49:810–20.PubMedCrossRef Komatsu M, Yazaki M, Tanaka N, Sano K, Hashimoto E, Takei Y, et al. Citrin deficiency as a cause of chronic liver disorder mimicking non-alcoholic fatty liver disease. J Hepatol. 2008;49:810–20.PubMedCrossRef
10.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference Tanaka N, Nagaya T, Komatsu M, Horiuchi A, Tsuruta G, Shirakawa H, et al. Insulin resistance and hepatitis C virus: a case-control study of non-obese, non-alcoholic and non-steatotic hepatitis virus carriers with persistently normal serum aminotransferase. Liver Int. 2008;28:1104–11.PubMedCrossRef Tanaka N, Nagaya T, Komatsu M, Horiuchi A, Tsuruta G, Shirakawa H, et al. Insulin resistance and hepatitis C virus: a case-control study of non-obese, non-alcoholic and non-steatotic hepatitis virus carriers with persistently normal serum aminotransferase. Liver Int. 2008;28:1104–11.PubMedCrossRef
12.
go back to reference Tanaka N, Sano K, Horiuchi A, Tanaka E, Kiyosawa K, Aoyama T. Highly purified eicosapentaenoic acid treatment improves nonalcoholic steatohepatitis. J Clin Gastroenterol. 2008;42:413–8.PubMedCrossRef Tanaka N, Sano K, Horiuchi A, Tanaka E, Kiyosawa K, Aoyama T. Highly purified eicosapentaenoic acid treatment improves nonalcoholic steatohepatitis. J Clin Gastroenterol. 2008;42:413–8.PubMedCrossRef
13.
go back to reference Nagaya T, Tanaka N, Suzuki T, Sano K, Horiuchi A, Komatsu M, et al. Down-regulation of SREBP-1c is associated with the development of burned-out NASH. J Hepatol. 2010;53:724–31.PubMedCrossRef Nagaya T, Tanaka N, Suzuki T, Sano K, Horiuchi A, Komatsu M, et al. Down-regulation of SREBP-1c is associated with the development of burned-out NASH. J Hepatol. 2010;53:724–31.PubMedCrossRef
14.
go back to reference Tsutsui M, Tanaka N, Kawakubo M, Sheena Y, Horiuchi A, Komatsu M, et al. Serum fragmented cytokeratin 18 levels reflect the histological activity score of nonalcoholic fatty liver disease more accurately than serum alanine aminotransferase levels. J Clin Gastroenterol. 2010;44:440–7.PubMed Tsutsui M, Tanaka N, Kawakubo M, Sheena Y, Horiuchi A, Komatsu M, et al. Serum fragmented cytokeratin 18 levels reflect the histological activity score of nonalcoholic fatty liver disease more accurately than serum alanine aminotransferase levels. J Clin Gastroenterol. 2010;44:440–7.PubMed
15.
go back to reference Tsuruta G, Tanaka N, Hongo M, Komatsu M, Horiuchi A, Hamamoto K, et al. Nonalcoholic fatty liver disease in Japanese junior high school students: its prevalence and relationship to lifestyle habits. J Gastroenterol. 2010;45:666–72.PubMedCrossRef Tsuruta G, Tanaka N, Hongo M, Komatsu M, Horiuchi A, Hamamoto K, et al. Nonalcoholic fatty liver disease in Japanese junior high school students: its prevalence and relationship to lifestyle habits. J Gastroenterol. 2010;45:666–72.PubMedCrossRef
16.
go back to reference Arai H, Yamamoto A, Matsuzawa Y, Saito Y, Yamada N, Oikawa S, et al. Prevalence of metabolic syndrome in the general Japanese population in 2000. J Atheroscler Thromb. 2006;13:202–8.PubMedCrossRef Arai H, Yamamoto A, Matsuzawa Y, Saito Y, Yamada N, Oikawa S, et al. Prevalence of metabolic syndrome in the general Japanese population in 2000. J Atheroscler Thromb. 2006;13:202–8.PubMedCrossRef
17.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
18.
go back to reference Neuschwander-Tetri BA, Clark JM, Bass NM, Van Natta ML, Unalp-Arida A, Tonascia J, et al. Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology. 2010;52:913–24.PubMedCrossRef Neuschwander-Tetri BA, Clark JM, Bass NM, Van Natta ML, Unalp-Arida A, Tonascia J, et al. Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology. 2010;52:913–24.PubMedCrossRef
19.
go back to reference Kato H, Isaji S, Azumi Y, Kishiwada M, Hamada T, Mizuno S, et al. Development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) after pancreaticoduodenectomy: proposal of a postoperative NAFLD scoring system. J Hepatobiliary Pancreat Surg. 2010;17:296–304.CrossRef Kato H, Isaji S, Azumi Y, Kishiwada M, Hamada T, Mizuno S, et al. Development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) after pancreaticoduodenectomy: proposal of a postoperative NAFLD scoring system. J Hepatobiliary Pancreat Surg. 2010;17:296–304.CrossRef
20.
go back to reference Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745–50.PubMedCrossRef Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002;123:745–50.PubMedCrossRef
21.
go back to reference Hatta T, Fujinaga Y, Kadoya M, Ueda H, Murayama H, Kurozumi M, et al. Accurate and simple method for quantification of hepatic fat content using magnetic resonance imaging: a prospective study in biopsy-proven nonalcoholic fatty liver disease. J Gastroenterol. 2010;45:1263–71.PubMedCrossRef Hatta T, Fujinaga Y, Kadoya M, Ueda H, Murayama H, Kurozumi M, et al. Accurate and simple method for quantification of hepatic fat content using magnetic resonance imaging: a prospective study in biopsy-proven nonalcoholic fatty liver disease. J Gastroenterol. 2010;45:1263–71.PubMedCrossRef
22.
go back to reference Nakanuma Y, Ohta G, Konishi I, Shima Y. Liver injury with perivenular fibrosis and alcoholic hyalin after pancreatoduodenectomy for pancreatic carcinoma. Acta Pathol Jpn. 1987;37:1953–60.PubMed Nakanuma Y, Ohta G, Konishi I, Shima Y. Liver injury with perivenular fibrosis and alcoholic hyalin after pancreatoduodenectomy for pancreatic carcinoma. Acta Pathol Jpn. 1987;37:1953–60.PubMed
23.
go back to reference Tanaka N, Horiuchi A, Yokoyama T, Kawa S, Kiyosawa K. Pancreatic exocrine insufficiency: a rare cause of nonalcoholic steatohepatitis. Am J Gastroenterol. 2008;103:245–6.PubMed Tanaka N, Horiuchi A, Yokoyama T, Kawa S, Kiyosawa K. Pancreatic exocrine insufficiency: a rare cause of nonalcoholic steatohepatitis. Am J Gastroenterol. 2008;103:245–6.PubMed
24.
go back to reference Rinella ME, Green RM. The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance. J Hepatol. 2004;40:47–51.PubMedCrossRef Rinella ME, Green RM. The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance. J Hepatol. 2004;40:47–51.PubMedCrossRef
25.
go back to reference Rinella ME, Elias MS, Smolak RR, Fu T, Borensztajn J, Green RM. Mechanisms of hepatic steatosis in mice fed a lipogenic methionine choline-deficient diet. J Lipid Res. 2008;49:1068–76.PubMedCrossRef Rinella ME, Elias MS, Smolak RR, Fu T, Borensztajn J, Green RM. Mechanisms of hepatic steatosis in mice fed a lipogenic methionine choline-deficient diet. J Lipid Res. 2008;49:1068–76.PubMedCrossRef
26.
go back to reference 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.PubMed 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.PubMed
27.
go back to reference Okiyama W, Tanaka N, Nakajima T, Tanaka E, Kiyosawa K, Gonzalez FJ, et al. Polyenephosphatidylcholine prevents alcoholic liver disease in PPARα-null mice through attenuation of increases in oxidative stress. J Hepatol. 2009;50:1236–46.PubMedCrossRef Okiyama W, Tanaka N, Nakajima T, Tanaka E, Kiyosawa K, Gonzalez FJ, et al. Polyenephosphatidylcholine prevents alcoholic liver disease in PPARα-null mice through attenuation of increases in oxidative stress. J Hepatol. 2009;50:1236–46.PubMedCrossRef
28.
go back to reference Kang X, Zhong W, Liu J, Song Z, McClain CJ, Kang YJ, et al. Zinc supplementation reverses alcohol-induced steatosis in mice through reactivating hepatocyte nuclear factor-4alpha and peroxisome proliferator-activated receptor-alpha. Hepatology. 2009;50:1241–50.PubMedCrossRef Kang X, Zhong W, Liu J, Song Z, McClain CJ, Kang YJ, et al. Zinc supplementation reverses alcohol-induced steatosis in mice through reactivating hepatocyte nuclear factor-4alpha and peroxisome proliferator-activated receptor-alpha. Hepatology. 2009;50:1241–50.PubMedCrossRef
29.
go back to reference Purohit V, Bode JC, Bode C, Brenner DA, Choudhry MA, Hamilton F, et al. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium. Alcohol. 2008;42:349–61.PubMedCrossRef Purohit V, Bode JC, Bode C, Brenner DA, Choudhry MA, Hamilton F, et al. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium. Alcohol. 2008;42:349–61.PubMedCrossRef
Metadata
Title
Clinical characteristics of de novo nonalcoholic fatty liver disease following pancreaticoduodenectomy
Authors
Naoki Tanaka
Akira Horiuchi
Takahide Yokoyama
Gengo Kaneko
Naoto Horigome
Takahiro Yamaura
Tadanobu Nagaya
Michiharu Komatsu
Kenji Sano
Shin-ichi Miyagawa
Toshifumi Aoyama
Eiji Tanaka
Publication date
01-06-2011
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 6/2011
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-011-0370-5

Other articles of this Issue 6/2011

Journal of Gastroenterology 6/2011 Go to the issue

Original Article—Liver, Pancreas, and Biliary Tract

Pomalidomide suppresses cerulein-induced acute pancreatitis in mice

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.