Gastrointestinal complications of obesity: Non-alcoholic fatty liver disease (NAFLD) and its sequelae

doi:10.1016/j.beem.2013.02.002

Best Practice & Research Clinical Endocrinology & Metabolism

Volume 27, Issue 2, April 2013, Pages 195-208

https://doi.org/10.1016/j.beem.2013.02.002 Get rights and content

Obesity is a major risk factor for malign and non-malign diseases of the gastrointestinal tract. Non-alcoholic fatty liver disease (NAFLD) is an outstanding example for the complex pathophysiology of the metabolic system and represents both source and consequence of the metabolic syndrome. NAFLD has a growing prevalence and will become the leading cause of advanced liver disease and cirrhosis. Obesity has a negative impact on NAFLD at all aspects and stages of the disease. The growing epidemic will strain health care resources and demands new concepts for prevention, screening and therapeutic approaches. A better understanding of the interplay of liver, gut and hormonal system is necessary for new insights in the underlying mechanisms of NAFLD and the metabolic syndrome including obesity. Identification of patients at risk for progressive liver disease will allow a better adaption of treatment strategies.

Introduction

Overweight and obesity have a growing incidence worldwide and are a major challenge for health care systems. According to the World Health Organization about 1.4 billion adults were classified as overweight in 2008. Among them, 500 million have a body mass index (BMI) >30 kg/m² fulfilling the definition of obesity.¹ In the United States and Western European countries more than one third of the adult population is overweight or obese.2, *3

In gastroenterology, obesity related complications are frequent and comprise both non-malignant and malignant diseases in all parts of the digestive system (Table 1).³ In addition to specific symptoms of the listed gastroenterologic diseases, obese patients frequently suffer from unspecific complaints like upper belly pain and dyspepsia and functional disorders like foregut-related nausea or hindgut associated diarrhoea or constipation.4, 5

The following review focuses on the consequences of obesity for the liver, because the liver is the central organ of metabolism and thus a key player in the pathogenesis of obesity related complications (Fig. 1). Non-alcoholic fatty liver disease (NAFLD) can be taken as the hepatic manifestation of the metabolic syndrome and is particularly associated with insulin resistance, obesity, and abnormalities of glucose and lipid metabolism.⁶ However, NAFLD may precede weight gain, and the resulting fundamental metabolic derangement in association with diabetes mellitus type 2 reflects its potential causality for obesity. The spectrum of NAFLD displays a wide range from simple hepatic steatosis to chronic non-alcoholic steatohepatitis (NASH) which can result in progressing fibrosis, liver cirrhosis, and ultimately hepatocellular carcinoma in a significant number of patients.⁷

Therefore, NAFLD will be discussed in detail as a paradigm of obesity related gastrointestinal complications and clinical challenges.

Section snippets

Definitions

Non-alcoholic fatty liver disease (NAFLD) is defined by evidence of hepatic steatosis, either by imaging or by histology, without any causes for secondary hepatic fat accumulation (e.g. significant alcohol consumption, steatogenic medication, hereditary disorders).²⁵ NAFLD is histologically further categorized into non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), depending on the absence or presence of hepatocellular inflammatory injury with or without fibrosis.²⁵

Incidence and prevalence of non-alcoholic fatty liver disease

NAFLD is the most common cause of chronic and advanced liver disease both in adults and in children in industrialized countries and affects up to 30% of the general adult population.²⁵ Its prevalence is increased in diabetic and obese patients (60–80%) and may be as high as 100% in morbidly obese individuals.26, 27 Changes in life style and dietary habits lead to a growing number of affected patients and thus fatty liver is epidemic in western countries.²⁸ In addition, NAFLD is affecting at

Pathophysiology of obesity and NAFLD

Hepatic steatosis is the result of increased hepatocellular incorporation and the novo synthesis of lipids exceeding oxidation and export via very low density lipoproteins (VLDL). NAFLD encompasses a wide spectrum of histopathological changes of liver tissue induced by complex interactions between glucose and lipid metabolism, genetic predisposition, environmental conditions, and modulation of the intestinal microbiota.

Diagnosis of NAFLD and NASH

The diagnosis of NAFLD requires evidence of hepatic steatosis without causes for secondary hepatic fat accumulation.²⁵ This implicates the necessity to exclude any other chronic hepatic disease like viral hepatitis, hereditary metabolic disorders, and in particular alcoholic liver disease or therapy with steatogenic medication.

The wide clinical spectrum of NAFLD demands a careful assessment with respect to additional risk factors for the presence of NASH and associated complications.²⁵ Table 2

Treatment strategies for NAFLD and NASH

The standard treatment for patients with any grade of NAFLD is life style intervention with the purpose of weight loss.*25, *57 Additional pharmacologic therapy is indicated in the presence of comorbidities, especially for components of the metabolic syndrome (e.g. diabetes mellitus type 2, dyslipidaemia), but cannot be recommended solely for NAFLD treatment.*25, *57, *82

Complications of NALFD

Simple hepatic steatosis has a benign nature in the majority of affected individuals. However, a significant number of patients has progressive disease and suffers from associated complications.²⁵ The risk of NAFLD complications increases with disease progression from simple steatosis over NASH and fibrosis to liver cirrhosis²⁶: Typical complications of NAFLD are summarized in Fig. 2.

Conclusion

Obesity is a major risk factor for both malign and non-malign diseases of the gastrointestinal tract. NAFLD is an outstanding example for the complex pathophysiology of the metabolic system and represents both source and consequence of the metabolic syndrome. Obesity has a negative impact on NAFLD and NASH at all aspects and stages of the disease. The growing epidemic of NAFLD will strain health care resources worldwide and demands urgent action for preventive measures.

A deeper understanding of

Acknowledgements

This work was supported by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001.

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9Gastrointestinal complications of obesity: Non-alcoholic fatty liver disease (NAFLD) and its sequelae

Introduction

Section snippets

Definitions

Incidence and prevalence of non-alcoholic fatty liver disease

Pathophysiology of obesity and NAFLD

Diagnosis of NAFLD and NASH

Treatment strategies for NAFLD and NASH

Complications of NALFD

Conclusion

Acknowledgements

Gastroenterology

European Journal of Cancer (Oxford, England 1990)

Journal of the American College of Surgeons

The American Journal of Gastroenterology

Biochimica et Biophysica Acta

Clinical Gastroenterology and Hepatology

Journal of Hepatology

Gastroenterology

Annals of Hepatology

Journal of Hepatology

Gastroenterology

Journal of Hepatology

Gastroenterology

Digestive and Liver Disease

Clinics and Research in Hepatology and Gastroenterology

Journal of Hepatology

Annals of Hepatology

Journal of Hepatology

European Journal of Radiology

Clinics and Research in Hepatology and Gastroenterology

Journal of Hepatology

Journal of Hepatology

Journal of Hepatology

Journal of Hepatology

Fact sheet no. 311

Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010

JAMA the Journal of the American Medical Association

Epidemic trends of obesity with impact on metabolism and digestive diseases

Digestive Diseases (Basel, Switzerland)

The relationship between obesity and functional gastrointestinal disorders: causation, association, or neither?

Gastroenterology & Hepatology

Prevalence and co-occurrence of upper and lower functional gastrointestinal symptoms in patients eligible for bariatric surgery

Obesity Surgery

Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults

Alimentary Pharmacology & Therapeutics

Association between body mass index and erosive esophagitis: a meta-analysis

World Journal of Gastroenterology WJG

Abdominal visceral adipose tissue volume is associated with increased risk of erosive esophagitis in men and women

Gastroenterology

Influence of obesity on the risk of esophageal disorders

Nature Reviews Gastroenterology & Hepatology

Higher prevalence of obesity in gastric cardia adenocarcinoma compared to gastric non-cardia adenocarcinoma

Digestive Diseases and Sciences

A brief report of the epidemiology of obesity in the inflammatory bowel disease population of Tayside, Scotland

Obesity Facts

Prevalence and epidemiology of overweight and obesity in children with inflammatory bowel disease

Inflammatory Bowel Diseases

Gender, anthropometric factors and risk of colorectal cancer with particular reference to tumour location and TNM stage: a cohort study

Biology of Sex Differences

Mechanisms linking obesity, inflammation and altered metabolism to colon carcinogenesis

Obesity Reviews

The aetiology of symptomatic gallstones quantification of the effects of obesity, alcohol and serum lipids on risk. Epidemiological and biomarker data from a UK prospective cohort study (EPIC-Norfolk)

European Journal of Gastroenterology & Hepatology

Influence of obesity on the severity and clinical outcome of acute pancreatitis

Gut and Liver

Obesity and cancer risk: evidence, mechanisms, and recommendations

Annals of the New York Academy of Sciences

Excess body mass index and risk of liver cancer: a nonlinear dose-response meta-analysis of prospective studies

PLoS One

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

Hepatology

Nonalcoholic fatty liver in Asia: firmly entrenched and rapidly gaining ground

Journal of Gastroenterology and Hepatology

Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography

Gut

Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes

Hepatology (Baltimore, Md.)

The elusiveness of “normal” ALT in fatty liver

Hepatology (Baltimore, Md.)

9
Gastrointestinal complications of obesity: Non-alcoholic fatty liver disease (NAFLD) and its sequelae