eMedicine Specialties > Gastroenterology > Liver

Fatty Liver: Treatment & Medication

Author: Dawn Sears, MD, Assistant Professor of Internal Medicine, Division of Gastroenterology and Hepatology, Scott and White Memorial Hospital
Contributor Information and Disclosures

Updated: Jan 6, 2009

Treatment

Medical Care

Abstinence from alcohol may reverse steatosis in patients with alcohol-related fatty liver. Weight loss and control of comorbidities appear to slow the disease and to possibly reverse some of the steatosis and fibrosis. No established treatment is available for NASH. Several empiric treatment strategies have been suggested, as outlined below.

  • Treatment of underlying disease
    • Patients with celiac sprue who follow a gluten-free diet can have reversal of fatty liver disease.
    • Patients with growth hormone deficiency who receive growth hormone can have reversal of NASH.14  
  • Dieting
    • Diets associated with improvement include those restricted in rapidly absorbed carbohydrates and those with a high protein-to-calorie ratio. Weight loss should be gradual, moderate, and controlled.15
    • Exercise added to diet appears to improve results and to increase insulin sensitivity by increasing muscle mass.
  • Multiple national studies are ongoing to evaluate the role of lipid-lowering agents as well as insulin sensitizers. Specifically, thiazolidinediones (eg, pioglitazone, rosiglitazone), metformin, gemfibrozil, and atorvastatin have all shown laboratory and histologic improvement in patients in small noncontrolled trials.
    • Thiazolidinediones (glitazones)
      • This class of drugs has been shown to decrease inflammation of the liver in both humans and rats and its effects only last as long as the medication is being delivered.16,17  
      • This class of medication results in improved insulin sensitivity and universal weight gain, which has recently been shown to be fat gain, not water.18
      • A randomized placebo-controlled trial evaluating pioglitazone (Actos) with diet versus diet alone has shown improvement of transaminases and steatosis. However, the fibrosis score improved only within the pioglitazone group before versus after the 6-month treatment. The differences posttreatment between the pioglitazone group and the placebo group were not statistically significant. This study is well done, with 55 patients undergoing liver biopsy before and after a treatment specifically for NASH. Larger, longer studies are expected.19
      • Rosiglitazone (Avandia) has been studied for 48 weeks in 30 patients with NASH and resulted in biochemical as well as histologic improvement.20
      • The US Food and Drug Administration issued an alert on May 21, 2007, to patients and health care professionals of rosiglitazone potentially causing an increased risk of myocardial infarction (MI) and heart-related deaths following the online publication of a meta-analysis. Rosiglitazone is an antidiabetic agent (thiazolidinedione derivative) that improves glycemic control by improving insulin sensitivity. The drug is highly selective and a potent agonist for peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Activation of PPAR-gamma receptors regulates insulin-responsive gene transcription involved in glucose production, transport, and utilization, thereby reducing both blood glucose concentrations and hyperinsulinemia. Potent PPAR-gamma agonists have been shown to increase the incidence of edema. A large scale phase III trial (RECORD) is currently underway that is specifically designed to study cardiovascular outcomes of rosiglitazone.
      • For more information, see FDA’s Safety Alert on Avandia. The online published meta-analysis entitled Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes can be viewed at The New England Journal of Medicine.
      • Additionally, responses to the controversy can be viewed at the Heartwire news (the heart.org from WebMD), including the following articles: (1) Rosiglitazone increases MI and CV death in meta-analysis, (2) The rosiglitazone aftermath: Legitimate concerns or hype?, and (3) RECORD interim analysis of rosiglitazone safety: No clear-cut answers. 
    • The published studies to date on metformin do not include histologic data but do show short-term radiologic and biochemical improvement.21,22,23,24,25
    • Cholesterol-lowering studies22,23,26
      • Atorvastatin was studied for 1 year with repeat biopsies and revealed improvement in ballooning degeneration and inflammation.
      • Gemfibrozil has resulted in biochemical improvement, but histologic data are lacking.
      • Pentoxifylline has received much attention in both animal models and human trials with conflicting results.27,28,29,30
  • Orlistat has shown histologic and chemical improvement in patients using the drug for several months.31
  • Vitamin E and ursodeoxycholic acid have shown improvement in specific populations.
  • Urso has conflicting data in both adults and children. Some studies show biochemical and histologic improvement, whereas other studies show no difference when compared to placebo.
  • Folic acid supplementation does not appear to improve biopsy-proven NASH.32
  • Angiotensin receptor blockers have been studied in rat models with nonuniform results.33,34
  • Experimental therapy
    • Ongoing research is revealing a possible link between obstructive sleep apnea and NAFLD/NASH. Studies are ongoing to evaluate if the treatment of obstructive sleep apnea results in the improvement of fatty liver disease.35,36,37
    • The novel therapy of using N -acetylcysteine38 and cannabinoid blockers is also being explored in animal studies.39,40

Surgical Care

  • Bariatric surgery
    • Several studies are emerging that indicate that bariatric surgery with appropriate weight loss results in both chemical improvement and histologic improvement of NASH.41
    • Roux-en-Y gastric bypass with repeat biopsy within 2 years has shown improvement in 100% of patients. One study showed 94% of repeat liver biopsies no longer met the pathologic criteria for NAFLD or NASH. Another study, which only rebiopsied livers of patients with NASH (not NAFLD), demonstrated that 89% no longer had NASH.42,43,44,45
    • Early studies reporting possible worsening hepatic function after rapid weight loss have not been substantiated. This may be a viable option in the appropriate candidate.

Consultations

The only way to firmly diagnosis NASH is with a liver biopsy. Often, a clinical picture of obesity, hypertriglyceridemia, and elevated transaminases is enough to conclude that a patient has NASH. However, underlying alcohol or other drug ingestion as well as smoldering autoimmune or hemochromatosis must be ruled out. Referral to a hepatologist with or without liver biopsy may help in staging and prognosis.

Diet

  • Abstinence from alcohol may reverse steatosis in patients with alcohol-related fatty liver.
  • A low-fat, American Diabetes Association (ADA) diet is recommended.
  • A weight loss goal of 1-2 pounds per week is recommended.

Activity

Exercise that includes both cardiovascular fitness and weight training should improve NASH. Cardiovascular fitness often results in weight loss. Weight training will increase muscle mass and improve insulin sensitivity. Both of these activities together help relieve the underlying derangements of NASH. However, no randomized trials with weight-bearing exercise have been published to date.

Medication

No proven medical therapy is available.

More on Fatty Liver

Overview: Fatty Liver
Differential Diagnoses & Workup: Fatty Liver
Treatment & Medication: Fatty Liver
Follow-up: Fatty Liver
References
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References

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Further Reading

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Keywords

fatty liver, fatty liver disease, steatosis, hepatic steatosis, steatohepatitis, alcohol-related fatty liver, alcoholic steatohepatitis, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, NASH, liver fibrosis, cirrhosis, hyperlipidemia, protein-calorie malnutrition, abetalipoproteinemia, galactosemia, glycogen storage disorder, hereditary fructose intolerance, homocystinuria, hypobetalipoproteinemia, Refsum disease, systemic carnitine deficiency, tyrosinemia, Weber-Christian disease, Wilson disease, variceal bleeding, encephalopathy, starvation,jejunoileal bypass, total parenteral nutrition, rapid weight loss

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Contributor Information and Disclosures

Author

Dawn Sears, MD, Assistant Professor of Internal Medicine, Division of Gastroenterology and Hepatology, Scott and White Memorial Hospital
Disclosure: Nothing to disclose.

Medical Editor

John Gunn Lee, MD, Director of Pancreaticobiliary Service, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, University of California at Irvine School of Medicine
John Gunn Lee, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Simmy Bank, MD, Chair, Professor, Department of Internal Medicine, Division of Gastroenterology, Long Island Jewish Hospital, Albert Einstein College of Medicine
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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