Non-alcoholic fatty liver disease overview: Difference between revisions
| Line 19: | Line 19: | ||
===History and Symptoms=== | ===History and Symptoms=== | ||
Most patients with [[NAFLD]] have no or few symptoms. Infrequently patients may complain of [[fatigue]], [[malaise]] and dull [[right upper quadrant]] [[abdominal pain|abdominal discomfort]]. Mild [[jaundice]] can rarely be noticed. More commonly it is diagnosed as a result of abnormal [[liver function tests]] during routine blood tests. Often following an asymptomatic course, the disease may present first with [[cirrhosis]] and/or the complication of [[portal hypertension]]. | Most patients with [[NAFLD]] have no or few symptoms. Infrequently patients may complain of [[fatigue]], [[malaise]] and dull [[right upper quadrant]] [[abdominal pain|abdominal discomfort]]. Mild [[jaundice]] can rarely be noticed. More commonly it is diagnosed as a result of abnormal [[liver function tests]] during routine blood tests. Often following an asymptomatic course, the disease may present first with [[cirrhosis]] and/or the complication of [[portal hypertension]]. | ||
===Laboratory Findings=== | |||
Elevated liver function tests are common. Typically, one finds a 2-4 fold elevation of the ALT above normal limit and an ALT/AST ratio of greater than 1.<ref>Powell et al. The Natural History of Nonalcoholic Steatohepatitis: A Follow-up Study of Forty-two Patients for Up to 21 YearsHEPATOLOGY 1990; 11: 74-80</ref> This ratio is imperfect, as AST tends to rise with the degree of fibrosis.<ref>Sorbi et al. The Ratio of Aspartate Aminotransferase to Alanine Aminotransferase: Potential Value in Differentiating Nonalcoholic Steatohepatitis From Alcoholic Liver DiseaseAm J Gastroenterol 1999;94:1018–1022</ref> Furthermore,high ALT values within the reference range (less than 40 IU) are still predictive of NAFLD/NASH.<ref>Chang Y et al. Higher Concentrations of Alanine Aminotransferase within the Reference Interval Predict Nonalcoholic Fatty Liver Disease. Clinical Chemistry 2007;53(4):686–692</ref> Another blood test that can be elevated is the ferritin. Typically, and except in very advanced disease, the liver's synthetic function is intact with normal albumin and INR. | |||
When considering NAFLD, other tests are generally performed, including those for associated conditions (e.g. glucose, hemoglobin A1C) and those to distinguish this disease from viral [[hepatitis]]. Additionally, autoimmune causes are ruled out with serology. [[Thyroid-stimulating hormone|TSH]] is warranted, as [[hypothyroidism]] is more prevalent in NASH patients.<ref>Liangpunsakul S, Chalasani N. Is hypothyroidism a risk factor for non-alcoholic steatohepatitis? ''J Clin Gastroenterol'' 2003;37:340-3. PMID 14506393</ref> | |||
==References== | ==References== | ||
Revision as of 18:23, 28 March 2013
|
Non-Alcoholic Fatty Liver Disease Microchapters |
|
Differentiating Non-Alcoholic Fatty Liver Disease from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case studies |
|
Non-alcoholic fatty liver disease overview On the Web |
|
American Roentgen Ray Society Images of Non-alcoholic fatty liver disease overview |
|
Directions to Hospitals Treating Non-alcoholic fatty liver disease |
|
Risk calculators and risk factors for Non-alcoholic fatty liver disease overview |
Editor in Chief: Elliot Tapper, M.D., Beth Israel Deaconess Medical Center, C. Michael Gibson, M.S., M.D. [1]
Overview
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease in the absence of excessive alcohol use that begins as fatty accumulation in the liver (hepatic steatosis). A fatty liver does not necessarily disturb the function of the liver, but by varying mechanisms and insults, it may progress to inflammation of the liver. When inflammation occurs in this setting, the condition is then called NASH - Non-alcoholic steatohepatitis.
Historical Perspective
NAFLD/NASH was first described in a 1980 series of obese, non-alcoholic patients of the Mayo Clinic.[1] Since that seminal description, our understanding of NAFLD has progressed minimally. [2]
Pathophysiology
The exact cause is still unknown. However both obesity and insulin resistance likely play a strong role in this disease process. The exact reasons and mechanisms by which this disease progresses from steatosis to steatohepatitis and fibrosis is a subject of much research and debate. The prevailing wisdom comes from the so-called ‘two-hit hypothesis.’ The first hit is steatosis. The second hit is controversial and is likely numerous; likely any injury which causes a change that leads from hepatic steatosis to hepatic inflammation and fibrosis by way of lipid peroxidation.[3]
Causes
Oxidative stress, hormonal imbalances, endotoxemia and mitochondrial abnormalities may all be potential causes. It can be caused by few medications which is termed as secondary NAFLD. The exact cause is still unknown.
Epidemiology and Demographics
Estimates are that between 30- 90 million Americans have some degree of NAFLD and 5-6% have NASH. [4]In the third National Health and Nutrition Examination Survey (NHANES III), the peak prevalence of NAFLD in men occurred in the fourth decade and in the sixth decade for women.[5][6]
Natural History, Complications and Prognosis
NASH may progress to fibrosis and, later, to cirrhosis. Studies of serial liver biopsies estimate a 26-37% rate of hepatic fibrosis and 2-15% rate of cirrhosis in less than 6 years. [7][8][9] In 2001, NASH represented 2.9% of the indications of liver transplantation.[10] The impact of NAFLD is manifest at each step along the spectrum of the disease. Studies in the United States and Sweden have revealed that both simple steatosis as well as steatohepatitis significantly reduce life expectancy, even when the diagnosis is made in children.[11][12]
Diagnosis
History and Symptoms
Most patients with NAFLD have no or few symptoms. Infrequently patients may complain of fatigue, malaise and dull right upper quadrant abdominal discomfort. Mild jaundice can rarely be noticed. More commonly it is diagnosed as a result of abnormal liver function tests during routine blood tests. Often following an asymptomatic course, the disease may present first with cirrhosis and/or the complication of portal hypertension.
Laboratory Findings
Elevated liver function tests are common. Typically, one finds a 2-4 fold elevation of the ALT above normal limit and an ALT/AST ratio of greater than 1.[13] This ratio is imperfect, as AST tends to rise with the degree of fibrosis.[14] Furthermore,high ALT values within the reference range (less than 40 IU) are still predictive of NAFLD/NASH.[15] Another blood test that can be elevated is the ferritin. Typically, and except in very advanced disease, the liver's synthetic function is intact with normal albumin and INR.
When considering NAFLD, other tests are generally performed, including those for associated conditions (e.g. glucose, hemoglobin A1C) and those to distinguish this disease from viral hepatitis. Additionally, autoimmune causes are ruled out with serology. TSH is warranted, as hypothyroidism is more prevalent in NASH patients.[16]
References
- ↑ Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434-438. PMID 7382552.
- ↑ Day, CP. Non-alcoholic steatohepatitis (NASH): where are we now and where are we going? Gut. 2002 May; 50(5): 585–588.
- ↑ Berson A, De Beco V, Lette´ron P, Robin MA, Moreau C, El KahwajiJ, Verthier N, Feldmann G, Fromenty B, Pessayre D. Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. Gastroenterology 1998;114:764–774.
- ↑ McCullough, AJ. Thiazolidinediones for NASH. NEJM 2006;355(22):2361-2363.
- ↑ Ong JP et al. Epidemiology and Natural History of NAFLD and NASH. Clin Liver Dis 11 (2007) 1–16
- ↑ Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the united states. Gastroenterology 2003;124(1):71–9.
- ↑ Adams LA, Sanderson S, Lindor KD, et al. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005;42(1):132–8.
- ↑ Harrison SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease:a clinical histopathological study. Am J Gastroenterol 2003;98(9):2042–7.
- ↑ Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006;44:865-73.
- ↑ Charlton M et al. Frequency of Nonalcoholic Steatohepatitis as a Cause of Advanced Liver Disease. Liver Transpl 2001;7:608-614
- ↑ Adams et al. The Natural History of Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study. GASTROENTEROLOGY 2005;129:113–121
- ↑ Feldstein AE et al. The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years. Gut 2009;58:1538–1544
- ↑ Powell et al. The Natural History of Nonalcoholic Steatohepatitis: A Follow-up Study of Forty-two Patients for Up to 21 YearsHEPATOLOGY 1990; 11: 74-80
- ↑ Sorbi et al. The Ratio of Aspartate Aminotransferase to Alanine Aminotransferase: Potential Value in Differentiating Nonalcoholic Steatohepatitis From Alcoholic Liver DiseaseAm J Gastroenterol 1999;94:1018–1022
- ↑ Chang Y et al. Higher Concentrations of Alanine Aminotransferase within the Reference Interval Predict Nonalcoholic Fatty Liver Disease. Clinical Chemistry 2007;53(4):686–692
- ↑ Liangpunsakul S, Chalasani N. Is hypothyroidism a risk factor for non-alcoholic steatohepatitis? J Clin Gastroenterol 2003;37:340-3. PMID 14506393