Steatohepatitis

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In medicine, steatohepatitis is a type of fatty liver disease characterized by lobular hepatitis.[1]

Hepatitis, inflammation of the liver, can be detected by liver biopsy, or can be suggested by elevated blood levels of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor beta (TGF-beta).[2]

Classification

Alcoholic steatohepatitis

Nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is associated with obesity, diabetes mellitus, or hyperlipidemia.[1] NASH may be caused by the single-nucleotide polymorphisms rs2854116 (c.455T>C) and rs2854117 (c.482C>T) of apolipoprotein C-III which are also associated with insulin resistance and hypertriglyceridemia.[3]

Treatment

Clinical practice guidelines direct management.[4]

Weight loss

Weight loss may help according to a randomized controlled trial[5]; however, "the sparse data and high risk of bias preclude us from drawing any definite conclusion on lifestyle programme or orlistat for treatment of NAFLD" according to the Cochrane Collaboration. [6]

Antioxidants

Vitamin E, an antioxidant, may improve liver histology in a randomized controlled trial of 247 patients who did not have diabetes.[7]

In 2005, a meta-analysis concluded that Vitamin E supplementation may actually be harmful when used for the prevention of vascular disease.[8]

Cholesterol reduction

Simvastatin did not help in a pilot study.[9]

Increasing insulin sensitivity

Metformin, a biguanide that increases insulin sensitivity and has additional effects, may help according to preliminary studies.[10][11][12][13]

Thiazolidinedione derivatives, normally used for treating diabetes mellitus type 2 by increasing sensitivity to insulin, have been studied for the treatment of nonalcoholic steatohepatitis.

Pioglitazone did not improve liver histology in a randomized controlled trial of 247 patients who did not have diabetes.[7]

Previously, pioglitazone improved nonalcoholic steatohepatitis in patients with impaired glucose tolerance or diabetes mellitus type 2 according to a preliminary randomized controlled trial of 55 patients.[2] Also, rosiglitazone improved histology and liver transaminases in a trial 63 patients that excluded patients taking insulin (30% had diabetes and were taking other drugs)[14], with longer treatment of 44 patients[15].

Surgery

While bariatric surgery would seem effective, it has not been studied.[16]

Prognosis

In a study of cirrhosis, obesity may be the cause in 12% of patients.[17][1]

Among patients with steatohepatitis, mortality at 10 - 13 years is 3%[18] to 7%[19].

References

  1. 1.0 1.1 1.2 Sheth SG, Gordon FD, Chopra S (1997). "Nonalcoholic steatohepatitis.". Ann Intern Med 126 (2): 137-45. PMID 9005748.
  2. 2.0 2.1 Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J et al. (2006). "A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis.". N Engl J Med 355 (22): 2297-307. DOI:10.1056/NEJMoa060326. PMID 17135584. Research Blogging.
  3. Petersen KF, Dufour S, Hariri A, Nelson-Williams C, Foo JN, Zhang XM et al. (2010). "Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease.". N Engl J Med 362 (12): 1082-9. DOI:10.1056/NEJMoa0907295. PMID 20335584. Research Blogging.
  4. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K et al. (2012). "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 55 (6): 2005-23. DOI:10.1002/hep.25762. PMID 22488764. Research Blogging.
  5. Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR et al. (2010). "Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis.". Hepatology 51 (1): 121-9. DOI:10.1002/hep.23276. PMID 19827166. PMC PMC2799538. Research Blogging.
  6. Peng L, Wang J, Li F (2011). "Weight reduction for non-alcoholic fatty liver disease.". Cochrane Database Syst Rev 6: CD003619. DOI:10.1002/14651858.CD003619.pub3. PMID 21678341. Research Blogging.
  7. 7.0 7.1 Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM et al. (2010). "Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis.". N Engl J Med. DOI:10.1056/NEJMoa0907929. PMID 20427778. Research Blogging.
  8. Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (January 2005). "Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality". Ann. Intern. Med. 142 (1): 37–46. PMID 15537682[e]
  9. Nelson A, Torres DM, Morgan AE, Fincke C, Harrison SA (2009 Nov-Dec). "A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis: A randomized placebo-controlled trial.". J Clin Gastroenterol 43 (10): 990-4. DOI:10.1097/MCG.0b013e31819c392e. PMID 19448566. Research Blogging.
  10. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N (2001). "Metformin in non-alcoholic steatohepatitis.". Lancet 358 (9285): 893-4. DOI:10.1016/S0140-6736(01)06042-1. PMID 11567710. Research Blogging.
  11. Nair S, Diehl AM, Wiseman M, Farr GH, Perrillo RP (2004). "Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial.". Aliment Pharmacol Ther 20 (1): 23-8. DOI:10.1111/j.1365-2036.2004.02025.x. PMID 15225167. Research Blogging.
  12. Uygun A, Kadayifci A, Isik AT, Ozgurtas T, Deveci S, Tuzun A et al. (2004). "Metformin in the treatment of patients with non-alcoholic steatohepatitis.". Aliment Pharmacol Ther 19 (5): 537-44. DOI:10.1111/j.1365-2036.2004.01888.x. PMID 14987322. Research Blogging.
  13. Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N et al. (2005). "A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease.". Am J Gastroenterol 100 (5): 1082-90. DOI:10.1111/j.1572-0241.2005.41583.x. PMID 15842582. Research Blogging.
  14. Ratziu V, Giral P, Jacqueminet S, Charlotte F, Hartemann-Heurtier A, Serfaty L et al. (2008). "Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial.". Gastroenterology 135 (1): 100-10. DOI:10.1053/j.gastro.2008.03.078. PMID 18503774. Research Blogging.
  15. Ratziu V, Charlotte F, Bernhardt C, Giral P, Halbron M, Lenaour G et al. (2010). "Long-term efficacy of rosiglitazone in nonalcoholic steatohepatitis: results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial.". Hepatology 51 (2): 445-53. DOI:10.1002/hep.23270. PMID 19877169. Research Blogging.
  16. Chavez-Tapia NC, Tellez-Avila FI, Barrientos-Gutierrez T, Mendez-Sanchez N, Lizardi-Cervera J, Uribe M (2010). "Bariatric surgery for non-alcoholic steatohepatitis in obese patients.". Cochrane Database Syst Rev (1): CD007340. DOI:10.1002/14651858.CD007340.pub2. PMID 20091629. Research Blogging.
  17. Wanless IR, Lentz JS (1990). "Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors.". Hepatology 12 (5): 1106-10. PMID 2227807.
  18. Ekstedt M, Franzén LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G et al. (2006). "Long-term follow-up of patients with NAFLD and elevated liver enzymes.". Hepatology 44 (4): 865-73. DOI:10.1002/hep.21327. PMID 17006923. Research Blogging.
  19. Rafiq N, Bai C, Fang Y, Srishord M, McCullough A, Gramlich T et al. (2009). "Long-term follow-up of patients with nonalcoholic fatty liver.". Clin Gastroenterol Hepatol 7 (2): 234-8. DOI:10.1016/j.cgh.2008.11.005. PMID 19049831. Research Blogging.