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In [[medicine]], '''steatohepatitis''' is a liver disease characterized by [[fatty liver]] and lobular hepatitis.<ref name="pmid9005748">{{cite journal| author=Sheth SG, Gordon FD, Chopra S| title=Nonalcoholic steatohepatitis. | journal=Ann Intern Med | year= 1997 | volume= 126 | issue= 2 | pages= 137-45 | pmid=9005748  
{{TOC|right}}
In [[medicine]], '''steatohepatitis''' is a type of [[fatty liver]] disease characterized by lobular hepatitis.<ref name="pmid9005748">{{cite journal| author=Sheth SG, Gordon FD, Chopra S| title=Nonalcoholic steatohepatitis. | journal=Ann Intern Med | year= 1997 | volume= 126 | issue= 2 | pages= 137-45 | pmid=9005748  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9005748 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9005748 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>


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).<ref name="pmid17135584">{{cite journal| author=Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J et al.| title=A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 22 | pages= 2297-307 | pmid=17135584  
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).<ref name="pmid17135584">{{cite journal| author=Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J et al.| title=A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 22 | pages= 2297-307 | pmid=17135584  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17135584 | doi=10.1056/NEJMoa060326 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17135584 | doi=10.1056/NEJMoa060326 }}</ref>


==Classification==
==Classification==


===Alcoholic steatohepatitis===
===Alcoholic steatohepatitis===
 
===Nonalcoholic steatohepatitis===
===Nonalcoholic steatohepatitis===
Nonalcoholic steatohepatitis (NASH) is associated with [[obesity]], [[diabetes mellitus]], or [[hyperlipidemia]].<ref name="pmid9005748">{{cite journal| author=Sheth SG, Gordon FD, Chopra S| title=Nonalcoholic steatohepatitis. | journal=Ann Intern Med | year= 1997 | volume= 126 | issue= 2 | pages= 137-45 | pmid=9005748
Nonalcoholic steatohepatitis (NASH) is associated with [[obesity]], [[diabetes mellitus]], or [[hyperlipidemia]].<ref name="pmid9005748"/> NASH may be caused by the [[single-nucleotide polymorphism]]s [http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=2854116  rs2854116] (c.455T>C) and [http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=2854117 rs2854117] (c.482C>T)  of [[apolipoprotein C-III]] which are also associated with [[insulin resistance]] and [[hypertriglyceridemia]].<ref  name="pmid20335584">{{cite journal| author=Petersen KF, Dufour S,  Hariri A, Nelson-Williams C, Foo JN, Zhang XM et al.|  title=Apolipoprotein C3 gene variants in nonalcoholic fatty liver  disease. | journal=N Engl J Med | year= 2010 | volume= 362 | issue= 12 |  pages= 1082-9 | pmid=20335584  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=9005748 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref> NASH   may be caused by the [[single-nucleotide polymorphism]]s [http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=2854116  rs2854116] (c.455T>C) and [http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=2854117 rs2854117] (c.482C>T)  of [[apolipoprotein C-III]] which are also associated with [[insulin resistance]] and [[hypertriglyceridemia]].<ref  name="pmid20335584">{{cite journal| author=Petersen KF, Dufour S,  Hariri A, Nelson-Williams C, Foo JN, Zhang XM et al.|  title=Apolipoprotein C3 gene variants in nonalcoholic fatty liver  disease. | journal=N Engl J Med | year= 2010 | volume= 362 | issue= 12 |  pages= 1082-9 | pmid=20335584  
|  url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20335584  | doi=10.1056/NEJMoa0907295 }} </ref>
|  url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20335584  | doi=10.1056/NEJMoa0907295 }} </ref>


==Treatment==
==Treatment==
[[Pioglitazone]], a [[thiazolidinedione]] derivative normally used for treating [[diabetes mellitus type 2]], can improve nonalcoholic steatohepatitis in patients with [[impaired glucose tolerance]] or [[diabetes mellitus type 2]] according to a preliminary [[randomized controlled trial]].<ref name="pmid17135584">{{cite journal| author=Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J et al.| title=A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 22 | pages= 2297-307 | pmid=17135584  
[[Clinical practice guideline]]s direct management.<ref name="pmid22488764">{{cite journal| author=Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K et al.| title=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. | journal=Hepatology | year= 2012 | volume= 55 | issue= 6 | pages= 2005-23 | pmid=22488764 | doi=10.1002/hep.25762 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22488764  }} </ref>
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17135584 | doi=10.1056/NEJMoa060326 }} <!--Formatted by http://sumsearch.uthscsa.edu/cite/--></ref>
 
===Weight loss===
Weight loss may help according to a [[randomized controlled trial]]<ref name="pmid19827166">{{cite journal| author=Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR et al.| title=Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. | journal=Hepatology | year= 2010 | volume= 51 | issue= 1 | pages= 121-9 | pmid=19827166
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=19827166 | doi=10.1002/hep.23276 | pmc=PMC2799538 }} </ref>; 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]]. <ref  name="pmid21678341">{{cite journal| author=Peng L, Wang J, Li F|  title=Weight reduction for non-alcoholic fatty liver disease. |  journal=Cochrane Database Syst Rev | year= 2011 | volume= 6 | issue=  |  pages= CD003619 | pmid=21678341 | doi=10.1002/14651858.CD003619.pub3 |  pmc= | url= }} </ref>
 
===Antioxidants===
[[Vitamin E]], an [[antioxidant]], may improve liver histology in a [[randomized controlled trial]] of 247 patients who did not have [[diabetes]].<ref name="pmid20427778">{{cite journal| author=Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM et al.| title=Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis. | journal=N Engl J Med | year= 2010 | volume=  | issue=  | pages=  | pmid=20427778
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20427778 | doi=10.1056/NEJMoa0907929 }} </ref>
 
In 2005, a [[meta-analysis]] concluded that Vitamin E  supplementation may actually be harmful when used for the prevention of [[vascular disease]].<ref name="pmid15537682">{{cite journal |author=Miller  ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E  |title=Meta-analysis:  high-dosage vitamin E supplementation may increase all-cause mortality  |journal=Ann.  Intern. Med. |volume=142 |issue=1 |pages=37–46 |year=2005 |month=January |pmid=15537682 |doi= |url= |issn=}}</ref>
 
===Cholesterol reduction===
[[Simvastatin]] did not help in a pilot study.<ref name="pmid19448566">{{cite journal| author=Nelson A, Torres DM, Morgan AE, Fincke C, Harrison SA| title=A pilot study using simvastatin in the treatment of nonalcoholic steatohepatitis: A randomized placebo-controlled trial. | journal=J Clin Gastroenterol | year= 2009 Nov-Dec | volume= 43 | issue= 10 | pages= 990-4 | pmid=19448566
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=19448566 | doi=10.1097/MCG.0b013e31819c392e }} </ref>
 
===Increasing insulin sensitivity===
[[Metformin]], a [[biguanide]] that increases insulin sensitivity and has additional effects, may help according to preliminary studies.<ref name="pmid11567710">{{cite journal| author=Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N| title=Metformin in non-alcoholic steatohepatitis. | journal=Lancet | year= 2001 | volume= 358 | issue= 9285 | pages= 893-4 | pmid=11567710 |doi=10.1016/S0140-6736(01)06042-1
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=11567710 }} </ref><ref name="pmid15225167">{{cite journal| author=Nair S, Diehl AM, Wiseman M, Farr GH, Perrillo RP| title=Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. | journal=Aliment Pharmacol Ther | year= 2004 | volume= 20 | issue= 1 | pages= 23-8 | pmid=15225167
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=15225167 | doi=10.1111/j.1365-2036.2004.02025.x }} </ref><ref name="pmid14987322">{{cite journal| author=Uygun A, Kadayifci A, Isik AT, Ozgurtas T, Deveci S, Tuzun A et al.| title=Metformin in the treatment of patients with non-alcoholic steatohepatitis. | journal=Aliment Pharmacol Ther | year= 2004 | volume= 19 | issue= 5 | pages= 537-44 | pmid=14987322 |doi=10.1111/j.1365-2036.2004.01888.x
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=14987322 }} </ref><ref name="pmid15842582">{{cite journal| author=Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, Villanova N et al.| title=A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. | journal=Am J Gastroenterol | year= 2005 | volume= 100 | issue= 5 | pages= 1082-90 | pmid=15842582
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=15842582 | doi=10.1111/j.1572-0241.2005.41583.x }} </ref>
 
[[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]].<ref name="pmid20427778"/>
 
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.<ref name="pmid17135584">{{cite journal| author=Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J et al.| title=A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. | journal=N Engl J Med | year= 2006 | volume= 355 | issue= 22 | pages= 2297-307 | pmid=17135584  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17135584 | doi=10.1056/NEJMoa060326 }}</ref> Also, [[rosiglitazone]] improved histology and liver [[transaminase]]s in a trial 63 patients that excluded patients taking insulin (30% had diabetes and were taking other drugs)<ref name="pmid18503774">{{cite journal| author=Ratziu V, Giral P, Jacqueminet S, Charlotte F, Hartemann-Heurtier A, Serfaty L et al.| title=Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. | journal=Gastroenterology | year= 2008 | volume= 135 | issue= 1 | pages= 100-10 | pmid=18503774
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=18503774 | doi=10.1053/j.gastro.2008.03.078 }} </ref>, with longer treatment of 44 patients<ref name="pmid19877169">{{cite journal| author=Ratziu V, Charlotte F, Bernhardt C, Giral P, Halbron M, Lenaour G et al.| title=Long-term efficacy of rosiglitazone in nonalcoholic steatohepatitis: results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial. | journal=Hepatology | year= 2010 | volume= 51 | issue= 2 | pages= 445-53 | pmid=19877169
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=19877169 | doi=10.1002/hep.23270 }} </ref>.
 
===Surgery===
While [[bariatric surgery]] would seem effective, it has not been studied.<ref name="pmid20091629">{{cite journal| author=Chavez-Tapia NC, Tellez-Avila FI, Barrientos-Gutierrez T, Mendez-Sanchez N, Lizardi-Cervera J, Uribe M| title=Bariatric surgery for non-alcoholic steatohepatitis in obese patients. | journal=Cochrane Database Syst Rev | year= 2010 | volume=  | issue= 1 | pages= CD007340 | pmid=20091629
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=20091629 | doi=10.1002/14651858.CD007340.pub2 }} </ref>
 
==Prognosis==
In a study of [[cirrhosis]], [[obesity]]  may be the cause in 12% of patients.<ref  name="pmid2227807">{{cite journal| author=Wanless IR, Lentz JS|  title=Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy  study with analysis of risk factors. | journal=Hepatology | year= 1990 |  volume= 12 | issue= 5 | pages= 1106-10 | pmid=2227807
|  url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=2227807}} </ref><ref name="pmid9005748"/>
 
Among patients with steatohepatitis, mortality at 10 - 13 years is 3%<ref name="pmid17006923">{{cite journal| author=Ekstedt M, Franzén LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G et al.| title=Long-term follow-up of patients with NAFLD and elevated liver enzymes. | journal=Hepatology | year= 2006 | volume= 44 | issue= 4 | pages= 865-73 | pmid=17006923
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=17006923 | doi=10.1002/hep.21327 }} </ref> to 7%<ref name="pmid19049831">{{cite journal| author=Rafiq N, Bai C, Fang Y, Srishord M, McCullough A, Gramlich T et al.| title=Long-term follow-up of patients with nonalcoholic fatty liver. | journal=Clin Gastroenterol Hepatol | year= 2009 | volume= 7 | issue= 2 | pages= 234-8 | pmid=19049831
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=19049831 | doi=10.1016/j.cgh.2008.11.005 }} </ref>.


==References==
==References==
<references/>
<small>
<references>
 
</references>
</small>

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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.

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