Steatohepatitis: Difference between revisions

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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  
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 }}</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>


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===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==
[[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>


Weight loss may help.<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  
===Weight loss===
| 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>
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===
===Antioxidants===
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[[Thiazolidinedione]]  derivatives, normally used for treating [[diabetes  mellitus type 2]] by  increasing sensitivity to [[insulin]], have been studied for the treatment of nonalcoholic  steatohepatitis.
[[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">{{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
[[Pioglitazone]] did not improve liver histology in a [[randomized  controlled trial]] of  247 patients who did not have [[diabetes]].<ref name="pmid20427778"/>
|  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>


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  
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  
Line 52: Line 53:


==Prognosis==
==Prognosis==
[[Obesity]]  may be the cause of cirrhosis 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  
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">{{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&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=2227807}} </ref><ref name="pmid9005748"/>
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&retmode=ref&cmd=prlinks&id=9005748  }} </ref>
 
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.