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NAFLD & NASH

Level: Meta-analyses, Systematic reviews, Practice guidelines: 31 Abstracts

Legend: : Key Development,  : Very Important,  : Important, [no star]: Special Mention

 

Therapeutic potential of fecal microbiota transplantation.
Smits LP(1), Bouter KE, de Vos WM, Borody TJ, Nieuwdorp M., Gastroenterology. 2013 Nov;145(5):946-53. doi: 10.1053/j.gastro.2013.08.058. Epub 2013 Sep 7.

Comments: Review of best methods for performing fecal microbiota transplantation and summary of clinical observations that have implicated the intestinal microbiota in various diseases.

 

A systematic review of follow-up biopsies reveals disease progression in patientswith non-alcoholic fatty liver.
Pais R(1), Charlotte F, Fedchuk L, Bedossa P, Lebray P, Poynard T, Ratziu V; LIDO Study Group., J Hepatol. 2013 Sep;59(3):550-6. doi: 10.1016/j.jhep.2013.04.027. Epub 2013 May 9.

Comments: A substantial proportion of patients with NAFL can progress towards well-defined NASH with bridging fibrosis, especially if metabolic risk factors deteriorate.

  

Comparative effectiveness of pharmacological interventions for nonalcoholic steatohepatitis: A systematic review and network meta-analysis.
Singh S, Khera R, Allen AM, Murad MH, Loomba R., Hepatology. 2015 Nov;62(5):1417-32. doi: 10.1002/hep.27999. Epub 2015 Oct 1. Review.

 

The effect of PNPLA3 on fibrosis progression and development of hepatocellularcarcinoma: a meta-analysis.
Singal AG(1), Manjunath H(2), Yopp AC(3), Beg MS(2), Marrero JA(1), Gopal P(4),Waljee AK(5)., Am J Gastroenterol. 2014 Mar;109(3):325-34. doi: 10.1038/ajg.2013.476. Epub 2014 Jan 21.

Comments: PNPLA3 is associated with an increased risk of advanced fibrosis among patients with a variety of liver diseases and is an independent risk factor for HCC among patients with nonalcoholic steatohepatitis or alcohol-related cirrhosis.

 

Modest alcohol consumption decreases the risk of non-alcoholic fatty liverdisease: a meta-analysis of 43 175 individuals.
Sookoian S(1), Castaño GO, Pirola CJ., Gut. 2014 Mar;63(3):530-2. doi: 10.1136/gutjnl-2013-305718. Epub 2013 Sep 11.

 

Pharmacological agents for NASH.
Ratziu V., Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):676-85. doi:10.1038/nrgastro.2013.193. Epub 2013 Oct 15.

Comments: Review

 

No difference between high-fructose and high-glucose diets on livertriacylglycerol or biochemistry in healthy overweight men.
Johnston RD(1), Stephenson MC, Crossland H, Cordon SM, Palcidi E, Cox EF, Taylor MA, Aithal GP, Macdonald IA., Gastroenterology. 2013 Nov;145(5):1016-1025.e2. doi:10.1053/j.gastro.2013.07.012. Epub 2013 Jul 19.

Comments: Comparison between high-fructose or high-glucose diet did not reveal significantly different effects on hepatic conc of TAGs or on serum liver enzymes, indicating energy-mediated, rather than specific macronutrient-mediated, effect.

 

Simple noninvasive systems predict long-term outcomes of patients withnonalcoholic fatty liver disease.
Angulo P(1), Bugianesi E, Bjornsson ES, Charatcharoenwitthaya P, Mills PR,Barrera F, Haflidadottir S, Day CP, George J., Gastroenterology. 2013 Oct;145(4):782-9.e4. doi: 10.1053/j.gastro.2013.06.057. Epub 2013 Jul 13.

Comments: NAFLD fibrosis score as simple noninvasive system can identify patients with NAFLD who are at increased risk for liver-related complications or death.

 

Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 RandomizedTrial).
Bacchi E(1), Negri C, Targher G, Faccioli N, Lanza M, Zoppini G, Zanolin E, Schena F, Bonora E, Moghetti P., Hepatology. 2013 Oct;58(4):1287-95. doi: 10.1002/hep.26393. Epub 2013 Aug 22.

Comments: Resistance training and aerobic training are equally effective in reducing hepatic fat content among type 2 diabetic patients with NAFLD.

 

Comprehensive screening of chymotrypsin C (CTRC) gene in tropical calcificpancreatitis identifies novel variants.
Paliwal S(1), Bhaskar S, Mani KR, Reddy DN, Rao GV, Singh SP, Thomas V, Chandak GR., Gut. 2013 Nov;62(11):1602-6. doi: 10.1136/gutjnl-2012-302448. Epub 2012 May 12.

Comments: Chymotrypsin C (CTRC) gene variants play a role in tropical calcific pancreatitis.

 

Modest alcohol consumption decreases the risk of non-alcoholic fatty liverdisease: a meta-analysis of 43 175 individuals.
Sookoian S(1), Castaño GO, Pirola CJ., Gut. 2014 Mar;63(3):530-2. doi: 10.1136/gutjnl-2013-305718. Epub 2013 Sep 11.

Comments: Meta-analysis showing that modest alcohol consumption (MAC) was beneficial in preventing NAFLD as well as the metabolic syndrome(BMI, blood pressure, HOMA, insulin resistance and CRP.

 

A systematic review of follow-up biopsies reveals disease progression in patientswith non-alcoholic fatty liver.
Pais R, Charlotte F, Fedchuk L, Bedossa P, Lebray P, Poynard T, Ratziu V; LIDO Study Group., J Hepatol. 2013 Sep;59(3):550-6. doi: 10.1016/j.jhep.2013.04.027. Epub 2013 May 9.

Comments: 16 of 25 NAFL patients developed NASH after a mean of 3,7 yrs. Older age and worsening of obesity and of diabetes were predictive. Progression co-existed with a reduction in ALT, higher weight gain, and a higher incidence of diabetes during follow-up.

 

Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review.
White DL, Kanwal F, El-Serag HB., Clin Gastroenterol Hepatol. 2012 Dec;10(12):1342-1359.e2. doi:10.1016/j.cgh.2012.10.001. Epub 2012 Oct 4.

 

A phase 2, randomized, double-blind, placebo-controlled study of GS-9450 insubjects with nonalcoholic steatohepatitis.
Ratziu V, Sheikh MY, Sanyal AJ, Lim JK, Conjeevaram H, Chalasani N, Abdelmalek M, Bakken A, Renou C, Palmer M, Levine RA, Bhandari BR, Cornpropst M, Liang W, King B, Mondou E, Rousseau FS, McHutchison J, Chojkier M., Hepatology. 2012 Feb;55(2):419-28. doi: 10.1002/hep.24747. Epub 2011 Dec 14.

Comments: Preliminary data with with a selective caspase inhibitor GS-9450 with a mild positive effect on the course of biopsy-proven NASH

 

The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence fromcase-control and intra-familial allele association studies.
Al-Serri A, Anstee QM, Valenti L, Nobili V, Leathart JB, Dongiovanni P, Patch J, Fracanzani A, Fargion S, Day CP, Daly AK., J Hepatol. 2012 Feb;56(2):448-54. doi: 10.1016/j.jhep.2011.05.029. Epub 2011 Jul 12.

Comments: Carriage of the SOD2 C47T polymorphism is associated with more advanced fibrosis in NASH.

 

Association Between Psychological Distress and Liver Disease Mortality: A Meta-analysis of Individual Study Participants.
Russ TC, Kivimäki M, Morling JR, Starr JM, Stamatakis E, Batty GD., Gastroenterology. 2015 May;148(5):958-966.e4. doi: 10.1053/j.gastro.2015.02.004. Epub 2015 Feb 11.
 

 

Challenges and opportunities in drug and biomarker development for nonalcoholic steatohepatitis: findings and recommendations from an American Association for the Study of Liver Diseases-U.S. Food and Drug Administration Joint Workshop.
Sanyal AJ, Friedman SL, McCullough AJ, Dimick-Santos L; American Association for the Study of Liver Diseases; United States Food and Drug Administration., Hepatology. 2015 Apr;61(4):1392-405. doi: 10.1002/hep.27678. Epub 2015 Mar 19.
 

 

Outcomes of liver transplantation for nonalcoholic steatohepatitis: a systematic review and meta-analysis.
Wang X(1), Li J(2), Riaz DR(1), Shi G(1), Liu C(1), Dai Y(1)., Clin Gastroenterol Hepatol. 2014 Mar;12(3):394-402.e1. doi:10.1016/j.cgh.2013.09.023. Epub 2013 Sep 25.

Comments: Similar proportions of patients with and without NASH survive for 1, 3, and 5 years after liver transplantation. However, pts with NASH are more likely to die from cardiovascular complications or sepsis.

 

Mitochondrial adaptations and dysfunctions in nonalcoholic fatty liver disease.
Begriche K(1), Massart J, Robin MA, Bonnet F, Fromenty B., Hepatology. 2013 Oct;58(4):1497-507. doi: 10.1002/hep.26226. Epub 2013 Aug 7.

Comments: Experimental investigations pointed to a progressive reduction of MRC activity during NAFLD. Developing drugs that further increase mtFAO and restore MRC activity could ameliorate steatosis, but also necroinflammation and fibrosis by reducing oxidative stress.

 

Evidence and Recommendations for Imaging Liver Fat in Children, Based onSystematic Review.
Awai HI(1), Newton KP(2), Sirlin CB(3), Behling C(4), Schwimmer JB(5)., Clin Gastroenterol Hepatol. 2014 May;12(5):765-773. doi:10.1016/j.cgh.2013.09.050. Epub 2013 Sep 30.

Comments: Review: Evidence does not support ultrasonography for diagnosis or grading of fatty liver in children. MRI might be promising, but data are insufficient.

 

A critical appraisal of advances in pediatric nonalcoholic Fatty liver disease.
Ovchinsky N, Lavine JE., Semin Liver Dis. 2012 Nov;32(4):317-24. doi: 10.1055/s-0032-1329905. Epub 2013 Feb 8.

 

Liver stiffness measurement using XL probe in patients with nonalcoholic fattyliver disease.
Wong VW, Vergniol J, Wong GL, Foucher J, Chan AW, Chermak F, Choi PC, MerroucheW, Chu SH, Pesque S, Chan HL, de Lédinghen V., Am J Gastroenterol. 2012 Dec;107(12):1862-71. doi: 10.1038/ajg.2012.331. Epub 2012 Oct 2.

 

Validation of terminal peptide of procollagen III for the detection andassessment of nonalcoholic steatohepatitis in patients with nonalcoholic fattyliver disease.
Tanwar S, Trembling PM, Guha IN, Parkes J, Kaye P, Burt AD, Ryder SD, Aithal GP, Day CP, Rosenberg WM., Hepatology. 2013 Jan;57(1):103-11. doi: 10.1002/hep.26030.

 

Intragastric balloon significantly improves nonalcoholic fatty liver diseaseactivity score in obese patients with nonalcoholic steatohepatitis: a pilotstudy.
Lee YM, Low HC, Lim LG, Dan YY, Aung MO, Cheng CL, Wee A, Lim SG, Ho KY., Gastrointest Endosc. 2012 Oct;76(4):756-60. doi: 10.1016/j.gie.2012.05.023. Epub 2012 Jul 27.

 

Pioglitazone and vitamin E for nonalcoholic steatohepatitis: a cost utilityanalysis.
Mahady SE, Wong G, Craig JC, George J., Hepatology. 2012 Dec;56(6):2172-9. doi: 10.1002/hep.25887.

 

Relationship between adipose tissue insulin resistance and liver histology innonalcoholic steatohepatitis: a pioglitazone versus vitamin E versus placebo for the treatment of nondiabetic patients with nonalcoholic steatohepatitis trialfollow-up study.
Bell LN, Wang J, Muralidharan S, Chalasani S, Fullenkamp AM, Wilson LA, Sanyal AJ, Kowdley KV, Neuschwander-Tetri BA, Brunt EM, McCullough AJ, Bass NM, Diehl AM, Unalp-Arida A, Chalasani N; Nonalcoholic Steatohepatitis Clinical Research Network., Hepatology. 2012 Oct;56(4):1311-8. doi: 10.1002/hep.25805. Epub 2012 Aug 21.

 

Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis:new evidence on the potential therapeutic mechanism.
Zein CO, Lopez R, Fu X, Kirwan JP, Yerian LM, McCullough AJ, Hazen SL, Feldstein AE., Hepatology. 2012 Oct;56(4):1291-9. doi: 10.1002/hep.25778.

 

Pioglitazone and vitamin E for nonalcoholic steatohepatitis: a cost utilityanalysis.
Mahady SE, Wong G, Craig JC, George J., Hepatology. 2012 Dec;56(6):2172-9. doi: 10.1002/hep.25887.

 

Effect of disodium EDTA chelation regimen on cardiovascular events in patientswith previous myocardial infarction: the TACT randomized trial.
Lamas GA, Goertz C, Boineau R, Mark DB, Rozema T, Nahin RL, Lindblad L, Lewis EF, Drisko J, Lee KL; TACT Investigators., JAMA. 2013 Mar 27;309(12):1241-50. doi: 10.1001/jama.2013.2107.

 

Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoidarthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial.
Gabay C, Emery P, van Vollenhoven R, Dikranian A, Alten R, Pavelka K, Klearman M, Musselman D, Agarwal S, Green J, Kavanaugh A; ADACTA Study Investigators., Lancet. 2013 May 4;381(9877):1541-50. doi: 10.1016/S0140-6736(13)60250-0. Epub 2013 Mar 18.

 

Maintenance, reduction, or withdrawal of etanercept after treatment withetanercept and methotrexate in patients with moderate rheumatoid arthritis(PRESERVE): a randomised controlled trial.
Smolen JS, Nash P, Durez P, Hall S, Ilivanova E, Irazoque-Palazuelos F, Miranda P, Park MC, Pavelka K, Pedersen R, Szumski A, Hammond C, Koenig AS, Vlahos B., Lancet. 2013 Mar 16;381(9870):918-29. doi: 10.1016/S0140-6736(12)61811-X. Epub 2013 Jan 17.

 

Prasugrel versus clopidogrel for acute coronary syndromes withoutrevascularization.
Roe MT, Armstrong PW, Fox KA, White HD, Prabhakaran D, Goodman SG, Cornel JH, Bhatt DL, Clemmensen P, Martinez F, Ardissino D, Nicolau JC, Boden WE, Gurbel PA, Ruzyllo W, Dalby AJ, McGuire DK, Leiva-Pons JL, Parkhomenko A, Gottlieb S, Topacio GO, Hamm C, Pavlides G, Goudev AR, Oto A, Tseng CD, Merkely B, GasparovicV, Corbalan R, Cinteza M, McLendon RC, Winters KJ, Brown EB, Lokhnygina Y, Aylward PE, Huber K, Hochman JS, Ohman EM; TRILOGY ACS Investigators., N Engl J Med. 2012 Oct 4;367(14):1297-309. doi: 10.1056/NEJMoa1205512. Epub 2012 Aug 25.