Foregut bypass vs.restrictive bariatric procedures for nonalcoholic fatty liver disease:a meta-analysis of 3,355 individuals

Background:Bariatric surgery represents an important treatment option for severely obese patients with nonalcoholic fatty liver disease(NAFLD).However,there remains inadequate data regarding the effects of different bariatric procedures on various NAFLD parameters,especially for histological outcomes.Thus,this meta-analysis aimed to compare the effects of restrictive bariatric procedures and foregut bypass on the metabolic,biochemical,and histological parameters for patients with NAFLD.Methods:Medline and Embase were searched for articles relating to bariatric procedures and NAFLD.Pairwise meta-analysis was conducted to compare efficacy of bariatric procedures pre-vs.post-procedure with subgroup analysis to further compare restrictive against foregut bypass procedures.Results:Thirty-one articles involving 3,355 patients who underwent restrictive bariatric procedures(n=1,460)and foregut bypass(n=1,895)were included.Both foregut bypass(P<0.01)and restrictive procedures(P=0.03)significantly increased odds of fibrosis resolution.Compared to restrictive procedures,foregut bypass resulted in a borderline non-significant decrease in fibrosis score(P=0.06)and significantly lower steatosis score(P<0.001).For metabolic parameters,foregut bypass significantly lowered body mass index(P=0.003)and low-density lipoprotein(P=0.008)compared to restrictive procedures.No significant differences were observed between both procedures for aspartate aminotransferase(P=0.17)and alkaline phosphatase(P=0.61).However,foregut bypass resulted in significantly lower gamma-glutamyl transferase than restrictive procedures(P=0.01)while restrictive procedures resulted in significantly lower alanine transaminase than foregut bypass(P=0.02).Conclusions:The significant histological and metabolic advantages and comparable improvements in biochemical outcomes support the choice of foregut bypass over restrictive bariatric procedures in NAFLD management.

Clinical utility of non-invasive tests to predict clinical outcomes in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease,and the fastest-growing cause of hepatocellular carcinoma(HCC)worldwide(1,2).As the number of people with NAFLD is too great to perform surveillance in all,risk-stratification strategies are increasingly important to identify those at the highest risk of decompensation and HCC(3,4).

Liver resection versus liver transplantation for hepatocellular carcinoma within Milan criteria:a meta-analysis of 18,421 patients

Background:Outcomes after liver resection(LR)and liver transplantation(LT)for hepatocellular carcinoma(HCC)are heterogenous and may vary by region,over time periods and disease burden.We aimed to compare overall survival(OS)and disease-free survival(DFS)between LT versus LR for HCC within the Milan criteria.Methods:Two authors independently searched Medline and Embase databases for studies comparing survival after LT and LR for patients with HCC meeting the Milan criteria.Meta-analyses and meta-regression were conducted using random-effects models.Results:We screened 2,278 studies and included 35 studies with 18,421 patients.LR was associated with poorer OS[hazard ratio(HR)=1.44;95%confidence interval(CI):1.14-1.81;P<0.01]and DFS(HR=2.71;95%CI:2.23-3.28;P<0.01)compared to LT,with similar findings among intention-to-treat(ITT)studies.In uninodular disease,OS in LR was comparable to LT(P=0.13)but DFS remained poorer(HR=2.95;95%CI:2.30-3.79;P<0.01).By region,LR had poorer OS versus LT in North America and Europe(P≤0.01),but not Asia(P=0.25).LR had inferior survival versus LT in studies completed before 2010(P=0.01),but not after 2010(P=0.12).Cohorts that underwent enhanced surveillance had comparable OS after LT and LR(P=0.33),but cohorts undergoing usual surveillance had worse OS after LR(HR=1.95;95%CI:1.24-3.07;P<0.01).Conclusions:Mortality after LR for HCC is nearly 50%higher compared to LT.Survival between LR and LT were similar in uninodular disease.The risk of recurrence after LR is threefold that of LT.

Characteristics and outcomes of hepatocellular carcinoma patients with macrovascular invasion following surgical resection: a meta-analysis of 40 studies and 8,218 patients

Background:Guidelines recommend that hepatocellular carcinoma(HCC)patients with portal vein tumor thrombosis(PVTT)and/or hepatic vein tumor thrombosis(HVTT)should undergo systemic therapy.However,recent data suggest that surgical resection may be beneficial in selected cases,but outcomes are heterogenous.We aimed to estimate pooled overall survival(OS),recurrence free survival(RFS)and complication rates in HCC patients with macrovascular invasion(MVI)following surgical resection.Methods:In this systematic review and meta-analysis,two investigators independently searched PubMed,Embase,and Cochrane databases from inception to Nov 10,2020,without language restrictions,for studies reporting outcomes of adult HCC patients with MVI who underwent liver resection with curative intent.Results:We screened 8,598 articles and included 40 studies involving 8,218 patients.Among all patients with MVI,the pooled median OS was 14.39 months[95%confidence interval(CI):10.99-18.84],1-year OS was 54.47%(95%CI:46.12-62.58%)and 3-year OS was 23.20%(95%CI:16.61-31.42%).Overall,1-and 3-year RFS were 27.70%(95%CI:21.00-35.57%)and 10.06%(95%CI:6.62-15.01%),respectively.Among patients with PVTT,median OS was 20.41 months in those with segmental/2nd order involvement compared to 12.91 months if 1st order branch was involved and 6.41 months if the main trunk was involved.The pooled rate of major complications was 6.17%(95%CI:3.53-10.56%).Conclusions:Overall median survival was 14.39 months for HCC patients with MVI following resection.Median survival was higher in PVTT with segmental/2nd order involvement at 20.41 versus 6.41 months if the main trunk was involved.

A Class Effect Network Meta-analysis of Lipid Modulation in Non-alcoholic Steatohepatitis for Dyslipidemia

Background and Aims:Pharmaceutical therapy for NASH is associated with lipid modulation,but the consensus on drug treatment is limited and lacks comparative analysis of effectiveness.A network meta-analysis was conducted to compare NASH drug classes in lipid modulation.Methods:Online databases were searched for randomized controlled trails(RCTs)evaluating NASH treatments in biopsy-proven NASH patients.Treatments were classified into four groups:(1)inflammation,(2)energy,(3)bile acids,and(4)fibro-sis based on the mechanism of action.A Bayesian network analysis was conducted with outcome measured by mean difference(MD)with credible intervals(Crl)and surface un-der the cumulative ranking curve(SUCRA).Results:Forty-four RCTs were included in the analysis.Bile acid modulat-ing treatments(MD:0.05,Crl:0.03-0.07)were the best treatment for improvement in high-density lipid(HDL)cho-lesterol,followed by treatments modulating energy(MD:0.03,Crl:0.02-0.04)and fibrosis(MD:0.01,Crl:−0.12 to 0.14)compared with placebo.The top three treatments for reduction in triglycerides were treatments modulating energy(MD:−0.46,Crl:−0.49 to−0.43),bile acids(MD:−0.22,Crl:−0.35 to−0.09),and inflammation(MD:−0.08,Crl:−0.13 to−0.03)compared with placebo.SUCRA found treatment modulating fibrosis(MD:−1.27,Crl:−1.76 to−0.79)was the best treatment for reduction in low-density lipid(LDL)cholesterol followed by treatment modulating in-flammation(MD:−1.03,Crl:−1.09 to−0.97)and energy(MD:−0.37,Crl:−0.39 to−0.34)compared with placebo,but LDL cholesterol was worsened by treatments modulat-ing bile acids.Conclusions:Network analysis comparing the class effects of dyslipidemia modulation in NASH found that treatment targets can include optimization of athero-genic dyslipidemia.Future studies are required to evaluate the cardiovascular outcomes.

The growing threat of non-alcoholic fatty liver disease-related hepatocellular carcinoma

Non-alcoholic fatty liver disease(NAFLD)is the fastest growing cause of hepatocellular carcinoma(HCC)worldwide(1).It is anticipated that the burden of NAFLD-related HCC will continue to increase in tandem with the global obesity epidemic(2,3).This has become a global issue of concern,as liver cancer is associated with significant morbidity and mortality,and is currently the third leading cause of cancer death(4).