PNPLA3 I148M variant affects non-alcoholic fatty liver disease in liver transplant recipients

De novo non-alcoholic fatty liver disease(NAFLD) is a common late complication for long-term survivors after liver transplantation. Genomic studies confirmed that PNPLA3 I148 M and TM6SF2 E167 K polymorphisms affected NAFLD susceptibility in the general population. However,this association was not validated in survivors after liver transplantation(LT). We performed a crosssectional survey to investigate this relationship. A comprehensive survey,including anthropometric measurements,fasting venous blood sampling,ultrasound,and questionnaires was performed in the shortterm. The clinical indications and patient's steatosis status before LT were collected from inpatient medical records. Sixty-five long-term recipients with a survival exceeding 10 years were enrolled in the final analysis. De novo NAFLD was more frequent in PNPLA3 GG carriers(0.33 vs 0.10 for GG vs CC + CG carriers,P = 0.018),while the genetic impact on NAFLD susceptibility was insignificant when categorized by the TM6SF2 polymorphism(0.19 in CC vs 0.14 in CT + TT carriers,P = 0.883). Multi-covariate analysis revealed that PNPLA3 exerted a significant genetic effect on de novoNAFLD following a recessive model(GG vs CC + CG,OR = 14.2,95%CI:1.78-113,P = 0.012). Compared to recipients with only the PNPLA3 GG allele or obesity(defined as body mass index > 25 kg/m2),steatosis was highly prevalent(71.4%) in PNPLA3 GG carriers Table 1 Current status of long-term recipients surviving more than 10 years Univariate Multivariate NAFLD(n = 12)Control(n = 53)P value OR P value Age(yr) 56.5 ± 8.4 53.6 ± 10.1 0.356 1.04(0.92-1.18)0.528Gender(M/F) 10/2 47/6 0.611 1.40(0.14-14.2)0.427 Indication for LT Hepatitis/cirrhosis/ cancer/others1/8/2/17/35/9/20.889 Survival time(yr) 11.2 ± 0.9 11.5 ± 1.4 0.541 BMI(kg/m2) 25.1 ± 3.0 22.5 ± 2.6 0.003 1.47(1.03-2.08)0.032 TG(mmol/L) 1.6 ± 1.1 1.1 ± 0.6 0.038 1.34(0.38-4.71)0.652 HDL-C(mmol/L) 1.2(1.0-1.4) 1.3(1.0-1.7) 0.267 FBG(mmol/L) 7.6 ± 3.4 5.7 ± 1.9 0.013 1.49(0.93-2.37)0.095 Hypertension(Yes/no)3/9 21/32 0.343 SUA(μmol/L) 381.6 ± 75.6 342.6 ± 76.4 0.116 Met S(Yes/no) 4/8 9/44 0.201 ALT(U/L) 36.7 ± 7.0 38.8 ± 6.7 0.882 Alcohol intake(g/wk)11.6 ± 7.3 21.0 ± 8.2 0.766 Smoking(cigar/d) 4.2 ± 3.4 4.3 ± 1.2 0.969 Exercise(min/d) 18.5 ± 6.0 22.9 ± 2.9 0.513 Immunosuppression Tacrolimus/ cyclosporine/ MMF/sirolimus/ none11/1/0/0/036/12/1/2/20.575 PNPLA3(CC/CG/GG)1/3/8 16/21/16 0.018 14.2(1.78-113)0.012 TM6SF2(CC/CT/TT)11/1/0 47/5/1 0.883 2.68(0.25-28.5)0.413 Continuous variables with equal variance are presented as the mean ± SD; Continuous variables with unequal variance are presented as the median(interquartile range); Categorical variables are presented as the number of subjects. One-way ANOVA was used for the comparison between continuous variables with equal variance,Mann-Whitney U test was used for the comparison between continuous variables with unequal variance,chi-square test was used for the comparison between categorical variables in univariate analysis,and logistic regression analysis was used in the multivariate analysis. The effect of the PNPLA3 I148 M polymorphism was evaluated by a recessive genetic model(GG vs CG + CC); the effect of the TM6SF2 E167 K polymorphism was evaluated by a dominant genetic model(CC + CT vs TT) for decreased prevalence of TT carrier. ALT:Alanine aminotransferase; BMI:Body mass index; F:Female; FBG:Fasting blood glucose; HBs Ag:Hepatitis B surface antigen; HDL-C:Highdensity lipoprotein cholesterol; LT:Liver transplantation; M:Male; Met S:Metabolic syndrome; MMF:Mycophenolatemofetil; SUA:Serum uric acid; TG:Triglyceride. De novo NAFLD Controlwith obesity. In conclusion,PNPLA3 I148 M,but not TM6SF2 E167 K,affects de novo NAFLD occurrence with a prominent interaction with obesity. Weight control might be a meaningful method to reduce the genetic susceptibility to NAFLD exerted by PNPLA3 variants.

Impact of metabolic disorders on gallstone disease and perioperative recovery after laparoscopic cholecystectomy

Background:Gallstone disease(GSD),nonalcoholic fatty liver disease(NAFLD),metabolic dysfunctionassociated fatty liver disease(MAFLD),and metabolic syndrome(MetS)are common medical disorders worldwide.This study aimed to ascertain how NAFLD,MAFLD,MetS,and other factors affect the development of GSD,and how the GSD-associated factors influence patient recovery after laparoscopic cholecystectomy(LC).Methods:We included 200 patients who were diagnosed with GSD and underwent LC between January 2017 and February 2022.A total of 200 subjects without GSD and“non-calculous causes”during the same period were also included as controls.We compared the metabolic disorder differences between GSD patients and controls.Furthermore,we sub-grouped patients based on the comorbidities of preoperative NAFLD,MAFLD,and MetS,and compared the impacts of these comorbidities on short-term post-LC functional recovery of the patients.Results:The prevalence of NAFLD and MetS were higher in GSD patients(P<0.05).Based on multivariate logistic regression analysis,hyperglycemia[odds ratio(OR)=2.2,95%confidence interval(CI):1.4–3.4,P=0.001]and low high-density lipoprotein cholesterol(HDL-C)level(OR=1.8,95%CI:1.1–3.1,P=0.048)were linked to GSD.NAFLD and MetS linked to liver enzymes after LC(P<0.05).MetS also linked to the levels of inflammatory indicators after LC(P<0.05).The obesity,hyperlipidemia,low HDLC level,and hyperglycemia linked to liver enzymes after LC(P<0.05).Hyperlipidemia,low HDL-C level,and hypertension linked to inflammation after LC(P<0.05).Conclusions:The prevalence of GSD may be linked to NAFLD and MetS.Hyperglycemia and low HDL-C level were independent risk factors of GSD.

Effect of Mn Modification on the Corrosion Susceptibility of Mg–Mn Alloys by Magnesium Scrap

The microstructure and anti-corrosion behavior of Mg–Mn alloys by magnesium scrap have been investigated in this study.The results show that the size of the Fe-rich particles in magnesium scrap decreases but the quantity increases with the Mn addition.Although the presence of Mn-containing Fe-rich particles with unique symbiotic structure can eff ectively weaken the micro-galvanic corrosion,the presence of more free Fe(Fe-rich particles)does not necessarily lead to severe corrosion of the alloy.The corrosion susceptibility of Mg–Mn–Fe alloy primarily depends on the solubility of iron in the Mg matrix,while it can be significantly reduced by suitable Mn addition.Besides,the tolerance limit of the Fe impurity can be expressed as Femax=0.0083 Mn(relative to the iron solubility).Only when the Fe/Mn ratio is below 0.0083 can the alloy have excellent corrosion resistance,with the corrosion rate changing in the scope of 0.38±0.09 to 0.54±0.15 mg/cm^(2) day and icorr from 3 to 9×10^(–4) A/cm^(2).