Keaveny, Andrew P.

The number of steatotic deceased donor livers encountered has continued to rise as a result of the obesity epidemic. Little is known about the histological characteristics of moderately macrosteatotic livers over time in the recipient following liver transplantation (LT). All recipients undergoing LT at Mayo Clinic Florida with donor livers with moderate macrosteatosis (30%‐60%) from 2000‐2017 were identified (n = 96). Routine protocol liver biopsies were performed 1‐week and 6‐months following LT. All liver donor and protocol biopsies were read by an experienced liver pathologist. Of the 96 moderate macrosteatosis LTs, 70 recipients had post‐LT protocol liver biopsies available and comprised the study cohort. Median donor allograft macrosteatosis at the time of transplant was 33% (IQR, 30%‐40%) compared with 0% (IQR, 0%‐2%) at 1‐week (P < 0.001) and 0% (IQR, 0%‐0%) at 6‐months (P < 0.001) following LT. Biopsies at 1‐week post‐LT displayed pericentral necrosis in 57.1% of recipients and lipopeliosis in 34.3% of recipients. In the 6‐month post‐LT biopsies, cholestasis was seen in 3 (4.3%) of the recipients, whereas grade 2 fibrosis was seen in 6 recipients (8.6%). Graft survival at 5 years in the present cohort was 74.0%. Moderate macrosteatosis (30%‐60%) in the donor allograft demonstrates complete reversal on liver biopsies performed as early as 7 days following LT and remains absent at 6‐months following LT. Both pericentral necrosis and lipopeliosis are common features on day 7 biopsies. Despite these encouraging findings, the perioperative risks of using these livers (postreperfusion cardiac arrest and primary nonfunction) should not be understated. Long‐term graft survival is acceptable in patients who are able to overcome the immediate perioperative risk of using moderately steatotic donor livers.

Abstract Background and Aim The association between palatin‐like phospholipase domain‐containing 3 ( PNPLA3 ) I148M ( rs738409 ) polymorphism and mortality is not well understood. We investigated the impact of PNPLA3 I148M ( rs738409 ) polymorphism on overall and cardiovascular mortality based on the presence of nonalcoholic fatty liver disease (NAFLD). Methods The third National Health and Nutrition Examination Survey (NHANES) from 1991 to 1994 and National Health and Nutrition Examination Survey III‐linked mortality data through 31 December 2015 were utilized in this study. Results Of 4814 participants, 50.7% were homozygous for the C‐allele and 12.6% were homozygous for the G‐allele. During a follow up of 20 years, there were a total of 1255 deaths, 422 attributed to cardiovascular disease. There was a significant association with overall mortality among those with the PNPLA3 I148M ( rs738409 ) GG genotype (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.02–1.77) or G‐allele (HR 1.22, 95% CI 1.09–1.36) in the general population. NAFLD with homozygous PNPLA3 I148M ( rs738409 ) GG genotype had higher overall mortality after adjusting for multiple metabolic risk factors (HR 1.45, 95% CI 1.01–2.08). The PNPLA3 I148M ( rs738409 ) G‐allele had a tendency of increased cardiovascular mortality in the total population. This association was not noted in those with NAFLD. Conclusions The homozygous PNPLA3 I148M ( rs738409 ) GG genotype showed an increase in overall mortality in the general population and NAFLD independent of multiple metabolic risk factors.

Renal dysfunction is common in liver transplantation (LT) candidates, but differentiating between reversible and irreversible renal injury can be difficult. Kidney biopsy might be helpful in differentiating reversible from irreversible renal injury, but it is associated with significant complications. We aimed to identify pre‐LT predictors of potentially reversible renal injury using histological information obtained on pre‐LT renal biopsy. Data on 128 LT candidates who underwent pre‐LT kidney biopsy were retrospectively collected and correlated with renal histological findings. Indications for kidney biopsy were iothalamate glomerular filtration rate (iGFR) ≤40 mL/minute, proteinuria >500 mg/day, and/or hematuria. According to the biopsy diagnosis, patients were grouped into the following categories: normal (n = 13); acute tubular necrosis (ATN; n = 25); membranoproliferative glomerulonephritis (n = 19); minimal histological changes (n = 24); and advanced interstitial fibrosis (IF) and glomerulosclerosis (GS) (n = 47). Compared with patients having advanced IF/GS, patients with normal biopsies and those with ATN had lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) and higher international normalized ratio and total bilirubin levels (<0.05 for all). Both SBP and DBP directly correlated with the degree of IF and GS (R = 0.3, P ≤ 0.02 for all). SBP ≤90 mm Hg was 100% sensitive and 98% specific in correlating with normal biopsies or ATN, whereas SBP ≥140 mm Hg was 22% sensitive and 90% specific in correlating with advanced IF/GS. Model for End‐Stage Liver Disease score, serum creatinine, iGFR, urinary sodium excretion, and renal size did not correlate with biopsy diagnosis or degree of IF or GS. In conclusion, SBP at the time of LT evaluation correlates with renal histology, and it should be included along with other clinical and laboratory markers in the decision‐making process to list patients with renal dysfunction for LT alone versus simultaneous liver‐kidney transplantation.

Objectives Recent studies have suggested that small intestinal bacterial overgrowth (SIBO) could be a predisposing factor for nonalcoholic fatty liver disease (NAFLD) although the results were inconsistent. This systematic review and meta-analysis was conducted with the aim to summarize all available data. Methods A comprehensive literature review was conducted utilizing MEDLINE and EMBASE databases through September 2018 to identify all studies that compared the risk of NAFLD among patients with SIBO versus those without SIBO. Effect estimates from each study were extracted and combined together using the random effect, generic inverse variance method of DerSimonian and Laird. Results A total of 10 studies with 1093 participants fulfilled the eligibility criteria and were included in the meta-analysis. A significant association between NAFLD and SIBO was observed with the pooled odds ratio of 3.82 (95% confidence interval, 1.93–7.59; I 2 65%). Funnel plot is relatively symmetric and is not suggestive of the presence of publication bias. Conclusion A significant association between NAFLD and SIBO was observed in this meta-analysis.