Leise, Michael D.

Objective: To evaluate the relationship between donor sex and hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation. Background: HCC shows a male predominance in incidence and recurrence after tumor resection due to sex differences in hepatic sex hormone receptors. There have been no studies evaluating the importance of donor sex on post-transplant HCC recurrence. Methods: Of 384 recipients of livers, from living donors, for HCC: 104/120 who received grafts from female donors were matched with 246/264 who received grafts from male donors using propensity score matching, with an unfixed matching ratio based on factors like tumor biology. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. Results: The median follow-up time was 39 months. Before matching, recurrence probability at 1/2/5 years after transplantation was 6.1/9.7/12.7% in recipients with female donors and 11.7/19.2/25.3% in recipients with male donors. Recurrence risk was significantly higher with male donors in univariable analysis (hazard ratio [HR] = 2.04 [1.15–3.60], P = 0.014) and multivariable analysis (HR=2.10 [1.20–3.67], P = 0.018). In the matched analysis, recurrence risk was also higher with male donors (HR=1.92 [1.05–3.52], P = 0.034): both in intrahepatic recurrence (HR=1.92 [1.05–3.51], P = 0.034) and extrahepatic recurrence (HR=1.93 [1.05–3.52], P = 0.033). Multivariable analysis confirmed the significance of donor sex (HR=2.08 [1.11–3.91], P = 0.023). Interestingly, the significance was lost when donor age was >40 years. Two external cohorts validated the significance of donor sex. Conclusions: Donor sex appears to be an important graft factor modulating HCC recurrence after living donor liver transplantation.

Background Bile leak after liver transplantation (LT) is commonly treated with endoscopic retrograde cholangiopancreatography (ERCP); however, there are limited data regarding the optimal treatment strategy. Objective We aimed to examine the role of ERCP in LT recipients with bile leaks at two large institutions. Methods We reviewed all ERCPs performed in LT recipients with bile leak and duct-to-duct biliary anastomosis at two high-volume transplant centers. Results Eighty patients were included. Forty-seven (59%) patients underwent ERCP with plastic stent placement (with or without sphincterotomy) and 33 patients (41%) underwent sphincterotomy alone. Complete resolution was obtained in 94% of the stent group vs. 58% of the sphincterotomy group ( p < 0.01). There was no difference in three-month survival among both groups. Percutaneous transhepatic therapy and surgery were required in 4% and 6% in the stent group vs. 12% and 42% in the sphincterotomy group, respectively ( p = 0.22 and p < 0.001). The only predictive factor of bile leak resolution was stent placement. Conclusion ERCP with plastic stent placement is highly successful and more effective than sphincterotomy alone for post-LT bile leak treatment. These results indicate that ERCP and plastic stent placement should be considered the standard of care for the treatment of bile leaks in LT.

Treatment options for refractory hepatic encephalopathy (HE) are limited. Patients who fail medical management may harbor large portosystemic shunts (PSSs) which are possible therapeutic targets. This study aims to describe patient selection, effectiveness, and safety of percutaneous PSS embolization in those with medically refractory HE. A retrospective evaluation of consecutive adult patients with medically refractory HE referred for PSS embolization at a tertiary center was performed (2003‐2015). Patient data collected included the type of HE, medications, Model for End‐Stage Liver Disease (MELD) score, shunt type, embolization approach, and materials used. Outcomes of interest were immediate (7 days), intermediate (1‐4 months), and longer‐term (6‐12 months) effectiveness and periprocedural safety. Effectiveness was determined based on changes in hospitalization frequency, HE medications, and symptoms. Twenty‐five patients with large PSS were evaluated for shunt embolization. Five were excluded due to high MELD scores (n = 1), comorbid conditions (n = 1), or technical considerations (n = 3). Of 20 patients who underwent embolization, 13 had persistent and 7 had recurrent HE; 100% (20/20) achieved immediate improvement. Durable benefit was achieved in 100% (18/18) and 92% (11/12) at 1‐4 and 6‐12 months, respectively. The majority (67%; 8/12) were free from HE‐related hospitalizations over 1 year; 10% developed procedural complications, and all resolved. Six developed new or worsening ascites. In conclusion, PSS embolization is a safe and effective treatment strategy that should be considered for select patients with medically refractory HE. Liver Transplantation 22 723–731 2016 AASLD.

PurposeTo evaluate with magnetic resonance elastography (MRE) whether patients with constrictive pericarditis (CP) have increased hepatic stiffness. CP results in reduced pericardial compliance, ventricular interdependence, and right heart failure. Patients with untreated CP may develop liver fibrosis and ultimately cirrhosis due to chronic venous congestion. Chronic venous congestion ± fibrosis may lead to increased liver stiffness.Materials and MethodsProspectively, patients with suspected CP underwent 2D transthoracic echocardiography, cardiac MRI, and liver MRE. An automated method was used to draw regions of interest (ROIs) on the stiffness maps to calculate the mean liver stiffness in kilopascals (kPa). A t‐test with α = 0.05 was performed between stiffness values of patients with positive and negative CP findings based on previously published echocardiography criteria.ResultsNineteen patients met inclusion criteria with a mean ± standard deviation (SD) age of 51 ± 16 years. Nine patients (47%) had CP. Mean liver stiffness trended higher in patients with CP compared to those without CP (4.04 kPa vs. 2.46; P = 0.045). Liver stiffness correlated with MRI septal bounce (P = 0.04), inferior vena cava size (P = 0.003), echo abnormal septal motion (P = 0.04), and echo mitral inflow variation >25% (P = 0.02). Only MRI septal bounce predicted CP by echocardiography (P < 0.001).ConclusionCP was associated with increased liver stiffness. The increased stiffness is most likely secondary to chronic hepatic venous congestion and/or fibrosis. MRE may be useful for noninvasive liver stiffness assessment in CP. J. Magn. Reson. Imaging 2016;44:81–88.

Interferon (IFN)‐free regimens are needed to treat hepatitis C virus (HCV) infection. Combined simeprevir (SMV) and sofosbuvir (SOF) with or without ribavirin (RBV) results in high sustained virological response (SVR) rates along with minimal adverse events (AEs) in patients with hepatitis C genotype 1 (HCV GT1). The aim of this study was to report on the virological response, safety, and tolerability of SOF and SMV with or without RBV in compensated and decompensated patients with cirrhosis with HCV GT1 infection. Patients treated with standardized clinical protocol utilizing SMV+SOF with or without RBV at three transplant centers were retrospectively reviewed. A total of 119 patients (61% male, 87% white, 69% subtype 1a, 30% Child‐Pugh‐Turcott [CPT]‐B liver cirrhosis [LC], and 82% were treatment experienced) received treatment and were followed for a median of 38 weeks (range, 12‐58). Sustained virological response (SVR) at week 12 (SVR12) was achieved in 78% (92 of 118) of patients (95% confidence interval: 69‐85). Lower pretreatment Model for End Stage Liver Disease (MELD) score was a predictor of SVR12 ( P = 0.018). Baseline viral load, previous treatment status, RBV use, or GT1 subtype did not impact SVR 12. The majority of patients with SVR12 showed stability or improvement in MELD score. Treatment was very well tolerated with mild degrees of AEs. Conclusions: The regimen of SMV+SOF with or without RBV for 12 weeks was very well tolerated and resulted in high SVR12 rates (78%) in HCV GT1 patients with LC. SVR12 was inversely related to pretreatment MELD. SVR12 had favorable short‐term impact on MELD score. Long‐term impact on disease stability is yet to be determined. Longer treatment duration or the use of different regimen may still be needed in this population. (H epatology 2015;62:1004‐1012)

The evolution of metabolic and cardiovascular disease (CVD) complications after liver transplantation (LT) is poorly characterized. We aim to illustrate the prevalence of obesity and metabolic syndrome (MS), define the cumulative incidence of CVD, and characterize risk factors associated with these comorbidities after LT. A retrospective review of 455 consecutive LT recipients from 1999 to 2004 with an 8‐ to 12‐year follow‐up was performed. Obesity increased from 23.8% (4 months) to 40.8% (3 years) after LT. Increase in body mass index predicted MS at 1 year after LT (odds ratio, 1.1; P < 0.001, per point). CVD developed in 10.6%, 20.7%, and 30.3% of recipients within 1, 5, and 8 years, respectively. Age, diabetes, hypertension, glomerular filtration rate < 60 mL/minute, prior CVD, ejection fraction < 60%, left ventricular hypertrophy, and serum troponin (TN) > 0.07 ng/mL were associated with CVD on univariate analysis. Age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01‐1.06; P = 0.019), diabetes (HR, 1.78; 95% CI, 1.09‐2.92; P = 0.022), prior history of CVD (HR, 2.46; 95% CI, 1.45‐4.16; P < 0.001), and serum TN > 0.07 ng/mL (HR, 1.98; 95% CI, 1.23‐3.18; P = 0.005) were independently associated with CVD in the long term. Smoking history (ever), sex, hyperlipidemia, and serum ferritin levels were not predictive of CVD. Tacrolimus use versus noncalcineurin‐based immunosuppression (HR, 0.26; 95% CI, 0.14‐0.49; P < 0.001) was associated with reduced risk of CVD but not versus cyclosporine (HR, 0.67; 95% CI, 0.30‐1.49; P = 0.322). CVD is common after LT. Independent of MS, more data are needed to identify nonconventional risk factors and biomarkers like serum TN. Curbing weight gain in the early months after transplant may impact MS and subsequent CVD in the long term. Liver Transpl 21:889‐896, 2015. © 2015 AASLD.

Treatment with an all‐oral interferon‐free antiviral regimen using simeprevir and sofosbuvir with or without ribavirin (RBV) for 12 weeks resulted in high sustained virologic response (SVR) rates along with minimal adverse events in non–liver transplant (LT) patients with hepatitis C virus (HCV) genotype 1 infection. This is the first multicenter report on the efficacy, safety, and tolerability of this regimen in LT recipients. A total of 123 patients (76% male, 74% white, 60% genotype 1a, 30% METAVIR F3‐F4, 4% decompensation, 11% cholestatic recurrence, 7% had kidney transplant, and 82% previously failed pegylated interferon/RBV‐based regimens) received treatment and were followed for a median of 30 weeks (range 12‐53 weeks). The median time from LT to treatment was 32 months (range 2‐317 months). Tacrolimus was the primary immunosuppression in 91% of patients. Minimal immunosuppression dose adjustments were required. An SVR 12 weeks after treatment completion (SVR12) was achieved in 90% of patients (95% confidence interval 84%‐96%). In patients with genotype 1a infection, the SVR12 rate was significantly lower in those with METAVIR F3‐F4 (71%) compared to those with F0‐F2 (91%). Half of the patients achieved undetected HCV RNA at treatment week 4, and their SVR12 rate was significantly higher (96%) compared to those with detectable HCV RNA (83%). Treatment was very well tolerated with mild degrees of adverse events, except for one death possibly due to drug‐induced lung injury. In the 25 patients who received RBV, 72% developed anemia requiring intervention. Conclusion : An all‐oral interferon‐free antiviral regimen using simeprevir and sofosbuvir with or without RBV for 12 weeks was very well tolerated and resulted in excellent SVR12 rates in LT recipients with HCV genotype 1 infection. (H epatology 2015;61:1880–1886)