James F. Trotter, M.D.

Asrani, S. K., J. Trotter, J. Lake, A. Ahmed, A. Bonagura, A. Cameron, A. DiMartini, S. Gonzalez, G. Im, P. Martin, P. Mathurin, J. Mellinger, J. P. Rice, V. H. Shah, N. Terrault, A. Wall, S. Winder and G. Klintmalm (2019). “Meeting Report: The Dallas consensus conference on liver transplantation for alcohol related hepatitis.” Liver Transpl Nov 19. [Epub ahead of print].

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Liver transplantation (LT) for alcohol related hepatitis (AH) remains controversial. We convened a consensus conference to examine various aspects of LT for AH. The goal was not to unequivocally endorse LT for AH; instead it was to propose recommendations for programs that perform or plan to perform LT for AH. Criteria were established to determine candidacy for LT in the setting of AH and included the following: (1) AH patients presenting for the first time with decompensated liver disease that are non-responders to medical therapy without severe medical or psychiatric comorbidities (2) A fixed period of abstinence prior to transplantation is not required (3) Assessment with a multidisciplinary psychosocial team including a social worker and a addiction specialist/mental health professional with addiction and transplantation expertise. Supporting factors include lack of repeated unsuccessful attempts at addiction rehabilitation, lack of other substance use/dependency, acceptance of diagnosis/insight with commitment of patient/family to sobriety and formalized agreement to adhere to total alcohol abstinence and counseling. LT should be avoided in AH patients that are likely to spontaneously recover. Short- and long-term survival comparable to other indications for LT must be achieved. There should not be further disparity in LT either by indication, geography, or other sociodemographic factors. Treatment of alcohol use disorders should be incorporated into pre and post-LT care. The restrictive and focused evaluation process described in the initial LT experience for AH worldwide may not endure as this indication gains wider acceptance at more LT programs. Transparency in selection process is crucial with collection of objective data to assess outcomes and minimize center variation in listing. Oversight of program adherence is important to harmonize listing practices and outcomes.

Asrani, S. K., L. W. Jennings, W. R. Kim, P. Kamath, J. Levitsky, M. K. Nadim, G. Testa, M. Leise, J. F. Trotter and G. Klintmalm (2019). “Meld-Grail-Na: Glomerular Filtration Rate and Mortality on Liver-Transplant Waiting List.” Hepatology Sep 16. [Epub ahead of print].

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BACKGROUND & AIMS: Among patients with cirrhosis awaiting liver transplantation, prediction of waitlist (WL) mortality is adjudicated by Model for End Stage liver disease-sodium (MELD-Na) score. Replacing serum creatinine (Scr) with estimated glomerular filtration rate (eGFR) in the MELD-Na score may improve prediction of WL mortality, especially for women and highest disease severity. METHODS: We developed (2014) and validated (2015) a model incorporating eGFR using national data (n=17,095) to predict WL mortality. Glomerular Filtration Rate (GFR) was estimated using GfR Assessment In Liver disease (GRAIL) developed amongst patients with cirrhosis (Asrani SK Hepatology.2018; www.bswh.md/grail). Multivariate Cox proportional hazards analysis models were utilized to compare predicted 90-day WL mortality between MELD-GRAIL-Na (re-estimated bilirubin, INR, sodium and GRAIL) vs. MELD-Na. RESULTS: Within 3 months, 27.8% were transplanted, 4.3% died on the WL and 4.7% were delisted for other reasons. GFR as estimated by GRAIL (HR 0.382, 95% CI 0.344-0.424) and the re-estimated model MELD-GRAIL-Na (HR 1.212, 95% CI 1.199-1.224) were significant predictors of mortality or being delisted on the WL within 3 months. MELD-GRAIL-Na was a better predictor of observed mortality at highest deciles of disease severity (>/=27-40). For score >/=32 (observed mortality 0.68), predicted mortality was 0.67 (MELD-GRAIL-Na) and 0.51 (MELD-Na). For women score >/=32 (observed mortality 0.67), predicted mortality was 0.69 (MELD-GRAIL-Na) and 0.55 (MELD-Na). In 2015, use of MELD-GRAIL-Na as compared to MELD-Na resulted in reclassification of 16.7% (n=672) of patients on the WL. CONCLUSION: Incorporation of eGFR likely captures true GFR better than Scr, especially among women. Incorporation of MELD-GRAIL-Na instead of MELD-Na may impact outcomes for 12-17% awaiting transplant and affect organ allocation.

Alsahhar, J. S., D. Hansen, J. Page, U. Sandkovsky, S. Burdick, J. F. Trotter and R. S. Rahimi (2019). “An Atypical Biliary Fistula in a Liver Transplant Recipient.” Liver Transpl 25(4): 664-666.

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Biliary complications affect up to a third of patients after liver transplantation with bile leaks accounting for the majority of these complications. In this patient, we believe the fistula occurred as a complication of the second pericardiocentesis (likely intrahepatic puncture) because the initial pericardiocentesis resulted in drainage of bloody fluid. The exact etiology of the initial pericardial fluid is unknown despite the extensive infectious and rheumatologic workup. To our knowledge, this is the first case of a pericardiobiliary fistula reported as a complication of pericardiocentesis in a liver transplant recipient. There are 4 cases of pericardiobiliary fistula in the literature, 1 of which occurred after a liver biopsy, after penetrating abdominal trauma, and the last in the setting of an encroaching hydatid cyst. Our approach to managing this complication was with conservative measures using biliary stents to promote prograde biliary drainage along with infection control using antibiotics. This preferential flow of bile by using biliary stents promoted closure of the fistula and the prevention of surgery in a patient with a recent abdominal manipulation and medical instability. As the first reported case of pericardiobiliary fistula in a simultaneous liver‐kidney transplant recipient from pericardiocentesis, where no treatment or management has been reported, ERCP with stent placement can be considered for decompression. (Excerpt from text, p. 666; no abstract available.).

Asrani, S. K., L. W. Jennings, J. F. Trotter, J. Levitsky, M. K. Nadim, W. R. Kim, S. A. Gonzalez, B. Fischbach, R. Bahirwani, M. Emmett and G. Klintmalm (2019). “A Model for Glomerular Filtration Rate Assessment in Liver Disease (GRAIL) in the Presence of Renal Dysfunction.” Hepatology 69(3): 1219-1230.

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Estimation of glomerular filtration rate (eGFR) in patients with liver disease is suboptimal in the presence of renal dysfunction. We developed a model for GFR assessment in liver disease (GRAIL) before and after liver transplantation (LT). GRAIL was derived using objective variables (creatinine, blood urea nitrogen, age, gender, race, and albumin) to estimate GFR based on timing of measurement relative to LT and degree of renal dysfunction (www.bswh.md/grail). The measured GFR (mGFR) by iothalamate clearance (n = 12,122, 1985-2015) at protocol time points before/after LT was used as reference. GRAIL was compared with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD-4, MDRD-6) equations for mGFR < 30 mL/min/1.73 m(2) . Prediction of development of chronic kidney disease (mGFR < 20 mL/min/1.73 m(2) , initiation of chronic dialysis) and listing or receipt of kidney transplantation within 5 years was examined in internal cohort (n = 785) and external validation (n = 68,217, 2001-2015). GRAIL had less bias and was more accurate and precise as compared with CKD-EPI, MDRD-4, and MDRD-6 at time points before/after LT for low GFR. For mGFR < 30 mL/min/1.73 m(2) , the median difference (eGFR-mGFR) was GRAIL: 5.24 (9.65) mL/min/1.73 m(2) as compared with CKD-EPI: 8.70 (18.24) mL/min/1.73 m(2) , MDRD-4: 8.82 (17.38) mL/min/1.73 m(2) , and MDRD-6: 6.53 (14.42) mL/min/1.73 m(2) . Before LT, GRAIL correctly classified 75% as having mGFR < 30 mL/min/1.73 m(2) versus 36.1% (CKD-EPI), 36.1% (MDRD-4), and 52.8% (MDRD-6) (P < 0.01). An eGFR < 30 mL/min/1.73 m(2) by GRAIL predicted development of CKD (26.9% versus 4.6% CKD-EPI, 5.9% MDRD-4, and 10.5% MDRD-6) in center data and needing kidney after LT (48.3% versus 22.0% CKD-EPI versus 23.1% MDRD-4 versus 48.3% MDRD-6, P < 0.01) in national data within 5 years after LT. Conclusion: GRAIL may serve as an alternative model to estimate GFR among patients with liver disease before and after LT at low GFR.

Idriss, R., J. Hasse, T. Wu, F. Khan, G. Saracino, G. McKenna, G. Testa, J. Trotter, G. Klintmalm and S. K. Asrani (2019). “Impact of Prior Bariatric Surgery on Perioperative Liver Transplant Outcomes.” Liver Transpl 25(2): 217-227.

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Bariatric surgery (BS) is effective in treating morbid obesity, but the impact of prior BS on candidacy for liver transplantation (LT) is unclear. We examined 78 patients with cirrhosis with prior BS compared with a concurrent cohort of 156 patients matched by age, Model for End-Stage Liver Disease score, and underlying liver disease. We compared rates of transplant denial after evaluation, delisting on the waiting list, and survival after LT. The median time from BS to LT evaluation was 7 years. Roux-en-Y gastric bypass was the most common BS procedure performed (63% of cohort). Nonalcoholic fatty liver disease was the leading etiology for liver cirrhosis (47%). Delisting/death on the waiting list was higher among patients with BS (33.3% versus 10.1%; P = 0.002), and the transplantation rate was lower (48.9% versus 65.2%; P = 0.03). Intention-to-treat (ITT) survival from listing to 1 year after LT was lower in the BS cohort versus concurrent cohort (1-year survival, 84% versus 90%; P = 0.05). On adjusted analysis, a history of BS was associated with an increased risk of death on the waiting list (hazard ratio [HR], 5.7; 95% confidence interval [CI], 2.2-15.1), but this impact was attenuated (HR, 4.9; 95% CI, 1.8-13.4) by the presence of malnutrition. When limited to matched controls by sex, mortality attributed to BS was no longer significant for females (P = 0.37) but was significant for males (P = 0.046). Sarcopenia, as captured by skeletal muscle index, was calculated in a subset of patients (n = 49). The total skeletal surface area was lower in the BS group (127 [105-141] cm(2) versus 153 [131-191] cm(2) ; P = 0.005). Rates of sarcopenia were higher among patients delisted after listing (71.4% versus 16.7%; P = 0.04). In conclusion, a history of BS was associated with higher rates of delisting on the waiting list as well as lower survival from the time of listing on ITT analysis. Presence of malnutrition and sarcopenia among patients with BS may contribute to worse outcomes.