Sumeet K. Asrani M.D.

Soape, M. P., A. Lichliter and S. K. Asrani (2018). “Uncoiling the Coil: Coil Extrusion After Coil Assisted Retrograde Transvenous Obliteration for Gastric Variceal Bleeding.” Clin Gastroenterol Hepatol 16(5): e59.

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An 83-year-old woman with cryptogenic cirrhosis (Model for End-stage Liver Disease score, 7) presented with melena 7 months after successful coil-assisted retrograde transvenous obliteration treatment of hemodynamically unstable bleeding gastric varices. Previously, embolization of the gastrorenal shunt and bleeding gastric varices was successful with 3% sotradecol, lipiodol, and terlock-35 fibered detachable coils (Boston Scientific, Marlborough, MA) and Azur detachable coils (Terumo, Tokyo, Japan). During her current hospitalization, she underwent standard medical management for suspected variceal bleeding. Endoscopy showed an embolization coil extruding through a decompressed gastric varix with mild intermittent oozing. Computed tomography of the abdomen confirmed migration of a coil into the stomach. The intraluminal coil was not removed given concerns for worsening of the bleed. The patient was managed conservatively for 72 hours. She was discharged home and seen 1 month later as an outpatient in good health with no reported melena. The complication rate of balloon-occluded retrograde transvenous obliteration is less than 5% and primarily includes thromboembolic events with complications relatively unknown with its modified version of coil-assisted retrograde transvenous obliteration. This endoscopic finding likely will increase in prevalence with the expansive use of coiling for acute gastric variceal hemorrhage given fewer contraindications compared with transjugular intrahepatic portosystemic shunt creation. (Excerpt from text, p. e59; no abstract available.)

Asrani, S. K., G. Saracino, J. G. O’Leary, S. Gonzales, P. Kim, G. McKenna, G. Klintmalm and J. Trotter (2018). “Recipient characteristics and morbidity and mortality after liver transplantation.” J Hepatol. Feb 14. [Epub ahead of print].

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BACKGROUND: Over the last decade, liver transplantation of sicker, older non-hepatitis C cirrhotics with multiple co-morbidities has increased in the United States. METHODS: We sought to identify a parsimonious set of recipient factors among HCV negative adult transplant recipients associated with significant morbidity and mortality within 5 years after liver transplantation using national (n=31,829, 2002-2015) and center specific data. Coefficients of relevant recipient factors were converted to weighted points and scaled from 0-5. Recipient factors associated with graft failure included: ventilator support (5 pts; HR 1.59, 95% CI 1.48-1.72); recipient age >60 years (3 pts; HR 1.29, 95% CI 1.23-1.36); hemodialysis (3 pts; HR 1.26, 95% CI 1.16-1.37); diabetes (2 pts; HR 1.20, 95% CI 1.14-1.27); or serum creatinine >/=1.5mg/dL without hemodialysis (2 pts; HR 1.15, 95% CI 1.09-1.22). RESULTS: Graft survival within 5 years based on points (any combination) was 77.2% (0-4), 69.1% (5-8) and 57.9% (>8). In recipients with > 8 points, graft survival was 42% (MELD<25) and 50% (MELD 25-35) in recipients receiving donors with donor risk index >1.7. In center specific data within the first year, subjects with >/= 5 points (vs. 0-4) had longer hospitalization (11 vs. 8 days, p<0.01), higher admissions for rehabilitation (12.3% versus 2.7%, p<0.01), and higher incidence of cardiac disease (14.2% vs. 5.3%, p<0.01) and stage 3 chronic kidney disease (78.6% vs. 39.5%, p=0.03) within 5 years. CONCLUSION: The impact of co-morbidities in a MELD based organ allocation system needs to be reassessed. The proposed clinical tool may be helpful for center specific assessment of risk of graft failure in non HCV patients and discussion regarding relevant morbidity in selected subsets. LAY SUMMARY: Over the last decade, liver transplantation of sicker, older patient with multiple co-morbidities has increased. In this study, we show that a set of recipient factors (recipient age>60 years, ventilator status, diabetes, hemodialysis and creatinine>1.5mg/dL) can help identify patients that may not do well after transplant. Transplanting sicker organs in patients with certain combinations of these characteristics further leads to lower survival.

Thompson, J., N. Jones, A. Al-Khafaji, S. Malik, D. Reich, S. Munoz, R. MacNicholas, T. Hassanein, L. Teperman, L. Stein, A. Duarte-Rojo, R. Malik, T. Adhami, S. Asrani, N. Shah, P. Gaglio, A. Duddempudi, B. Borg, R. Jalan, R. Brown, H. Patton, R. Satoskar, S. Rossi, A. Parikh, A. ElSharkawy, P. Mantry, L. Sher, D. Wolf, M. Hart, C. Landis, A. Wigg, S. Habib, G. McCaughan, S. Colquhoun, A. Henry, P. Bedard, L. Landeen, M. Millis, R. Ashley, W. Frank, A. Henry, J. Stange and R. Subramanian (2018). “Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial.” Liver Transpl 24(3): 380-393.

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Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin >/=8 mg/dL, Maddrey’s discriminant function >/= 32, and Model for End-Stage Liver Disease (MELD) score less than or equal to 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent-to-treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated.

Kwong, A. J. and S. K. Asrani (2018). “Artificial neural networks and liver transplantation: Are we ready for self-driving cars?” Liver Transpl 24(2): 161-163.

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The persistent shortage of donor organs has motivated efforts to predict posttransplant outcome, maximize survival benefit, and encourage the appropriate allocation of donor organs. Machine learning, a branch of statistics and computer science that has revolutionized the analysis of large and complex data sets, and its application to medicine has accelerated in recent years. Not only have machine-learning algorithms been used to develop the technology for Google Home, Siri, and self-driving cars, they have also been used to predict hospitalization in patients with heart failure, remission in patients with inflammatory bowel disease, and graft failure after solid organ transplantation. In this issue of Liver Transplantation, Ayllón et al. applied an artificial neural network (ANN), a type of machine-learning algorithm, to a cohort of 858 liver transplantation (LT) recipients from 2002 to 2010 at King’s College Hospital (KCH) using 55 donor, procurement, and recipient variables. This ANN had been previously used to develop a model in a Spanish multicenter cohort (Model for Allocation of Donor and Recipient in España [MADR-E]) of 1003 LT recipients with an area under the curve (AUC), or c-statistic, of 0.82 for 3-month graft failure. The KCH model was developed using the same ANN architecture (although the predictive model was different) used for the MADR-E study, which is designed to maximize the accuracy of graft survival by the correct classification rate (CCR) and the sensitivity of graft failure by minimum sensitivity (MS). In the KCH cohort, the ANN resulted in an AUC of 0.94 for 3-month graft failure, superior to other published models. This result implies that for 2 randomly drawn grafts, 1 of graft survival and 1 of graft failure, the model would correctly assign higher 3-month graft risk to the failed graft 94% of the time—compared with AUCs of 0.73 for donor Model for End-Stage Liver Disease (D-MELD), 0.82 for survival outcomes following liver transplantation (SOFT), and 0.84 for balance of risk (BAR), in this cohort. The ANN was also trained to predict 1-year graft failure and resulted in an AUC of 0.82, also superior to previously developed scores (AUCs of 0.63 for D-MELD, 0.65 for SOFT, and 0.71 for BAR). Variables reported to have the highest weight in the KCH model included pretransplant status, Model for End-Stage Liver Disease (MELD) at transplant, time on waiting list, etiology of liver disease, cold ischemia time, and donor hypertension, cause of death, and aspartate aminotransferase (AST) levels. [Excerpt from text of this commentary; abstract unavailable.]

Thompson, J., N. Jones, A. Al-Khafaji, S. Malik, D. Reich, S. Munoz, R. MacNicholas, T. Hassanein, L. Teperman, L. Stein, A. Duarte-Rojo, R. Malik, T. Adhami, S. Asrani, N. Shah, P. Gaglio, A. Duddempudi, B. Borg, R. Jalan, R. Brown, H. Patton, R. Satoskar, S. Rossi, A. Parikh, A. ElSharkawy, P. Mantry, L. Sher, D. Wolf, M. Hart, C. Landis, A. Wigg, S. Habib, G. McCaughan, S. Colquhoun, A. Henry, P. Bedard, L. Landeen, M. Millis, R. Ashley, W. Frank, A. Henry, J. Stange and R. Subramanian (2017). “Extracorporeal cellular therapy (elad) in severe alcoholic hepatitis – a multinational, prospective, controlled, randomized trial.” Liver Transpl: 2017 Nov [Epub ahead of print].

Full text of this article.

Severe Alcoholic Hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal liver treatment (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin >/=8 mg/dL, Maddrey’s Discriminant Function (DF) >/=32 and Model for End-Stage Liver Disease (MELD) score