Identifying the early predictors of non-response to steroids in patients with flare of autoimmune hepatitis causing acute-on-chronic liver failure.

BACKGROUND AND AIMS: Early identification of non-response to steroids is critical in patients with autoimmune hepatitis (AIH) causing acute-on-chronic liver failure (ACLF). We assessed if this non-response can be accurately identified within first few days of treatment. METHODS: Patients with AIH-ACLF without baseline infection/hepatic encephalopathy were identified from APASL ACLF research consortium (AARC) database. Diagnosis of AIH-ACLF was based mainly on histology. Those treated with steroids were assessed for non-response (defined as death or liver transplant at 90 days for present study). Laboratory parameters, AARC, and model for end-stage liver disease (MELD) scores were assessed at baseline and day 3 to identify early non-response. Utility of dynamic SURFASA score [- 6.80 + 1.92*(D0-INR) + 1.94*(∆%3-INR) + 1.64*(∆%3-bilirubin)] was also evaluated. The performance of early predictors was compared with changes in MELD score at 2 weeks. RESULTS: Fifty-five out of one hundred and sixty-five patients (age-38.2 ± 15.0 years, 67.2% females) with AIH-ACLF [median MELD 24 (IQR: 22-27); median AARC score 7 (6-9)] given oral prednisolone 40 (20-40) mg per day were analyzed. The 90 day transplant-free survival in this cohort was 45.7% with worse outcomes in those with incident infections (56% vs 28.0%, p = 0.03). The AUROC of pre-therapy AARC score [0.842 (95% CI 0.754-0.93)], MELD [0.837 (95% CI 0.733-0.94)] score and SURFASA score [0.795 (95% CI 0.678-0.911)] were as accurate as ∆MELD at 2 weeks [0.770 (95% CI 0.687-0.845), p = 0.526] and better than ∆MELD at 3 days [0.541 (95% CI 0.395, 0.687), p < 0.001] to predict non-response. Combination of AARC score > 6, MELD score > 24 with SURFASA score ≥ - 1.2, could identify non-responders at day 3 (concomitant- 75% vs either - 42%, p < 0.001). CONCLUSION: Baseline AARC score, MELD score, and the dynamic SURFASA score on day 3 can accurately identify early non-response to steroids in AIH-ACLF.

Living Donor Liver Transplantation in a Cohort of Recipients With Left Ventricular Systolic Dysfunction.

Background: Data on feasibility, management, and outcomes of liver transplantation (LT) in patients with pre-existing left ventricular systolic dysfunction (LVSD), severe coronary artery disease (CAD) or cirrhotic cardiomyopathy (CCM) is scarce. Methods: We reviewed outcomes of living donor liver transplantation (LDLT) in recipients with LVSD (ejection fraction [EF] < 50%) from our series of 1946 LDLT's performed between July 2010 and July 2018. Results: LVSD was detected in 12 male patients with a mean age, BMI and MELD of 52 ± 9 years, 25 ± 5 kg/m2, and 19 ± 4 respectively. Out of these, 6 patients had CAD (2 with previous coronary artery bypass graft, 1 following recent percutaneous transluminal coronary angioplasty, 2 post myocardial infarction, 1 noncritical CAD), and 6 had CCM. The EF ranged from 25% to 45%. Ethanol was the predominant underlying etiology for cirrhosis (50%). During LDLT, 2 patients developed ventricular ectopic rhythm and were managed successfully with intravenous lidocaine. Stress cardiomyopathy manifested in 3 patients post operatively with decreased EF, of which 2 improved, while 1 needed IABP support and succumbed to multiorgan failure on 8th postoperative day (POD). Another patient died on POD30 due to septic shock. Both these patients had higher MELD scores (actual MELD), extremes of BMI (17.3and 35.8 kg/m2) and were diabetic. There were no long-term cardiac deaths. The 1-year, and 5-year survival were 75%, and 66%, respectively. Conclusion: Among potential LT recipients with LVSD, those with stable CAD and good performance status, and well optimized CCM patients may be considered for LDLT after careful risk stratification in experienced centers.

Incorporating Tumor Biology to Predict Hepatocellular Carcinoma Recurrence in Patients Undergoing Living Donor Liver Transplantation Using Expanded Selection Criteria.

Conventional selection criteria for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are based on tumour size/number only, and do not consider vital surrogates of tumor biology such as alpha-fetoprotein (AFP) and tumor [18 F]fluorodeoxyglucose positron emission tomography ([18 F]FDG PET) avidity. We analyzed survival outcomes, and predictors of HCC recurrence in 405 patients with cirrhosis and HCC (HCC-cirr) who underwent living donor LT (LDLT) using our expanded selection criteria: no extrahepatic disease or major vascular invasion, irrespective of tumor size/number. Fifty-one percent patients had tumours beyond Milan, and 43% beyond the University of California San Francisco [UCSF] criteria. The 5-year overall survival (OS) and recurrence-free survival (RFS) were 64% and 70%, respectively. Three preoperatively available factors predicted recurrence: pre-LT AFP ≥100 ng/mL (P = 0.005; hazard ratio [HR], 2.190), tumor burden beyond the UCSF criteria (P = 0.001; HR, 2.640), and [18 F]FDG PET avidity (P = 0.004; HR, 2.442). A prognostic model based on the number and combination of the aforementioned preoperative risk factors was developed using a competing-risk RFS model. Three risk groups were identified: low (none or a single risk factor present, 9.3% recurrence), moderate (AFP ≥100 ng/mL and [18 F]FDG PET avidity, or beyond UCSF tumor and [18 F]FDG PET avidity, 25% recurrence), and high (AFP ≥100 ng/mL and beyond UCSF, or presence of all 3 risk factors, 46% recurrence). Acceptable long-term outcomes were achieved using our expanded selection criteria. Our prognostic model to predict recurrence based on preoperative biological and morphological factors could guide pretransplant management (downstaging versus upfront LDLT) with the aim of reducing post-LDLT recurrence.

Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study).

BACKGROUND AND AIMS: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. METHODS: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19. RESULTS: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1-3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9-38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3-163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients. CONCLUSIONS: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.

Correction to: Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update.

The article Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update, written by [Shiv Sarin], was originally published electronically on the publisher's internet portal (currently SpringerLink) on June 06, 2019 without open access.

Leishmania donovani and Pneumocystis jirovecii (carinii) diagnosed on bronchoalveolar lavage cytology in a liver transplant recipient with Cytomegalovirus infection.

Liver transplant recipients are prone to several infections, including lung infections, which can lead to substantial morbidity and mortality. Bronchoalveolar lavage (BAL) cytology is a rapid and sensitive diagnostic tool to identify the etiologic agents. We report a rare case of a 24-year-old male, post Live donor liver transplantation for autoimmune chronic liver disease, who presented with cough, fever, weight loss, and cavitatory lesion in lung. BAL cytology revealed Leishmania donovani (LD) and Pneumocystis jirovecii/carinii (PCP). Cytomegalovirus deoxyribonucleic acid polymerase chain reaction (CMV DNA PCR) test showed markedly raised levels. Patient was put on treatment for these multiple infections and showed significant improvement. Thus, rapid diagnosis of infections through BAL cytology is crucial in transplant recipients to institute timely therapy and avoid undesirable empirical treatments. Moreover, this case highlights a rare finding of LD bodies along with PCP in BAL cytology.

Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update.

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the "APASL ACLF Research Consortium (AARC)" was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the 'Golden Therapeutic Window', extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.

Cytomegalovirus infection in living donor liver transplant recipients significantly impacts the early post-transplant outcome: A single center experience.

BACKGROUND: Cytomegalovirus (CMV) is the most common viral infection in liver transplant recipients that influences the outcomes of liver transplantation. However, its impact on early outcomes following living donor liver transplantation (LDLT) is not fully defined in the Indian subcontinent. This study was done to assess the impact of CMV infection on early post-transplant outcomes in LDLT recipients. METHODS: Out of 272 LDLTs performed from January 2012 to April 2013, 151 recipients underwent CMV viral load analysis in plasma within 90 days post LDLT based on clinical suspicion. Patients with CMV infection (n = 55) were compared with those without CMV infection (n = 96). RESULTS: The median time interval of CMV infection from LDLT was 25 days (range 2-90 days). The mean age of study population was 48.92 years. About 116 (76.8%) of the patients were male. Hepatitis C virus (HCV) (39.1%)-related chronic liver disease (CLD) was most common indication for liver transplant. No statistically significant difference was observed in etiology of liver disease (P = .38), Chid-Turcotte-Pugh (CTP) (P = .41), and Model for End-stage Liver Disease (MELD) (P = .12) scores between the groups. Patients with CMV infection had significantly higher incidence of acute cellular rejection (16.1% vs 5.4%, P = .02); longer ICU stay (P = .01); and a higher overall 90-day mortality (24.2% vs 6.7%, P = .001). Bacteremia and fungemia were significantly more common in the CMV infection group. CONCLUSION: Cytomegalovirus infection significantly influences the early post LDLT outcomes and contributes to increased overall mortality.

Fast tracking in adult living donor liver transplantation: A case series of 15 patients.

BACKGROUND AND AIMS: Fast tracking (FT) for more efficacious use of resources may be difficult after living donor liver transplantation (LDLT) due to a partial liver graft, complex vascular anastomoses and longer operating time. Our study was aimed at reporting our experience with FT (on table extubation) in LDLT recipients. A secondary objective of our study was to look at defining a subgroup of patients who could be prospectively planned for FT. METHODS: We studied the demographics and outcomes of 15 LDLT recipients extubated immediately in the operating suite based on an uneventful intraoperative course, haemodynamic stability after graft reperfusion and improvement of metabolic parameters post-implantation and vascular anastomoses. RESULTS: Twelve recipients were males, and mean age, body mass index (BMI) and Model for End Stage Liver Disease (MELD) score were 43 ± 12 years, 23 ± 3 kg/m2 and 15.5 ± 6, respectively, most were Child-Turcotte-Pugh Class B. Diabetes and hypothyroidism were present in 1 and 2 patients, respectively. Post-extubation, none required immediate re-intubation and one patient needed non-invasive ventilation for 2 h. CONCLUSION: Fast tracked recipients were young, with a low BMI, low MELD scores, minimal comorbidities and good immediate graft function post-reperfusion.

Nutritional status using subjective global assessment independently predicts outcome of patients waiting for living donor liver transplant.

BACKGROUND: Malnutrition is an important risk factor for adverse outcomes in patients awaiting liver transplant. Living donor liver transplant, being an elective procedure, allows nutritional rehabilitation and optimization of these patients before transplant. AIM: This paper aimed to evaluate the outcome of end-stage liver disease (ESLD) patients with various degrees of malnutrition waiting for living donor liver transplant. METHODS: Nutritional status was assessed using subjective global assessment (SGA) in patients who were evaluated for a liver transplant at our center from January 2015 to September 2015. All the data were collected prospectively. Predictive factors for mortality were analyzed using logistic regression and survival was obtained using Kaplan-Meier curves. RESULTS: One hundred and seventeen patients were grouped based on their nutrition status into normal, mild-moderate, and severe malnutrition. The groups were comparable in terms of age, sex, etiology of liver disease except alcoholic liver disease. Graft recipient weight ratio was comparable among groups. There was no significant difference in hospital stay. However, severe malnourished patients had higher incidence of sepsis (p=0.005) and death due to sepsis (p=0.01). Nutritional status was the only independent predictor of mortality on multivariate analysis. CONCLUSION: Nutritional status measured with SGA independently predicts short-term outcome of ESLD patients waiting and after living donor liver transplant.

Outcome of 200 Pediatric Living Donor Liver Transplantations in India.

OBJECTIVE: To describe our experience of pediatric living donor liver transplantation from India over a period of 12 years. MATERIALS AND METHODS: A retrospective analysis of 200 living donor liver transplantation in children (18 years or younger) was done for demographic features, indications, donor and graft profile and outcome. RESULTS: Between September 2004 and July 2016, 200 liver transplants were performed on 197 children. Fifty transplants were done in initial 6 years and 150 in next 6 years. All donors (51% mothers) were discharged with a mean stay of 7 days. The leading indications of liver transplants were cholestatic liver disease (46%) followed by metabolic liver disease (33%) and acute liver failure/acute on chronic liver failure (28.5%). Biliary leakage (8.5%), biliary stricture (9%), hepatic artery thrombosis (4.5%) and portal vein thrombosis (4%) were the most common surgical complications; all could be managed by surgical or interventional radiological measures, except in one child who died. Sepsis, acute rejection and CMV hepatitis in first 6 months were seen in 14.5%, 25% and 17% cases, respectively. Post-transplant lymphoproliferative disease was seen in only 1.5%. Re-transplant rate was 1.5%. The overall 1 year survival rate was 94% and 5 year actuarial survival was 87% with no statistically significant difference between children weight <10 kg vs. >10 kg. Outcome in acute liver failure did not differ significantly between those with acute on chronic liver failure vs. those with chronic liver disease. CONCLUSIONS: Advances in medical and surgical techniques associated with multidisciplinary teams including skilled pediatric liver transplant surgeons, anesthetists, dedicated pediatric hepatologists, pediatric intensivists, interventional radiologists and pathologists resulted in an excellent outcome of living related liver transplants in children. Low age and weight of the baby does not seem to be a contraindication for liver transplantation as outcome were comparable in our experience.

Robotics in hepatobiliary surgery-initial experience, first reported case series from India.

INTRODUCTION: Robotic surgical system's ability to perform complex hepatobiliary surgeries is gaining momentum with outcomes similar to open surgery and advantages of minimal access surgery. The authors present their initial experience of a heterogenous spectrum of robotic hepatobiliary cases and the first reported case series from India. METHODS: Retrospective review of hepatobiliary cases done robotically from February 2015 to January 2016 was done. RESULTS: The series has ten patients; with median age of 45 years (range 15-72). Etiologies were choledochal cyst type IVa, benign lower end common bile duct stricture (biliary reconstruction group); incidental gallbladder carcinoma, hepatocellular carcinoma, recurrent pyogenic cholangitis, polycystic liver disease, hemangioma, liver metastases, hydatid cyst (resection group). Median operative duration was 510min; one patient needed intra-operative blood transfusion and there were no conversions to open surgery. One patient developed bile leak which was managed by biliary stenting and another thrombotic thrombocytopenic purpura during post-operative period. Median length of hospital stay was 6days with average cost of robotic surgery being $1700 USD more for major hepatectomy and $900 USD more for biliary reconstruction compared to open procedure. CONCLUSION: This initial series adds to existing data on the feasibility of robotic hepatobiliary cases with inherent advantages of minimal invasive surgery, however with limitation of availability and use of devices like cavitron ultrasonic surgical aspirator (CUSA) and higher operative cost.

Hepatic Venous and Inferior Vena Cava Morphology No Longer a Barrier to Living Donor Liver Transplantation for Budd-Chiari Syndrome: Surgical Techniques and Outcomes.

BACKGROUND: Living donor liver transplantation (LDLT) for Budd-Chiari syndrome (BCS) has been reported with <10 inferior vena cava (IVC) replacements with vascular/synthetic graft. The goal of this study was to review outcomes of LDLT for BCS at our center, with an emphasis on surgical techniques and postoperative anticoagulation therapy. METHODS: Between October 2011 and December 2015, a total of 1027 LDLTs were performed. Nine of these patients had BCS. We analyzed their etiologies, operative details, postoperative complications, and outcomes. RESULTS: The indication was chronic liver disease for all patients. Two patients required retrohepatic IVC replacement with a polytetrafluoroethylene graft due to severe adhesions and thrombosis, respectively. One patient required V-Y plasty for suprahepatic IVC narrowing. Five patients had portal venous thrombosis, 3 treated by thrombectomy, and 1 by renoportal anastomosis. The mean follow-up time was 18 ± 16 months. Only 1 early death occurred due to sepsis. The anticoagulation therapy involved heparin infusion from postoperative day 1, conversion to low-molecular-weight-heparin on postoperative days 3 to 6, followed by warfarin (postoperative days 9-16 to maintain an international normalized ratio of 2-3 long term), along with low-dose aspirin for 6 months. There was no recurrence of thrombosis. CONCLUSIONS: LDLT for BCS is well documented in literature. Prevention of recurrent thrombosis depends on meticulous surgical technique, perfect and wide outflow anastomoses, and a strict anticoagulation protocol. A synthetic (polytetrafluoroethylene) graft for IVC interposition is a safe and feasible option for reconstruction with good results. Low-dose aspirin with low-molecular-weight-heparin later converted to warfarin provides excellent results and prevents recurrence of thrombosis.

Living donor liver transplantation in maple syrup urine disease - Case series and world's youngest domino liver donor and recipient.

MSUD occurs due to deficiency of enzyme BCKAD required for metabolism of leucine, isoleucine, and valine leading to the accumulation of these and their ketoacids causing acute metabolic decompensation manifesting as encephalopathy or sudden death. The patient requires special protein-restricted diet to survive. As this enzyme is expressed in liver, liver transplantation has been successfully performed as a cure. We report two patients of MSUD who underwent LDLT while their livers were used as a domino graft for other biliary cirrhotic patients. A 22-month-old male child diagnosed as a case of classic MSUD underwent LDLT from an altruistic aunt as donor following which his serum leucine levels normalized on an unrestricted protein diet. His liver was used as a domino graft. A 38-month-old female child with diagnosed MSUD underwent LDLT from a swap donor, and her liver was used as a domino graft. Her DQ improved post-transplant. LDLT from non-heterozygous donors is a cure for classical MSUD. Their livers can be used as domino grafts for non-MSUD cases.

Robotic Left Hepatectomy: a Case Report (First Reported Case of Robotic Hepatectomy in India).

Robotic surgical platform is being increasingly used by liver surgeons for performing minimal invasive liver surgery, with results comparable to open surgery and added benefits of laparoscopic approach. The authors describe a case of robotic left hepatectomy done for recurrent pyogenic cholangitis. This is the first reported case of robotic hepatectomy done in India.

First living-related liver transplant to cure factor VII deficiency.

Congenital factor VII deficiency is an autosomal recessive serious disorder of blood coagulation with wide genotypic and phenotypic variations. The clinical presentation can vary from asymptomatic patients to patients with major bleedings in severe deficiency (factor VII <1%). Investigations show prolonged PT and low factor VII. Treatment modalities include FFP and repeated recombinant factor VII infusions. We hereby report the first successful LRLT for factor VII deficiency in an infant, the first-ever youngest baby reported worldwide. A six-month-old male child presented with easy bruisability, ecchymotic patches, hematuria, and convulsions. CT of the head showed subdural hemorrhage, which was treated conservatively. He had markedly increased PT (120 s) with normal platelets, and aPTT with factor VII level <1%. Despite the treatment by rFVIIa administration weekly, which was very expensive, he still had repeated life-threatening bleeding episodes. LRLT was performed with mother as the donor, whose factor VII level was 57%. A factor VII infusion plan for pre-, intra- and postoperative periods was formulated and TEG followed. Postoperatively, his factor VII started increasing from third day and was 38% on 24th day with PT <14 s. He had uneventful intraoperative and postoperative courses. LT is a safe and definite cure for factor VII deficiency.

Low-dose short-term hepatitis B immunoglobulin with high genetic barrier antivirals: the ideal post-transplant hepatitis B virus prophylaxis?

BACKGROUND: Low-dose hepatitis B immunoglobulin (HBIG) and nucleos(t)ides analogs (lamivudine/adefovir) used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT) are associated with some risk of HBV recurrence and antiviral resistance. METHODS: The study cohort included 176 patients (at least >12 months follow-up) with HBV cirrhosis/hepatocellular carcinoma who received secondary prophylaxis with indefinite entecavir/tenofovir after living-donor LT (LDLT). All patients received 10,000 IU intravenous HBIG in anhepatic phase followed by 600-1000 IU intramuscularly daily for 7 days, weekly for 3 weeks, and then monthly, to keep antiHBs levels >100 mIU/mL for 1 year. Hepatitis B surface antigen (HBsAg) and HBV DNA were tested every 6 months. RESULTS: The study cohort is composed of 157 men and 19 women, mean age 47.9 ± 10.1 years, all HBsAg positive, 35 (19.8%) had HBV DNA >2000 IU/mL before LT. After LT, patients received entecavir (n = 126, 71.5%), tenofovir (n = 20, 11.3%), or a combination of entecavir and tenofovir (n = 30, 17% for 3 months), followed by entecavir alone. During follow-up of 43 (12-117) months, 2 patients (including 1 with non-compliance) had HBV recurrence. CONCLUSION: In a large cohort of LDLT recipients for HBV-related liver disease, use of low-dose short-term HBIG with high genetic barrier drugs results in a substantially lower incidence of HBV recurrence, even in high-risk patients.

India's first successful intestinal transplant: the road traveled and the lessons learnt.

Intestinal transplant is a therapeutic challenge not just surgically but also logistically because of the multidisciplinary expertise and resources required. A large proportion of patients who undergo massive bowel resection and develop intestinal failure have poor outcome, because of inability to sustain long-term parenteral nutrition and limited availability of intestinal and multi-visceral transplantation facilities. We report the first successful isolated intestinal transplant from India.