Intravenous BCAA infusion does not lead to a sustained recovery from overt HE in ACLF – An open label randomized clinical trial

Background –Hepatic encephalopathy(HE) in acute-on-chronic liver failure(ACLF) is associated with significant morbidity and mortality. We conducted a prospective, randomized controlled clinical trial to study efficacy of intravenous branched chain amino acids(IV-BCAA) with lactulose versus lactulose alone for improvement in HE at 24h, day 3 & day 7. Primary outcome was improvement in encephalopathy by ≥ 1 grade at 72 hours. Patients and Methods –EASL defined ACLF patients with overt HE were assessed and randomized into experimental arm (IV-BCAA - 500mL/day for 3 days + Lactulose;n=39) and comparator arm (Lactulose alone;n=37). Six patients developed COVID-19 after randomization & were excluded (4-experimental arm & 2-comparator arm). Results –Of 222 screened patients, 70 (35 in each arm) were included in analysis. Baseline characteristics including HE grade (2.9 ± 0.7 vs 2.8 ± 0.7;P = 0.86) and CLIF-C ACLF score (54.2 ± 5.6 vs 54.8 ± 5.7;P = 0.65) were similar. Overall survival was 40% at 28 days (48.5% vs 31.4%;P=0.14). Improvement in HESA by ≥1 grade at 24h occurred in 14 patients (40%) in BCAA arm and 6 patients (17.1%) in control group (P=0.03) which translated to shorter ICU stay. Median change in HESA at 24h was more in BCAA arm than control arm(P=0.006) which was not sustained at day 3 or 7. Ammonia levels did not correlate with grade of HE (Spearman's correlation coefficient(ρ) = - 0.0843;P=0.29). Conclusion Intravenous BCAA does not lead to a sustained improvement in HE grade in ACLF. Trial registration no NCT04238416 (clinicaltrials.gov)

Good outcomes of living donor liver transplant in primary sclerosing cholangitis: an experience from North India.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. In the absence of effective medical therapy, liver transplant is the definitive treatment for advanced stage. However, recurrence of PSC after liver transplant is of concern which can lead to graft failure and may require retransplant. There are limited data on outcomes of living donor liver transplant (LDLT) in PSC. Also, in LDLT as donors are genetically related there can be an increased risk of recurrence. We conducted this retrospective study to analyze the outcomes of LDLT in PSC at a tertiary liver transplant center in north India. METHODS: We conducted a retrospective analysis of 3213 transplant recipients who underwent LDLT from January 2006 to May 2021. Of these 26 (0.80%) patients had PSC as indication for liver transplantation (PSC = 24, PSC-AIH overlap = 2). Data analysis was done to look for baseline demographics, clinical details, transplant outcomes, PSC recurrence, and survival. RESULTS: Mean age of study group was 42 (± 13.8) years and 19 patients (73.1%) were males. All patients had decompensated cirrhosis at the time of transplant. Mean CTP score and MELD score were 9.5 (± 1.8) and 18.9 (± 7.1), respectively. Sixteen patients received modified right lobe graft, seven extended right lobe graft and five patients received left lateral graft. Median graft weight and mean graft to recipient weight ratio (GRWR) were 633.5 (IQR 473.5-633.5) grams and 1.23 (± 0.42), respectively. Most common biliary anastomosis was hepaticojejunostomy, done in 19 (73.1%) while duct to duct anastomosis was performed in 7 (26.9%) patients. Median follow-up was 96 (36-123) months. One patient had ulcerative colitis and none had cholangiocarcinoma. Two (7.7%) patients had bile leak during early post-transplant period. Three (11.1%) patients developed graft rejection and were managed successfully with steroid pulses. Three patients died during early post-transplant period while seven deaths occurred during long-term follow-up including one death due to COVID-19. Five (21.73%) patients had recurrence of PSC of which two patients had graft loss including one after retransplantation. The one year graft and patient survival rate was 88.5%. CONCLUSION: LDLT can be performed in PSC with good long-term outcomes with a risk of PSC recurrence in about one-fifth patients.

Invasive Pulmonary Aspergillosis and Tuberculosis Complicated by Hemophagocytic Lymphohistiocytosis - Sequelae of COVID-19 in a Liver Transplant Recipient.

Liver transplant recipients are at an increased risk of opportunistic infections due to the use of immunosuppression. Coronavirus disease of 2019 (COVID-19) increases the risk of these infections further due to associated immune dysfunction and the use of high-dose steroids. We present a case of a liver transplant recipient who developed disseminated tuberculosis and invasive pulmonary aspergillosis complicated by acquired hemophagocytic lymphohistiocytosis after recovering from severe COVID-19.