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)

Antibody Response and Safety of ChAdOx1-nCOV (Covishield) in Patients with Cirrhosis: A Cross-Sectional, Observational Study.

INTRODUCTION: Patients with cirrhosis have a higher risk of severe COVID-19 and mortality and are high-priority patients for vaccination. However, cirrhotics were excluded from the phase 2/3 vaccine trials. Hence, we aimed to assess the antibody response and safety of Covishield (ChAdOx1nCoV-19) among patients with cirrhosis. METHODS: Patients who attended the tele-hepatology services at our institute from March 2020 to June 2021 and diagnosed with cirrhosis as per their medical records were telephonically interviewed in July 2021 using a pre-specified questionnaire. Patients who had completed 2 doses of ChAdOx1-nCOV (with the 2nd dose administered at least 2 weeks back) and without history of documented COVID-19 infection (pre- or post-vaccination) were tested for antibodies against the spike protein. Seropositive patients were divided into high, moderate, and low antibody responses based on the signal/cut-off. RESULTS: We interviewed 784 patients with cirrhosis. At least 1 dose of ChAdOx1-nCOV was received by 231 patients among whom 134 (58%) had received 2 doses. Documented COVID-19 was reported in 3.9% patients who received at least 1 dose of ChAdOx1-nCOV including breakthrough infections in 3.7% patients vaccinated with 2 doses. Local and systemic adverse events were reported by 42% and 22.1% patients. None developed anaphylaxis, acute decompensation, acute-on-chronic liver failure, or other serious adverse events requiring hospitalization. Seroconversion was documented in 81 (92%) out of 88 patients. No difference was observed in level of antibody response between patients with compensated and decompensated cirrhosis (p = 0.12). CONCLUSION: Our preliminary data suggest that ChAdOx1-nCOV is safe with high seroconversion rates in patients with cirrhosis.

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.

Feasibility, Outcomes, and Safety of Telehepatology Services During the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) has hampered health care delivery globally. We evaluated the feasibility, outcomes, and safety of telehepatology in delivering quality care amid the pandemic. A telemedicine setup using smartphones by hepatologists was organized at our tertiary-care center after pilot testing. Consecutive patients availing telehepatology services were recruited between March and July 2020. An adapted model for assessment of telemedicine was used after validity and reliability testing, to evaluate services 7-21 days after index teleconsultation. Of the 1,419 registrations, 1,281 (90.3%) consultations were completed. From 245 randomly surveyed patients, 210 (85.7%) responded (age [years, interquartile range]: 46 [35-56]; 32.3% females). Seventy percent of patients belonged to the middle or lower socio-economic class, whereas 61% were from rural areas. Modes of teleconsultation were audio (54.3%) or hybrid video call (45.7%). Teleconsultation alone was deemed suitable in 88.6% of patients. Diagnosis and compliance rates were 94% and 82.4%, respectively. Patients' convenience rate, satisfaction rate, improvement rate, success rate, and net promoter scores were 99.0%, 85.2%, 49.5%, 46.2% and 70, respectively. Physical and mental quality of life improved in 67.1% and 82.8% of patients, respectively, following index teleconsultation. Person-hours and money spent by patients were significantly lower with teleconsultation (P < 0.001); however, person-hours spent by hospital per teleconsultation were higher than in physical outpatient services (P < 0.001). Dissatisfied patients were more likely to have lower diagnosis rate, unsuitability for teleconsultation, noncompliance, poorer understanding, and uncomfortable conversation during teleconsultation. Connectivity issues (22.9%) were the most common barrier. Three patients, all of whom were advised emergency care during teleconsultation, succumbed to their illness. Conclusion: Telehepatology is a feasible and reasonably effective tool for rendering health care services using smartphones during the COVID-19 pandemic. Systematic implementation, possible integration into routine health care delivery, and formal cost-effectiveness of telehepatology services need further exploration.