Downstaging with Atezolizumab-Bevacizumab: A Case Series.

Background/aims: Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC (uHCC) for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezobev remains unknown. Methods: In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging. Results: Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age: 58.5 years; women-17%; Barcelona Clinic Liver Cancer Stage System B/C:5/7) had received 3-12 cycles of atezo-bev, and 4 of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 (54-114) days following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 (4-30) months, none of the alive patients developed HCC recurrence or graft rejection. Conclusions: Surgical therapy, including LT, is possible after atezo-bev therapy in wellselected patients after downstaging.

Standard-Volume Is As Effective As High-Volume Plasma Exchange for Patients With Acute Liver Failure.

Background/Aims: Acute liver failure (ALF) is associated with fatal outcomes without liver transplantation. Two randomized studies reported standard volume (SV) and high volume (HV) plasma exchange (PLEX) as effective therapeutic modalities for patients with ALF. However, no studies have compared the safety and efficacy of SV with HV PLEX, which we aimed to assess. Methods: This retrospective study included patients with ALF admitted between March 2021 and March 2023 who underwent PLEX. All patients underwent HV PLEX until May 2022, and then thereafter, SV PLEX was performed. The objectives of the study were to compare transplant-free survival (TFS) at 30 days, efficacy in reducing severity scores, biochemical variables, and adverse events between SV (total plasma volume x 1) and HV (total plasma volume x 1.5-2) PLEX. Results: Forty two ALF patients (median age: 23.5 years; females: 57.1%; MELD Na: 34.67 ± 6.07; SOFA score- 5.24 ± 1.42) underwent PLEX. Of these, 22 patients underwent SV-PLEX, and 20 underwent HV-PLEX. The mean age, sex, etiology distribution, and severity scores were similar between the groups. The median number of PLEX sessions (2) was similar in both groups. On Kaplan-Meier analysis, TFS was 45.5% in SV group and 45% in HV group (P = 0.76). A comparable decline in total bilirubin, PT/INR, ammonia, and MELD Na scores was noted in both groups. The cumulative number of adverse events was similar between the HV group (77.3%) and SV group (54.5%; P = 0.12). Conclusions: SV PLEX is safe and as effective as HV PLEX in patients with ALF. Further randomized controlled trials with a larger sample size are needed to validate these findings.

Liver transplantation for post-COVID-19 cholangiopathy: A case series.

BACKGROUND: Post-COVID-19 cholangiopathy is an emerging cholestatic liver disease observed in patients recovering from severe COVID-19 infection. Its prognosis is poor, necessitating liver transplantation in some cases. This study aimed to investigate the outcomes of liver transplantation for post-COVID-19 cholangiopathy. METHODS: Seven patients who underwent liver transplantation for post-COVID-19 cholangiopathy at three institutions between 2020 and 2022 were included in this retrospective multi-center case series. RESULTS: At the time of initial COVID-19 infection, all patients developed acute respiratory distress syndrome, and six patients (86%) required ICU admission. Median time intervals from the initial COVID-19 diagnosis to the diagnosis of post-COVID-19 cholangiopathy and liver transplantation were 4 and 12 months, respectively. Four patients underwent living donor liver transplantation, and three patients underwent deceased donor liver transplantation. The median MELD score was 22 (range, 10-38). No significant intraoperative complications were observed. The median ICU and hospital stays were 2.5 and 12.5 days, respectively. One patient died due to respiratory failure 5 months after liver transplantation. Currently, the patient and graft survival rate is 86% at a median follow-up of 11 months. CONCLUSIONS: Liver transplantation is a viable option for patients with post-COVID-19 cholangiopathy with acceptable outcome. Timely identification of this disease and appropriate management, including evaluation for liver transplantation, are essential.

Healthcare utilization and outcomes of living donor liver transplantation for patients with APASL-defined acute-on-chronic liver failure.

BACKGROUND: Liver transplantation (LT) is associated with excellent survival in patients with acute-on-chronic liver failure (ACLF). There is a lack of data assessing the healthcare utilization and outcomes of patients with APASL-defined ACLF undergoing living donor liver transplantation (LDLT). Our aim was to assess pre-LT healthcare utilization and post-LT outcomes in such patients. METHODS: Patients with ACLF who underwent LDLT at our center between 1st April 2019 and 1st October 2021 were included. RESULTS: Seventy-three ACLF patients willing to undergo LDLT were listed; eighteen patients died within 30 days. Fifty-five patients underwent LDLT (age:38.05 ± 14.76 years; alcohol:52.7%; males:81.8%). Most were in grade II ACLF (87.3%) at the time of LDLT (APASL ACLF Research Consortium [AARC] score: 9.05 ± 1; MELD NA: 28.15 ± 4.13). Survival rate was 72.73%; mean follow-up period of 925.21 days; 58.2% (32/55) developed complications during the first year post-LT; 45% (25/55) and 12.7% (7/55) developed infections within and after 3 months. Pre-LT, each patient required a median of 2 (1-4) admissions for 17 (4-45) days. Fifty-six percent (31/55) of patients underwent plasma exchange pre-LDLT. A median amount of Rs. 8,25,090 (INR 26,000-43,58,154) was spent to stabilize the patient (who were sicker and waited longer to undergo LDLT); though post-LT survival benefit was not observed. CONCLUSIONS: LDLT was associated with 73% survival and, thus, is a viable option in those with APASL-defined ACLF. There was a pre-LT high healthcare resource utilization of plasma exchange, with the intention of optimization, while survival benefit has not been demonstrated.

Early living donor liver transplantation for alcohol-associated hepatitis.

INTRODUCTION AND OBJECTIVES: Lately, there has been a steady increase in early liver transplantation for alcohol-associated hepatitis (AAH). Although several studies have reported favorable outcomes with cadaveric early liver transplantation, the experiences with early living donor liver transplantation (eLDLT) are limited. The primary objective was to assess one-year survival in patients with AAH who underwent eLDLT. The secondary objectives were to describe the donor characteristics, assess the complications following eLDLT, and the rate of alcohol relapse. MATERIALS AND METHODS: This single-center retrospective study was conducted at AIG Hospitals, Hyderabad, India, between April 1, 2020, and December 31, 2021. RESULTS: Twenty-five patients underwent eLDLT. The mean time from abstinence to eLDLT was 92.4 ± 42.94 days. The mean model for end-stage liver disease and discriminant function score at eLDLT were 28.16 ± 2.89 and 104 ± 34.56, respectively. The mean graft-to-recipient weight ratio was 0.85 ± 0.12. Survival was 72% (95%CI, 50.61-88) after a median follow-up of 551 (23-932) days post-LT. Of the 18 women donors,11 were the wives of the recipient. Six of the nine infected recipients died: three of fungal sepsis, two of bacterial sepsis, and one of COVID-19. One patient developed hepatic artery thrombosis and died of early graft dysfunction. Twenty percent had alcohol relapse. CONCLUSIONS: eLDLT is a reasonable treatment option for patients with AAH, with a survival of 72% in our experience. Infections early on post-LT accounted for mortality, and thus a high index of suspicion of infections and vigorous surveillance, in a condition prone to infections, are needed to improve outcomes.

Postliver Transplantation Rhino-Orbital Mucormycosis, an Unexpected Cause of a Downhill Course.

The COVID-19 pandemic has impacted transplantation worldwide in a major way with infections and post-COVID-19 complications contributing to increased mortality and morbidity. We present a case of a 42-year-old lady who developed rhino-orbital mucormycosis in a postliver transplantation period. The initial presentation of the patient was very subtle. She never had overt COVID-19 infection before surgery and in the recovery period. Though cases of mucormycosis in the wound site have been reported, this would be one of the rare cases of rhino-orbital mucormycosis postliver transplantation. This infection leads to a rapid downhill course and the death of the patient. Atypical infections and presentations need to be monitored in postliver transplantation patients who are getting operated on during this pandemic, and a high level of clinical suspicion is required to pick up these cases at an early stage.

Post-COVID-19 Cholestasis: A Case Series and Review of Literature.

Background: Coronavirus disease-2019 (COVID-19) cholangiopathy is a recently known entity. There are very few reports of liver transplantation (LT) for COVID-19-induced cholangiopathy. It is well known that vaccines can prevent severe disease and improve outcomes. However, there are no reports on the impact of COVID-19 vaccines on cholestasis. Therefore, we aimed to compare the course and outcome of patients who developed cholestasis following COVID-19 infection among vaccinated and unvaccinated individuals. Methods: Patients diagnosed with post-COVID cholestasis during the pandemic were included in the study after excluding other causes of cholestasis. Results: Eight unvaccinated and seven vaccinated individuals developed cholestasis following COVID-19 infection. Baseline demographics, presentation, severity, and management of COVID-19 were similar in both groups. However, patients in the unvaccinated group had a protracted course. The peak ALP was 312 (239-517) U/L in the vaccinated group and 571.5 (368-1058) U/L in the unvaccinated group (P = 0.02). Similarly, the peak γ-glutamyl transpeptidase values were lower in the vaccinated (325 [237-600] U/L) than in the unvaccinated group (832 [491-1640] U/L; P = 0.004). However, the peak values of total bilirubin, transaminases, and INR were similar in both groups. Five patients developed ascites gradually in the unvaccinated group whereas none in the vaccinated group developed ascites. Plasma exchange was done in five patients, and two were successfully bridged to living donor LT in the unvaccinated group. Only two patients recovered with conservative management in the unvaccinated group, whereas all recovered with conservative management in the vaccinated group. The other four patients in the unvaccinated group were planned for LT. Conclusion: Post-COVID-19 cholestasis is associated with high morbidity and mortality, meriting early identification and appropriate management. Vaccination can modify the course of severe COVID-19 infection and improve outcomes.