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.

Lower relapse rates with good post-transplant outcome in alcoholic liver disease: Experience from a living donor liver transplant center.

INTRODUCTION: Post-transplant relapse is a major factor influencing the long-term outcome in alcoholic liver disease (ALD) patients. AIMS: The aim of this study was to evaluate the relapse rates following living donor liver transplantation (LDLT) in patients with ALD in the Indian context with strong family support. METHODS: Of 458 patients who underwent LDLT for ALD, 408 were included in the study. Post-transplant relapse was determined by information provided by the patient and/or family by means of outpatient and e-mail questionnaire, supported by clinical/biochemical parameters/liver histopathology. RESULTS: All except one were males, with a mean age of 46.9 ± 8.5 years. The overall rate of relapse was 9.5 % at 34.7 months (interquartile range (IQR) 15-57.6), lower than that reported in the literature from the West. The relapse rate was higher in patients with a shorter duration of pre-transplant abstinence (17.4 % and 15.4 % for recipients with pre-transplant abstinence of <3 and <6 months, respectively, p < 0.05). The overall survival was 88.5 % at 3 years. Of 39 patients with relapse, 16 (41 %) were occasional drinkers, 14 (35.8 %) were moderate drinkers, and 9 (23 %) were heavy drinkers. All the heavy drinkers presented with features of graft dysfunction. CONCLUSIONS: Good results can be obtained following LDLT for ALD, with significantly lower relapse rates in our setup as compared to the West.

Genotype 3 and higher low-density lipoprotein levels are predictors of good response to treatment of recurrent hepatitis C following living donor liver transplantation.

BACKGROUND: Treatment of recurrent hepatitis C after liver transplantation is associated with poor sustained virological response (SVR) in genotype 1, and data on genotype 3 is limited to small numbers. We report one of the largest series of genotype 3 patients treated for recurrent hepatitis C following living donor liver transplantation (LDLT). METHODS: From January 2002 to November 2013, of 1349 transplants, 359 patients had hepatitis C. Patients with histological recurrence were treated with pegylated interferon in escalating dose regimen for 48 weeks and weight-based ribavirin. Virological response was defined as rapid virological response (RVR-4 weeks), early virological response (EVR-12 weeks), end of treatment response (ETR-48 weeks), and SVR (24 weeks after end of treatment). SVR and no-SVR groups were compared for age, sex, body mass index (BMI), diabetes, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, ferritin, genotype, and hepatitis C virus (HCV) RNA levels before initiation of treatment. RESULTS: The study included 67 patients who had at least 18 months of follow up after treatment initiation (45 males), aged 51 ± 6.3 years. Treatment was started after 16 months (median); baseline median RNA was 2.7 × 10(6) IU/mL. There was no significant difference between the SVR and no-SVR groups regarding age, sex ratio, follow up period, total cholesterol, triglycerides, HDL, BMI, prevalence of diabetes, HCV RNA, and ferritin levels. Genotype 3, RVR, EVR, ETR, and higher LDL levels were significantly associated with SVR. Genotype 3 had a significantly higher SVR rate of 71 % as compared to an SVR rate of only 14 % in genotype 1, p = 0.0003. Absence of RVR and EVR predicted treatment failure with a specificity of 88 % and 92 %, respectively. CONCLUSION: Genotype 3 and higher LDL levels predict SVR in patients treated for hepatitis C recurrence following LDLT, whereas absence of RVR and EVR strongly predict treatment failure.

Surgical management of gastrointestinal posttransplant lymphoproliferative disorders in liver transplant recipients.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is a well-established complication of immunosuppression. The involvement of the gastrointestinal (GI) tract occurs in 25% of all cases of PTLD. Fortunately, surgical intervention is seldom required. We report our experience of surgical treatment of complicated GI-PTLD after liver transplantation (LTx). METHODS: A retrospective analysis of 5677 adult patients who underwent LTx between 1983 and 2009 was conducted. RESULTS: Thirty-six patients presented with GI-PTLD. Sixteen patients presented with complications associated with GI-PTLD requiring emergency surgery. The average (SD) time from LTx to GI surgery was 7.9 (5.8) years (range, 4 months to 17 years). Indications for surgical intervention were small bowel obstruction (seven cases), perforation (six cases), and GI bleeding (three cases). Most GI-PTLD occurred in the small bowel or right colon (81%). In addition to the surgery, treatment of PTLD consisted of reduction of immunosuppression, use of rituximab (n=10), and systemic chemotherapy (n=7). Overall mortality was 69%, with most of the deaths occurring within 8 months after emergency laparotomy. GI bleeding and perforation were associated with higher mortality (>66%). Despite higher early mortality in the surgical group, no differences on long-term outcome were observed between patients with GI-PTLD who required surgery and those who did not (P=0.371). CONCLUSIONS: In summary, GI-PTLD requiring surgical intervention is an extremely rare condition with high early mortality. Most of the cases are monoclonal, present a late onset, and involve the lower GI tract. Intestinal obstruction is the main indication for surgical intervention and is associated with better prognosis.