Outcomes of early vs late treatment initiation in solid organ transplantation from hepatitis C virus nucleic acid test-positive donors to hepatitis C virus-uninfected recipients: Results from the HCV-TARGET study.

Curative hepatitis C virus (HCV) therapy has increased transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients (D+/R-). We evaluated outcomes of early and late HCV treatment among D+/R- nonliver organ transplants. Patients received HCV regimens per local standard (n = 10 sites). Outcomes were compared between early and late treatments. Early treatment regimens (ETR) (n = 56) were initiated pretransplantation to day 7 posttransplant. Late treatment regimens (LTRs) (n = 102) began median 31 (range, 8-114) days posttransplant. There were 79 kidney, 50 lung, 23 heart, and 6 mixed transplants, similar between groups. HCV RNA was quantifiable in 98% of LTR versus 44.6% of ETR recipients (P < .001). Mean (range) days on treatment were 28 (7-93) ETR and 81 (51-111) LTR (P < .0001). There were no virological failures with ETR, but relapse (n = 3) and nonresponse (n = 2) in LTR (P = .16), including fibrosing cholestatic hepatitis postrelapse (n = 1). Sustained virological response was 100% (95% confidence interval, 93.4-100.0) in ETR (n = 54) and 94.9% (95% confidence interval, 88.5-98.3) in LTR (n = 98). Acute rejection occurred in 11 (19.6%) ETR and 25 (24.5%) LTR. In total, 11 HCV-unrelated deaths occurred: 8 ETR and 3 LTR. Organ transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients was safe. ETR led to fewer virological failures with shorter treatment duration, supporting recommendations to initiate treatment promptly posttransplant.

Outcomes of kidney, liver, and simultaneous liver and kidney transplants from hepatitis c infected donors to hepatitis c naïve recipients: A large single center experience.

BACKGROUND: With the introduction of direct-acting antiviral therapies (DAAs), the non-use rate of hepatitis C virus (HCV)-positive donor organs (D+) has decreased significantly. We present the donor, recipient, and transplant allograft characteristics, along with recipient outcomes, in one of the largest cohorts of HCV-D+ transplants into HCV-naïve recipients (R-). METHODS: Charts of HCV D+/R- kidney (KT), liver (LT), and simultaneous liver-kidney (SLKT) transplant recipients between January 2019 and July 2022 were reviewed. Primary outcomes of interest included waitlist times and 1-year graft failure. Secondary outcomes included hospital and intensive care unit length of stay, post-transplant complications, effectiveness of DAA therapy, and characteristics of patients who relapsed from initial DAA therapy. RESULTS: Fifty-five HCV D+/R- transplants at our center [42 KT (26 nucleic acid testing positive [NAT+], 16 NAT-), 12 LT (eight NAT+, four NAT-), and one SLKT (NAT+)] had a median waitlist time of 69 days for KT, 87 days for LT, and 15 days for SLKT. There were no graft failures at 1 year. All viremic recipients were treated with a 12-week course of DAAs, of which 100% achieved end of treatment response (EOTR)-85.7% (n = 30) achieved sustained virologic response (SVR) and 14.3% relapsed (n = 5; four KT, one LT). All relapsed recipients were retreated and achieved SVR. The most common post-transplantation complications include BK virus infection (n = 9) for KT and non-allograft infections (n = 4) for LT. CONCLUSIONS: Our study has demonstrated no graft failures or recipient deaths at 1 year, and despite a 14.3% relapse rate, we achieved 100% SVR. Complications rates of D+/R- appeared comparable to national D-/R- complication rates. Further studies comparing D+/R- to D-/R- outcomes are needed.

Donor-to-recipient transmission of factor XII deficiency by orthotopic liver transplantation.

Transmission of congenital clotting factor deficiencies following orthotopic liver transplantation is rare. There has been one reported case of donor-to-recipient transmission of factor XII deficiency in a transplant, and we report the second case.

Effect of Downstaging and Bridging of Hepatocellular Carcinoma on Survival Following Liver Transplant: A Single Center Experience.

OBJECTIVES: Hepatocellular carcinoma is among the leading causes of cancer death. The Milan criteria are the first and most widely used criteria for selecting patients with hepatocellular carcinoma for a good transplant outcome. Studies have shown that patients with hepatocellular carcinoma outside the Milan criteria have good outcomes if they are successfully downstaged before transplant. We report our experience with locoregional therapy for hepatocellular carcinoma, either for bridging or for downstaging prior to transplant. MATERIALS AND METHODS: We retrospectively reviewed the electronic charts and our institutional database for adult patients diagnosed with hepatocellular carcinoma between 2001 and 2016. We recorded patient demographics, the type of transplant (living donor or deceased donor), radiologic findings, the type of locoregional intervention, and overall survival. RESULTS: A total of 642 adult liver transplants were performed during the study period (290 living donor and 352 deceased donor), of which 158 (24.6%) were conducted in patients with hepatocellular carcinoma (104 men and 54 women). Hepatocellular carcinoma was associated with hepatitis C in 80 patients (51%), hepatitis B in 44 (28%), and was cryptogenic in 13 (8%). Patients were grouped based on their radiologic staging (within Milan, within and beyond University of California, San Francisco), and subsequently described by whether they received locoregional therapy. Median survival and mortality were noted. Kaplan-Meier survival curves showed no statistically significant difference for patients within the Milan criteria, with or without locoregional therapy (P = .5). When patients within the Milan criteria were combined with patients within the University of California, San Francisco criteria, those who were downstaged from outside the latter criteria had similar survival. CONCLUSIONS: We demonstrate that carefully selected patients beyond the Milan criteria and even beyond the University of California, San Francisco criteria can be bridged and downstaged successfully for liver transplant.

Treatment of Patients With Hepatitis C Virus Infection With Ledipasvir-Sofosbuvir in the Liver Transplant Setting.

BACKGROUND: Hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma and the leading indication for liver transplantation. In the Middle East, genotype 4 HCV infection is the most common genotype. However, limited data exists on the treatment of genotype-4 in the liver transplant setting. We evaluated the safety and efficacy of ledipasvir (LDV)-sofosbuvir (SOF) in treating HCV genotype-4 infected patients with cirrhosis or postliver transplantation. METHODS: This prospective, single-arm, observational study includes cohort of patients with cirrhosis before liver transplantation (cohort A) and a cohort of postliver transplantation patients (cohort B). Patients received LDV/SOF (90-400 mg) once daily for 12 to 24 weeks with or without ribavirin (RBV). Patients with creatinine clearance below 30 were excluded. RESULTS: A total of 111 patients (61 cirrhotic; 50 postliver transplants) with HCV genotype 4 were treated in King Faisal Specialist Hospital and Research Center; 55% cohort A and 44% cohort B received RBV. Sustained virological response sustain virological response (SVR)12 was 91.8% and 86% of cohorts A and B, respectively. There were no treatment-related mortality or serious adverse effects. RBV dose reduction occurred in 25% without any treatment discontinuation. SVR12 rates in cohort A were significantly higher in patients with a viral load below 800 000 (100% vs 83.9%, P value = 0.022). Viral load did not impact SVR rates in cohort B. The use of RBV did not increase SVR12 and was associated with anemia. CONCLUSIONS: LDV/SOF without RBV is an effective and safe treatment option for patients with HCV genotype 4 infection in preliver and postliver transplant settings.

Low Utility of Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography for Detecting Hepatocellular Carcinoma in Patients Before Liver Transplantation.

OBJECTIVES: Our program routinely used fluorodeoxyglucose-positron emission tomography/computed tomography as part of the liver transplant evaluation of patients with hepatocellular carcinoma. The aim of this study was to evaluate the role of this imaging modality in the pretransplant work-up. MATERIALS AND METHODS: This was a retrospective chart review of our liver transplant database from January 2011 to December 2014 for all patients with hepatocellular carcinoma who underwent a liver transplant. Collected data included age, sex, cause of liver disease, imaging modality, fluorodeoxyglucose-positron emission tomography/computed tomography results, explant tissue analysis, type of transplant, and transplant outcome. RESULTS: During the study period, 275 liver transplants were performed. Fifty-three patients had hepatocellular carcinoma; 41 underwent fluorodeoxyglucose-positron emission tomography/computed tomography. Twenty-nine patients underwent living-donor liver transplant, and 12 patients underwent deceased-donor liver transplant. One of the 41 patients with negative FDG-imaging results had no evidence of hepatocellular carcinoma in the explant and was excluded from the study. The patients' average age was 58 years (range, 22-72 y), and 28 patients were men. The cause of liver disease was hepatitis C virus in 24 patients, cryptogenic cirrhosis in 12 patients, and hepatitis B virus in 5 patients. One patient had no hepatocellular carcinoma on explants and was excluded from the study. Twenty-five patients had hepatocellular carcinoma that met the Milan criteria, 7 were within the UCSF (University of California, San Francisco) criteria, and 8 exceeded the UCSF criteria. Of the 40 patients, 11 had positive fluorodeoxyglucose-positron emission tomography/computed tomography results (27.5%) with evidence of hepatocellular carcinoma in the explant; the remaining 29 patients (72.5%) had negative results. The fluorodeoxyglucose-positron emission tomography/computed tomography results were positive in 16% (4 of 21) of patients who met the Milan criteria, 28% (2 of 7) of patients who met the UCSF criteria and 62% (5 of 8) of patients who exceeded the UCSF criteria. CONCLUSIONS: Fluorodeoxyglucose-positron emission tomography/computed tomography has a low degree of use in patients with hepatocellular carcinoma that falls within the Milan criteria and should not be routinely used as part of the liver transplant work-up.

Immunology of alcoholic liver disease.

Alcohol-induced liver injury is a reflection of the immunologic response of the liver to this stimulus. Reported studies of immunologic abnormalities in alcoholic liver disease (ALD) patients suggest that immunologic response plays a key role in the pathogenesis of chronic liver disease in alcoholics, and have contributed to the understanding of how some patients with ALD progress into alcoholic liver cirrhosis. The immunologic response of the liver is reflected in alcoholic fatty liver disease, hyaline necrosis, and cirrhosis, promoted by the role of neutrophils in damaging liver cells through cytotoxicity, and lymphocytes through cytotoxicity, inducing fibrogenesis of the liver and formation of immune complexes responsible for immune complex-mediated cytotoxicity, in addition to the role of different chemokines in attracting leucocytes, inducing fibrogenesis and liver cell apoptosis, with the established mechanism by which Mallory bodies evoke both cellular and humoral immunity contributing to the process of alcoholic liver cirrhosis, which plays a key role in transformation of alcoholic hepatitis to cirrhosis. At present, research is underway to find modalities to correct the induced immunologic changes, so at this time, it is necessary to avoid alcoholism, with the use of social and educational programs to stop alcoholism.