Liver Transplantation from Brain-Dead Donors with Hepatitis B or C in South Korea: A 2014-2020 Korean Organ Transplantation Registry Data Analysis.

BACKGROUND According to the current guidelines for liver transplantation (LT) of brain-dead donors with hepatitis B or C virus (HBV or HCV) in Korea, grafts from hepatitis B surface antigen (HBsAg)(+) or HCV antibody (anti-HCV)(+) donors must be transplanted only to HBsAg(+) or anti-HCV(+) recipients, respectively. We aimed to determine the current status and outcomes of brain-dead donor LT with HBV or HCV in Korea. MATERIAL AND METHODS This retrospective observational study included all LTs from brain-dead donors in the Korean Organ Transplantation Registry between April 2014 and December 2020. According to donor hepatitis status, 24 HBV(+), 1 HCV(+), and 1010 HBV(-)/HCV(-) donors were included. RESULTS Baseline/final model for end-stage liver disease score (MELD) for HBV(+), HCV(+), and HBV(-)/HCV(-) were 22.4±9.3/27.8±7.8, 16/11, and 33.0±15.4/35.5±7.1, respectively. MELD score of HBV (+) were lower than those of HBV(-)/HCV(-) (P<0.01). Five-year graft and patient survival rates of HBV(+) and HBV(-)/HCV(-) recipients were 81.7%/85.6%, and 76.6%/76.7%, respectively (P=0.73 and P=0.038). One-year graft and patient survival rates of HCV (+) graft recipients were both 100%. CONCLUSIONS No differences in graft and patient survival rates between HBV(+) and HBV(-)/HCV(-) groups were observed. Although accumulating the results of transplants from HBV (+) or HCV(+) grafts to HBV(-) or HCV(-) recipients is not possible owing to domestic regulations, Korea should conditionally permit transplantations from HBV(+) or HCV(+) grafts to HBV(-) or HCV(-) recipients by considering the risks and benefits based on foreign studies. Thereafter, we can accumulate the data from Korea and analyze the outcomes.

An Anatomically Complicated Living Donor Kidney Transplantation from Hepatitis B Surface Antigen-Positive Donor to Negative Recipient With Size Discrepancy.

The deficiency of organ donors remains a barrier to kidney transplantation. Living donor kidney transplantation (LDKT) can overcome graft shortage, resulting in better outcomes. Many efforts are being made to expand the donor pool, such as hepatitis B surface antigen (HBsAg)-positive donors to negative recipients and anatomically complicated donor kidneys with size discrepancies. We report a case in which we overcame various problems in LDKT. The recipient was a 56-year-old, 106-kg, HBsAg negative male with diabetic nephropathy. The donor was a 63-year-old female, 56-kg, hepatitis B virus (HBV) carrier with dual renal arteries. Preoperative antiviral medication was provided to the donor for negative conversion of HBV-DNA. The recipient was given HBV vaccination (antihepatitis B antibody: 2.25-36.16 mIU/mL). Anti-HBV immunoglobulin was intraoperatively administered to prevent transmission. The donor and recipient had an absolute weight difference (50 kg). In addition, the donor's kidney had a main and an accessory artery in the upper pole, which were anastomosed to the recipient's right external iliac and inferior epigastric artery, respectively. Follow-up serum creatinine levels decreased. Doppler ultrasonography showed good vascular flow within the reference range of the resistive index. The recipient's follow-up HBV-DNA titer was negative with antiviral medication. We successfully performed LDKT from an HBV-positive donor to a negative recipient by perioperative antiviral treatment and overcame a significant size discrepancy and anatomic challenges by preserving even a small portion of the kidney graft.

Hepatitis B Virus DNA-Level Change is Associated With Tumor Recurrence in Patients With Resected Hepatitis B Virus Hepatocellular Carcinoma.

INTRODUCTION: To investigate the significance of perioperative hepatitis B virus (HBV) DNA changes for predicting recurrence in patients with HBV-related hepatocellular carcinoma (HCC) undergoing liver resection (LR). METHODS: From 2013 to 2020, 241 patients with HBV-related HCC who underwent LR in five Hallym university-affiliated hospitals were enrolled. The serum HBV DNA level, together with other clinicopathological variables, was analyzed for association with HCC recurrence. RESULTS: Preoperatively, 99 patients had undetectable HBV DNA and 142 had detectable viral levels. Of those with detectable viral levels, 72 rapidly progressed to undetectable levels within 3 mo after LR (Rapid group), and 70 showed persistently detectable levels (Nonrapid group). The Rapid group had a better recurrence-free survival (RFS) rate than the Nonrapid group (1-y, 3-y RFS = 75.4%, 57.3%, versus 54.7%, 39.9%, respectively, P = 0.012). In the subgroup analysis, the Rapid group had a better RFS rate in early stages (1-y, 3-y RFS = 82.6%, 68.5%, versus 62.8%, 45.8%, respectively, P = 0.005); however, the RFS rates between the two groups were comparable in the advanced stage (1-y, 3-y RFS = 61.1%, 16.7% versus 45.5%, 22.7%, respectively, P = 0.994). Among the 142 patients with preoperatively detectable HBV DNA, persistently detectable HBV DNA within 3 mo postoperatively (hazard ratio [HR] = 1.7, P = 0.022), large tumor size (HR = 2.7, P < 0.001), multiple tumors (HR = 3.2, P < 0.001), and microvascular invasion (HR = 1.7, P = 0.028) were independent risk factors for RFS in multivariate analysis. CONCLUSIONS: Rapidly undetectable HBV DNA after LR is associated with a better prognosis for recurrence in patients with HCC. Therefore, appropriate treatment and/or screening may be necessary for patients who do not return to undetectable HBV DNA after LR.

Serum immune biomarker levels combined with hepatitis B virus infection status predict early recurrence of early-stage hepatocellular carcinoma with microvascular invasion after liver resection.

INTRODUCTION: The tumor immune response plays a vital role in cancer recurrence in patients with malignancies. We aim to clarify the risk factors for early recurrence and investigate the efficacy of blood-based biomarkers to predict the risk of early recurrence in early-stage hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) after hepatectomy. MATERIALS AND METHODS: A total of 101 cases of HCC with MVI who underwent liver resection were enrolled. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors of early recurrence. We calculated the area under the receiver operating characteristic curve to evaluate the performance of the four biomarkers identified as risk factors for early recurrence. RESULTS: Multiple logistic regression analysis indicated that complement (C)4, cluster of differentiation (CD)4+, immunoglobulin A (IgA), and hepatitis B virus (HBV) DNA of greater than 500 IU/mL were correlated with early recurrence of HCC. The area under the curve was greater for the combination model than for the HBV DNA, CD4+, IgA, or C4 models alone. CONCLUSION: Preoperative serum CD4+, C4, IgA, and HBV DNA levels were linked with early recurrence of early-stage HCC with MVI and the combination model was of considerable predictive value for the prognosis of HCC with MVI.

Novel postoperative nomograms for predicting individual prognoses of hepatitis B-related hepatocellular carcinoma with cirrhosis.

BACKGROUND: Liver cirrhosis is a well-known risk factor for carcinogenesis of hepatocellular carcinoma (HCC). The aim of the present study was to construct individual prognostic models for HCC with cirrhosis. METHODS: The clinical differences between HCC patients with and without cirrhosis were compared using a large cohort of 1003 cases. The patients with cirrhosis were randomly divided into a training cohort and a validation cohort in a ratio of 2:1. Univariate and multivariate analyses were performed to reveal the independent risk factors for recurrence-free survival (RFS) and overall survival (OS) in HCC patients with cirrhosis. These factors were subsequently used to construct nomograms. RESULTS: Multivariate analyses revealed that five clinical variables (hepatitis B e antigen (HBeAg) positivity, alpha-fetoprotein (AFP) level, tumour diameter, microvascular invasion (MVI), and satellite lesions) and seven variables (HBeAg positivity, AFP level, tumour diameter, MVI, satellite lesions, gamma-glutamyl transpeptidase level, and histological differentiation) were significantly associated with RFS and OS, respectively. The C-indices of the nomograms for RFS and OS were 0.739 (P < 0.001) and 0.789 (P < 0.001), respectively, in the training cohort, and 0.752 (P < 0.001) and 0.813 (P < 0.001), respectively, in the validation cohort. The C-indices of the nomograms were significantly higher than those of conventional staging systems (P < 0.001). The calibration plots showed optimal consistence between the nomogram-predicted and observed prognoses. CONCLUSIONS: The nomograms developed in the present study showed good performance in predicting the prognoses of HCC patients with hepatitis B virus-associated cirrhosis.

Development of a Novel Model for Predicting Postoperative Short-Term Outcome in Patients with Hepatitis B-Related Acute-on-Chronic Liver Failure Undergoing Liver Transplantation.

BACKGROUND We aimed to create a novel predictive model through comparing the prognostic accuracy of the current mainstream scoring models in predicting the short-term outcome of patients with hepatitis B-related acute-on-chronic liver failure (HBACLF) undergoing liver transplantation (LT). MATERIAL AND METHODS Data on patients with HBACLF undergoing LT were retrospectively collected and analyzed. The area under the time-dependent receiver operating characteristic curve of 16 scoring models was calculated to evaluate their performance in predicting short-term survival after LT. Univariate analyses and LASSO regression were used to identify the independent variables, which were further selected by Cox stepwise regression. RESULTS A total of 135 patients were enrolled. Among the 16 scoring models, MELD-Na performed the best in predicting 3-month mortality after LT, with an AUC of 0.716. LASSO regression analysis revealed that only the MELD-Na was confirmed as an independent predictor (HR 1.0481, 95% C.I [1.0136, 1.0838], P<0.05). Cox stepwise regression identified 4 variables - MELD-Na, sex, systemic infection, and placement of T-tube during operation - which were used to construct a novel prognostic model with a C-index of 0.844 and a Brier score of 0.131 after internal validation and a C-index of 0.824 (95% C.I [0.658, 0.989]) and a Brier score of 0.119 in the external validation cohort at 3 months. CONCLUSIONS Compared with other scoring models, MELD-Na was an independent factor in predicting short-term outcome after LT. The constructed novel predictive model could exert clinical benefits on early prognostic assessment and case selection.

Predictors of portal vein thrombosis after laparoscopic splenectomy and azygoportal disconnection in hepatitis B cirrhosis: a prospective study.

BACKGROUND: The thrombosis of the main and intrahepatic branches of the portal vein (TMIP) is potentially lethal and deemed a common complication following laparoscopic splenectomy and azygoportal disconnection (LSD) in patients with cirrhosis and portal hypertension (PH). The predictors of TMIP after LSD remain unclear. The aim of this prospective study was to explore the predictive and risk factors for TMIP after LSD in cirrhotic patients with PH caused only by hepatitis B virus. METHODS: From September 2014 to March 2017, we enrolled 115 patients with hepatitis B cirrhosis and PH who successfully underwent LSD. Patients were subdivided into a TMIP group and a non-TMIP group. Univariate and multivariate logistic regression analysis was conducted on 24 items of demographic and preoperative data, to explore the risk factors of TMIP. RESULTS: Twenty-nine (25.22%) patients developed TMIP on postoperative day (POD) 7 and 26 (22.81%) patients developed TMIP on POD 30. From POD 7 to POD 30, 12 patients who did not have TMIP at POD 7 were newly diagnosed with TMIP, with portal vein diameter 15.05 ± 2.58 mm. Another 14 patients in whom TMIP had resolved had portal vein diameter 14.02 ± 1.76 mm. Univariate analysis and multivariate logistic regression revealed that portal vein diameter ≥ 13 mm [relative risk (RR) 5.533, 95% confidence interval (CI) 1.222-25.042; P = 0.026] and portal vein diameter ≥ 15 mm (RR 3.636, 95% CI 1.466-9.021; P = 0.005) were significant independent risk factors for TMIP on POD 7 and 30, respectively. CONCLUSION: Portal vein diameter ≥ 13 mm and ≥ 15 mm were significant independent predictors for TMIP after LSD in patients with hepatitis B cirrhosis and PH on POD 7 and POD 30, respectively. TRIAL REGISTRATION: We registered our research at https://www. CLINICALTRIALS: gov/ . The name of research registered is "Warfarin Prevents Portal Vein Thrombosis in Patients After Laparoscopic Splenectomy and Azygoportal Disconnection." The trial registration identifier at clinicaltrials.gov is NCT02247414.

A Stepwise Evaluation of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure to Optimize the Indication for Urgent Liver Transplantation.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a dynamic but reversible disease. AIM: We aimed to clarify whether the change in Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF) grade in HBV-ACLF patients can be used to predict prognosis, and to explore the appropriate conditions for performing urgent liver transplantation. METHODS: We assessed the COSSH-ACLF grades of HBV-ACLF patients at different time points from June 2013 to May 2019 at Huashan Hospital in Shanghai, China, and analyzed the relationship between the change in grade and patient prognosis. RESULTS: A total of 207 HBV-ACLF patients were enrolled, of which 79 underwent urgent liver transplantation. Their COSSH-ACLF grades were calculated at diagnosis, 3-7 days after diagnosis, and on the final day. Most of the final ACLF grades were consistent with their corresponding grades at days 3-7 after diagnosis (62.5%), while only 44.5% were in accordance with the initial grades at diagnosis. In patients who had a poor prognosis (initial ACLF-3 and ACLF-2 or -3 at days 3-7), the 28-day survival rate was 93.3% in those who underwent transplantation and 6.8% in those who did not (P < 0.0001). However, in patients who had a good prognosis (ACLF-0 or ACLF-1 at days 3-7), the 28-day survival rate was 100% in transplanted patients and 91.5% in non-transplanted patients (P = 0.236). CONCLUSIONS: Reevaluation of the COSSH-ACLF grade 3-7 days after diagnosis could potentially show an indication for urgent liver transplantation.

Liver transplantation in acute liver failure due to Hepatitis B. Two clinical cases.

Hepatitis B virus (HBV) related acute liver failure (ALF) is uncommon in our region, and there is limited HBV literature regarding the optimal management of these cases. In this article, we report two clinical cases of young men who have sex with men (MSM), both developed severe acute hepatitis caused by HBV, progressed to ALF and afterward required liver transplantation. Antiviral post-transplant treatment included entecavir without Hepatitis B Immunoglobulin (HBIG), and immunosuppression therapy with steroids, tacrolimus, and mycophenolate. Serologic follow-up showed early Hepatitis B surface Antigen (HBsAg) seroconversion, undetectable HBV viral load, and positive Anti-HBs titers. During later follow-up, Anti-HBs titers gradually fell (<10mUI/L after six months), with normal liver function. DISCUSSION: In cases of HBV-related ALF, the liver develops a robust immune response, leading to, an early undetectable viral load and seroconversion, with loss of HBsAg, and the appearance of Anti-HBs as a result of the inflammatory response. The management varies depending on whether this is a de novo acute infection or a reactivation of a previous chronic infection. In both cases, the use of antiviral therapy is recommended, with entecavir or tenofovir, among others, but the use of specific HBIG is supported only in ALF related to chronic HBV infection. The optimal length of the antiviral therapy after liver transplantation is still under discussion. CONCLUSION: These cases of HBV related ALF with an early HBsAg seroconversion demonstrates the relevance of requesting IgM antibody against hepatitis B core antigen (anti-HBc IgM) for the etiological study of ALF with negative HBsAg. Usage of HBIG does not seem essential during the post-transplantation period in these cases.

Immunosuppressive Drug-Resistant Armored T-Cell Receptor T Cells for Immune Therapy of HCC in Liver Transplant Patients.

BACKGROUND AND AIMS: HBV-specific T-cell receptor (HBV-TCR) engineered T cells have the potential for treating HCC relapses after liver transplantation, but their efficacy can be hampered by the concomitant immunosuppressive treatment required to prevent graft rejection. Our aim is to molecularly engineer TCR-T cells that could retain their polyfunctionality in such patients while minimizing the associated risk of organ rejection. APPROACH AND RESULTS: We first analyzed how immunosuppressive drugs can interfere with the in vivo function of TCR-T cells in liver transplanted patients with HBV-HCC recurrence receiving HBV-TCR T cells and in vitro in the presence of clinically relevant concentrations of immunosuppressive tacrolimus (TAC) and mycophenolate mofetil (MMF). Immunosuppressive Drug Resistant Armored TCR-T cells of desired specificity (HBV or Epstein-Barr virus) were then engineered by concomitantly electroporating mRNA encoding specific TCRs and mutated variants of calcineurin B (CnB) and inosine-5'-monophosphate dehydrogenase (IMPDH), and their function was assessed through intracellular cytokine staining and cytotoxicity assays in the presence of TAC and MMF. Liver transplanted HBV-HCC patients receiving different immunosuppressant drugs exhibited varying levels of activated (CD39+ Ki67+ ) peripheral blood mononuclear cells after HBV-TCR T-cell infusions that positively correlate with clinical efficacy. In vitro experiments with TAC and MMF showed a potent inhibition of TCR-T cell polyfunctionality. This inhibition can be effectively negated by the transient overexpression of mutated variants of CnB and IMPDH. Importantly, the resistance only lasted for 3-5 days, after which sensitivity was restored. CONCLUSIONS: We engineered TCR-T cells of desired specificities that transiently escape the immunosuppressive effects of TAC and MMF. This finding has important clinical applications for the treatment of HBV-HCC relapses and other pathologies occurring in organ transplanted patients.

Epidemiology of hepatitis B and C virus infections among patients who booked for surgical procedures at Felegehiwot referral hospital, Northwest Ethiopia.

BACKGROUND: Hepatitis B virus(HBV) and hepatitis C virus(HCV) are the main causes of cirrhosis, liver cancer, and death. This study aimed to determine the seroprevalence and associated factors of HBV surface antigen(HBsAg) and anti-HCV among patients screened for surgery at Felegehiwot referral hospital, Northwest Ethiopia. METHODS: A hospital-based cross-sectional study was conducted among 433 patients in 2018. Data on socio-demographic and risk factors were collected by an exit interview using a pretested structured questionnaire. A venous blood sample of 5ml was collected from each participant, and serum was tested for HBsAg and anti-HCV using one-step rapid test kits and enzyme-linked immunosorbent assay. Multivariable logistic regression analysis was computed to identify factors associated with HBV and HCV infections. The odds ratio with 95%CI was used to describe the strength of association and statistical significance. RESULTS: A total of 422 patients gave data and included in the analysis. The mean age of patients was 36±5 years. About two-thirds, 269(64%) and 274(65%) patients were males, and from rural areas, respectively. The seroprevalence of HBsAg was 34(8%) followed by 18(4.3%) anti-HCV and 4(0.9%) co-infections. Being single(AOR = 1.96, 95%CI = 1.12-3.10), rural residence (AOR = 2.68, 95%CI = 1.28-5.61), ever heard about HBV (AOR = 2.41, 95%CI = 1.18-5.20), having multiple sexual partners(AOR = 2.85, 95%CI = 1.30-5.58), HIV positive(AOR = 3.14, 95%CI = 1.31-7.61), history of tooth extraction(AOR = 3.0, 95%CI = 1.40-6.56), hospitalization history(AOR = 2.95, 95%CI = 1.26-5.81), sharing of sharp instruments (AOR = 3.86, 95%CI = 1.82-8.79), and had blood contact(AOR = 2.64, 95%CI = 1.14-5.42) were statistically significant factors to HBV infection. Similarly, sharing of sharp instruments(AOR = 4.65, 95%CI = 1.32-15.1), tooth extraction practice(AOR = 2.81, 95%CI = 1.12-6.56), surgical history (AOR = 3.68, 95%CI = 1.64-9.82), hospitalization history(AOR = 4.51, 95%CI = 1.62-8.35) and had blood contact(AOR = 3.2, 95%CI = 1.56-8.51) were significant factors to HCV infection. CONCLUSION: The seroprevalence of HBsAg and ant-HCV was high compared to WHO and previous study findings. Giving special attention to awareness creation, rural settings, improving personal behaviors, infection prevention activities of health facilities, quality of healthcare procedures is crucial to prevent viral hepatitis infection.

Shifting from donor to donor-recipient matching perspective in defining indications for machine perfusion in liver transplantation.

Optimization of donor-recipient matching is a common concept in liver transplantation. In emergency transplant for acute liver failure, outcome is influenced by timing, patient clinical condition, and graft quality. Although factors like advanced donor age have been linked to a poorer outcome, use of suboptimal or marginal grafts can be inevitable in very unstable patients, if no other graft is available. We present a case of a liver transplant performed in an extremely sick patient suffering from HBV-related fulminant hepatitis, in which a compatible graft from a 76-year-old deceased donor became available only after 3 days of waiting time, during which his conditions further deteriorated. Given the suboptimal matching, normothermic machine perfusion was applied to minimize ischemia-reperfusion injury. Use of machine perfusion could find an indication to modulate the risk associated with an unfavorable donor-recipient matching in high-risk cases.

Clinical characteristics and immunosuppressant management of coronavirus disease 2019 in solid organ transplant recipients.

Over 1 000 000 cases of coronavirus disease 2019 (COVID-19) have been confirmed since the worldwide outbreak began. Not enough data on infected solid organ transplant (SOT) recipients are available, especially data about the management of immunosuppressants. We report two cases of COVID-19 in two transplant recipients, with different treatments and prognoses. The first patient received liver transplantation due to hepatitis B virus-related hepatocellular carcinoma and was confirmed to have COVID-19 9 days later. Following a treatment regimen consisting of discontinued immunosuppressant use and low-dose methylprednisolone-based therapy, the patient developed acute rejection but eventually recovered. The other patient had undergone a renal transplant from a living-related donor 17 years ago, and was admitted to the hospital because of persistent fever. This patient was also diagnosed with COVID-19. His treatment regimen consisted of reduced immunosuppressant use. No signs of rejection were observed during the regimen. In the end, the patient successfully recovered from COVID-19. These effectively treated cases can provide a basis for immunosuppressant management of COVID-19-positive SOT recipients.

Fatal outcome in a liver transplant recipient with COVID-19.

Liver injury is common in patients with COVID-19, but little is known about its clinical presentation and severity in the context of liver transplant. We describe a case of COVID-19 in a patient who underwent transplant 3 years ago for hepatocellular carcinoma. The patient came to clinic with symptoms of respiratory disease; pharyngeal swabs for severe acute respiratory syndrome coronavirus 2 were positive. His disease progressed rapidly from mild to critical illness and was complicated by several nosocomial infections and multiorgan failure. Despite multiple invasive procedures and rescue therapies, he died from the disease. The management of COVID-19 in the posttransplant setting presents complex challenges, emphasizing the importance of strict prevention strategies.

Successful treatment of severe COVID-19 pneumonia in a liver transplant recipient.

Coronavirus disease 2019 (COVID-19) pandemic spreads rapidly and may be an increasing challenge for transplant community. Clinical data on COVID-19 infection in transplant population is very limited. Herein we presented the clinical course and outcome of a 50-year-old male post liver transplantation who contracted COVID-19, with subsequent infection of his wife. The process of illness was representative. A therapeutic regime with temporary immunosuppression withdrawal and systemic low-dose corticosteroid as principle was involved in the management of the patient which made him recover from severe COVID-19 pneumonia.

Prevention and treatment of temporal lobe epilepsy: lessons from hepatitis B story!

Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy and hippocampal sclerosis (HS) is the most common pathological substrate of TLE. Considering the significant consequences of uncontrolled seizures (e.g. increased morbidity and mortality), epilepsy prevention remains a necessity that potentially could save many lives. Human herpes virus-6 (HHV-6) has been linked to TLE in humans. The relationship between HHV-6 and HS-TLE could be attributed to a neuro-inflammatory cascade triggered by the infection, involving direct neuronal damage and production of several pro-inflammatory cytokines under certain conditions that are still incompletely understood. Hepatitis B virus (HBV) infection is another chronic viral infection with a life-long latency. HBV infection is linked to various clinical conditions, including liver cirrhosis. There are currently three ways to fight HBV infection and its consequences; primary prevention (by vaccination), secondary prevention (by drug therapy), and tertiary prevention (by liver transplantation). Considering the similarities between the natural histories of HHV-6 and HBV infections, and also the successful strategies which are currently available to fight HBV infection and its long-term consequences, here, we propose three strategies to fight HHV-6 and its possible long-term consequence (i.e. HS-TLE): Primary prevention: by developing vaccines to prevent HHV-6 infection; Secondary prevention: by considering trials of antiviral drugs to treat HHV-6 infection, when it happens in the childhood to hopefully prevent its long-term consequences; and, Tertiary prevention: by stem cell therapy for drug-resistant epilepsy.

Nucleoside analog monotherapy for prophylaxis in Hepatitis B liver transplant patients is safe and efficacious.

BACKGROUND: Combination therapy with HBIG and NAs has reduced HBV recurrence post LT. Despite its efficacy, costs of HBIG remain prohibitive. With high-potency NAs, HBIG's use has been questioned. We aim to evaluate the efficacy and safety of HBIG-free regimens in patients transplanted for HBV-related liver disease. METHODS: A review of LT patients at the National University Hospital, Singapore from 2001 to 2015 was performed. Patients transplanted for HBV were divided by antiviral treatment received: high- or low-potency NAs, or a combination of HBIG with high-potency NAs. Post-transplant outcomes were reviewed till data censure. Primary outcome was recurrence of HBV viremia post-transplant, while secondary outcomes were HBsAg sero-clearance, graft survival and mortality. RESULTS: Among 58 patients, 51 (88%) had persistent HBV viral suppression. Patients on a high-potency agent had significantly higher viral suppression compared to those on a low-potency agent (97% vs 72%, p = 0.02). This was also seen in patients with VL detectable at transplant (100% vs 50%, p < 0.01). None of the 16 patients with VL detectable at transplant and treated with high-potency agents developed recurrence. 42 patients (72%) achieved persistent HBsAg sero-clearance. Although this was higher in the high-potency NA-only group, it was not statistically significant (p = 0.56). There were no graft failures or mortalities attributed to HBV recurrence. CONCLUSION: With the use of high-potency agents, HBIG may not be necessary in the treatment of patients transplanted for HBV-related liver disease, even in the presence of detectable VL at time of transplant.