Skin conditions in liver transplant recipients in a Singapore academic medical center: A retrospective cohort study.

BACKGROUND: Liver transplant recipients are at lifelong risk of immunosuppression-related cutaneous complications, such as malignancy and infection. OBJECTIVE: Our study aims to assess the epidemiology of dermatologic conditions among liver transplant recipients in an academic medical center in Singapore. METHODS: Medical records of liver transplant recipients on follow-up with gastroenterology and dermatology departments at the Singapore General Hospital between 2006 and 2021 were retrospectively reviewed. A literature review was subsequently performed on the keywords "liver transplant" and "dermatology." RESULTS: A total of 99 liver transplant recipients were identified in this study. Sixty-nine patients (70%) had at least 1 dermatologic condition. Inflammatory skin conditions were the most common (53%), followed by cutaneous infection (36%) and benign cutaneous tumors (30%). Malignant and premalignant lesions were the least common skin conditions reported (10%). Our study results concurred with many other studies reported worldwide, demonstrating a low cutaneous malignancy burden after liver transplantation. LIMITATIONS: The study included a small population size in a single center and did not have a pre-existing protocol for pretransplant dermatologic surveillance. CONCLUSION: Although the incidence of skin cancer after liver transplant in Singapore is low, the patients will benefit from long-term dermatology surveillance, given the long-term risks of infection and malignant skin conditions.

Tacrolimus Monotherapy in Recipients of Liver Transplant: A Single-Center Experience.

INTRODUCTION: Following liver transplantation (LT), the majority of patients are treated with reduced-dose calcineurin inhibitors (CNIs) in combination with mycophenolate mofetil. The optimal timing for subsequent conversion to CNI monotherapy is not clearly defined. This study aims to evaluate the safety of conversion to CNI monotherapy after LT. METHODS: This was a single-center retrospective study of 100 consecutive patients who received CNI and mycophenolate mofetil combination regimen after LT at Singapore General Hospital from 2006 to 2018. Patient demographics, clinical parameters, and posttransplant complications (ie, rates of graft rejection, de novo malignancy, cytomegalovirus infection and renal impairment) were recorded. RESULTS: One hundred patients were recruited and mean follow-up time in months ± standard deviation was 60.36 ± 41.73. Patients were divided into 2 groups based on institution of CNI monotherapy within (group 1) or beyond (group 2) 6 months. Twenty-five (25%) patients were on CNI monotherapy within 6 months post-LT. Overall patient survival was 83.7% at 5-years posttransplant. There was no statistical difference in the rates of posttransplant complications including liver graft rejection (4.0% vs 18.7%, P = .11); de novo malignancy (0.0% vs 8.0%, P = .33); cytomegalovirus infection (4.0% vs 1.3%, P = .44); and renal impairment (20.0% vs 40.0%, P = .069) between the 2 groups. CONCLUSIONS: Successful institution of CNI monotherapy within 6 months is safe, and does not increase the risk of rejection.

Use of Expression Profiles of HBV-DNA Integrated Into Genomes of Hepatocellular Carcinoma Cells to Select T Cells for Immunotherapy.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is often associated with hepatitis B virus (HBV) infection. Cells of most HBV-related HCCs contain HBV-DNA fragments that do not encode entire HBV antigens. We investigated whether these integrated HBV-DNA fragments encode epitopes that are recognized by T cells and whether their presence in HCCs can be used to select HBV-specific T-cell receptors (TCRs) for immunotherapy. METHODS: HCC cells negative for HBV antigens, based on immunohistochemistry, were analyzed for the presence of HBV messenger RNAs (mRNAs) by real-time polymerase chain reaction, sequencing, and Nanostring approaches. We tested the ability of HBV mRNA-positive HCC cells to generate epitopes that are recognized by T cells using HBV-specific T cells and TCR-like antibodies. We then analyzed HBV gene expression profiles of primary HCCs and metastases from 2 patients with HCC recurrence after liver transplantation. Using the HBV-transcript profiles, we selected, from a library of TCRs previously characterized from patients with self-limited HBV infection, the TCR specific for the HBV epitope encoded by the detected HBV mRNA. Autologous T cells were engineered to express the selected TCRs, through electroporation of mRNA into cells, and these TCR T cells were adoptively transferred to the patients in increasing numbers (1 × 104-10 × 106 TCR+ T cells/kg) weekly for 112 days or 1 year. We monitored patients' liver function, serum levels of cytokines, and standard blood parameters. Antitumor efficacy was assessed based on serum levels of alpha fetoprotein and computed tomography of metastases. RESULTS: HCC cells that did not express whole HBV antigens contained short HBV mRNAs, which encode epitopes that are recognized by and activate HBV-specific T cells. Autologous T cells engineered to express TCRs specific for epitopes expressed from HBV-DNA in patients' metastases were given to 2 patients without notable adverse events. The cells did not affect liver function over a 1-year period. In 1 patient, 5 of 6 pulmonary metastases decreased in volume during the 1-year period of T-cell administration. CONCLUSIONS: HCC cells contain short segments of integrated HBV-DNA that encodes epitopes that are recognized by and activate T cells. HBV transcriptomes of these cells could be used to engineer T cells for personalized immunotherapy. This approach might be used to treat a wider population of patients with HBV-associated HCC.