Donor-derived herpes simplex virus hepatitis in a kidney transplant recipient and review of the literature.

Donor-derived (DD) herpes simplex virus (HSV) hepatitis in solid organ transplant (SOT) recipients is extremely uncommon but carries a high mortality rate. The diagnosis is challenging due to the non-specific presentation and lack of clinical suspicion. We report a case of DDHSV hepatitis in a HSV2 pre-transplant seronegative kidney recipient who received the organ from a HSV2 seropositive donor. The case is highlighted by a few unusual features, namely severe thrombocytopenia and the development of cutaneous, oral and esophageal HSV lesions several weeks after symptom onset while recovering on appropriate treatment. A review of nine proven and probable DDHSV hepatitis cases (including eight previously published ones) showed that fever is a common presenting feature while gastrointestinal symptoms and cutaneous manifestations are uncommon. The symptoms almost always occurred within 2 weeks of transplant. Six out of the nine DDHSV hepatitis patients, including five patients who were on appropriate treatment, died within a month after transplant.

Late onset CMV disease presenting as a colonic stricture in a liver transplant recipient.

Cytomegalovirus (CMV) is a common opportunistic infection in solid organ transplant (SOT) recipients in the first 6 months after transplant. Late onset CMV infection or disease outside the classical risk period is uncommon and can present with atypical signs and symptoms. Here, we report a case of late onset CMV presenting as a colonic stricture more than 10 years after liver transplantation in the absence of traditional CMV risk factors. We also briefly review CMV colitis presenting as a mass or stricture in SOT recipients.

Clinical narrative: autoimmune hepatitis.

Autoimmune hepatitis (AIH) is an inflammatory liver disease that is characterized by circulating autoantibodies, hypergammaglobulinemia, and a lymphoplasmocytic infiltration with interface hepatitis on liver biopsy. Treatment with corticosteroids and other immunosuppressive agents is effective and early diagnosis can result in near-normal life expectancy. Untreated patients, however, can progress to cirrhosis and liver failure. The clinical presentation is heterogeneous and may pose diagnostic and therapeutic dilemmas. This case-based review will address the diagnosis and management of this disease, in addition to difficult but commonly encountered clinical scenarios.

A prospective study of a protocol that reduces readmission after liver transplantation.

Health care has shifted to placing priority on quality and value instead of volume. Liver transplantation uses substantial resources and is associated with high readmission rates. Our goal was to determine if a protocol designed to reduce readmission after liver transplant was effective. We conducted a prospective study of a protocol designed to reduce readmission rates after liver transplantation by expanding outpatient services and alternatives to readmission. The 30-day readmission rate 1 year after implementing the protocol was compared to the 30-day rate for 2 years prior to implementation. Multivariate analysis was used to control for potential confounding factors. Over the study period, 167 adult primary liver transplants were performed with a mean biological Model for End-Stage Liver Disease score of 21 ± 8. Fifty-seven (34%) patients were readmitted. The most common reason for readmission was biliary complications (n = 13). The 30-day readmission rate decreased from 40% before implementing the protocol to 20% after implementation (P = 0.02). In multivariate analysis, the protocol remained associated with readmission (odds ratio, 0.39; 95% confidence interval, 0.16-0.92; P = 0.03). The mean length of stay after transplant was 13 ± 12 days preprotocol and 9 ± 5 days postprotocol (P = 0.09). Alternatives to readmission, including hospital lodging and observation status, were main factors in reducing readmission rates. If the most recent definitions of inpatient admission and observation status were applied over the entire study period, then the readmission rates preprotocol and postprotocol were 31% and 20% indicating that the revised definition of observation status accounted for 45% of the reduction in the readmission rate. Readmission after liver transplantation can be reduced without increasing length of stay by implementing a specifically designed protocol that expands outpatient services and alternatives to inpatient admission. Liver Transplantation 22 765-772 2016 AASLD.

Liver injury from nonsteroidal anti-inflammatory drugs in the United States.

BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used and have been associated with hepatotoxicity. Studies of liver injury from NSAIDs have been retrospective and prospective data are lacking. The aim was to report the features and outcomes of the subjects with severe drug-induced liver injury from NSAIDS. METHODS: The U.S. Drug Induced Liver Injury Network is a prospective registry of idiosyncratic drug hepatotoxicity. All patients are evaluated in a standard fashion and followed up for at least 6 months. RESULTS: Of 1221 Drug Induced Liver Injury Network cases that were adjudicated, 30 cases were attributed to eight different NSAIDs. The mean age was 52 years old, 24 (80%) were women, and 21 (70%) were Caucasian. The mean latency was 67 days. Common signs and symptoms at presentation were nausea (73%), jaundice (67%) and dark urine (67%). Mean peak serum aspartate aminotransferase, alanine aminotransferase, total bilirubin and alkaline phosphatase were 898 U/L, 1060 U/L, 12.2 mg/dl and 326 U/L. The most common pattern of injury was hepatocellular (70%) and autoantibodies were detected in 33% of cases. Diclofenac, was the most frequently implicated NSAID (16/30 cases), and characterized by hepatocellular injury. Seventeen cases resulted in hospitalization or prolongation of hospitalization and one patient died from complications of Stevens-Johnson syndrome because of diclofenac. CONCLUSIONS: Hepatocellular injury is the most common pattern seen with NSAID hepatotoxicity, and diclofenac is the most frequently implicated agent. Given the number of NSAID alternatives, diclofenac should be reserved for patients who fail other NSAIDs and a high level of suspicion for hepatotoxicity should be maintained.

Systematic Review of Prognostic Models Compared to the Mayo Risk Score for Primary Sclerosing Cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with a variable clinical course that can ultimately lead to end-stage liver disease, cholangiocarcinoma, and the need for liver transplantation. Several prognostic models have been developed to predict clinical outcomes and have been compared to the revised Mayo Risk Score (rMRS). AIM: To conduct a systematic review comparing the rMRS to other non-invasive prognostic tests for PSC. METHODS: A systematic review of studies from 2000 to 2020 was performed that compared non-invasive biochemical prognostic models to the rMRS in predicting outcomes in patients with PSC. RESULTS: Thirty-seven studies were identified, of which five studies that collectively included 3230 patients were reviewed. Outcomes included transplant-free survival or composite clinical outcomes. The rMRS was better than the Amsterdam-Oxford model for predicting 1-year transplant-free survival, c-statistics 0.75 and 0.70, respectively. The UK-PSC score outperformed the rMRS for 10-year transplant-free survival, c-statistics 0.85 and 0.69, respectively. An enhanced liver fibrosis score was independently associated with transplant-free survival after adjusting for rMRS. PREsTo predicts 5-year hepatic decompensation with a c-statistic modestly higher than rMRS; 0.90 and 0.85, respectively. CONCLUSION: Newer prognostic models, including the UK-PSC score and PREsTo, are more accurate at predicting clinical endpoints in PSC compared to the rMRS. Time frames and clinical endpoints are not standard among studies.

Recurrent hepatitis C after liver transplant.

End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28B genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5B polymerase inhibitors and NS5A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients.

Noninvasive tools to assess hepatic fibrosis: ready for prime time?

Often regarded as the gold standard for fibrosis assessment, liver biopsy carries associated risks; however, it is less than ideal. The need for noninvasive assessment of hepatic fibrosis for disease staging, prognosis, progression, and treatment response is clear. Advances in serologic testing and conventional imaging techniques have reduced the need for liver biopsy. Areas of research include defining cutoff values for specific diseases, further head-to-head comparisons of noninvasive modalities, examination of algorithms using both serum markers and imaging, and the cost-effectiveness of these various tests for diagnostic as well as screening purposes.