Overview of Immunosuppressive Therapy in Solid Organ Transplantation.

Mechanisms of rejection, new pharmacologic approaches, and genomic medicine are major foci for current research in transplantation. It is hoped that these new agents and personalized immunosuppression will provide for less toxic regimens that are effective in preventing both acute and chronic allograft rejection. Until new agents are available, practitioners must use various combinations of currently approved agents to find the best regimens for improved long-term outcomes.

Paritaprevir/ritonavir/ombitasvir and dasabuvir for the treatment of chronic hepatitis C virus infection.

Introduction: The use of direct-acting antiviral (DAA) agents against chronic hepatitis C virus (HCV) infections can result in the successful treatment of nearly all patients. Effective antiviral treatments can prevent the progression to cirrhosis and hepatocellular malignancy, and decrease liver-related morbidity and mortality.

Areas Covered: Paritaprevir-ritonavir-ombitasvir and dasabuvir (PrOD), with or without ribavirin, is an all-oral regimen approved for the treatment of HCV genotype 1 infections, including patients with compensated cirrhosis.

Multicenter review of liver transplant for hepatitis B-related liver disease: disparities in gender and ethnicity.

Orthotopic liver transplantation (OLT) is the preferred treatment for selected patients with hepatitis B virus (HBV)-related liver disease. This study aimed to (i) define long-term outcomes following OLT for HBV; (ii) to quantify the incidence of HBV recurrence (rHBV) as it relates to anti-HBV treatment; and (iii) to determine outcomes for specific patient subgroups. We performed a retrospective chart review of 738 patients undergoing OLT between 1985 and 2010 at seven US transplant centers and divided the patients into 3 eras, 1985-1994, 1995-2004, and 2005-2010, based on hepatitis B immunoglobulin and antiviral therapies.

The evolution of liver transplantation during 3 decades: analysis of 5347 consecutive liver transplants at a single center.

Objective: To analyze a 28-year single-center experience with orthotopic liver transplantation (OLT) for patients with irreversible liver failure.

Background: The implementation of the model for end-stage liver disease (MELD) in 2002 represented a fundamental shift in liver donor allocation to recipients with the highest acuity, raising concerns about posttransplant outcome and morbidity.

Methods: Outcomes and factors affecting survival were analyzed in 5347 consecutive OLTs performed in 3752 adults and 822 children between 1984 and 2012, including comparisons of recipient and donor characteristics, graft and patient outcomes, and postoperative morbidity before (n = 3218) and after (n = 2129) implementation of the MELD allocation system.

Liver transplantation for hepatitis B liver disease and concomitant hepatocellular carcinoma in the United States With hepatitis B immunoglobulin and nucleoside/nucleotide analogues.

Reinfection with hepatitis B virus (HBV) after liver transplantation (LT) may favor the recurrence of hepatocellular carcinoma (HCC), and combination therapy with hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogues may reduce HBV recurrence after LT. To test associations between HBV, HCC, and survival, we performed a retrospective chart review of patients undergoing LT for HBV between January 1985 and December 2010 at 7 US transplant centers. After we divided the patients into 3 eras based on evolving strategies in antiviral therapy (1985-1994, 1995-2004, and 2005-2010), we reviewed 16 variables to determine whether there were associations between survival and HCC recurrence.

Liver transplantation for nonalcoholic steatohepatitis: the new epidemic.

Objective: To analyze incidence, outcomes, and utilization of health care resources in liver transplantation (LT) for nonalcoholic steatohepatitis (NASH).

Summary Of Background Data: With the epidemic of obesity and metabolic syndrome in nearly 33% of the US population, NASH is projected to become the leading indication for LT in the next several years. Data on predictors of outcome and utilization of health care resources after LT in NASH is limited.

Liver transplant: a primer.

Liver transplant has been accepted as a successful therapeutic option for patients with end-stage liver disease. Patient and graft survival has incrementally increased over the past 2 decades, mainly because of immunosuppressive regimens. However, the nonspecific nature of immunosuppressive agents is associated with an increased risk of development of opportunistic infections, renal impairment, metabolic derangements, neurotoxicity, de novo malignancies, and recurrence of the primary disease.

Decision analysis model for hepatitis B prophylaxis one year after liver transplantation.

In patients receiving orthotopic liver transplantation, hepatitis B recurrence rates have decreased significantly with the use of various methods for prophylaxis. At present, a combination of hepatitis B immunoglobulin (HBIG) and lamivudine is the standard of care, resulting in recurrence rates of 0% to 11%. Recent data suggest that the addition of adefovir to lamivudine is successful in treating patients with recurrent hepatitis B infection.

Therapeutic drug monitoring of mycophenolate mofetil in transplantation.

A roundtable meeting to discuss the use of therapeutic drug monitoring (TDM) to guide immunosuppression with mycophenolate mofetil was held in New York in December 2004. Existing recommendations for the initial months after transplantation were updated. After ensuring adequate levels of mycophenolic acid (MPA, the active metabolite of mycophenolate mofetil) immediately after transplantation, optimal efficacy may require only a few dose adjustments, because intrapatient variability in exposure seems low.

Mortality predictors in liver transplant recipients with recurrent hepatitis C cirrhosis.

Background/aim: Recipients of orthotopic liver transplant for hepatitis C (HCV) invariably develop recurrent disease. The risk factors for death and retransplantation following the development of cirrhosis from HCV are unclear. The aim of this study was to identify predictors of survival in liver transplant recipients who develop cirrhosis from recurrent HCV.

Analysis of long-term outcomes of 3200 liver transplantations over two decades: a single-center experience.

Objective: Few studies have evaluated long-term outcomes after orthotopic liver transplantation (OLT). This work analyzes the experience of nearly 2 decades by the same team in a single center. Outcomes of OLT and factors affecting survival were analyzed.

A comparison of tacrolimus and cyclosporine in liver transplantation: effects on renal function and cardiovascular risk status.

A retrospective chart review of 1065 consecutive liver allograft recipients in 11 centers from January 1997 to September 1998 was performed. Patients were followed for 3 years or until graft loss. Patients received either tacrolimus (n = 594), cyclosporine (n = 450) or no calcineurin inhibitor (n = 21).

MELD fails to measure quality of life in liver transplant candidates.

Previous studies have demonstrated an association between Child Turcotte-Pugh (CTP) class and impaired quality of life. However, the relationship between the model for end-stage liver disease (MELD) score and quality of life (QOL) has not been well studied. In this study, quality of life questionnaires (Medical Outcomes Short Form 36 [SF-36] and the Chronic Liver Disease Questionnaire [CLDQ]) were administered to 150 adult patients awaiting liver transplantation.

Liver transplantation for fulminant hepatic failure: experience with more than 200 patients over a 17-year period.

Objective: To analyze outcomes after liver transplantation (LT) in patients with fulminant hepatic failure (FHF) with emphasis on pretransplant variables that can potentially help predict posttransplant outcome.

Summary Background Data: FHF is a formidable clinical problem associated with a high mortality rate. While LT is the treatment of choice for irreversible FHF, few investigations have examined pretransplant variables that can potentially predict outcome after LT.

Operative parameters that predict the outcomes of hepatic transplantation.

Background: A growing discrepancy between the number of patients awaiting liver transplantation and the number of organs available mandates the use of even marginal organ donors in whom there is major risk of suboptimal graft function. A comprehensive analysis of operative parameters on the outcomes of liver transplantation has not been reported.

Study Design: We analyzed the impact of 24 operative variables on the survival of 942 consecutive primary liver allografts performed at a single center from June 1992 through December 1997.

Conversion from intravenous to intramuscular hepatitis B immune globulin in combination with lamivudine is safe and cost-effective in patients receiving long-term prophylaxis to prevent hepatitis B recurrence after liver transplantation.

Recurrent hepatitis B infection after liver transplantation was previously frequent and associated with significant allograft failure and mortality. Recurrence rates of hepatitis B were improved with the use of passive immunoprophylaxis with hepatitis B immune globulin, and later, lamivudine monotherapy. Combination prophylaxis with intravenous hepatitis B immune globulin and lamivudine substantially decreased rates of hepatitis B recurrence, but intravenous administration of hepatitis B immune globulin was expensive and associated with significant adverse effects.

Pretransplant model to predict posttransplant survival in liver transplant patients.

Objective: To develop a prognostic model that determines patient survival outcomes after orthotopic liver transplantation (OLT) using readily available pretransplant variables.

Summary Background Data: The current liver organ allocation system strongly favors organ distribution to critically ill recipients who exhibit poor survival outcomes following OLT. A severely limited organ resource, increasing waiting list deaths, and rising numbers of critically ill recipients mandate an organ allocation system that balances disease severity with survival outcomes.

New era of liver transplantation for hepatitis B: a 17-year single-center experience.

Objective: To evaluate the variables affecting orthotopic liver transplantation (OLT) outcome for hepatitis B virus (HBV) in a large patient cohort over a 17-year period.

Summary Background Data: Historically, OLT for chronic HBV infection has been associated with aggressive reinfection and poor survival results. More recently, OLT outcome has been improved with the routine use of antiviral therapy with either hepatitis B immune globulin (HBIg) or lamivudine; however, HBV recurrence remains common.