Combined heart and liver transplantation in a patient supported by left ventricular assist device (LVAD) with propionic acidemia.

Propionic acidemia (PA) is a rare inherited metabolic disease due to inborn errors of metabolism. PA results in the accumulation of abnormal organic acid metabolites in multiple systems, mainly the central nervous system and the heart. Cardiac complications include dilated cardiomyopathy (DCM) and carry a 40-50% increased mortality risk. Liver transplantation (LT) is required in PA patients when medical treatment fails and may prevent or slow down the cardiomyopathy progression. However, severe heart disease may be a serious contraindication to LT. We present a complicated case of a PA patient, supported with a Left Ventricular Assist Device, who underwent a heart and Liver transplant. PA patients are at increased risk for metabolic acidosis during surgery, with increased anion gap and hyperammonemia. A strict multi-disciplinary approach is needed to prevent and treat metabolic decompensation. The patient had a successful heart and liver transplant after a strict treatment protocol in the pre, intra, and post-operative periods. His case highlights the complexity of PA patients and the increased risk for metabolic decompensation during surgery and provides an insight into how to manage such complicated patients.

Long-Term Management: Modern Measures to Prevent Readmission in Patients with Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is a frequent indication for hospitalization and represents a common manifestation of portal hypertension and decompensated liver disease that contributes to hospital readmissions. Multiple new techniques are being evaluated to assist in preventing readmissions in these high-risk patients. Techniques to improve medication adherence are paramount. The use of telemedicine and on-demand patient assessment is likely to diminish hospitalizations for HE. Wearable technology has the potential to assist in HE diagnosis and prevent HE progression, with an anticipated diminution in hospital readmissions. This article discusses current and potential future techniques to improve outcomes in these vulnerable patients.

The Prevalence and Pathobiology of Nonalcoholic Fatty Liver Disease in Patients of Different Races or Ethnicities.

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common cause of liver disease in the United States. The prevalence varies dramatically when comparing individuals of different races and ethnicities. Rates are highest in Hispanic patient populations compared with non-Hispanic whites and African Americans, despite similar rates of the metabolic syndrome and risk factors. This observation remains poorly characterized; variations in genes that effect lipid metabolism may play a role. This article describes the prevalence of NAFLD in patients of different races or ethnicities, and discusses pathophysiologic mechanisms that may explain why these differences exist.

Meet the Classes of Directly Acting Antiviral Agents: Strengths and Weaknesses.

This article discusses direct-acting antiviral agents that target hepatitis C virus replication, their mechanism of action, strengths, and weaknesses. In addition, varying strategies using combinations of these agents are discussed.

Cardiac failure after liver transplantation requiring a biventricular assist device.

Increased hepatic iron load in extrahepatic organs of cirrhotic patients with and without hereditary hemochromatosis portends a poorer long term prognosis after liver transplant. Hepatic as well as nonhepatic iron overload is associated with increased infectious and postoperative complications, including cardiac dysfunction. In this case report, we describe a cirrhotic patient with alpha 1 antitrypsin deficiency and nonhereditary hemochromatosis (non-HFE) that developed cardiogenic shock requiring mechanical circulatory support for twenty days after liver transplant. Upon further investigation, she was found to have significant iron deposition in both the liver and heart biopsies. Her heart regained complete and sustained recovery following ten days of mechanical biventricular support. This case highlights the importance of preoperatively recognizing extrahepatic iron deposition in patients referred for liver transplantation irrespective of etiology of liver disease as this may prevent postoperative complications.

Expedited liver allocation in the United States: a critical analysis.

The fate of donor livers allocated via an out-of-sequence expedited placement (EP) pathway has not been previously examined. We determined the originating and receiving United Network for Organ Sharing (UNOS) regions of all donor livers procured between January 1, 2010 and October 31, 2012 and placed out of sequence with UNOS bypass code 863 (EP attempt) or 898 (miscellaneous). We reviewed the early function of these liver grafts and assessed the effect of EP allocation on wait-listed patients at our center. Registrants at our center were eligible to receive 1298 liver offers during the interval studied: 218 (16.8%) of these liver offers bypassed our center and were allocated to other centers and used in patients lower on the match-run list. During the study interval, 560 livers were allocated in the United States by EP. Regions 1, 5, 7, 9, and 10 used the greatest number of EP-placed grafts. Region 1 (New England) used the greatest proportion of all EP livers (33% of all imported EP livers in the United States, P < 0.001 versus all other regions). Graft function data were available for 560 livers placed by EP: 491 (88%) of these grafts were functioning at a mean of 399.5 days after transplantation. In conclusion, the transplantation of livers allocated by means of an expedited refusal code is asymmetric across regions and, in some instances, results in the bypassing of patients with higher wait-list priority but without notification of the bypassed center. Short-term graft function after EP allocation is excellent. Policies governing EP allocation should be created in order to improve access to available organs.

Complications in patients with alcohol-associated liver disease who undergo liver transplantation.

Cirrhosis caused by alcohol-associated liver disease is a common indication for liver transplantation worldwide. Patients with alcohol-associated liver disease who undergo liver transplantation face multiple challenging comorbid medical issues that enhance the potential for perioperative and postoperative complications. Awareness of these issues and appropriate therapeutic intervention may minimize the negative effect of these complications on posttransplantation survival. This article reviews important posttransplantation problems in patients transplanted for alcohol-associated liver disease.

Social barriers to listing for adult liver transplantation: their prevalence and association with program characteristics.

Social barriers to effective medical care are mandated to be routinely assessed as part of an evaluation for liver transplantation. This study explores how frequently liver transplant programs encounter these barriers in patients undergoing an evaluation and whether programs with higher proportions of Medicaid patients, historically disadvantaged minority patients, and rural patients encounter social barriers more frequently. A survey for assessing patient demographics and social barriers was electronically completed by representatives of 61 of 104 eligible US adult liver transplant programs (59%). Fifty-eight of the 61 programs identified themselves, and their characteristics were similar to those of all 104 US programs according to publicly available data from the Organ Procurement and Transplantation Network. Social barriers were reported to be encountered sometimes (10%-30%) or frequently (>30%) by the 61 programs as follows: inadequate or unstable health insurance (68.9% of the programs), a chaotic social environment (63.9%), a lack of a care partner (60.7%), an inability to obtain transportation (49.2%), a low educational level (36.1%), inadequate housing (23.0%), a language barrier (19.7%), no reliable way of contacting the patient (16.4%), difficulty in obtaining child care (11.5%), and food insecurity (8.2%). The frequencies of perceived social barriers did not differ significantly between programs reporting higher or lower proportions of Medicaid, minority, or rural patients. Our analysis suggests that program-level operational planning for addressing social barriers to transplant listing should be considered regardless of the proportions of Medicaid-insured, racial or ethnic minority, and rural patients in the population.

Direct-acting antiviral therapy for hepatitis C: attitudes regarding future use.

INTRODUCTION: Response to current therapy of hepatitis C virus (HCV) is suboptimal. Direct-acting antiviral therapies (DAA) are expected to improve treatment outcomes. Additional treatments for HCV will invariably make therapeutic choices and patient management more complex. We hypothesize that current perceptions regarding the complexity of DAA therapy will influence attitudes towards future use by practitioners who are currently treating HCV. METHODS: An Internet-based survey was sent to 10,082 AASLD and AGA members to determine if they treat HCV infection, their knowledge of DAA therapies, attitudes towards current and future HCV treatments, and if they participated in clinical trials using DAA agents. RESULTS: Out of a total of 1,757 individuals responding to the survey, 75% treat HCV; 79% were MDs, 67% were Gastroenterologists, and 24% were Hepatologists. Of the respondents, 77% indicated they were "very aware" or "aware" of DAA therapies, 20% participated in clinical trials, and 3% had minimal knowledge of DAA agents. Comparing treatment "today" versus in the future when DAAs were available, 85 vs. 81% would treat (p = 0.0054), 6 vs. 10% would refer to an "HCV expert" (p = 0.016), and 1% would refer to an ID specialist. Of respondents with "minimal knowledge" of DAA, 52% stated that they would use them in the future. CONCLUSIONS: Although the majority of respondents appear ready to utilize DAA agents in the future, referrals to "hepatitis C experts" will increase. More than half of respondents with "minimal knowledge" of DAA therapies also appear to be willing to utilize these compounds, raising concerns regarding their inappropriate use. Broad education of healthcare providers to prevent inappropriate use of these agents will be critical.

Effectiveness of hepatitis C treatment with pegylated interferon and ribavirin in urban minority patients.

Randomized controlled trials of hepatitis C virus (HCV) therapy with pegylated interferon and ribavirin have demonstrated sustained viral response rates (SVRs) of 54%-63% (efficacy). Treatment results in clinical practice (effectiveness) may not be equivalent. The goal of this study was to assess the effectiveness of HCV treatment with pegylated interferon and ribavirin in a treatment-naïve, human immunodeficiency virus (HIV)-negative, United States urban population with many ethnic minority patients. We evaluated 2,370 outpatients for HCV therapy from 2001 to 2006 in the Faculty Practice of the Albert Einstein College of Medicine or the attending-supervised Montefiore Medical Center Liver Clinic. Care was supervised by one experienced physician under conditions of everyday clinical practice, and appropriate ancillary resources were made available to all patients. Two hundred fifty-five patients were treated with a mean age of 50 years (60% male, 40% female; 58% Hispanic, 20% African American, 9% Caucasian, 13% other; 68% genotype 1, the remainder genotypes 2 or 3). Patients had at least one liver biopsy. Intention-to-treat analysis (ITT) showed SVR in 14% of genotype 1 patients and 37% in genotype 2/3 patients (P < 0.001). SVR was significantly higher in faculty practice (27%) than in clinic patients (15%) by intention-to-treat (P = 0.01) but not per-protocol analysis (46% faculty practice, 34% clinic). 3.3% of 1,656 treatment-naïve, HIV antibody-negative individuals ultimately achieved SVR. Current hepatitis C therapies may sometimes be unavailable to, inappropriate for, and ineffective in United States urban patients. Treatment with pegylated interferon and ribavirin was less effective in this population than is implied by multinational phase III controlled trials. New strategies are needed to care for such patients.

Treatment of chronic hepatitis C in a slow responder: a case for extended therapy.

BACKGROUND: A 49-year-old white man presented to his primary-care clinic with fatigue and poor concentration. He had an enlarged liver with a minimally tender edge and was subsequently referred to our liver clinic. INVESTIGATIONS: Physical examination, laboratory investigations (including tests for HCV-RNA, antibodies to hepatitis B surface and core antigens, and HBV-DNA), and liver biopsy. DIAGNOSIS: The patient had chronic hepatitis C infection and was a slow responder to treatment. MANAGEMENT: Administration of pegylated interferon alpha2b plus ribavirin for 72 weeks. Escitalopram was given to manage his depression.

Anti-erythropoietin antibody-mediated pure red cell aplasia in a living donor liver transplant recipient treated for hepatitis C virus.

After liver transplantation, reinfection of the newly engrafted liver with hepatitis C virus is essentially universal in patients who are viremic at the time of transplantation. Treatment with interferon preparations with or without ribavirin is recommended in patients with marked histologic injury; however, hematologic toxicity associated with therapy has been reported, which is usually treated with growth factor support, including erythropoietin analogues. We present the first reported case of anti-erythropoietin antibody-mediated pure red cell aplasia arising in the setting of hepatitis C virus therapy in a patient who underwent living donor liver transplantation.

Hepatitis B virus and HIV coinfection: results of a survey on treatment practices and recommendations for therapy.

BACKGROUND: The management of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection is challenged by the selection of patients for therapy, options for antiviral medications, and inconsistency in published treatment guidelines. METHODS: A survey was sent to 161 sites in a multicenter HIV clinical trials group to assess HBV screening, criteria for initiation of therapy, and treatment choices for patients coinfected with HBV and HIV. RESULTS: Of 161 sites, 78 completed the survey (response rate, 48.4%). Of these sites, 98.7% screened for HBV infection, 86% vaccinated HIV-infected patients who were not immune to HBV infection, and 79% made treatment decisions without referral to a hepatologist or gastroenterologist. Treatment recommendations varied; 42% of the sites initiated therapy when patients' levels of alanine aminotransferase and aspartate aminotransferase were elevated and HBV DNA level was >10(5) copies/mL, whereas 49% of the sites initiated therapy in the presence of any detectable HBV DNA level. Antiviral treatment choices for patients who were not concurrently receiving antiretroviral therapy were lamivudine plus tenofovir, adefovir, or interferon. Patients concurrently receiving antiretroviral therapy received lamivudine plus tenofovir preferentially, followed by tenofovir plus emtricitabine, adefovir, or interferon. Ninety-one percent of the sites screened for hepatocellular carcinoma. CONCLUSIONS: The majority of HIV-infected patients were screened and vaccinated for HBV infection and underwent surveillance for hepatocellular carcinoma. Decisions regarding the performance of liver biopsy, threshold to initiate therapy, and criteria to discontinue therapy varied, reflecting inconsistencies in available treatment guidelines. Treatment decisions reflected concerns regarding future drug resistance in patients who are naive to antiretroviral therapy and the emergence of drug resistance in patients receiving antiretroviral therapy.

Comparison of clinical outcomes in chronic hepatitis B liver transplant candidates with and without hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) receive a higher MELD score and may undergo liver transplantation (OLT) earlier compared to patients with cirrhosis, potentially decreasing waiting list mortality. However, post-OLT survival may be reduced by recurrence of HCC. We compared clinical outcomes between patients with HBV-cirrhosis and no HCC and patients with HBV-HCC. A total of 279 patients (HBV-cirrhosis = 183; HBV-HCC = 96) in the US HBV-OLT study were followed for a median of 30.2 months from listing. Patients with HCC were older, more likely to be Asian, and had less severe liver impairment than patients with HBV-cirrhosis. Despite a higher rate of OLT in patients with HCC (78.1% vs. 51.4%; P < 0.001), intention-to-treat (ITT) survival (73% vs. 78%) and survival without OLT (82% vs. 79%) at 5 years were similar for patients with and without HCC. Cox regression analysis identified higher albumin, lower MELD, no HCC at listing, and being transplanted to be associated with better ITT survival. Ninety-four patients with HCC (including 19 new HCC) and 75 with HBV-cirrhosis underwent OLT. Post-OLT survival (83% vs. 90%) and HBV recurrence (11% vs. 10%) at 3 years were similar, while disease (HBV and/or HCC) recurrence (19% vs. 10%; P = 0.043) was higher in patients with HBV-HCC vs. HBV-cirrhosis. Disease recurrence was the only independent predictor of post-OLT survival. In conclusion, despite more advanced liver disease and a lower rate of transplantation, ITT survival of patients listed for HBV-cirrhosis was comparable to those with HBV-HCC, possibly related to beneficial effects of antiviral therapy.

Racial differences in response rates to consensus interferon in HCV infected patients naive to previous therapy.

BACKGROUND: Despite a rapid evolution in the treatment of Hepatitis C (HCV), response to therapy among different racial and ethnic groups is poorly characterized. STUDY: Three hundred and thirty HCV infected patients naive to previous therapy received induction therapy followed by every other day dosing with consensus interferon. Greater than 30% of treated patients were not white, allowing comparison of response among different races/ethnicities and genotypes. RESULTS: An overall sustained virologic response (SVR) was achieved in 24% of white, 12% of Hispanic, and 4% of AA patients (P = 0.003 white vs. non-white). 15% of white and 13% of Hispanic Genotype 1 patients achieved an SVR; 2% of AA patients achieved an SVR (P = 0.001 AA vs. non AA). Surprisingly, an SVR of 50% and 40% was achieved by AA and White Genotype 2 patients, compared with 10% in Hispanic patients (P = 0.001). CONCLUSION: Significant differences in response rates to induction therapy followed by every other day dosing with consensus Interferon was observed when comparing white to non-white patients, particularly when comparing response rates by genotype. These observations reinforce the requirement that prospective studies that enroll a significant percentage of non-whites are needed to adequately characterize response rates to anti-HCV directed therapy.

Increased risk of cholestatic hepatitis C in recipients of grafts from living versus cadaveric liver donors.

Histologic injury caused by recurrent hepatitis C virus (HCV) has been reported in up to 90% of HCV-infected patients who undergo liver transplantation with a cadaveric graft. However, the natural history of HCV after living donor liver transplantation (LDLT) is not well described. We performed a retrospective analysis of 68 consecutive HCV-infected adult patients: 45 recipients of cadaveric grafts (CAD) were compared with 23 LDLT patients. Elevated serum transaminases, positive HCV RNA, and liver biopsy consistent with histologic evidence of HCV defined recurrence. When comparing CAD with LDLT, both the incidence of HCV recurrence and time to recurrence were not different. The overall incidence of severe sequelae of HCV recurrence, either cholestatic hepatitis, grade III-IV inflammation, and/or HCV-induced graft failure requiring retransplantation, was also not different when comparing CAD with LDLT. However, when comparing CAD versus LDLT, no CAD patient developed cholestatic hepatitis C, compared with 17% of LDLT who developed this complication (P =.001). Thus, in this patient population, the timing and incidence of HCV recurrence were not different when comparing CAD versus LDLT, but the incidence of cholestatic hepatitis was significantly greater in patients with HCV who underwent LDLT.