Search

Previous studies have found that Asian patients transplanted for hepatitis B virus (HBV) infection had worse outcomes than white patients. The aim of this study was to compare outcomes in Asian and white patients listed for liver transplantation for HBV infection. Data of all patients with HBV infection listed for liver transplantation between January 1996 and June 1998 from 20 centers in North America were collected using a survey. Total patients enrolled were 325 (171 whites, 126 Asians, 28 other races). There was no difference in demographics, liver biochemistry, and HBV replicative status between Asians and whites at the time of listing. More Asians had hepatocellular carcinoma and fewer Asians had hepatitis C or D virus coinfection. At the time of this survey, 70 Asians (55%) and 99 whites (58%) had been transplanted. Actuarial 2-year survival posttransplantation for Asians (88%) and whites (92%) was similar. Recurrent HBV infection occurred in 8 (11%) Asians and 12 (12%) whites. Five patients with recurrent HBV infection died, 4 of whom were Asian. Actuarial 2-year survival for Asians versus whites with recurrent HBV infection was 60% versus 90% (P =.04). In this large cohort of patients, overall survival and recurrent HBV infection posttransplantation were comparable between Asians and whites. However, Asians with recurrent HBV infection posttransplantation had significantly higher mortality.

In 1997, liver disease was implicated in more than 25,000 deaths and was the 10th leading cause of mortality in the United States. 24 In addition to decreased life expectancy, advanced liver disease also results in a diminished quality of life. 103 Therapy for decompensated liver disease has, until recently, been merely supportive. Orthotopic liver transplantation (OLT) now offers definitive therapy for decompensated liver disease. Whereas the one-year survival for patients with decompensated cirrhosis is less than 10%, OLT offers overall 5-year survival rates of greater than 60% to 70%. 128 Orthotopic liver transplantation is limited, however, by the number of available donor organs. Since 1988, the number of individuals on the waiting list for OLT has grown from 616 to just over 12,000 (United Network of Organ Sharing [UNOS] data) in the United States (Fig. 1). The timing of referral for OLT is a difficult decision in the care of patients with liver disease. Fortunately, the American Association for the Study of Liver Diseases has recently developed practice guidelines that address when patients should be referred and perioperative risks. 21 Although innovations such as split-liver transplants and living related donations (see article by Drs. Ghobrial and Busuttill) will likely expand the donor pool, the donor shortage will likely remain critical for the foreseeable future. Patients listed for OLT usually have a protracted wait and are at risk of potentially lethal complications of liver disease. The prolonged waiting period is reflected in the increased disease severity of patients undergoing OLT. 103 An increasing number of recipients are sent to transplant surgery from intensive care unit beds. Between 1988 and 1997, the percentage of patients waiting more than 6 and 12 months has increased from 36% to 69% and from 22% to 48.3%, respectively. Two important factors associated with prolonged waiting times are older age of entry (50 to 64 years) and blood type B. 103

Background & Aims T cells play a critical role in viral infection. We examined whether T-cell effector and regulatory responses can define clinical stages of chronic hepatitis B (CHB). Methods We enrolled 200 adults with CHB who participated in the National Institutes of Health−supported Hepatitis B Research Network from 2011 through 2013 and 20 uninfected individuals (controls). Peripheral blood lymphocytes from these subjects were analyzed for T-cell responses (proliferation and production of interferon gamma and interleukin 10) to overlapping hepatitis B virus (HBV) peptides (preS, S, preC, core, and reverse transcriptase), influenza matrix peptides, and lipopolysaccharide. T-cell expression of regulatory markers FOXP3, programmed death-1, and cytotoxic T lymphocyte-associated antigen-4 was examined by flow cytometry. Immune measures were compared with clinical parameters, including physician-defined immune-active, immune-tolerant, or inactive CHB phenotypes, in a blinded fashion. Results Compared with controls, patients with CHB had weak T-cell proliferative, interferon gamma, and interleukin 10 responses to HBV, with increased frequency of circulating FOXP3 + CD127 − regulatory T cells and CD4 + T-cell expression of programmed death-1 and cytotoxic T lymphocyte-associated antigen-4. T-cell measures did not clearly distinguish between clinical CHB phenotypes, although the HBV core-specific T-cell response was weaker in hepatitis B e antigen (HBeAg) + than HBeAg − patients (percent responders: 3% vs 23%; P = .00008). Although in vitro blockade of programmed death-1 or cytotoxic T lymphocyte-associated antigen-4 increased T-cell responses to HBV, the effect was weaker in HBeAg + than HBeAg − patients. Furthermore, T-cell responses to influenza and lipopolysaccharide were weaker in CHB patients than controls. Conclusions HBV persists with virus-specific and global T-cell dysfunction mediated by multiple regulatory mechanisms, including circulating HBeAg, but without distinct T-cell−based immune signatures for clinical phenotypes. These findings suggest additional T-cell−independent or regulatory mechanisms of CHB pathogenesis that warrant further investigation.

Currently, no disease-targeted instrument is available for measuring health-related quality of life (HRQOL) in liver transplant recipients. We developed and tested a post-liver transplant quality of life (pLTQ) instrument. Item selection for the pLTQ instrument was based on responses from liver transplant recipients, 12 liver experts, and a literature search. Impact scores were generated, and a factor analysis was conducted to organize the items into domains. Questions were constructed for each item, and redundant questions were removed. The pLTQ instrument was initially administered to 196 liver transplant patients and then was again administered to 77 patients 6 to 9 months later with a generic HRQOL survey [Medical Outcomes Study Short Form 36 (SF-36)]. Analysis of variance was used to compare the scores of patients at different times since transplantation and with various indications for transplantation. After redundancies were eliminated, the pLTQ instrument included 32 items in 8 domains: Emotional Function, Worry, Medications, Physical Function, Healthcare, Graft Rejection Concern, Financial, and Pain. We found stable pLTQ instrument and SF-36 instrument scores over time. Data 6 to 9 months after the initial assessment indicated stable quality of life outcomes. The pLTQ instrument is applicable to a variety of liver transplant recipients. The questionnaire was tested with a cross-sectional and longitudinal approach. © 2011 American Association for the Study of Liver Diseases.

Patients with chronic hepatitis B virus infection are at increased risk for the development of cirrhosis and hepatocellular carcinoma. Viral suppression with antiviral therapy has been shown to decrease the risk of these complications. Criteria for initiation of antiviral therapy have evolved over time to include serum alanine aminotransferase elevation, serum hepatitis B virus DNA elevations, and histologic assessment. Current societal guidelines and a treatment algorithm have been developed to guide decision-making as regards to antiviral therapy. More recent data has shown the importance of basal core/core promoter mutations, serum albumin, and platelet count in predicting complications of chronic hepatitis B. We present a new treatment strategy for determining the need for antiviral therapy in patients with chronic hepatitis B.

Purpose: To evaluate regional cerebral metabolic and structural changes in patients with minimal hepatic encephalopathy (MHE) using two-dimensional (2D) MR spectroscopy (MRS) and T-weighted MRI, to correlate the observed MR changes with neuropsychological (NP) test scores, and to compare the diagnostic accuracy of MRI, 2D MRS, and NP tests in discriminating between patients and healthy subjects. Materials and Methods: Thirty-three MHE patients and 30 healthy controls were investigated. The 2D localized correlated spectroscopy (L-COSY) was performed in the frontal and occipital brain on a 1.5 Tesla (T) MR scanner. The NP test battery included 15 tests, grouped into 6 cognitive domains. Globus pallidus signal intensities were calculated from T1-weighted images. Results: The 2D MRS showed significant differences in ratios of the following metabolite(s) peaks with respect to creatine (Cr): decreased myo-inositol (mI), choline (Ch), mICh, and increased (glutamate plus glutamine) (Glx) in patients compared with healthy subjects in both occipital and frontal lobes. Frontal lobe taurine also showed a decline in patients. The NP test results revealed declines in cognitive speed, motor function, executive function, and global cognitive status. Significant correlations were found between the altered metabolites and NP tests. Alteration in the mICh/Cr ratio was noted as a powerful discriminant between healthy subjects and the patients. Conclusion: The study demonstrates that relative metabolite levels determined by 2D MRS, in particular mICh/Cr, provide the best diagnostic prediction for MHE. The results suggest that depletions of myo-inositol, choline and taurine with respect to creatine correlate with measures of neuropsychological impairment. J. Magn. Reson. Imaging 2010;32:35–43. © 2010 Wiley-Liss, Inc.

Background and Aims Hepatitis B viral markers and liver tests were used as predictors for development of hepatocellular carcinoma and progression to end-stage liver disease in 128 cirrhosis patients with hepatitis B. Results During a median follow-up of 63.5 months, 28 patients (21.9%) developed HCC and 36 (28.1%) died from non-HCC liver deaths. By multivariate analysis, independent predictors of HCC development and their hazard ratios were high alfa-fetoprotein (HR2.83, 95% CI 1.60–5.00, P = 0.0003), negative HBeAg (HR2.33, 95% CI 1.04–5.29, P = 0.04), and low alanine aminotransferase value (HR1.42, 95% CI 1.08–1.89, P = 0.02). Independent predictors of non-HCC liver deaths were HBeAg positivity (HR3.39, 95% CI 1.16–9.93, P = 0.02), decrease albumin (HR1.61, 95% CI 0.99–2.63, P = 0.05), decrease platelet count (HR2.54, 95% CI 1.03–6.25, P = 0.04), high ALT value (HR1.22, 95% CI 1.03–1.43, P = 0.02), and onset of encephalopathy (HR3.34, 95% CI 1.21–9.27, P = 0.02). Concusions HBeAg negativity, elevated AFP, and low ALT values predicted HCC development, while HBeAg positivity, abnormal liver tests, and low platelet counts identified patients with non-HCC liver deaths.

Close monitoring of patients’ overall status and interventions, such as prompt recognition of GI bleeding or SBP, is crucial to increase the likelihood of a patient surviving to benefit from OLT, the curative intervention for liver cirrhosis. Ameliorating some of the major causes of morbidity of cirrhosis, such as malnutrition, pruritus, and encephalopathy, improve the likelihood of a patient surviving until OLT.

Background Acute alcoholic hepatitis (AAH) is a clinical diagnosis associated with increased hepatic artery diameter and flow. Duplex Doppler ultrasound (DDU) has been shown to accurately measure arterial flow in both liver and kidney transplant patients. The authors conducted a blinded, controlled study to evaluate the accuracy of measuring hepatic artery parameters with DDU in diagnosing AAH. Study Duplex Doppler ultrasound was performed by an investigator, blinded to group makeup, on 22 consecutive hospital inpatients with the clinical diagnosis of AAH. The diagnosis of AAH was based on specific criteria, including the following: recent alcohol abuse, hyperbilirubinemia, prolonged prothrombin time, leukocytosis, hepatomegaly, hepatic bruit, and marked redistribution of isotope on 99mTc-sulfur colloid liver-spleen scan. Controls were 12 cirrhotic patients without AAH and 17 healthy volunteers. Duplex Doppler ultrasound measurements were obtained most consistently from the proximal right hepatic artery. Measured parameters included the following: peak systolic velocity (PSV); resistive index = (PSV - end diastolic velocity [EDV])/PSV; pulsatility index = (PSV - EDV)/mean velocity; and hepatic artery diameter. Results The mean hepatic artery diameter was significantly larger in patients with AAH (3.55 +/- 0.72 mm) than in patients with cirrhosis (2.75 +/- 0.69 mm; p = 0.003) and healthy controls (2.68 +/- 0.69 mm; p = 0.001). The mean PSV was significantly higher in patients with AAH (187 +/- 52 cm/s) compared with cirrhotic (67 +/- 51 cm/s) and healthy (66 +/- 51 cm/s) controls (p = 0.0001). The mean resistive index was lower in AAH patients (0.60 +/- 0.11) compared with cirrhotic (0.69 +/- 0.10; p value was not significant) and healthy controls (0.72 +/- 0.11; p = 0.004). The mean pulsatility index was lower in AAH patients (1.04 +/- 0.47) compared with cirrhotic (1.36 +/- 0.45; p value was not significant) and healthy controls (1.53 +/- 0.45; p = 0.01). Conclusions In the appropriate clinical setting, an elevated hepatic artery diameter or PSV measurement is suggestive of AAH. Duplex Doppler ultrasound offers a noninvasive test to assist in the diagnosis of AAH.

Nephrogenic ascites is an entity that manifests as refractory ascites in patients with end-stage renal disease, where portal hypertensive, infectious, and malignant processes have been excluded. Most of these patients are undergoing hemodialysis. Hypoalbuminemia may predispose these uremic patients to ascites formation. The characteristics of the ascitic fluid suggest that the pathogenesis of the ascites is an alteration in peritoneal membrane permeability or impaired resorption due to peritoneal lymphatic channel obstruction. The ascitic fluid has a high protein content, low serum-ascites albumin gradient (SAAG), and low leukocyte count. Daily hemodialysis should be the initial therapy and is successful in one-third to three-fourths of patients within 3 weeks. Continuous ambulatory peritoneal dialysis or insertion of a peritoneovenous shunt are alternative treatments. Other therapies include instillation of intraperitoneal corticosteroids and binephrectomy, which have less predictable outcomes. Renal transplantation is the definitive treatment for nephrogenic ascites. Control of ascites reverses the progressive cachexia associated with uncontrolled disease, resulting in improved quality of life and survival approaching that of end-stage renal disease patients without ascites.

Direct-acting antiviral (DAA) protease inhibitors, boceprevir (BOC) and telaprevir (TVR) were FDA-approved in 2011 to be used in combination with pegylated interferon (peg-IFN) and ribavirin for the treatment of chronic hepatitis C virus infection (HCV) genotype 1. The addition of these new DAAs increased cure rates but also increased rates of adverse events and drug interactions. This review will evaluate HCV treatment-related side-effects, toxicity, and drug-interactions and management. Understanding and identifying adverse events and drug interactions will help enable the provider to minimize treatment discontinuation, prevent serious adverse events, and optimize treatment for patients.

Introduction: Long-term immunoprophylaxis with HBIG monotherapy reduces HBV recurrence in OLT patients, although the IV form has a number of limitations including expense and a HBV recurrence rate of approximately 20%. Combination prophylaxis with HBIG and lamivudine reduces recurrence rates further although the disadvantages of IV HBIG remain. The cost of IV HBIG has become prohibitive and thus we now report the use of 1M HBIG in maintaining adequate HBsAb titers. Methods: This was a retrospective study evaluating 49 patients transplanted between 6/93 and 8/99. Patients were treated with lamivudine, 150 mg po qd, and HBIG, 10,000 ru IV, in standard protocol (one dose intraoperatively, qd for six days, and then qmo indefinately) and then changed to 1M given as 5 ml qmo. HBsAb, HBsAg, and HBV DNA were checked monthly. Patients were changed back to IV if HBsAb levels dropped below 100 IV. All patients were continued on lamivudine. Two patients died of unrelated causes. Mean follow-up for the remaining 47 patients was 200 days (range, 40 to 353). Results: 38147 (81%) patients treated with 1M HBIG were able to maintain adequate HBsAb titers. Nine patients (19%) required intermittent IV administration for low titers or poor tolerance. No patients had recurrence of HBsAg or HBV DNA. Conclusions: 81% of patients tolerated conversion to 1M administration of HBIG with adequate HBsAb titers and without recurrence of HBV. The potential cost savings and ease of administration make 1M HBIG a viable alternative in OLT patients, Longterm follow up will determine whether 1M HBIG provides durable protection against HBV recurrence, although our initial experience suggests that excellent protection against HBV recurrence is possible. 1155

Hepatitis B infection remains a major public health problem globally and in the United States, with significant use of healthcare resources. Several therapeutic agents active against viral and host targets are currently available for its treatment. The success of combination therapy in HIV infection, which has similarities to hepatitis B in both therapeutic targets and treatment options, stimulated studies on the efficacy and safety of various combinations of available drugs in the treatment of hepatitis B infection. In this review, we analyze the current role of combination therapy in chronic hepatitis B infection.