Imatinib mesylate (gleevec) hepatotoxicity.
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Aged↗
Biomedical subjects
Eugene R Schiff
Publications and source records attributed to Eugene R Schiff.
Prevention of mortality from hepatitis B and hepatitis C.
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Carcinoma, Hepatocellular↗
Hepatitis B virus reactivation after cytotoxic chemotherapy: the disease and its prevention.
Reactivation of hepatitis B virus (HBV) is a well-recognized complication in patients with chronic HBV infection who receive cytotoxic or immunosuppressive therapy. In most cases, reactivations occur in patients who are carriers of HBV infection showing positive hepatitis B surface antigen (HBsAg). Reactivation also may occur in patients with resolved infection who are HBsAg negative, anti-HBs positive, and anti-hepatitis B core positive. HBV reactivations can lead to severe flares that may be life-threatening unless recognized and treated promptly. Physician awareness is essential because prophylactic antiviral treatment can diminish the occurrence and improve the outcome of such episodes. Patients undergoing cytotoxic therapy should be checked routinely for HBV serologic markers and serum HBV DNA levels. Patients who are HBV carriers or anti-hepatitis B core positive should be monitored closely during and after the administration of cytotoxic chemotherapy. Prophylactic treatment with a nucleoside or nucleotide analogue should be considered strongly to prevent HBV reactivation in these patients.
Hepatitis B↗
A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update.
Chronic hepatitis B (CHB) is an important public health problem worldwide and in the United States, with approximately 25% of patients infected as neonates dying prematurely from cirrhosis or liver cancer. A treatment algorithm for CHB previously developed and published by a panel of United States hepatologists was revised based on new developments in the understanding of CHB, the availability of more sensitive molecular diagnostic testing, the addition of new treatments, and better understanding of the advantages and disadvantages of approved therapies. This updated algorithm is based on available evidence using a systematic review of the scientific literature. Where data are lacking, the panel relied on clinical experience and consensus expert opinion. Serum HBV DNA can be detected at levels as low as 10 IU/mL using molecular assays and should be determined to establish a baseline level before treatment, monitor response to antiviral therapy, and survey for the development of drug resistance. The primary aim of antiviral therapy is durable suppression of serum HBV DNA to the lowest levels possible. The threshold level of HBV DNA for determination of candidacy for therapy is 20,000 IU/mL or more for patients with hepatitis B e antigen-positive CHB. A lower serum HBV DNA threshold of 2000 IU/mL or more is recommended for patients with hepatitis B e antigen-negative CHB, and 200 IU/mL or more for those with decompensated cirrhosis. Interferon alfa-2b, lamivudine, adefovir, entecavir, and peginterferon alfa-2a all are approved as initial therapy for CHB and have certain advantages and disadvantages. Issues for consideration include efficacy, safety, incidence of resistance, method of administration, and cost.
Algorithms↗
Prevention and treatment of recurrent Hepatitis B after liver transplantation: the current role of nucleoside and nucleotide analogues.
The Hepatitis B virus (HBV) is a DNA virus that can cause both acute and chronic liver disease in humans. Approximately 350-400 million people are affected worldwide and up to one million deaths occur annually from cirrhosis and hepatocellular carcinoma. When cirrhosis and liver failure develop, the definitive treatment of choice remains orthotopic liver transplantation (OLT). In the past, an unacceptable HBV recurrence rate with a high rate of graft loss was noted. The use of Hepatitis B immunoglobulin (HBIG) has resulted in improved patient and graft survival rates. The addition of the nucleoside analog Lamivudine (LAM) to HBIG has improved these survival curves to an even greater degree. Prolonged use of LAM will almost invariably lead to the development of viral mutations resistant to the drug. There are now several other nucleoside and nucleotide analogs (Adefovir, Entecavir, Tenofovir, and Truvada) available for the clinician to utilize against these resistant strains. It should be possible to prevent recurrence in most, if not all, post-transplant patients and also to significantly reduce viral loads with normalization of transaminases in those who have developed recurrent infection. The antiviral regimen should be robust and minimize the risk of breakthrough mutations. A prudent approach may be the implication of combination antiviral therapy. This review summarizes the efficacy of previous regimens utilized to prevent and treat recurrent HBV following OLT. Particular attention will be paid to the newer nucleoside and nucleotide analogs and the direction for future strategies to treat HBV in the post transplant setting.
Adenine↗
Acquired hepatocerebral degeneration in a patient with HCV cirrhosis: complete resolution with subsequent recurrence after liver transplantation.
Acquired (non-Wilsonian) hepatocerebral degeneration (AHD) is a chronic brain disorder caused by liver dysfunction and long-standing portal-systemic shunting. It typically presents with dysathria, ataxia, tremor, involuntary movements and altered mental status, and often does not respond to conventional medical therapy for hepatic encephalopathy. There is scarce and conflicting information regarding the clinical course of AHD after liver transplantation (OLT). We present a case of a 47-year-old woman with hepatitis C (HCV) cirrhosis who developed severe manifestations of AHD after multiple bouts of hepatic encephalopathy. Her first OLT was complicated with primary nonfunction requiring immediate retransplantation. The second OLT led to complete clinical and radiological resolution of the AHD. However the patient developed recurrence of AHD 11 months post-transplant due to recurrent HCV and chronic rejection leading to cirrhosis of the graft. The patient developed severe neurological symptoms, despite mild synthetic graft dysfunction. A third OLT led again to disappearance of the clinical and radiological manifestations of AHD. AHD may show complete resolution after OLT; however it may rapidly recur following recurrent liver disease or graft dysfunction.
Female↗
Predictors of cirrhosis in Hispanic patients with nonalcoholic steatohepatitis.
It is estimated that 43% of patients with nonalcoholic steatohepatitis (NASH) will progress to liver fibrosis or cirrhosis. Although NASH is more common in Hispanics, most studies have been conducted on Caucasians, and there is scarce information regarding ethnic differences in this disease. The aim of this study was to identify the independent predictors of cirrhosis in Hispanic patients with NASH. A retrospective case-control study was conducted on 80 patients with biopsy-proven NASH. Forty-two were Hispanic (study group) and 38 were Caucasians controlled for age and BMI (control group). Clinical, biochemical, and histologic features were analyzed for correlation with cirrhosis. There were no significant differences in demographic features between the two groups. In multivariate analysis, independent predictors of cirrhosis among Hispanic patients were age (OR, 1.07; 95% CI, 1.01-1.14) and AST/ALT ratio (OR, 10.56; 95% CI; 2.46-45.29), while independent predictors among non-Hispanic patients were age (OR, 1.085; 95% CI, 1.0-1.186), and diabetes mellitus (OR, 6.46; 95% CI, 1.19-35.07). In patients with NASH, predictors of cirrhosis varied according to ethnic background. Age was an independent predictor in both groups, however, AST/ALT ratio was found to be an independent predictor of cirrhosis only in Hispanic patients, and diabetes mellitus only in non-Hispanic patients.
Age Factors↗
Chronic hepatitis B: a critical appraisal of current approaches to therapy.
BACKGROUND & AIMS: Treatment of chronic hepatitis B (CHB) involves a number of complex and controversial issues. Expert opinions may differ from those of practicing hepatologists and gastroenterologists. We aimed to explore this issue further after a critical review of the literature. METHODS: A panel of 14 international experts graded the strength of evidence for 16 statements addressing 3 content areas: patient selection, therapeutic end points, and treatment options. Available data relating to the statements were reviewed critically in 3 small work groups. After discussion of each statement with the entire panel, the experts voted anonymously to accept or reject statements based on the strength of evidence and their experience. A total of 241 members of the American Association for the Study of Liver Diseases (AASLD) responded to the same statements and their responses were compared with those of the experts. A discordant response was defined as a difference of more than 20% in any of the 5 graded levels of response (accept or reject) between the 2 groups. RESULTS: With the exception of 2 statements, the experts' responses were relatively uniform. However, the responses of the AASLD members were discordant from the experts in 12 statements, spanning all 3 content areas. CONCLUSIONS: Several areas of disagreement on the management of CHB exist between experts and AASLD members. Our results indicate a potential knowledge gap among practicing hepatologists. Better educational efforts are needed to meet the challenge of managing this complex disorder in which even expert opinion occasionally may disagree.
Adenine↗
Does the heterozygous state of alpha-1 antitrypsin deficiency have a role in chronic liver diseases? Interim results of a large case-control study.
BACKGROUND: The role of the heterozygous PiZ state of alpha-1 antitrypsin deficiency (alpha1ATD) in the pathogenesis of chronic liver disease (LD) is still a matter of controversy. AIM: To determine the prevalence of alpha1ATD heterozygote states in a large population of patients with established LD compared with individuals with no LD, and to determine whether the prevalence of PiZ is increased in patients with more severe LD. METHODS: A cross sectional case-control study among patients with and without LD. Blood samples were tested for alpha1AT levels and alpha1AT phenotype. The severity of LD was determined by clinical evaluation, lab tests, imaging studies and histopathology. RESULTS: In total, 1405 patients were enrolled; 651 with, and 754 without LD. Out of them, 173 patients had decompensated cirrhosis requiring liver transplantation. PiMZ was significantly more prevalent in White patients (3.5%) compared with Hispanics (1.7%; P = 0.029). There was no difference in PiMZ prevalence between the total LD group and the group with no LD (2.1% vs. 1.7%; P = 0.64). Within the LD group, 5.7% of 173 patients with decompensated LD, listed for liver transplantation, had PiMZ, compared with 2.1% of 478 patients with less severe LD (P = 0.016). Similarly, there was a disproportionately higher prevalence of PiZ among hepatitis C virus (HCV) patients (5.6%) and patients with nonalcoholic fatty liver disease (NAFLD) (5.0%) with decompensated LD, compared with HCV patients (1.2%) and NAFLD patients (1.9%) with less severe LD (P = 0.044 and 0.017, respectively). Patients with cryptogenic cirrhosis, who were not considered NAFLD patients, did not have a higher prevalence of PiMZ compared with patients with LD of known etiologies (1.9% vs. 2.3%; P = 0.12). CONCLUSIONS: We found no association between the heterozygous PiZ state of alpha1ATD and the presence of chronic LD in-general or the presence of cryptogenic cirrhosis. In contrast, patients with decompensated LD of any etiology had a significantly higher prevalence of PiMZ compared with patients with compensated LD. Furthermore, in patients with chronic LD due to HCV or NAFLD there was a significant association between the PiMZ heterozygous state and increased severity of LD and the need for liver transplantation. These interim results suggest that the PiMZ alpha1ATD heterozygous state may have a role in worsening LD due to HCV or NAFLD.
Adult↗
Epithelioid hemangioendothelioma of the liver.
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Factor VIII↗
Colchicine treatment of alcoholic cirrhosis: a randomized, placebo-controlled clinical trial of patient survival.
BACKGROUND & AIMS: Colchicine improved survival and reversed cirrhosis in several small clinical trials. We compared the efficacy and safety of long-term colchicine, as compared with placebo, in patients with advanced alcoholic cirrhosis. METHODS: Five hundred forty-nine patients with advanced (Pugh B or C) alcoholic cirrhosis were randomized to receive either colchicine 0.6 mg twice per day (n = 274) or placebo (n = 275). Treatment lasted from 2 to 6 years. The primary outcome was all-cause mortality. Secondary outcomes were liver-related morbidity and mortality. Liver biopsy was requested prior to entry and after 24 months of treatment. RESULTS: Attendance at scheduled clinic visits and adherence with study medication were similar in colchicine and placebo groups. Alcohol intake was less than 1 drink per day in 69% of patients. In an intention-to-treat analysis, all-cause mortality was similar in colchicine (49%) and placebo (45%) patients (P = .371). Mortality attributed to liver disease was 32% in colchicine and 28% in placebo patients (P = .337). Fewer patients receiving colchicine developed hepatorenal syndrome. In 54 patients with repeat liver biopsies after 24 or more months of treatment, cirrhosis improved to septal fibrosis in 7 patients (3 colchicine, 4 placebo) and to portal fibrosis in 1 patient (colchicine). CONCLUSIONS: In patients with advanced alcoholic cirrhosis, colchicine does not reduce overall or liver-specific mortality. Liver histology improves to septal fibrosis in a minority of patients after 24 months of treatment, with similar rates of improvement in patients receiving placebo and colchicine. Colchicine is not recommended for patients with advanced alcoholic cirrhosis.
Colchicine↗
A dose-ranging study of the efficacy and tolerability of entecavir in Lamivudine-refractory chronic hepatitis B patients.
BACKGROUND & AIMS: Entecavir is a nucleoside analogue with potent in vitro activity against lamivudine-resistant hepatitis B virus (HBV). This randomized, dose-ranging, phase 2 study compared the efficacy and safety of entecavir with lamivudine in lamivudine-refractory patients. METHODS: Hepatitis B e antigen (HBeAg)-positive and -negative patients (n = 182), viremic despite lamivudine treatment for > or =24 weeks or having documented lamivudine resistance substitutions, were switched directly to entecavir (1.0, 0.5, or 0.1 mg daily) or continued on lamivudine (100 mg daily) for up to 76 weeks. RESULTS: At week 24, significantly more patients receiving entecavir 1.0 mg (79%) or 0.5 mg (51%) had undetectable HBV DNA levels by branched chain DNA assay compared with lamivudine (13%; P < .0001). Entecavir 1.0 mg was superior to entecavir 0.5 mg for this end point (P < .01). After 48 weeks, mean reductions in HBV DNA levels were 5.06, 4.46, and 2.85 log(10) copies/mL on entecavir 1.0, 0.5, and 0.1 mg, respectively, significantly higher than 1.37 log(10) copies/mL on lamivudine. Significantly higher proportions of patients achieved normalization of alanine aminotransferase levels on entecavir 1.0, 0.5, and 0.1 mg (68%, 59%, and 47%, respectively) than on lamivudine (6%). One virologic rebound due to resistance occurred (in the 0.5-mg group). CONCLUSIONS: In HBeAg-positive and HBeAg-negative lamivudine-refractory patients, treatment with entecavir 1.0 and 0.5 mg daily was well tolerated and resulted in significant reductions in HBV DNA levels and normalization of alanine aminotransferase levels. One milligram of entecavir was more effective than 0.5 mg in this population.
Adult↗
Budd-Chiari-like presentation of hepatic adenoma.
Hepatic adenoma is a benign tumor characterized by its hypervascularity. Hepatic adenoma tends to occur more frequently in women and is related to the use of contraceptive hormones, androgenic/anabolic steroids, pregnancy, glycogen storage diseases and hemochromatosis. Hepatic venous obstruction, or Budd-Chiari syndrome, is a condition of hepatic vein occlusion that has many causes. A 35-year-old woman presented shortly after pregnancy with a huge cystic lesion in the liver. The lesion compressed the hepatic vein and created an early stage of Budd-Chiari syndrome. Tumor resection was carried out successfully. The final diagnosis of this case was multiple hepatic adenomas.
Adenoma↗
Multiple normal deliveries in a woman with severe portal hypertension due to congenital hepatic fibrosis: the importance of preserved hepatocellular function.
We report a 26-year-old woman with congenital hepatic fibrosis (CHFib), adult polycystic kidney disease, type II diabetes mellitus, and von Willebrand disease, who despite persistent advice to the contrary because of severe portal hypertension, had 5 pregnancies delivering 6 healthy infants over 8 yr. During this time, she experienced several episodes of esophageal variceal bleeding and severe ascites with persistently normal liver and renal function. CHFib is one of the prototypes of portal hypertension with preserved hepatocellular function. Although pregnancy is ill-advised in most women with portal hypertension and particularly with severe manifestations, this report illustrates the importance of preserved hepatocellular function for the outcome of pregnancy in these patients.
Adult↗
Focal nodular hyperplasia in identical twins.
A unique case of a focal nodular hyperplasia (FNH) in identical twins is presented. The computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen demonstrated in both twins a mass of identical size in the same segment of their liver. Histopathologic examination of both masses confirmed the diagnosis of focal nodular hyperplasia. This case report strongly supports the theory of a congenital vascular anomaly playing a major role in the etiology of focal nodular hyperplasia.
Adult↗
Treatment of established recurrent hepatitis C in liver-transplant recipients with pegylated interferon-alfa-2b and ribavirin therapy.
INTRODUCTION: The management issues of transplant patients with hepatitis C virus (HCV) are complex, and interferon therapy is often ineffective. We present data from a retrospective review in liver-transplant recipients suffering from HCV recurrence that were treated with pegylated alpha-2b interferon and ribavirin. METHODS: A retrospective review of transplant recipients that received combination pegylated alpha-2b interferon (1.5 mcg/kg/wk) and ribavirin (400-600 mg/day) therapy intended for at least 48 weeks. Complications were recorded and included neutropenia (<750 cells), anemia (hemoglobin <8 g) with and without treatment consisting of blood transfusions, erythropoietin, or dose reduction of ribavirin, and depression. The diagnosis of HCV recurrence was determined by an increase in liver chemistries, histopathologic findings with inflammation along with viral recurrence using the COBAS AMPLICOR HCV test. RESULTS: Fifty-seven liver-transplant recipients were included, 29 naive (group 1) to therapy and 28 nonresponders (group 2) to at least 6 months of interferon and ribavirin therapy. Eight (27.6%) patients in group 1 and six (21%) patients in group 2 were HCV nondetectable at the end of 48 weeks of therapy. Ribavirin therapy was decreased in 13 of 29 (45%) for group 1 and 11 of 28 (39%) in group 2. Therapeutic interventions were 4 of 57 (7%) blood transfusions, 23 of 57 (40%) erythropoietin, and 17 of 57 (30%) filgrastim. CONCLUSION: Combination pegylated interferon with ribavirin appears to effective therapy in HCV recurrence and in HCV nonresponsive to interferon and ribavirin. This data reveals the difficulty and caution that must be taken when treating HCV-R liver-transplant recipients with combination pegylated alpha-2b interferon and ribavirin therapy.
Adult↗
Tenofovir therapy for lamivudine resistance following liver transplantation.
BACKGROUND: Resistant hepatitis B virus (HBV) strains develop in 30% of liver transplant recipients treated with lamivudine within 2 years from the time of transplantation. OBJECTIVE: To assess safety and outcomes of tenofovir salvage therapy for patients with lamivudine resistance in a retrospective cohort of liver-transplanted patients. METHODS: Medical records were retrospectively evaluated for patients who received tenofovir. Data collected included demographics, HBV serologic information prior to and during tenofovir therapy, drug-related complications, and creatinine clearance. Criteria for lamivudine resistance included elevation of liver chemistries along with reappearance of hepatitis B surface antigen, hepatitis Be antigen, and/or HBV DNA. RESULTS: Sixteen patients showed resistance to lamivudine at 10-85 months (median 26) following liver transplantation. Tenofovir 300 mg/day orally was added in 8 patients 1-66 months after the development of viral lamivudine resistance and continued for 14-26 months (median 19.3). All 8 patients experienced HBV DNA viral suppression, with 7 currently nondetectable. No adverse events were reported, and creatinine clearance was not impaired. CONCLUSIONS: Our results suggest that tenofovir safely and markedly decreases replication of lamivudine-resistant HBV variants after liver transplantation and is another potential option for the treatment of HBV lamivudine resistance.
Adenine↗