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E R Schiff

Publications and source records attributed to E R Schiff.

At least 19 recordsLinked to original sources
PubMed2006

The impact of nonalcoholic fatty liver disease and the metabolic syndrome on progression of fibrosis in patients with recurrent HCV after liver transplantation.

Nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome (MS) have been shown to play a role in disease progression and response to therapy in patients with chronic hepatitis C virus (HCV) infection. The primary objective of this study was to evaluate the impact of coexisting NAFLD and MS on the progression of fibrosis in patients with recurrent HCV treated with interferon (IFN)/ribavirin after orthotopic liver transplantation (OLT). From 1998 to 2004, a total of 418 patients underwent OLT in our center for HCV-related cirrhosis. Thirty-five patients with recurrent HCV on IFN/ribavirin treatment, who had at least 2 posttransplant liver biopsies at least 6 months apart, were included in the study. Patients who had MS at the time of their first posttransplant biopsy were identified. The first and last posttransplant biopsies were assessed for the presence and severity of NAFLD, grade of inflammation, and stage of fibrosis. The fibrosis progression rate (FPR) was calculated and expressed in fibrosis units per month (FU/mo). Among 35 patients, 34% were diagnosed with NAFLD in the first posttransplant biopsy. The mean FPR was 0.05+/-0.16 FU/mo in the presence of NAFLD compared to 0.07+/-0.10 FU/mo in its absence (P=.68) and 0.03+/-0.06 FU/mo in the presence of MS versus 0.10+/-0.15 FU/mo in its absence (P=.06). When FPR values were divided into two categories of <0.16 FU/mo or >or=0.16 FU/mo (below/above the 25% upper quartile) or <0.08 FU/mo or >or=0.08 FU/mo (below/above the 50% upper quartile), there was no correlation between FPR categories and the presence of NAFLD with or without MS, only MS, or the absence of both in the first liver transplant biopsy (P=.13). Coexisting NAFLD or MS had no significant effect on the progression of fibrosis after OLT in patients with treated hepatitis C after OLT.

Adult↗
PubMed2005

Activity of adefovir dipivoxil against all patterns of lamivudine-resistant hepatitis B viruses in patients.

One hundred and thirty-one post-liver transplantation patients with chronic hepatitis B and failing lamivudine therapy with detectable serum hepatitis B virus (HBV) deoxyribonucleic acid by hybridization assays or > or =1 x 10(6) copies/mL by polymerase chain reaction, and elevated alanine transaminase levels despite continuous lamivudine, were enrolled in an open-label study of adefovir dipivoxil. The B and C domains of HBV polymerase were sequenced for baseline samples to determine the presence of lamivudine resistance mutations. The results showed that 98% of the samples had tyrosine-methionine-aspartate-aspartate (YMDD) mutations, indicating a strong correlation between the above clinical definition of lamivudine treatment failure and the presence of YMDD mutations. In addition to the rtM204V/I and the rtL180M mutations, the mutation rtV173L was identified in 19% of patients. Four major patterns of lamivudine-resistant HBV were identified: rtL180M + rtM204V (60%), rtV173L + rtL180M + rtM204V (19%), rtM204I (9%) and rtL180M + rtM204I (9%). Treatment with adefovir dipivoxil showed similar antiviral efficacy in patients with lamivudine-resistant virus from all four patterns.

Adenine↗
PubMed2005

Current and future treatment of chronic hepatitis B.

Hepatitis B virus (HBV) infection is an ongoing worldwide pandemic. In general, the mode of transmission is different according to its prevalence in different areas: mostly perinatal in highly prevalent zones and predominantly sexual and/or parenteral in low prevalence areas. The variation in presentations of chronic hepatitis B (CHB) make its management complex. Aminotransferase levels, viral load, histologic changes, age of the patient, viral mutations (e.g. hepatitis B e antigen negative) and pregnancy are all factors that impact on treatment decisions. The ideal drug that will eradicate the HBV has yet to be developed. This review focuses on the currently available medications for CHB: alpha-interferon, lamivudine, adefovir, as well as new drugs that have proven to be active against HBV in clinical trials and are closer to licensure; pegylated interferon tenofovir, entecavir, emtricitabine, telbivudine and clevudine. The antiviral properties and the advantages and disadvantages in HBeAg-positive and negative patients are discussed. Combinations of different medications currently under study were not included in this review. A suggested algorithm, developed from recent literature, may serve as a practical guide on tailoring drug selection based on viral load, aminotransferases, hepatitis B e antigen status and histological findings. Finally, practical management questions are raised.

Algorithms↗
PubMed2003

Sirolimus therapy in orthotopic liver transplant recipients with calcineurin inhibitor related chronic renal insufficiency.

UNLABELLED: Calcineurin inhibitor-related renal toxicity affects patient and graft survival in transplant recipients. Our clinical experience has revealed sirolimus to be an effective agent in treating renal insufficiency related to calcineurin inhibitor toxicity. METHODS: We performed a retrospective review of the medical records of OLT recipients suffering from chronic renal insufficiency and treated with sirolimus at the University of Miami. RESULTS: Fourteen patients (nine men and five women) of mean age 57 years who had been treated with tacrolimus for at least 30 days were converted to sirolimus after developing nephrotoxicity. Mean creatinine clearances collected on day 0, 30, 60, and 90 after conversion were 40.1 mL/min, 49.6 mL/min, 53.9 mL/min, and 51.4 mL/min, respectively. Episodes of acute cellular rejection were not increased during the sirolimus conversion. CONCLUSION: This retrospective review suggests that OLT patients suffering from tacrolimus-related renal insufficiency successfully converted to sirolimus may benefit from this therapy.

Creatinine↗
PubMed2003

Preservation injury patterns in liver transplantation associated with poor prognosis.

Preservation injury (PI) is defined as hepatic dysfunction that occurs within 10 days of liver transplantation (OLT) but spontaneously resolves. However, we noted two new patterns: one characterized by histologic evidence of preservation injury that occurs at later than 10 days post-OLT (late PI), and a second, of persistent charge in liver biopsies > 10 days post-OLT (persistent PI). To characterize these new patterns, we performed a retrospective study of patients who underwent liver biopsies for hepatic dysfunction post-OLT from September 1993 to March 1998. The outcome of the 61 patients with preservation injury on liver biopsy after OLT was followed until the last clinic visit or death. Thirty patients had early PI, 16 patients had persistent preservation injury and 15 patients, late onset preservation injury. There were no significant differences in the age (P =.28), sex (P =.77), follow-up time (P =.78), cold ischemia (P =.3), or warm ischemia time (P =.16) between these groups. There was also no significant association between early preservation injury or persistent preservation injury with the development of acute or chronic rejection (P =.19). The overall survival rates at 1, 3, and 5 years was 52%, 45%, and 45%, respectively. There was no significant difference in survival between early, persistent, and late PI patterns (P =.59), although there was a trend toward better survival for patients with early preservation injury. The survival of OLT patients with persistent or late preservation injury is poor and should prompt consideration for retransplantation.

Adolescent↗
PubMed2001

Dilatation of biliary strictures through the afferent limb of a Roux-en-Y choledochojejunostomy in patients with sclerosing cholangitis.

Repeated dilatation of biliary strictures in patients with sclerosing cholangitis through a subcutaneously placed afferent limb of a choledochojejunostomy is technically feasible and safe. This study is a prospective 15-year evaluation of 36 patients treated by repeat dilatation through this jejunal limb. There was one operative death and one major complication of dilatation. The 5-year survival of all patients was 74%. If patients with cirrhosis or unproven cholangiocarcinoma at the time of operation are not included, the 5-year survival is 86%. The 15-year survival of all patients was 30%; it was 64% if those with cirrhosis and unproven cholangiocarcinoma at the time of operation are not included. Six patients are presently alive with an average survival of 159 months. The study suggests that a combination of repeated dilatations combined with transplantation is the approach of choice in selected patients.

Adolescent↗
PubMed2001

Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B.

BACKGROUND: Activation of hepatic stellate cells is the earliest step in fibrogenesis. Alpha-smooth muscle actin (alpha-SMA), expressed by activated hepatic stellate cells, and C-terminal procollagen alpha1(III) propeptide (PIIICP) are early markers of fibrogenesis and should precede fibrosis. AIM: Determine if suppression of hepatitis B virus replication with lamivudine would decrease fibrogenesis as measured by immunohistochemical markers. METHODS: Paired liver biopsies from patients with hepatitis B before and after therapy with lamivudine (n=47) or placebo (n=33) were studied. alpha-SMA and PIIICP were detected in paraffin-embedded tissue by immunohistochemistry and quantified in a blinded manner by video imaging analysis. RESULTS: Liver biopsies from patients treated with lamivudine showed a significant decrease in alpha-SMA expression (1.06+/-0.23 vs. 0.58+/-0.11, pre vs. post, P<0.05). Placebo recipients had increased levels of alpha-SMA (0.82+/-0.14 vs. 1.32+/-0.21, P<0.05). PIIICP was similarly decreased after lamivudine. Among subjects whose Histologic Activity Index fibrosis score was unchanged or worsened, the mean change in alpha-SMA expression was significantly decreased in the lamivudine group compared with placebo. CONCLUSIONS: Lamivudine decreased markers of hepatic stellate cell activation and collagen synthesis. Immunohistochemical techniques are sensitive for assessing fibrogenesis and will be useful in trials of antiviral and antifibrotic agents.

Actins↗
PubMed2001

Liver disease in the elderly.

Despite several morphologic and functional changes that have been described in the aging liver, most relevant studies fail to identify a significant age-related deficit in liver function in humans. One of the important age-related changes is a decrease in regenerative capacity, which may partly explain the impaired recovery after severe viral and toxic injury in the elderly. Nevertheless, livers from older subjects are used successfully for transplantation. Substantial morbidity and mortality in the elderly is attributable to liver diseases, and the number of patients older than 65 years of age with chronic liver disease is increasing rapidly. Although there are no liver diseases specific to advanced age, the presentation, clinical course and management of liver diseases in the elderly may differ in important respects from those of younger individuals.

Aged↗
PubMed2001

Large cystic lesions of the liver in adults: a 15-year experience in a tertiary center.

BACKGROUND: Cystic lesions of the liver consist of a heterogeneous group of disorders and may present a diagnostic and therapeutic challenge. Large hepatic cysts tend to be symptomatic and can cause complications more often than smaller ones. STUDY DESIGN: We performed a retrospective review of adults diagnosed with large (> or = 4 cm) hepatic cystic lesions at our center, over a period of 15 years. Polycystic disease and abscesses were not included. RESULTS: Seventy-eight patients were identified. In 57 the lesions were simple cysts, in 8 echinococcal cysts, in 8 hepatobiliary cystadenomas, and in 1 hepatobiliary cystadenocarcinoma. In four patients, the precise diagnosis could not be ascertained. Mean size was 12.1 cm (range, 4 to 30 cm). Most simple cysts were found in women (F:M, 49:8). Bleeding into a cyst (two patients) and infection (one patient) were rare manifestations. Percutaneous aspiration of 28 simple cysts resulted in recurrence in 100% of the cases within 3 weeks to 9 months (mean 4(1/2) months). Forty-eight patients were treated surgically by wide unroofing or resection (laparoscopically in 18), which resulted in low recurrence rates (11% for laparoscopy and 13% for open unroofing). Four of the eight patients with echinococcal cysts were symptomatic. All were treated by open resection after irrigation of the cavity with hypertonic saline. There was no recurrence during a followup period of 2 to 14 years. Hepatobiliary cystadenomas occurred more commonly in women (F:M, 7:1) and in the left hepatic lobe (left:right, 8:0). Seven were multiloculated. All were treated by open resection, with no recurrence, and none had malignant changes. Cystadenocarcinoma was diagnosed in a 77-year-old man, and was treated by left hepatic lobectomy. CONCLUSIONS: Large symptomatic simple cysts invariably recur after percutaneous aspiration. Laparoscopic unroofing can be successfully undertaken, with a low recurrence rate. Open resection after irrigation with hypertonic saline is a safe and effective treatment for echinococcal cysts. Hepatobiliary cystadenomas have predilection for women and for the left hepatic lobe. Malignant transformation is an uncommon but real risk. Open resection is a safe and effective treatment for hepatobiliary cystadenoma, and is associated with a low recurrence rate.

Adenoma, Bile Duct↗
PubMed2001

Transient hepatopulmonary syndrome in a patient with acute hepatitis A.

The hepatopulmonary syndrome is defined as the triad of liver disease, hypoxaemia and intrapulmonary vascular dilatation. This syndrome has been described in patients with liver cirrhosis, noncirrhotic portal hypertension, and fulminant hepatic failure, however, there are no previous descriptions of hepatopulmonary syndrome in patients with acute nonfulminant viral hepatitis. We report a 47-year-old, previously healthy man that presented with acute hepatitis A, and developed progressive dyspnoea, platypnoea and orthodeoxia with no evidence of parenchymal or thromboembolic lung disease. PaO2 on room air was 58 mmHg, O2 saturation was 88% and alveolar-arterial O2 gradient was 62%. During his hospitalization serum albumin level decreased to 3.1 g/dl and prothrombin time was prolonged to 16.8 s, however, he remained alert with no signs of hepatic encephalopathy. Contrast echocardiography revealed left heart chamber opacification 3-4 cardiac cycles after the opacification of the right heart chamber, consistent with hepatopulmonary syndrome. During the following days there was a gradual improvement in the patient's condition, with resolution of his dyspnoea and gradual increase of PaO2. Repeat contrast echocardiography and PaO2 determinations, 3 weeks later, were normal. On long-term follow-up the patient remained asymptomatic with normal liver function tests and normal O2 saturation. This report indicates that hepatopulmonary syndrome may be a transient manifestation of acute hepatitis A in the absence of fulminant liver failure.

Acute Disease↗
PubMed2001

Long-term mortality and morbidity of transfusion-associated non-A, non-B, and type C hepatitis: A National Heart, Lung, and Blood Institute collaborative study.

Persons with non-A, non-B hepatitis (cases) identified in 5 transfusion studies in the early 1970s have been followed ever since and compared for outcome with matched, transfused, non-hepatitis controls from the same studies. Previously, we reported no difference in all-cause mortality but slightly increased liver-related mortality between these cohorts after 18 years follow-up. We now present mortality and morbidity data after approximately 25 years of follow-up, restricted to the 3 studies with archived original sera. All-cause mortality was 67% among 222 hepatitis C-related cases and 65% among 377 controls (P = NS). Liver-related mortality was 4.1% and 1.3%, respectively (P =.05). Of 129 living persons with previously diagnosed transfusion-associated hepatitis (TAH), 90 (70%) had proven TAH-C, and 39 (30%), non-A-G hepatitis. Follow-up of the 90 TAH-C cases revealed viremia with chronic hepatitis in 38%, viremia without chronic hepatitis in 39%, anti-HCV without viremia in 17%, and no residual HCV markers in 7%. Thirty-five percent of 20 TAH-C patients biopsied for biochemically defined chronic hepatitis displayed cirrhosis, representing 17% of all those originally HCV-infected. Clinically evident liver disease was observed in 86% with cirrhosis but in only 23% with chronic hepatitis alone. Thirty percent of non-A, non-B hepatitis cases were unrelated to hepatitis viruses A,B,C, and G, suggesting another unidentified agent. In conclusion, all-cause mortality approximately 25 years after acute TAH-C is high but is no different between cases and controls. Liver-related mortality attributable to chronic hepatitis C, though low (<3%), is significantly higher among the cases. Among living patients originally HCV-infected, 23% have spontaneously lost HCV RNA.

Aged↗
PubMed2001

A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C.

This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared peginterferon alfa-2b (PegIntron) to interferon alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon alfa-2b dose (3 MIU) or the once-weekly (QW) peginterferon alfa-2b (0.5, 1.0, or 1.5 microg/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 peginterferon alfa-2b doses significantly (P < or =.042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not dose-related above 1.0 microg/kg peginterferon alfa-2b because of a higher relapse rate among patients treated with 1.5 microg/kg peginterferon alfa-2b, particularly among patients infected with genotype 1. All 3 peginterferon alfa-2b doses decreased liver inflammation to a greater extent than did interferon alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, peginterferon alfa-2b maintained (0.5 microg/kg) or surpassed (1.0, 1.5 microg/kg) the clinical efficacy of interferon alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 microg/kg peginterferon alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation.

Adult↗
PubMed2001

A multicenter study of lamivudine treatment in 33 patients with hepatitis B after liver transplantation.

Hepatitis B virus (HBV) infection after liver transplantation (LT) may lead to severe and rapidly progressive graft failure. Antiviral treatment may be of benefit in selected patients with recurrent hepatitis B post-LT. The aim of this prospective open-label study is to determine the safety and efficacy of lamivudine in 33 liver transplant recipients with active HBV infection. The median time from LT to study enrollment was 51 months, all patients were hepatitis B surface antigen positive, and 75% and 94% of subjects had detectable hepatitis B e antigen (HBeAg) and HBV DNA at entry, respectively. The median duration of lamivudine treatment on study was 85 weeks, during which time median HBV DNA levels became undetectable by 16 weeks and 9% of patients lost previously detectable HBeAg. Serum alanine aminotransferase (ALT) levels improved in most patients and normalized in 27% of patients with elevated values pretreatment. Serum bilirubin and albumin levels significantly improved in patients with abnormal values at entry (P <.05). Virological breakthrough was detected in 13 subjects after a median of 61 weeks of lamivudine treatment and was confirmed to be caused by YMDD mutants in all patients tested. None of the patients with virological breakthrough showed a complete loss of clinical response to lamivudine. Serum ALT and bilirubin levels in patients with and without virological breakthrough were not significantly different at last study follow-up. Study results show that lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B. However, the high rate of virological breakthrough with prolonged therapy indicates the need for further studies of combination antiviral therapy in this patient population. Our results and others further establish the improving long-term outcomes with LT for patients with hepatitis B through advances in prevention of reinfection, as well as the availability of safe and effective antiviral therapies to treat patients with HBV recurrence.

Adult↗
PubMed2001

Viral hepatitis.

Viral hepatitis constitutes the most common entity seen in hepatology practice. Hepatitis A vaccination is recommended for patients with chronic hepatitis. Both lamivudine and interferon are established therapies against chronic hepatitis B, with other treatments not equally effective. Adefovir dipivoxil is a promising new treatment for lamivudine-resistant hepatitis B mutants. Lamivudine and hepatitis B immunoglobulin are effective in preventing recurrence of hepatitis B after transplantation. The combination of interferon and ribavirin has been shown to be effective for treatment of hepatitis C. Studies support the antiviral, antifibrotic, and antineoplastic effect of interferon therapy. Recurrence of hepatitis C after transplantation has been associated with more rapid progression to cirrhosis. Other major advances in the field of viral hepatitis during the past year are highlighted.

Journal Article↗
PubMed2001

Hepatitis C, cryoglobulinemia, and cutaneous vasculitis associated with unusual and serious manifestations.

Hepatitis C viral infection is currently the leading cause of chronic hepatitis and cirrhosis. It also is a major predisposing factor for the development of hepatocellular carcinoma. It is estimated that approximately 1-2% of patients with hepatitis C infection have nonhepatic manifestations that are protean in nature. In this report, we describe six unusual cases of nonhepatic manifestations: abdominal vasculitis in two, peripheral neuropathy in two, and one patient each with central nervous system vasculitis and necrotizing cutaneous vasculitis. All patients had cutaneous vasculitis and cryoglobulinemia. None of our patients had cirrhosis, yet three of the six patients died. Because of the severe manifestations, aggressive therapy was instituted with interferon, immunosuppressive medications, i.v. immunoglobulin, and plasmapheresis. Our report underscores the importance of recognizing nonhepatic manifestations in patients with hepatitis C infection that may be associated with high morbidity and mortality.

Adult↗
PubMed2001

Prospective multicenter clinical evaluation of AMPLICOR and COBAS AMPLICOR hepatitis C virus tests.

We conducted a multicenter clinical evaluation of the second versions of the manual AMPLICOR and the semiautomated COBAS AMPLICOR tests for hepatitis C virus (HCV) RNA (Roche Molecular Systems, Inc., Pleasanton, Calif.). The performance characteristics of these HCV RNA tests for diagnosis of active viral infection were determined by comparison to anti-HCV serological test results, alanine aminotransferase levels, and liver biopsy histology results. A total of 878 patients with clinical or biochemical evidence of liver disease were enrolled at four hepatology clinics. A total of 1,089 specimens (901 serum and 188 plasma) were tested with the AMPLICOR test. Sensitivity compared to serology was 93.1% for serum and 90.6% for plasma. The specificity was 97% for serum and 93.1% for plasma. A total of 1,084 specimens (896 serum and 188 plasma) were tested with the COBAS test. Sensitivities for serum and plasma were the same as with the AMPLICOR test. The specificity was 97.8% for serum and 96.6% for plasma. Of the 69 specimens with false-positive and false-negative AMPLICOR test results relative to those of serology, alternative primer set (APS) reverse transcription (RT)-PCR analysis showed that the AMPLICOR test provided the correct result relative to the specimens containing HCV RNA in 64 (92.7%) specimens. Similarly, 66 of 67 (98.5%) false-positive and false-negative COBAS test results were determined to be correct by APS RT-PCR analysis. There were no substantive differences in clinical performances between study sites, patient groups, specimen types, storage conditions (-20 to -80 degrees C versus 2 to 8 degrees C), or anticoagulants (EDTA versus acid citrate dextrose) for either test. Both tests showed >99% reproducibility within runs, within sites, and overall. We conclude that these tests can reliably detect the presence of HCV RNA, as evidence of active infection, in patients with clinical or biochemical evidence of liver disease.

Adolescent↗
PubMed2001

Impact of histological grade of hepatocellular carcinoma on the outcome of liver transplantation.

HYPOTHESIS: Histological grade of hepatocellular carcinoma (HCC) is an important prognostic factor affecting patient survival after orthotopic liver transplantation (OLT). DESIGN: Retrospective analysis. SETTING: University-based teaching hospital. PATIENTS: Of 952 OLTs performed between June 1991 and January 1999, 56 OLT recipients had histologically proven HCC in the explant liver. Of those, 53 patients with complete clinicopathologic data were analyzed. A single pathologist blinded to the outcome of each patient reviewed all histological specimens. RESULTS: Median follow-up was 709 days. Overall survival for patients with tumors sized 5 cm or less at 1, 3, and 5 years was 87%, 78%, and 71%, respectively (Kaplan-Meier). Univariate analysis revealed the size, number, and distribution of tumors; the presence of microscopic vascular invasion and lymph node metastasis; histological differentiation; and pTNM stage to be statistically significant factors affecting survival. Multivariate analysis revealed histological differentiation and pTNM stage to be the independent and statistically significant factors affecting survival (P =.002 and.03, respectively). When pTNM stage was excluded from multivariate analysis, histological differentiation and size remained the significant independent factors (P =.02 and.03, respectively). Three-year survival for patients with small (</=5 cm) tumor with well- to moderately differentiated and poorly differentiated HCC was 82% and 67%, respectively. Three-year survival for patients with large (>5 cm) tumor with well- to moderately differentiated and poorly differentiated HCC was 62.5% and 0%, respectively. CONCLUSIONS: In our retrospective experience, histological differentiation had a statistically significant effect on the prognosis of HCC after OLT. However, before altering the current OLT selection criteria for patients with HCC, prospective studies are required to confirm the impact of histological grade on clinical outcome.

Carcinoma, Hepatocellular↗