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E B Keeffe

Publications and source records attributed to E B Keeffe.

At least 19 recordsLinked to original sources
PubMed2006

Systematic review: lamivudine prophylaxis for chemotherapy-induced reactivation of chronic hepatitis B virus infection.

BACKGROUND: Reactivation of hepatitis B virus infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well-documented and potentially fatal complication. Data supporting the use of lamivudine for primary prophylaxis have emerged, but its use remains controversial and is not standardized. AIM: To review current randomized-controlled trials, randomized trials and prospective case series to provide a clinically applicable, evidence-based recommendation. METHODS: The published literature was identified using a MEDLINE/PubMed search with secondary review of cited publications, and inclusion of all prospective studies. RESULTS: In nine prospective trials and one randomized-controlled trial, the rate of hepatitis among subjects receiving lamivudine prophylaxis ranged from 0% to 20% (16 of 173, 9.2%), compared with 33-67% among controls. Of patients receiving prophylaxis, 0-24% (15 of 173, 8.7%) developed hepatitis B virus reactivation, compared with 29-56% of controls. Three reactivation-related mortalities were reported (one receiving prophylaxis, two controls). No patients withdrew secondary to toxicity or development of lamivudine-resistant mutations. CONCLUSIONS: The available data show a four- to sevenfold decrease in the rate of hepatitis and hepatitis B virus reactivation in patients who receive lamivudine prophylaxis. It is thus recommended that all hepatitis B surface antigen carriers receive lamivudine, or a comparable anti-viral agent, as prophylaxis from the initiation of chemotherapy until at least 1 year following its completion.

Antineoplastic Agents↗
PubMed2004

Cost-effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C.

BACKGROUND: Screening for hepatocellular carcinoma in cirrhotic patients using abdominal ultrasonography and alpha-foetoprotein levels is widely practiced. AIM: To evaluate its cost-effectiveness using a Markov decision model. METHODS: Several screening strategies with abdominal ultrasonography or computerized tomography and serum alpha-foetoprotein at 6-12-month intervals in 40-year-old patients with chronic hepatitis C and compensated cirrhosis were simulated from a societal perspective, resulting in discounted costs per quality-adjusted life-year saved. Extensive sensitivity analysis was performed. RESULTS: For the least efficacious strategy, annual alpha-foetoprotein/ultrasonography, the incremental cost-effectiveness ratio (vs. no screening) was $23 043/quality-adjusted life-year. Biannual alpha-foetoprotein/annual ultrasonography, the most commonly used strategy in the United States, was more efficacious, with a cost-effectiveness ratio of $33 083/quality-adjusted life-year vs. annual alpha-foetoprotein/ultrasonography. The most efficacious strategy, biannual alpha-foetoprotein/ultrasonography, resulted in a cost-effectiveness ratio of $73 789/quality-adjusted life-year vs. biannual alpha-foetoprotein/annual ultrasonography. Biannual alpha-foetoprotein/annual computerized tomography screening resulted in a cost-effectiveness ratio of $51 750/quality-adjusted life-year vs. biannual alpha-foetoprotein/annual ultrasonography screening. CONCLUSIONS: Screening for hepatocellular carcinoma is as cost-effective as other accepted screening protocols. Of the strategies evaluated, biannual alpha-foetoprotein/annual ultrasonography gives the most quality-adjusted life-year gain while still maintaining a cost-effectiveness ratio <$50 000/quality-adjusted life-year. Biannual alpha-foetoprotein/annual computerized tomography screening may be cost-effective.

Carcinoma, Hepatocellular↗
PubMed2004

Review article: hepatitis vaccination in patients with chronic liver disease.

Evidence regarding the outcomes of viral super-infection in patients with chronic liver disease and practical strategies for hepatitis A and B vaccination of these individuals are reviewed. Patients with acute hepatitis A and chronic hepatitis B have a more severe clinical course and a higher death rate compared with otherwise healthy individuals with hepatitis A, and these differences are most pronounced in older patients and those with histological evidence of chronic hepatitis or cirrhosis, rather than in asymptomatic hepatitis B carriers. Patients with acute hepatitis A super-infection and chronic hepatitis C have an increased risk of fulminant hepatitis and death. In addition, patients with other chronic liver diseases also appear to be at increased risk for more severe disease with superimposed hepatitis A. Patients with chronic hepatitis B and hepatitis C virus co-infection have more severe laboratory abnormalities, more severe histological disease, a greater frequency of cirrhosis and complications of cirrhosis, and a higher incidence of hepatocellular carcinoma. Vaccines for both hepatitis A and B are safe and effective if used early in the course of chronic liver disease. Hepatitis A and B vaccination should be part of the routine management of patients with chronic liver disease, preferably as early as possible in the natural course of their disease.

Acute Disease↗
PubMed2004

Diagnosis and treatment of chronic hepatitis B.

The diagnosis of chronic hepatitis B virus (HBV) infection is made using a combination of serological, virological, biochemical, and histological markers. The natural history of HBV infection can be divided into 3 phases: immune tolerant, immune active with chronic hepatitis B, and inactive carrier; patients in the immune active phase are candidates for antiviral therapy. The primary goal of therapy for chronic hepatitis B is suppression of viral replication, which has been shown to reduce hepatic necroinflammation and retard progression of hepatic fibrosis. Long-term suppression of serum HBV DNA is likely to reduce progression to cirrhosis and hepatic decompensation and may also decrease the risk of hepatocellular carcinoma. Current antiviral therapy for chronic hepatitis B includes interferon alpha, lamivudine and adefovir, with recent studies demonstrating good safety and efficacy of peginterferon and other nucleoside analogues that will soon become additional treatment options. In patients with HBeAg-positive chronic hepatitis B, antiviral treatment is indicated when the serum HBV DNA level is = or >10(5) copies/mL and the alanine aminotransferase (ALT) level is elevated, particularly greater than 2 times the upper limits of normal. For HBeAg-negative patients, the threshold for initiation of therapy is a HBV DNA level = or >10(4) in association with an elevated ALT level. The presence of at least moderate necroinflammation and the presence of fibrosis on liver biopsy, which is optional and not mandatory before therapy, may be useful in supporting the decision to initiate therapy. While undergoing therapy, patients require monitoring every 3 to 6 months to ensure compliance and to test for the development of resistance if an oral agent is used. Issues that remain controversial or need to be studied further are the necessity of a baseline liver biopsy, the HBV DNA and ALT thresholds for initiation of therapy, the optimal duration of antiviral therapy, selection of one agent over another, and the role of combination therapy.

Hepatitis B e Antigens↗
PubMed2003

Systematic review: peginterferon vs. standard interferon in the treatment of chronic hepatitis C.

BACKGROUND: Randomized controlled trials over the last decade have demonstrated incremental improvement in the treatment efficacy of chronic hepatitis C with combination interferon and ribavirin therapy when compared with interferon monotherapy. AIM: To perform a systematic review of clinical trials directly comparing interferon formulations to test the hypothesis that a true difference in terms of efficacy exists between standard interferon (with and without ribavirin) and peginterferon (with and without ribavirin). METHODS: A search of the on-line bibliographic databases MEDLINE and PUBMED was performed independently by two authors to identify all relevant articles. In addition, the reference sections of all relevant articles were manually searched to identify any missed articles. Quality was assessed using the Jadad scale, which is an accepted scale specific for randomized controlled trials. A priori, it was decided to include only articles with a Jadad score of three or higher in the final analysis. Data were abstracted on to pre-determined abstraction sheets. The inclusion of articles, the data abstracted and the methodological score differences were adjudicated by consensus with agreement of the authors performing the search. RESULTS: Seven citations of randomized controlled trials, comparing at least two different interferon formulations and evaluating the sustained virological response as a primary end-point, were identified. These relevant articles were abstracted, and five of the seven were found to have a Jadad score of three or higher and comprised the final set of citations reviewed. The studies consistently demonstrated that peginterferon monotherapy was superior to standard interferon, even in patients with advanced fibrosis. With regard to combination interferon therapy, only two high-quality articles compared peginterferon plus ribavirin with standard interferon plus ribavirin. Both studies demonstrated that the overall sustained virological response was statistically better with peginterferon plus ribavirin. CONCLUSIONS: On the basis of this systematic review, peginterferon-based regimens are superior to standard interferon-based regimens for the treatment of chronic hepatitis C.

Adult↗
PubMed2003

Patient selection criteria for liver transplantation.

The demand for liver transplantation has progressively increased in the setting of a relatively fixed cadaveric organ supply over the past 5 years. An increasing percentage of listed patients are dying waiting for an organ, with additional listed candidates being disqualified as they became too sick for transplantation. This disparity between organ demand and supply has led to continued reassessment of selection and listing criteria for transplantation as well as periodic revisions of allocation and distribution policies for cadaveric livers. The minimal listing criteria adopted in the United States in the late 1990s initially served to prevent inappropriate organ allocation to patients who had risen to high priority for a donor organ simply because they had been listed early and had a longer total waiting time. Many of these patients had lesser disease severity and immediate need for transplantation than other patients competing for the same donor organ but listed later in the natural history of their end-stage liver disease. The United Network for Organ Sharing has continuously revised organ allocation and distribution policies in an attempt to balance the ethical principles of medical justice and utility, which potentially conflict with one another. The principle of justice advocates for the sickest patient who has been waiting for the longest time, whereas that of utility favors the patient with the highest likelihood of achieving successful outcome. Throughout all of the changes in organ allocation rules, patients with fulminant hepatic failure have continued to receive the highest priority for organs. The Model for End-Stage Liver Disease (MELD) has replaced the Child-Turcotte- Pugh system for assessing disease severity and predicted mortality in patients with chronic liver failure. However, the use of MELD has favored listed candidates who have the worst post-transplant survivals. Other options that are being explored to expand the donor pool include the use of marginal donors, split liver transplants, living donors, and domino transplants, with xenotransplantation still remaining experimental.

Humans↗
PubMed2001

Quantitative analysis of hepatitis C virus in peripheral blood and liver: replication detected only in liver.

Prior studies seeking evidence of viral replication in peripheral lymphocytes of hepatitis C virus (HCV)-infected patients have yielded conflicting results. This study sought to quantitatively determine whether a permissive HCV cell interaction could be detected in leukocytes from infected patients. Peripheral leukocytes from chronically infected patients were purified and were tested for HCV RNA. The results show that virus load is highest in B cells. Other subsets of peripheral leukocytes consistently had very low levels of viral RNA or were negative. Negative-strand HCV was found only in hepatocytes. To determine whether HCV replication could be induced by activation, B cells from HCV-infected patients were stimulated in vitro. No HCV replicating in peripheral leukocytes was detected by a highly sensitive assay. If HCV replication occurs in the leukocyte subsets analyzed here, it is at extremely low levels or occurs under alternate physiological conditions.

Adult↗
PubMed2001

Impaired dendritic cell maturation in patients with chronic, but not resolved, hepatitis C virus infection.

Dendritic cells (DCs) are important for the initiation of immune responses to foreign antigens. Their antigen uptake and presentation capacities enable them to prime and activate T cells. Immature DCs capture antigens; however, they must be activated to mature before serving as efficient antigen-presenting cells. The antigen-presenting capacity of DCs can be diminished during viral infection and as a consequence of tumor formation. Chronic infection with hepatitis C virus (HCV) has been shown to affect the allostimulatory function of DCs. In this study, it is demonstrated that monocyte-derived DCs from patients with chronic HCV infection do not respond to maturation stimuli. Instead, they maintain their immature phenotype, reflected by the pattern of cell surface markers and by their continued capacity to uptake antigen. Moreover, their allostimulatory abilities are impaired compared with those of mature DCs derived from healthy donors. To investigate a possible correlation between viral clearance and this DC maturation defect, patients with resolved HCV infection after a course of antiviral therapy were studied. Results demonstrate that DCs from patients who cleared HCV behaved like DCs from healthy donors: in response to maturation stimuli, they decrease antigen uptake, up-regulate expression of appropriate surface markers, and are potent stimulators of allogeneic T cells. (Blood. 2001;97:3171-3176)

Adult↗
PubMed2001

Primary biliary cirrhosis: lessons learned from an organ-specific disease.

Primary biliary cirrhosis is an autoimmune liver disease that predominantly affects women and is characterized by chronic progressive destruction of small intrahepatic bile ducts with portal inflammation and subsequent fibrosis. The serological hallmark is the presence of antimitochondrial antibodies, which are found in 95% of patients. These antibodies are directed against the 2-oxo-acid dehydrogenase complexes located on the inner membrane of mitochondria. Although the role of antimitochondrial antibodies in the pathogenesis is unknown, the presence of antibodies has allowed detailed immunological definition of the antigenic epitopes, the autoantibodies, and the T-cell response. Theories have been proposed regarding the mechanism of immune-mediated bile duct damage in primary biliary cirrhosis, including the possible role of T-cell-mediated cytotoxicity and molecular mimicry. Primary biliary cirrhosis is usually diagnosed based on the triad of elevated alkaline phosphatase, antimitochondrial antibodies, and characteristic histological changes on liver biopsy. Biochemical liver abnormalities are consistent with the presence of cholestasis and include an elevation of both serum alkaline phosphatase and gamma-glutamyl transpeptidase, with or without elevation of aminotransferase levels. Ursodeoxycholic acid, a dihydroxy bile acid, appears to be the only effective therapy in preventing or delaying the need for liver transplantation. However, a number of patients receiving ursodeoxycholic acid still develop progressive disease and require transplantation; at present, liver transplantation is the only effective therapy for end-stage primary biliary cirrhosis.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed2001

Ascitic fluid carcinoembryonic antigen and alkaline phosphatase levels for the differentiation of primary from secondary bacterial peritonitis with intestinal perforation.

BACKGROUND/AIMS: In cirrhotic patients, spontaneous bacterial peritonitis (SBP) may be difficult to distinguish from secondary peritonitis with occult intestinal perforation; Runyon's criteria (based on ascitic fluid glucose, protein and lactate dehydrogenase levels) are sensitive but not specific. Ascitic fluid carcinoembryonic antigen (CEA) and alkaline phosphatase (AP) are potential markers for secondary peritonitis. METHODS: Ascitic fluid CEA and AP levels were prospectively compared among three subject groups--cirrhotic patients with sterile ascites, cirrhotic patients with SBP, and patients (cirrhotic and non-cirrhotic) with perforation-related secondary peritonitis. RESULTS: The secondary peritonitis group (n = 38 including 11 cirrhotic patients) had significantly higher mean CEA and AP levels than the SBP (n = 34) and sterile ascites patients (n = 63). Of secondary peritonitis patients, 92% fulfilled predetermined criteria (either CEA >5 ng/ml or AP >240 units/l) versus only 12% of SBP patients; sensitivity was 92% and specificity 88% for differentiating secondary peritonitis from SBP. Runyon's criteria had a sensitivity of 97% and specificity of 56%. Stratification of secondary peritonitis patients by the presence or absence of cirrhosis did not alter our results. CONCLUSIONS: Ascitic fluid CEA or AP elevations appear to be sensitive and specific markers for perforation-related secondary peritonitis in cirrhotic as well as non-cirrhotic patients.

Adult↗
PubMed2001

Hepatitis C virus and liver transplantation.

Advances in immunosuppressive therapy, operative techniques, and perioperative management have resulted in long-term patient survival rates approaching 90% following liver transplantation for chronic viral hepatitis. The increasing number of referrals for liver transplantation reflects the impact of chronic HCV infection as a cause of end-stage liver disease. Unlike hepatitis B, there is still no effective treatment in preventing recurrent hepatitis C after liver transplantation. The spectrum of allograft injury related to universal HCV infection recurrence ranges from no evidence of histologic injury to mild inflammation to severe disease with allograft failure in small proportion of patients. Various factors may explain these differing outcomes, including degree of pretransplantation viremia, HLA compatibility, presence of more pathogenic HCV genotypes, integrity of cellular immune response, and type of immunosuppression. Fortunately, patient survival does not seem to be affected short-term; the long-term outcome of liver transplantation for chronic hepatitis C is unclear but is likely to be decreased. Combination therapy with interferon plus ribavirin seems to be a promising treatment strategy for posttransplantation recurrent hepatitis C, and the use of pegylated interferon plus ribavirin may improve these results. Patients with moderate to severe allograft hepatitis are appropriate candidates for combination antiviral therapy. Histopathologically documented recurrent hepatitis C in liver transplant recipients is associated with impaired quality of life, inferior physical condition, and a higher incidence of depression compared with patients who did not have HCV and in those without HCV recurrence. In conclusion, it is possible that the continued improvements in antiviral therapy against HCV infection may ultimately decrease the number of patients needing liver transplantation. Suitable candidates with chronic HCV infection thus warrant treatment with pegylated interferon plus ribavirin combination therapy in the hope of decreasing disease progression. Recent studies, which require confirmation, suggest that nonresponders to standard antiviral therapy may benefit from maintenance therapy. The donor pool for patients with chronic hepatitis C and decompensated cirrhosis can be improved by using HCV-positive donors and by increasing utilization of newer surgical techniques, including adult-to-adult living-donor liver transplantation and split-liver transplantation.

Antiviral Agents↗
PubMed2001

Liver transplantation: current status and novel approaches to liver replacement.

The major challenge currently facing liver transplantation is the performance of a greater number of liver transplants, which has been fueled by the large and growing disparity between the increasing number of qualified patients listed for transplantation and the relatively static number of available cadaver donor organs. In the past 2 years, approximately 4500 liver transplants have been performed annually, with 1-year survival rates in the 85%-90% range, while the waiting list has expanded as of November 2000 to more than 16,000 patients, resulting in an increasing death rate among listed patients. In the short term, there will continue to be a major focus on more effective use of available cadaver donor organs to balance the competing principles of justice (patients with most urgent need for transplant and lower probability of posttransplant survival) and medical utility (patients with less urgent need for transplant and higher odds of postoperative survival). Over the long term, there will be an increasing application of novel approaches to liver replacement including cadaver split liver transplantation and adult living donor liver transplantation and possibly, in the more distant future, xenotransplantation and hepatocyte transplantation. The treatment, and ideally the prevention, of recurrent disease after liver transplantation, particularly chronic hepatitis C-the most common indication for transplantation-is a major priority to optimize the use of liver grafts. Finally, improved immunosuppressive strategies, including movement toward minimal immunosuppression and steroid withdrawal and the development of safer and more effective drugs, is another important factor that has the potential to increase the success of liver transplantation.

Animals↗
PubMed2001

Liver transplantation in patients with hepatitis B virus infection: outcome in Asian versus white patients.

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.

Antiviral Agents↗
PubMed2001

Employment and alcohol use after liver transplantation for alcoholic and nonalcoholic liver disease: a systematic review.

The purpose of the study is to evaluate patterns of employment and alcohol use among liver transplant recipients with alcoholic (ALD) and nonalcoholic liver disease (non-ALD). MEDLINE, EMBASE, and bibliographic searches identified 5,505 potentially relevant articles published between January 1966 and October 1998. Eighty-two studies reporting data on 5,020 transplant recipients met our inclusion criteria. Pre-orthotopic liver transplantation (OLT), 29% of transplant recipients with ALD and 59% of those with non-ALD worked versus 33% and 80% at 3 years for transplant recipients with ALD and non-ALD, respectively (P <.00001 for each interval). We found no difference in the proportion of transplant recipients with ALD and non-ALD reporting early alcohol use post-OLT: 4% versus 5% at 6 months and 17% versus 16% at 12 months. However, among post-OLT drinkers, transplant recipients with non-ALD were more likely to drink moderately and those with ALD to drink excessively. At 7 years post-OLT, 32% of the patients with ALD reported using alcohol. The odds ratio for alcohol use among patients who maintained abstinence for fewer than 6 months pre-OLT versus those who maintained abstinence for greater than 6 months was 7.8 (95% confidence interval, 4.0 to 15.3). Before OLT and at long-term follow-up, substantially more transplant recipients with non-ALD than ALD were employed. The proportions of transplant recipients with ALD and non-ALD reporting alcohol use did not differ, although those with ALD tended to consume greater quantities.

Adult↗
PubMed2001

Detection and treatment of coronary artery disease in liver transplant candidates.

Patients with end-stage liver disease and coronary artery disease (CAD) being considered for orthotopic liver transplantation (OLT) present a difficult dilemma. The availability of multiple screening tests and newer treatment options for CAD prompted this review. Recent data suggest that the prevalence of CAD in patients with cirrhosis is much greater than previously believed and likely mirrors or exceeds the prevalence rate in the healthy population. The morbidity and mortality of patients with CAD who undergo OLT without treatment are unacceptably high, making identification of patients with CAD before OLT an important consideration. Patients with documented CAD or major clinical predictors of CAD should undergo cardiac catheterization before OLT. Those with advanced CAD not amenable to interventional therapy or with poor cardiac function are not candidates for OLT. Dobutamine stress echocardiogram appears to be an excellent means of screening patients with intermediate or minor clinical predictors of CAD before OLT. Patients found to have mild or moderate CAD should be aggressively treated medically and, if necessary and feasible based on hepatic reserve, by percutaneous or, less likely, surgical intervention pre-OLT to correct obstructive coronary lesions. Prospective studies regarding optimal screening strategies for the presence of CAD and the indications, timing, and outcomes of interventional therapy in patients with advanced cirrhosis are lacking and much needed.

Coronary Disease↗
PubMed2001

Quality of life and employment after liver transplantation.

1. In general, the health-related quality of life (QOL) of transplant recipients is impaired before and improves after liver transplantation. 2. Transplant recipients report largest gains in those aspects of QOL most affected by physical health and smaller improvements in areas affected by psychological functioning. 3. No utility-based measures have been used with liver transplant recipients; therefore, the necessary QOL weights for use in cost-effectiveness evaluations of liver transplantation are lacking. 4. Pretransplantation, the percentage of candidates with alcoholic liver disease (ALD) who work is less than that of candidates without ALD. However, there is no difference in rates of employment posttransplantation. 5. No study has described types of wages and benefits associated with jobs before or after transplantation or the extent to which health insurance benefits associated with employment motivate changes in work status. 6. Many studies in this field used non-validated heterogeneous instruments to measure QOL and employment, thus limiting the opportunity to combine results across studies and compare outcomes for liver transplant recipients with other patient populations.

Employment↗
PubMed2001

Delayed fatal hemorrhage from pseudoaneurysm of the hepatic artery after percutaneous liver biopsy.

Hemorrhage is the most common serious complication of percutaneous liver biopsy. Liver biopsy is usually done in an outpatient setting because most significant hemorrhage is evident within a few hours after biopsy. Delayed hemorrhage occurs much less frequently but carries a much higher mortality. We present a 41-yr-old man with chronic hepatitis C who underwent a percutaneous liver biopsy uneventfully but was found to have a pseudoaneurysm of the hepatic artery 5 days later. Shortly after admission, the patient experienced bleeding into the liver from the pseudoaneurysm, which was controlled initially by angiographic embolization. However, recurrent bleeding could not be controlled by repeat angiography and surgical intervention, and the patient expired. The diagnosis and management of pseudoaneurysm of the hepatic artery complicating liver biopsy is reviewed.

Adult↗