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Biomedical subjects

Emmet B Keeffe

Publications and source records attributed to Emmet B Keeffe.

At least 19 recordsLinked to original sources
PubMed2007

New and emerging treatment of chronic hepatitis B.

Conventional treatment of chronic hepatitis B with interferon alfa-2b, lamivudine, and adefovir is limited by low rates of sustained hepatitis B virus DNA suppression and hepatitis B e antigen (HBeAg) seroconversion, increasing rates of drug resistance to the oral agents, and poor tolerability of interferon. Recently several promising new antiviral agents have emerged that possess potent antiviral effects, less toxicity, and have little or no risk of drug resistance. Two new agents, entecavir and peginterferon alfa-2a, have received recent approval by regulatory authorities in the United States and several other countries for the treatment of adults with chronic hepatitis B. In large phase III clinical trials, these agents have demonstrated superior efficacy over lamivudine in both HBeAg-positive and HBeAg-negative patients. Drug resistance occurs at a low rate in lamivudine-refractory patients treated with entecavir or is, to date, nonexistent in nucleoside-naïve patients treated with entecavir and all patients receiving peginterferon. In addition, several novel agents in clinical development, such as emtricitabine, clevudine, telbivudine, valtorcitabine, and tenofovir, have shown promising clinical profiles in patients with chronic hepatitis B. This review summarizes the recent clinical studies of these new agents and discusses the implications of these data for the management of chronic hepatitis B.

Antiviral Agents↗
PubMed2007

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

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

Adult↗
PubMed2006

Dermatologic disorders associated with chronic hepatitis C: effect of interferon therapy.

Chronic hepatitis C virus infection (HCV) is associated with extrahepatic manifestations, including such dermatologic conditions as mixed cryoglobulinemia, porphyria cutanea tarda, and lichen planus. Patients with chronic HCV and extrahepatic manifestations are often excluded from clinical trials evaluating interferon (IFN) therapy due to concerns about poor response, adverse events, and toxicity. Thus, data regarding the efficacy of IFN not only on the underlying chronic HCV, but also on extrahepatic manifestations, are limited in these patients. Case reports suggest that the response of dermatologic extrahepatic manifestations to IFN in patients with chronic HCV is highly variable. This review summarizes available data on dermatologic conditions associated with chronic HCV and their response to IFN therapy.

Antiviral Agents↗
PubMed2006

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↗
PubMed2006

Do we still need a liver biopsy? Are the serum fibrosis tests ready for prime time?

Liver biopsy has been in use for more than a century for diagnosis and staging of acute and chronic liver diseases. Several serum markers and panels offer the opportunity to assess the extent of liver disease noninvasively and spare some patients the risks associated with percutaneous liver biopsy, but only a few of the noninvasive serum markers allow the determination of different stages of fibrosis on a continuum similar to that achieved with liver biopsy. This article reviews the results of recent published and preliminary studies on serum markers, focusing on their comparison with liver biopsy and their clinical utility.

Alanine Transaminase↗
PubMed2006

Hepatitis B vaccines.

Immunization is the most effective way to prevent transmission of HBV and, hence, the development of acute or chronic hepatitis B. The national strategy to eliminate transmission of the virus in the United States includes vaccination of all newborn infants, children, adolescents, and high-risk adults. Postexposure prophylaxis is also advocated, depending on the vaccination and anti-HBs status of the exposed person. Seroprotection after vaccination, defined as anti-HBs > or = 10 mIU/mL, is achieved in over 95% of all vaccinees. The hepatitis B vaccines are very well tolerated with usually minimal adverse effects. Predictors of non-response include increasing age, male gender, obesity, tobacco smoking, and immunocompromising chronic dis-ease. For those who remain nonresponders after the second series of vaccination, adjuvants such as GM-CSF may be considered, but their results are variable.

Journal Article↗
PubMed2006

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↗
PubMed2006

Escherichia coli O157:H7 infection in nursing homes: review of literature and report of recent outbreak.

Escherichia coli O157:H7 is a well-described cause of hemorrhagic colitis in isolated cases and outbreaks. The postdiarrhea complications of this infection (thrombotic thrombocytopenic purpura and hemolytic uremic syndrome) have historically been linked to illness in children aged 5 to 10, but in an elderly, institutionalized population, E. coli O157:H7 is associated with high morbidity and mortality. This geriatric population is at high risk for developing gastrointestinal infections for a number of reasons, including age- and medication-related achlorhydria, antibiotic usage, and comorbid medical conditions. The combination of age-related risk factors with those associated with group living makes nursing facilities a high-risk environment for outbreaks of infectious diseases. E. coli O157:H7 may be more likely to cause disease outbreaks in this population because of the low inoculum required for clinical infection. Moreover, the prevalence of potential competing diagnoses, such as lower gastrointestinal bleeding from neoplastic or diverticular disease, complicates the diagnosis. Clinical presentation and laboratory studies are unpredictable and pose diagnostic challenges. This report reviews the literature on nursing home outbreaks of E. coli O157:H7 and presents an outbreak that occurred in an assisted living community in San Mateo County, California, in October 2003. The purpose of this literature review and report of an outbreak is to heighten awareness of the unique susceptibility of elderly, institutionalized patients for E. coli O157:H7 infection and its sequelae.

Aged↗
PubMed2006

Best of DDW 2006.

Highlights from the 2006 Digestive Disease Week May 20-25, 2006, Los Angeles, CA. In this meeting review, many of our editorial board members report on Digestive Disease Week 2006. They highlight the most noteworthy presentations in their respective areas of expertise, including the latest treatments, technologies, and diagnostic advances in ulcerative colitis, Crohn's disease, Helicobacter pylori infection, gastroesophageal reflux disease, irritable bowel syndrome, colorectal cancer, pancreatic and biliary disease, and liver disease.

Digestive System Diseases↗
PubMed2005

Natural history and treatment of hepatitis B virus and hepatitis C virus coinfection.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is not uncommon as a result of similar routes of infection. Patients who are coinfected represent a unique group with diverse serologic profiles. Combined chronic hepatitis B and C leads to more severe liver disease and an increased risk of hepatocellular carcinoma. Furthermore, coinfected patients represent a treatment challenge. No standard recommendations exist for treatment of viral hepatitis due to dual HBV/HCV infection, and therefore treatment must be individualized based on patient variables such as serologic and virologic profiles, patient's prior exposure to antiviral treatment, and the presence of other parenterally transmitted viruses such as hepatitis D virus and human immunodeficiency virus. The natural history and treatment of patients with HBV and HCV coinfection is reviewed.

Carcinoma, Hepatocellular↗
PubMed2005

Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation.

BACKGROUND/AIMS: The susceptibility of adefovir-resistant hepatitis B virus (HBV) mutants is only reduced by 3-10-fold in in vitro studies, suggesting that virologic breakthrough and clinical deterioration are unlikely. The aim of this study was to describe the clinical course of patients with adefovir-resistant HBV infection. METHODS: Testing for adefovir-resistant mutations was performed on patients who had a suboptimal response or virologic breakthrough on adefovir. Adefovir-resistant mutations were detected using a line probe assay and direct sequencing of the HBV P-gene. RESULTS: Eight male patients with pre-existing lamivudine resistance or breakthrough (mean age 47+/-13 years) were found to have adefovir-resistant mutations rtA181V/T or rtN236T. Baseline median ALT was 66 IU/L (range, 27-1161) and median HBV DNA 7.9 log10 copies/ml (range, 6-8.3). At the time of adefovir resistance (mean of 20+/-9 months), HBV DNA increased to > or = 5 log10 copies/ml in 7 patients. After detection of adefovir resistance, hepatic decompensation occurred in 2 patients, 1 of whom died. Salvage therapy with lamivudine, entecavir or tenofovir was given to 7 patients and a reduction in HBV DNA by > or = 3 log10 was seen in 3 patients. CONCLUSIONS: In conclusion, adefovir resistance can be associated with significant viral rebound and hepatic decompensation which may be fatal.

Adenine↗
PubMed2005

T cell immunity in hepatitis B and hepatitis C virus infection: implications for autoimmunity.

T cells are involved in the pathogenesis of important liver diseases including both autoimmune liver diseases and viral hepatitis. In addition to playing a crucial role in the control of hepatitis viruses, T cell responses are also responsible for the liver injury during acute and chronic phases of viral hepatitis. In this article, we reviewed current literature on T cell immunity to hepatitis B and C viruses. In addition, antigen presenting cells that are critical for T cell immunity against these viruses are also discussed. This will provide insights to the understanding of T cell immunity in autoimmune liver diseases due to the similar role of T cells in autoimmune liver diseases and viral hepatitis.

Antigen-Presenting Cells↗
PubMed2005

Acute hepatitis A and B in patients with chronic liver disease: prevention through vaccination.

Retrospective and prospective studies have demonstrated that the occurrence of acute hepatitis A in patients with chronic liver disease is associated with higher rates of morbidity and mortality than in previously healthy individuals with acute hepatitis A. The mortality associated with acute hepatitis A may be particularly high in patients with preexisting chronic hepatitis C. Although acute hepatitis B in patients with preexisting chronic liver disease is less well studied, worse outcomes than in previously healthy individuals are apparent. However, numerous studies convincingly demonstrate that chronic hepatitis B virus coinfection with hepatitis C virus (or hepatitis D virus) is associated with an accelerated natural history of liver disease and worse outcomes. These observations led to studies that demonstrated the safety and efficacy of hepatitis A and hepatitis B vaccination in patients with mild-to-moderate chronic liver disease. Hepatitis A and B vaccination is less effective in patients with advanced liver disease, especially after decompensation, such as in patients awaiting liver transplantation, and in liver transplant recipients. The emerging lower rates of inherent immunity in younger individuals, higher morbidity and mortality of acute hepatitis A or B superimposed on chronic liver disease, and greater vaccine efficacy in milder forms of chronic liver disease suggest that it is a reasonable policy to recommend hepatitis A and B vaccination in patients early in the natural history of chronic liver disease.

Acute Disease↗
PubMed2005

General management.

Hepatocellular carcinoma is one of the most common malignancies worldwide. The general management of hepatocellular carcinoma begins with an accurate diagnosis. With advances in imaging studies, noninvasive diagnosis has become an accepted standard of care for hepatocellular carcinoma, though pathologic examination is still required in selected cases. Following diagnosis, accurate staging is the next most important step in selecting the most appropriate treatment modality. Patients with localised tumor and compensated liver disease should be considered for partial hepatectomy, and patients with poor hepatic function but early tumor stage are candidates for liver transplantation. Patients who do not qualify for either of these curative treatments may be evaluated for palliative therapy, of which transarterial chemoembolisation is most widely used. This review will discuss the role of biopsy, the pros and cons of noninvasive and pathologic tissue diagnosis as well as the general approach to choose the most appropriate treatment for patients with hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed2005

Chronic hepatitis C: genotypes 4 to 9.

Infection with hepatitis C virus (HCV) genotypes 1, 2, or 3 is widely distributed throughout the world and has been the focus of the majority of studies on the epidemiology and treatment of chronic hepatitis C. Infection with HCV genotypes 4 through 9 is prevalent in some geographic areas where the disease burden of chronic hepatitis C approaches endemic levels (eg, HCV genotype 4 in Egypt where there is an HCV infection prevalence of approximately 18%). This article reviews the existing literature, which suggests that chronic hepatitis C with genotypes 4 through 9 may exhibit epidemiologic, clinical, and treatment outcome differences from infection with genotypes 1, 2, or 3.

Africa↗