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Biomedical subjects

Emmet B Keeffe

Publications and source records attributed to Emmet B Keeffe.

70 records · Page 4Linked to original sources
PubMed2003

Management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) ranks fifth in frequency worldwide among all malignancies and causes 1 million deaths annually. The management of HCC begins with diagnostic confirmation by radiologic imaging or histology. Staging is essential, as the choice of therapy depends on the functional state of the liver and the extent of tumor growth. Surgery, in the form of either hepatic resection or orthotopic liver transplantation, is the only potentially curative treatment. Transarterial chemoembolization is commonly used as either palliative treatment or adjunctive therapy to surgery, and a survival benefit with this therapy has just recently been demonstrated in a randomized, controlled trial. Patients with inoperable HCC may benefit from local ablative therapy that may still have curative potential in those with sufficiently small lesions and adequate liver function. For patients with advanced HCC, systemic chemotherapy has been widely employed, despite low efficacy and significant complication rate. Tamoxifen did not improve survival in large clinical trials. Gene therapy is an exciting approach to treating HCC but is still largely confined to preclinical and experimental settings.

Anticarcinogenic Agents↗
PubMed2003

Chronic hepatitis B and hepatitis C in Asian Americans.

Both chronic hepatitis B and hepatitis C are prevalent among the 12 million Asians and Pacific Islanders living in the United States. Significant epidemiological and clinical differences exist between Asian Americans and the general U.S. population, most notably the higher rate of primary liver cancer and the differential response to various antiviral therapies. Perinatal and childhood transmission is common for hepatitis B virus. Transmission of hepatitis C virus probably also occurs early in life and results from nosocomial transmission and person-to-person spread. Asian patients with chronic hepatitis B commonly have hepatitis B e antigen-negative hepatitis B with either the precore or core-promoter mutant hepatitis B virus, which may require long-term antiviral viral therapy because of high rates of relapse following therapy. Asian patients with chronic hepatitis C may have a substantially higher risk of liver cancer but a better response to interferon-based therapy, both in terms of sustained virological response and reduced future incidence of liver cancer. Understanding these differences will lead to improved care for Asian Americans with viral hepatitis and better disease control for hepatitis B and hepatitis C for the entire U.S. population. This review briefly summarizes the major issues in the clinical care of patients with chronic viral hepatitis and focuses on pertinent epidemiological and clinical differences between Asian-American and Caucasian patients.

Adult↗
PubMed2002

Clinical evaluation (phase I) of a combination of two human monoclonal antibodies to HBV: safety and antiviral properties.

Treatment of chronic hepatitis B virus (HBV) infection with interferon alfa and lamivudine is characterized by lack of viral clearance, loss of response, or emergence of drug-resistant mutants. Thus, new and multiple drug approaches are needed. We have developed two fully human monoclonal antibodies, directed against different epitopes of hepatitis B surface antigen (HBsAg) that bind to all major HBV subtypes. A phase I clinical study was conducted to evaluate the safety, tolerability, and efficacy of a mixture of these two monoclonal antibodies, HBV-AB(XTL). A total of 27 chronic HBV patients were enrolled. In part A of the study 15 patients in 5 cohorts received a single intravenous infusion of antibodies with doses ranging from 0.26 mg (260 IU) to 40 mg (40,000 IU). All patients completed 16 weeks of follow-up. In the second part of the study (part B), 12 patients in 4 cohorts received 4 weekly infusions of 10, 20, 40, or 80 mg each of HBV-AB(XTL) and were followed for 4 additional weeks. Administration of antibodies was well tolerated. Patients administered doses at an Ab:Ag molar ratio of 1:2 to 1:20 showed a rapid and significant decrease in HBsAg to undetectable levels, with a corresponding reduction of HBV-DNA levels. In part B, HBV-AB(XTL) induced a significant reduction in both HBsAg and HBV-DNA levels repeatedly after administration. In conclusion, these data suggest that HBV-AB(XTL) binds HBV particles and reduces serum viral titers and HBsAg levels. HBV-AB(XTL) could be combined with other monotherapies that are currently used to treat HBV carriers.

Adult↗
PubMed2002

Racial differences in effectiveness of alpha-fetoprotein for diagnosis of hepatocellular carcinoma in hepatitis C virus cirrhosis.

alpha-Fetoprotein (AFP) is frequently used as a diagnostic marker for hepatocellular carcinoma (HCC). Most available data concerning AFP come from studies of patients with chronic hepatitis B or other chronic liver diseases of mixed etiologies. Limited data concerning the diagnostic value of AFP for hepatitis C virus (HCV)-related HCC have to date come only from Asian and European studies, and results are conflicting. There may be significant differences in AFP levels depending on racial backgrounds and etiologies of primary liver disease. We conducted a multicenter, retrospective, case-control study of 163 HCC patients with HCV infection and 149 control patients with HCV-related cirrhosis. The positive likelihood ratios for AFP at 0 to 20, 21 to 50, 51 to 100, and 101 to 200 ng/mL were 0.46, 1.31, 1.15, and 6.90, respectively. No controls had AFP greater than 200 ng/mL. The sensitivity of AFP for the diagnosis of HCC in African Americans with HCV infection was lower than that of patients of all other ethnic groups combined (57.1% vs. 81.6% for AFP > 10 ng/mL, P =.02, and 42.9% vs. 66.0% for AFP > 20 ng/mL, P =.05). The area under the receiver operating characteristics curve was 0.81 for non-African Americans but only 0.56 for African Americans. In conclusion, AFP greater than 200 ng/mL can be used to confirm HCC in patients with HCV-related cirrhosis and a hepatic mass. However, AFP is insensitive for the diagnosis of HCC in African Americans.

Adult↗
PubMed2002

Effect of lamivudine treatment on survival of 309 North American patients awaiting liver transplantation for chronic hepatitis B.

The primary aim of this study is to determine whether treatment with lamivudine improved pre-liver transplantation (pre-LT) and LT-free survival of patients awaiting LT for hepatitis B virus (HBV)-related cirrhosis. Data from 162 lamivudine-treated and 147 untreated transplant candidates managed at 20 North American transplant centers between 1996 and 1998 were collected and compared. Lamivudine-treated patients were more likely to be men, hepatitis B e antigen positive, HBV DNA positive, and have lower serum albumin levels at listing (P <.05). Actuarial pre-LT and LT-free survival were similar in lamivudine-treated and untreated patients. Using Cox regression analysis, the only significant predictor of pre-LT patient survival was the modified Child-Turcotte-Pugh (mCTP) score, whereas significant predictors of LT-free survival included ethnic background, lamivudine treatment, indication for LT, baseline serum alanine aminotransferase level, and baseline mCTP score. Lamivudine had no apparent effect on liver disease severity in patients undergoing LT, but appeared to improve disease severity in patients still awaiting LT. Breakthrough infection was noted in 11% of lamivudine-treated patients. We conclude that lamivudine therapy is not associated with improved pre-LT or LT-free survival in LT candidates with chronic hepatitis B. However, a subset of patients with less advanced liver failure may derive clinical benefit from lamivudine therapy, thus delaying the need for LT. In the absence of prospective, randomized, controlled trials of lamivudine in patients with decompensated cirrhosis, careful selection of patients and optimal timing of treatment are needed to balance the risk versus benefit of lamivudine therapy in LT candidates.

Antiviral Agents↗
PubMed2002

Immunopathogenesis of primary biliary cirrhosis.

Although the autoantigens of antimitochondrial antibodies (AMA) have been defined and epitope mapped for both autoreactive B and T cells, the pathogenesis of primary biliary cirrhosis (PBC) still remains a mystery. The data gathered so far address several important aspects of this intriguing puzzle. First, biliary epithelial cells (BECs) seem to be immunologically active because they express molecules such as major histocompatibility complex (MHC) antigens, and adhesion and costimulatory molecules. Second, although pyruvate dehydrogenase complex (PDC)-E2, the major autoantigen in PBC, is upregulated in BECs when examined immunohistochemically, this abnormal staining seems to be secondary to immune complexes of AMA bound to PDC-E2 present in the BECs. Third, in addition to CD4(+) T cells, CD8(+) T cells also recognize the inner lipoyl domain of PDC-E2. Fourth, modification of mitochondrial antigens by xenobiotics may lead to the induction of the disease. These findings help to clarify the pathogenic mechanism of PBC and suggest that (l) induction may be secondary to a primary response to a xenobiotic that is normally metabolized in an estrogen-dependent pathway and (2) pathology is mediated by and orchestrated by a highly directed and specific CD4, CD8 and autoantibody response to the lipoyl domain of the mitochondrial autoantigens, with tissue destruction based on the immunoglobulin A (IgA) receptor, apoptosis, and the mucosal organization of biliary and salivary duct cells.

Autoantibodies↗
PubMed2002

Acute pancreatitis after gastrointestinal endoscopy.

Acute pancreatitis is a well-recognized complication of endoscopic retrograde cholangiopancreatography but is not considered to be a complication associated with other endoscopic procedures. We present a case of acute pancreatitis that occurred after uneventful upper and lower gastrointestinal endoscopy. The temporal relationship of the endoscopic procedures and development of acute pancreatitis suggests a causal relation. Furthermore, the patient had none of the usual etiologic factors associated with pancreatitis, i.e., alcoholism, cholelithiasis, hypertriglyceridemia, hypercalcemia, or use of a drug associated with pancreatitis. The causal mechanism of acute pancreatitis is uncertain but might potentially involve local trauma to the pancreas during a procedure or release of as yet undefined inflammatory mediators. In summary, three previous reports of clinical pancreatitis associated with endoscopy, in addition to the current case, suggests that acute pancreatitis should be considered as a rare complication of routine upper endoscopy or colonoscopy.

Acute Disease↗
PubMed2002

Viral hepatitis and other infectious diseases in a homeless population.

GOALS: To determine the prevalence of four common infectious diseases-hepatitis B, hepatitis C, human immunodeficiency virus (HIV), and tuberculosis-as well as co-infection rates and risk factors in a homeless population. BACKGROUND: The prevalence of infectious diseases, especially viral hepatitis, among the homeless population is largely unknown. STUDY: This study consists of a retrospective analysis of the history and laboratory data collected from all homeless veterans admitted to a Veterans Administration (VA) domiciliary from May 1995 to March 2000. RESULTS: Of the homeless veterans admitted to a VA domiciliary program, 597 of 829 were screened for markers of all four infectious diseases. The overall prevalence of anti-hepatitis C virus (HCV) antibody, and positive result for purified protein derivative (PPD), anti-HIV antibody, and hepatitis B surface antigen (HbsAg) were 41.7%, 20.6%, 1.84% and 1.17%, respectively. At least one of the four markers was positive in 52.6% and more than one in 12%. Co-infection with HCV occurred commonly in veterans who were positive for anti-HIV (72.7%) and HBsAg (57.1%). Four self-reported major risk factors (intravenous drug use, alcohol abuse, previous imprisonment, and prior stay in a shelter) were evaluated. Multivariate analysis indicates that intravenous drug use and anti-HBs reactivity are independent risk factors for HCV infection, HCV infection for anti-hepatitis B surface antibody reactivity, and older age for PPD positivity. CONCLUSIONS: Chronic hepatitis C and co-infections are common among the homeless population. Patients infected with HIV and hepatitis B virus frequently are co-infected with HCV. Infections frequently are associated with certain identifiable risk factors.

Adult↗
PubMed2002

Nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) encompasses a broad clinicopathologic spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which may advance to cirrhosis and end-stage liver disease. Steatosis alone does not appear to be progressive. The prevalence of NAFLD averages 20% and that of NASH, 2% to 3%, making these conditions the most common liver diseases in the United States. NAFLD is associated with insulin resistance, which may be evident clinically with obesity, type 2 diabetes mellitus, and hypertriglyceridemia. The pathogenesis of NAFLD consists of hepatic fat accumulation and oxidative stress with formation of free radicals. The clinical diagnosis is based on the presence of the insulin resistance syndrome and exclusion of alcohol abuse as well as viral, autoimmune, genetic, and drug-induced liver diseases. Liver biopsy is essential for diagnosis but may not be necessary for clinical management. Treatment is aimed at correcting the risk factors for NAFLD and using potentially hepatoprotective agents. Ursodeoxycholic acid and betaine appear particularly promising in early trials.

Biopsy, Needle↗
PubMedDate not supplied

Screening for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is common throughout the world and most often develops as a late complication of chronic viral hepatitis or cirrhosis of any cause. As a result of the high prevalence rate of chronic hepatitis C, the incidence of HCC is rising in the United States, as well as in European and Asian countries. The overall survival rate of HCC is poor, and surgical resection and liver transplantation are the only curative treatment options. Screening for HCC offers the best hope for early detection, eligibility for treatment, and improved survival. Most physicians routinely screen at-risk patients with chronic viral hepatitis and cirrhosis for HCC, despite the lack of official guidelines. The current consensus recommendations are to screen healthy hepatitis B virus carriers with annual or semiannual serum alpha-fetoprotein; carriers with chronic hepatitis or cirrhosis and patients with cirrhosis of any etiology are surveyed with twice yearly serum alpha-fetoprotein and liver ultrasound. This article will review the current recommendations for HCC screening, the rationale that led to these recommendations, and the challenges of cost-effectiveness research in this area.

Biomarkers, Tumor↗
PubMedDate not supplied

Occupational risk for hepatitis A: a literature-based analysis.

Hepatitis A virus is the most frequently occurring vaccine-preventable disease. Although generally self-limiting, acute hepatitis A is associated with substantial morbidity and related economic burden. Hepatitis A virus is transmitted by the fecal-oral route, and children are a main source of infection. Some occupational workers are at risk for hepatitis A virus infection based on the potential for contact with infected fecal matter and, in many regions in the United States and other developed countries, low overall rates of natural immunity. These at-risk occupations include daycare providers, hospital workers who have direct patient contact (nurses, nurses' aides, laundry workers), and sewage workers. Additionally, food handlers, particularly in the hospital setting, should be vaccinated if seronegative for hepatitis A virus because of their ability to rapidly spread disease among vulnerable populations if infected.

Hepatitis A↗
PubMedDate not supplied

[Acute liver failure].

Acute liver failure, also called fulminant hepatic failure, is characterized by sudden hepatic synthetic dysfunction associated with coagulopathy and hepatic encephalopathy. Acute liver failure has most recently been defined based on the timing from onset of jaundice to encephalopathy as follows: 1) hyperacute (1-7 days); 2) acute (8-28 days), and 3) subacute (29-60 days). Rapid onset of encephalopathy in hyperacute liver failure is paradoxically associated with highest rate of spontaneous recovery, and subacute liver failure is associated with worst prognosis. The etiology of liver failure is established by history, serologic assays, and exclusion of alternative causes. Acute liver failure is most frequently caused by drug hepatotoxicity, including acetaminophen toxicity and idiosyncratic drug reactions, with viral hepatitis playing a lesser role in recent surveys. A substantial number of cases have an indeterminate etiology. Major complications of acute liver failure that require active intervention include metabolic disorders, coagulopathy, cerebral edema, renal failure, and infection. The focus of management of acute liver failure is comprehensive supportive care in an intensive care unit and assessment of the need for liver transplantation.

Humans↗