Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of hepatocellular carcinoma (HCC), a frequent and incurable complication of cirrhosis, continues to rise. Orthotopic liver transplantation (OLT) has been proposed as a treatment for unresectable, intrahepatic HCC limited in extent to the Milan criteria adopted by the United Network of Organ Sharing (UNOS) in 1998. More recently, somewhat less restrictive University of California, San Francisco (UCSF)10, criteria were proposed. To examine the long-term outcomes of OLT for HCC patients and to assess the UNOS policy of assigning weighted allocation points to patients with HCC, we retrospectively analyzed 144 patients (113 after 1998) with HCC who underwent OLT over an 11-year period at 3 institutions from UNOS Region 1. We compared their outcomes with 525 patients (272 after 1998) who underwent OLT for nonmalignant liver disease. The 1- and 5-year survival rates were 80.3% and 46.7%, respectively, for patients with HCC and 81.5% and 70.6%, respectively, for patients without HCC (P = .020). However, there was no difference in survival between HCC and non-HCC patients after implementation of disease-specific allocation for HCC in 1998. A higher proportion of the HCC cohort was older and male and had chronic HCV infection and alcoholic liver disease. In univariate analysis, having alpha-fetoprotein (AFP) levels of 10 ng/mL or less and meeting clinical and pathologic UCSF criteria were each significant predictors of improved survival (P = .005, P = .02, and P = .03, respectively). AFP greater than 10 ng/mL and exceeding pathologic UCSF criteria were also significant predictors of recurrence (P = .003 and P = .02, respectively). In conclusion, taken together, our data suggest that OLT is an acceptable option for patients with early HCC and that UCSF criteria predict outcome better than Milan or UNOS criteria. Regardless of which criteria are adopted to define eligibility, strict adherence to the criteria is important to achieve acceptable outcomes.
 ...
PMID:Liver transplantation outcomes for early-stage hepatocellular carcinoma: results of a multicenter study. 1549 58

Icatibant [HOE 140, JE 049] is a potent, specific and selective peptidomimetic bradykinin beta2-receptor antagonist. It has a modified peptide structure, and is the first bradykinin receptor antagonist to act on the guinea-pig trachea without demonstrating agonist effects. Icatibant was originated by Hoechst Marion Roussel (now Sanofi-Aventis). Jerini is seeking a partner for development and marketing of icatibant for the treatment of refractory ascites in liver cirrhosis, angioedema and burns. In August 2004, Aventis merged with Sanofi-Synthelabo to form Sanofi-Aventis.Icatibant has shown an excellent safety profile in phase I studies. In December 2003, Jerini demonstrated positive results in the phase IIa study. Results obtained were statistically significant and clinically relevant. At the BIO 2004 International Annual Convention (BIO-2004) [San Francisco, CA, USA; 6-9 June 2004], Jerini reported plans to initiate phase IIb trials in this indication in the second half of 2004. Positive results from an icatibant formulation comparative study, in patients with acute attacks of hereditary angioedema, were announced in August 2004; IV and SC formulations showed no difference in efficacy and safety. It was announced in September 2004 by Jerini that a pivotal study, known as For Angioedema Subcutaneous Treatment (FAST) 1, had been initiated in the US and Canada. The protocol of a European study, to be known as FAST 2, is to be submitted to the authorities in September 2004. Jerini expects to launch the product in 2006. The US FDA granted icatibant, for the treatment of hereditary angioedema, fast-track designation in July 2004. In January 2003, the European Agency for the Evaluation of Medicinal Products granted icatibant orphan drug status in Europe for the treatment of angioedema. In November 2003, Jerini announced that effective December 2003, icatibant had orphan drug status in the US for the same indication.
 ...
PMID:Icatibant: HOE 140, JE 049, JE049. 1556 38

In patients with cirrhosis and hepatocellular carcinoma (HCC), orthotopic liver transplantation (OLT) offers hope for cure of both the complicating HCC and the underlying chronic liver disease. Excellent 5 year survival has been reported when the restrictive Milan criteria are used to select transplant candidates. Alternative recommendations have recently been proposed by groups at University of California San Francisco, University of Pittsburgh and Mount Sinai. We review current and evolving concepts regarding selection criteria for OLT in patients with HCC, along with strategies to reduce waiting times, such as the impact of the implementation of the model for end-stage liver disease (MELD) scoring system on organ distribution and the role of living donor OLT for this indication. The possible efficacy of adjuvant anti-tumour therapies in limiting HCC growth while waiting for OLT, along with factors influencing the risk of HCC recurrence post-OLT, the major cause of death in this setting, are also discussed.
 ...
PMID:Liver transplantation for hepatocellular carcinoma. 1575 10

Icatibant [HOE 140, JE 049] is a potent, specific and selective peptidomimetic bradykinin B2-receptor antagonist. It has a modified peptide structure, and is the first bradykinin receptor antagonist to act on the guinea-pig trachea without demonstrating agonist effects. Icatibant was originated by Hoechst Marion Roussel (now sanofi-aventis). Jerini AG is seeking a worldwide partner for the development and marketing of icatibant for the treatment of refractory ascites in liver cirrhosis and seeking a partner in Asia, North America, South America and Australia for angioedema. In August 2004, Aventis merged with Sanofi-Synthelabo to form sanofi-aventis. Icatibant has shown an excellent safety profile in phase I studies. In December 2003, Jerini demonstrated positive results in the phase IIa study. Results obtained were statistically significant and clinically relevant. At the BIO 2004 International Annual Convention (BIO-2004) [San Francisco, CA, USA; 6-9 June 2004], Jerini reported plans to initiate phase IIb trials in this indication in the second half of 2004. It was announced in September 2004 by Jerini that a pivotal registration study, known as FAST 1 (For Angioedema Subcutaneous Treatment), had been initiated in the US and Canada. The protocol of a European study, known as FAST 2, was submitted to the authorities in September 2004. Jerini is currently conducting pivotal/registration trials for angioedema in the US, Canada and Europe. During the 3rd Annual BioPartnering North America Conference (BPN-2005), Jerini announced that it expects to complete registration trials in the second half of 2005/first half of 2006, with a launch of icatibant for HAE in 2007. The US FDA granted fast-track status to icatibant in July 2004 for the treatment of HAE. Effective December 2003, icatibant gained orphan drug status in the US for the same indication. Previously, in January 2003, the European Agency for the Evaluation of Medicinal Products granted icatibant orphan drug status in Europe for the treatment of angioedema.
 ...
PMID:Icatibant: HOE 140, JE 049, JE049. 1599 85

Hepatitis C infection is the most common chronic blood-borne pathogen in the United States associated with liver cirrhosis and hepatocellular carcinoma and is the leading reason for liver transplantation. It has been estimated that hepatitis C infection may lead to a substantial health and economic burden over the next 10 to 20 years. The prevalence of hepatitis C virus (HCV) infection varies worldwide, with an estimated overall prevalence of 3%. However, the only available data of hepatitis C in the general population of Puerto Rico suggest an elevated prevalence of hepatitis C infection in the municipality of San Juan (6.3%) in comparison with estimates for the adult population residing in the United States (0.9%-3.9%). Much of the inter-region variability in the prevalence of hepatitis C can be attributable to the frequency and extent to which different risk factors have contributed to the transmission of the virus. Established risk factors for infection include injection drug use, transfusion of blood and solid organ transplantation from infected donors prior to July 1992 and blood clotting products before 1987, occupational injury, vertical transmission, sex with an HCV infected partner, and multiple sexual partners. Other potential exposures for infection that have been investigated in epidemiologic studies include history of intranasal cocaine use, sharing of contaminated equipment and personal care items, tattooing, body piercing, imprisonment, acupuncture, and use of contaminated healthcare instruments. The high incidence of AIDS in Puerto Rico and the large prevalence observed in Puerto Rican inmates and in adults residing in the municipality of San Juan indicate that HCV infection is an emerging public health concern. From a public health perspective, potential targets for intervention to decrease the spread of HCV infection, ongoing surveillance, increased clinician awareness of disease reporting systems and the epidemiology and management of hepatitis C, availability of diagnosis and treatment facilities, and recognition of the need for local resources will be of paramount importance to face this silent infection in Puerto Rico.
 ...
PMID:Epidemiology of hepatitis C infection and its public health implications in Puerto Rico. 1692 83

The use of methotrexate in the treatment of psoriatic arthritis is associated with risk of hepatotoxicity. However, monitoring of liver-associated enzymes often lacks sensitivity, and guidelines for serial liver biopsies in psoriatic arthritis are not yet well established. We performed a retrospective review of all patients with psoriatic arthritis receiving methotrexate who were enrolled in the disease-modifying anti-rheumatic drug clinics (DMARD clinics) at the Air Force and Army hospitals in San Antonio, Texas. Information was obtained regarding methotrexate regimen, liver-associated enzyme results, and liver biopsy results. Thirty psoriatic arthritis patients were taking methotrexate in the DMARD clinics. Seventeen patients had a total of 21 biopsies. Biopsies were performed for surveillance dictated by cumulative dose. Liver biopsies were graded on Roenigk scale of I-IV where I is mild steatosis, II is moderate steatosis, IIIa is mild fibrosis, IIIb is severe fibrosis, and IV is cirrhosis. Ten biopsies were grade I, 5 were grade II, 5 were grade IIIa, 1 was grade IIIb, and none were grade IV. In this very small retrospective study, regular monitoring of liver-associated enzymes did not correlate with histologic deterioration in our patients. Until prospective studies are performed, we suggest that routine liver biopsies are necessary to monitor for methotrexate hepatotoxicity in psoriatic arthritis.
 ...
PMID:Liver biopsy in psoriatic arthritis to detect methotrexate hepatotoxicity. 1703 36

Chronic hepatitis B is the most common cause of cirrhosis and liver cancer worldwide. Approximately 45% of the world's population lives in regions where chronic hepatitis B virus (HBV) infection is endemic, including most of Asia and the Pacific Islands, Africa, and the Middle East. Nearly one fourth of the population of San Francisco was born in Asia and the Pacific Islands. In 2006, the San Francisco Department of Public Health (SFDPH) received reports consistent with probable chronic HBV infection for 2,238 persons. To characterize persons with reported confirmed chronic HBV infection in San Francisco in 2006, SFDPH collected additional data on a subset of 567 cases reported to the SFDPH chronic hepatitis B registry. Eighty-four percent of the persons were Asians/Pacific Islanders (A/PIs), 80% of whom were foreign born. Fewer than half had been referred to a gastroenterologist/hepatologist for evaluation at the time of reporting. Persons with chronic HBV infection can benefit from medical care by providers with expertise in viral hepatitis. In addition, close contacts of infected persons should be screened and offered vaccination if found to be susceptible to HBV infection. Culturally appropriate counseling for and follow-up of persons with chronic HBV infection and their contacts could help reduce the transmission of HBV infection.
 ...
PMID:Characteristics of persons with chronic hepatitis B--San Francisco, California, 2006. 1749 91

Living donor liver transplantation of the right lobe might offer the possibility to extend the eligibility criteria of patients with hepatocellular carcinoma (HCC) in cirrhosis without penalizing patients who are waiting for a graft from a deceased donor. From 1988 to 2005, surgical treatment of HCC was performed in 580 patients (187 transplantation, 393 resection) in a European center. In the transplantation group, 21 patients with HCC in cirrhosis underwent LDLT (11% of all transplantations for HCC; 22% of 96 LDLT). Solitary HCC were accepted irrespective of their diameter unless vascular invasion was detectable. Multiple HCC nodes were considered acceptable up to a diameter of the largest node of 6 cm and a total tumor diameter of 15 cm. The median follow-up period was 26 months (range, 1-65 months). Vascular invasion had occurred in 12 patients (57%). One patient (4.8%) died within 60 days after transplantation from sepsis. Rates of 3-year survival and 3-year recurrence-free survival were 68% and 64%, respectively. Overall 3-year survival rates in patients with HCC in cirrhosis not meeting the Milan criteria (n = 13) or the San Francisco criteria (n = 8) were 62% and 53%, respectively. LDLT is a safe procedure. However, small sample sizes do not yet permit a definitive comparison to be made between the former results obtained after cadaveric donation. So far, the outcome of the patients is in favor of a careful extension of the selection criteria for HCC in cirrhosis.
 ...
PMID:Living donor liver transplantation of the right lobe for hepatocellular carcinoma in cirrhosis in a European center. 1753 94

HIV and hepatitis B virus (HBV) coinfection increases HIV and HBV replication, hepatitis flares, and risk of progression to chronic HBV infection, cirrhosis, and hepatocellular carcinoma. HIV and HBV coinfection decreases frequency of hepatitis Be antibody (anti-HBe) and hepatitis B surface antibody (anti-HBs) seroconversion, increases risk of antiretroviral therapy-related hepatotoxicity, and reduces efficacy of HBV therapy. All newly diagnosed HIV patients should be screened for hepatitis A, B, and C viruses and vaccinated if not immune to hepatitis A or B viruses. HBV serology often is atypical in coinfection. Diagnosis of HBV coinfection in HIV infection is made on the basis of hepatitis B surface antigen (HBsAg)-positive, hepatitis B core antibody (anti-HBc total)-positive, anti-HBs-positive status. Alanine aminotransferase levels in coinfected patients often are not reliable markers of liver inflammation. HBV infection should always be treated if coinfected patients are receiving antiretroviral therapy, since immune reconstitution under antiretroviral therapy poses risk for immune-associated liver damage in these patients. This article summarizes a presentation on HIV and HBV coinfection made by Marion G. Peters, MD, at an International AIDS Society-USA Continuing Medical Education course in San Francisco in May 2007.
 ...
PMID:Diagnosis and management of hepatitis B virus and HIV coinfection. 1807 52

The significance of gallbladder wall thickness (GBWT) in regard to gallbladder disease (GBD) is not completely understood. Thickening of the gallbladder wall has been observed in patients with acute calculous and acalculous cholecystitis and chronic cholecystitis. However, various pathologic processes, such as gallbladder cancer and nonbiliary disorders such as liver cirrhosis and viral hepatitis, could also cause thickening of the gallbladder wall. To date, there is no report available on the genetic factors influencing GBWT. Therefore we sought to estimate the heritability (h2) of GBWT and to perform a genome-wide search to identify the susceptibility genes for GBWT, using data from the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), a family study of Mexican Americans. GBWT was measured by ultrasound. After adjusting for the significant effects of age, sex, GBD (i.e., asymptomatic gallstones), metabolic syndrome, and duration of type 2 diabetes (T2DM), GBWT was found to be under significant and appreciable additive genetic influences (h2 +/- SE = 0.38 +/- 0.09, P < 0.0001). The strongest evidence for linkage occurred between markers D11S912 and D11S968 on chromosome 11q24-q25 (LOD = 2.7), where we have already shown suggestive evidence for linkage of GBD (LOD = 2.7) in a subset of our SAFDGS data. Potential evidence for linkage occurred at markers D1S1728 (1p31.1; LOD = 1.4) and D16S748 (16p13.1; LOD = 1.4), respectively. In conclusion, our study provides suggestive evidence for linkage of GBWT on chromosome 11q in Mexican Americans, and future tasks of mapping susceptibility gene(s) for GBD and its related traits, such as GBWT, in this chromosomal region can be fruitful.
 ...
PMID:Autosomal genome-wide linkage analysis to identify loci for gallbladder wall thickness in Mexican Americans. 1850 42


<< Previous 1 2 3 4 5 Next >>