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

The aim of chronic hepatitis B therapy is to suppress hepatitis B virus replication, to control disease activity and progression towards cirrhosis. The first-line drug is the pegylated interferon a, which suppresses HBV replication in 40% of cases, albeit burdened with several contraindications and side effects. Lamivudine, a nucleoside analog inhibiting HBV reverse transcriptase, is indicated in case of failure or contraindication to interferon, may however lead to the selection of resistant mutant HBV strains (20% yearly). In that case, adefovir is indicated and has a lower risk of selection of resistant strains (5% yearly). More effective drugs (telbivudine and entecavir) will soon be available in Switzerland. Two inhibitors of HIV (tenofovir and emtricitabine) may also be used to treat hepatitis B in selected cases. Drug combinations, although supported by theoretical considerations, bring no known clinical benefit and are not reimbursed.
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PMID:[Therapy of chronic hepatitis B]. 1700 54

Survival after liver transplantation has steadily improved, in part because of newer immunosuppression, which may offer decreased long-term side effects. Reduction of steroids early in the course of transplant continues to be a goal, with satisfactory results in terms of both risk of rejection and reduction of side effects. Dominating the literature and the press in 1999 was the controversy surrounding the way in which livers are allocated. Regulation by the federal government was proposed to change the way the United Network of Organ Sharing distributes and allocates livers. Prompted by the shortage of organs, living-donor liver transplantation has blossomed. Continued experience in pediatric patients has shown excellent survival rate and quality of life. In adults, further experience is being gained with respect to the use of right lobes for transplantation. Early data suggest that this is a potential alternative to cadaveric transplantation in adults, with acceptable risk to the donor. Despite advances made in improving the technical aspects of transplantation, recurrent disease remains a significant issue. Lamivudine appears to be a potent inhibitor of hepatitis B virus DNA replication after liver transplantation, although resistance remains a significant problem. Further review of transplantation for hepatitis C virus is encouraging, with excellent five-year survival rate. However, studies evaluating the evolution of fibrosis in these patients throw caution on those results, showing increased progression to cirrhosis over time. Further follow-up of these patients is needed to more accurately assess long-term impact of hepatitis C on morbidity and mortality rates after liver transplantation.
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PMID:Liver transplantation. 1702 88

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.
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PMID:Viral hepatitis. 1703 Nov 67

Hepatitis A is still the most frequently reported vaccine preventable disease. A reduction in the incidence will only be achieved by routine childhood vaccination rather than by targeted vaccination of high-risk groups. A larger vaccine program is warranted. Hepatitis B remains a large public health problem. Vaccination targeted to high-risk adults failed to decrease the incidence of hepatitis B virus (HBV) infection. Sexual as well as nosocomial transmission remain serious problems. Vaccine escape variants have also been identified in newborns from infected mothers who had been vaccinated at birth. Clearance of HBV infection results from complex immune mechanisms including TH1 cytokines significantly associated with HLA class II alleles. Escape HBV mutants, especially precore mutants, influence the outcome. The sequences of the promoter and other critical regions were associated with severe activity. Lamivudine is a major advance in therapy of chronic hepatitis B which was recently approved in many countries. Although drug resistant mutants may be selected during therapy, additional nucleoside analogues including adefovir are promising. Optimal combination strategies of different active compounds need to be researched. Three per cent of the world population has been infected with hepatitis C virus (HCV). Epidemiology has shifted from transfusion to non-transfusion settings. Intravenous drug abuse is currently the main risk but nosocomial infection is also of concern. Three independent factors seem associated with fibrosis progression: age, daily alcohol consumption of 50 g or more and male gender. Median duration of progression to cirrhosis is about 30 years. At the cirrhotic stage, about 3-5% of patients per year develop hepatocellular carcinoma. There is little evidence that direct cytopathicity plays a significant role in liver cell injury. HCV also infects extrahepatic cells which seems critical in the pathogenesis of the many extrahepatic manifestations. The recent identification of CD81 protein as one of the HCV receptor candidates may help us to understand how chronic HCV infection may trigger a wide spectrum of clinical manifestations, autoimmune or even lymphoproliferative, through potent continuous B cell activation in the context of various host and/or environmental cofactors. Direct measurement of HCV RNA has clarified HCV replication kinetics and variability. Among patients with chronic hepatitis C, 48 weeks of treatment with interferon/ribavirin therapy produced a response rate of 28% among those with genotype 1 and 66% with other genotypes. Similar differences were found for combination therapy among patients who had relapsed following previous interferon (IFN) therapy. Viral load prior to treatment has been clearly shown to be predictive of response to interferon treatment, with increased viral load associated with decrease rates of response. In patients non-responsive to interferon, a second course of interferon alone has no beneficial effect whereas combination therapy may induce response in 25%. In conclusion, combination therapy should be given in all situations. Viral eradication should not be the only objective of the treatment since histological improvement may be obtained despite persisting viral replication with prolonged maintenance of antiviral therapy.
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PMID:Viral hepatitis. 1703 15

Chronic hepatitis B virus infection afflicts 400 million people worldwide and untreated will progress to cirrhosis in 15-40% of individuals, with an associated increased risk for the development of hepatocellular carcinoma. The 'inactive carrier state' carries a benign prognosis with a very low risk of cirrhosis or hepatocellular carcinoma. However, the hepatitis B e antigen (HBeAg)-positive chronic hepatitis state is an active disease state with increased risk for progressing to cirrhosis and hepatocellular carcinoma. The HBeAg-negative mutant variety of chronic hepatitis B has been associated with a higher incidence of cirrhosis at initial presentation and more frequent progression to hepatocellular carcinoma compared with the wild-type hepatitis B. Five medications are currently approved by the US FDA for the treatment of chronic hepatitis B: interferon-alpha, lamivudine, adefovir dipivoxil, entecavir and peginterferon-alpha-2a. Interferon-alpha therapy has been shown to increase the rate of HBeAg and hepatitis B DNA loss with a small chance of hepatitis B surface antigen loss, but has significant adverse effects and is ineffective against the HBeAg-negative mutant. Lamivudine is a safely used, orally administered drug with good efficacy, but is associated with the development of a lamivudine-resistant (Lam-R) mutant in a large proportion of patients after long-term therapy. High relapse rates after lamivudine therapy make this medication less effective in the HBeAg-negative mutant also. Adefovir dipivoxil is a safely used, orally administered drug, which is effective against the Lam-R mutant. Adefovir dipivoxil is effective against the wild-type and HBeAg-negative hepatitis B and has a very low incidence of resistance development. Entecavir is a highly potent and selective new oral drug against hepatitis B. It has demonstrated no resistance development in treatment-naive patients, but a low incidence of resistance in patients infected with prior Lam-R mutants. Peginterferon-alpha-2a is administered once weekly and has improved efficacy compared with standard interferon-alpha and lamivudine. However, it has a similar adverse-effect profile to standard interferon-alpha. Pharmacoeconomic studies have demonstrated a cost benefit in treating chronic hepatitis B patients compared with no therapy. However, results have been conflicting, with earlier studies showing a cost advantage of lamivudine over interferon-alpha and a more recent, comprehensive study favouring interferon-alpha monotherapy in HBeAg-negative patients and adefovir dipivoxil 'salvage' after lamivudine resistance development in HBeAg-positive patients.
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PMID:Natural course, therapeutic options and economic evaluation of therapies for chronic hepatitis B. 1704 Jan 14

Chronic hepatitis B progresses to cirrhosis in the majority of immunosuppressed patients. The outcome of long-term antiviral therapy in HBV-infected organ transplant recipients is unknown. In 1996, we included 20 heart transplant (HT) recipients in a pilot trial to treat chronic hepatitis B with famciclovir. At that time, bridging fibrosis or cirrhosis was evident in 15 individuals (75%). From 1998 onwards, patients were switched to lamivudine in case of primary or secondary virological nonresponse to famciclovir. Adefovir or tenofovir became available at our centre for HT recipients in 2002. After 103 months, one patient was still on famciclovir showing a complete virological response. Sixteen patients were switched to lamivudine after 0.5-4 years of famciclovir therapy. Six of those showed a long-term response to lamivudine therapy lasting for up to 7 years. Lamivudine resistance developed in the remaining 10 patients (63%), in 4 of them successful rescue therapy (adefovir n = 3, tenofovir n = 1) could be initiated. Only one hepatocellular carcinoma developed, which was successfully treated by locoregional ablative therapy. Nine patients died (45%), with lamivudine-resistance-related liver failure as the cause of death in five cases. Significant improvement of Ishak fibrosis scores could be demonstrated in six of the seven patients with more than two sequential liver biopsies available. Long-term antiviral therapy of chronic hepatitis B can lead to regression of liver cirrhosis in patients after organ transplantation, unless viral resistance occurs. This study demonstrates the urgent need for further antivirals to overcome antiviral resistance.
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PMID:Improved outcome of chronic hepatitis B after heart transplantation by long-term antiviral therapy. 1705 72

Hepatitis B immunoglobulin (HBIg) and lamivudine combination has been accepted as the best way to control hepatitis B recurrence after liver transplantation. However, the optimal dose of HBIg and the target titer of hepatitis B surface antibody (HBsAb) remain unclear. We report our satisfactory experience with high-dose HBIg in the early period followed by low-dose HBIg with lamivudine. Subjects comprised five patients with fulminant hepatitis (FH) and 18 patients with liver cirrhosis (LC) who underwent liver transplantation. HBIg at a dosage of 200 IU/kg per day was administered for one week postoperatively. Thereafter, HBIg was administered only for HBsAb titer <100 IU/L. After six months, HBIg was withdrawn in FH and administered in LC only for HBsAb titer <10 IU/L. Lamivudine was administered to two FH and all LC cases. Although two patients with LC showed transient hepatitis B surface antigen (HBsAg) recurrence, all patients remained HBsAg-negative at the final follow-up date. This method allows reliable and cost-effective control of hepatitis B recurrence.
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PMID:Short-term high-dose followed by long-term low-dose hepatitis B immunoglobulin and lamivudine therapy prevented recurrent hepatitis B after liver transplantation. 1726 22

Infection with hepatitis B virus (HBV) is extremely widespread - it infects two billion people out of the six billion world population. It is estimated that between 350 and 400 million people are chronically infected with HBV. Chronic HBV infection leads to development of complications, such as cirrhosis and hepatocellular carcinoma (HCC), which arise in 15-40% of patients. HBV-related liver disease and its complications result in approximately one million deaths each year. The ultimate goals of chronic hepatitis B (CHB) therapy are decreases in the incidence of cirrhosis, end-stage liver disease and HCC. The following six medications are currently approved by the U.S. Food and Drug Administration for the treatment of CHB: interferon (INF)-alpha2b, pegylated INF-alpha2a, lamivudine, adefovir dipivoxil, entecavir and, recently, telbivudine. Interferon therapy has many contraindications and commonly causes multiple intolerable adverse effects. Lamivudine therapy leads to increased development of resistant mutations with each year of use. Entecavir, a new guanosine nucleoside analogue with specific activity against HBV DNA polymerase, represents a third agent within the nucleoside/nucleotide HBV polymerase inhibitor class. It has distinct advantages over lamivudine and adefovir dipivoxil: it has a three-step mechanism of action, is the most potent inhibitor of HBV DNA polymerase, is not associated with any major adverse effects and has a limited potential for resistance. In clinical trials, entecavir was superior to lamivudine in all primary endpoints in both nucleoside-naive and lamivudine-refractory hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. Preliminary data support entecavir efficacy in patients with cirrhosis and HIV/HBV coinfected patients. No resistance occurred after two years of entecavir therapy in nucleoside-naive patients. Up to 9% resistance developed in patients with documented prior lamivudine resistance during 96 weeks of entecavir therapy. Currently, entecavir should be considered a first- or second-line treatment option for the management of HBeAg-positive or -negative nucleoside-naive or lamivudine-refractory CHB patients.
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PMID:Entecavir: a new nucleoside analogue for the treatment of chronic hepatitis B. 1746 Jul 84

Chronic hepatitis B virus (HBV) infection leads to long-term sequelae such as cirrhosis and hepatocellular carcinoma. Antiviral therapy aims at controlling the viral replication and thus, decreasing the likelihood of such complications. In this study, we evaluated the dynamics of biochemical and virological parameters over 10 years of antiviral therapy in a Thai patient with chronic HBeAg-negative HBV infection, who had relapsed after two courses of interferon alfa treatment. Lamivudine administration initially led to a significant reduction in alanine aminotransferase (ALT) and HBV DNA levels, but a subsequent emergence of YIDD mutants caused an ALT flare and a virus breakthrough. A 4-log HBV DNA decrease and normalization of the ALT level were achieved within 3 months of adefovir monotherapy without any relapse during follow-up exceeding 20 months. Thus, careful monitoring during treatment and knowledge of cross-resistance to antiviral salvage therapy are crucial for the management of patients with chronic hepatitis B.
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PMID:Dynamics of HBV DNA levels, HBV mutations and biochemical parameters during antiviral therapy in a patient with HBeAg-negative chronic hepatitis B. 1803 7

Chronic viral hepatitis remains a major problem among patients with chronic renal failure. Hepatitis B and C viruses are frequent among dialysis patients and after renal transplantation and may significantly diminish the survival of both the patient and the graft. Hepatitis B and C viral infection in these patients is often characterized by normal transaminase levels despite viremia and progressive liver lesions. Liver biopsy remains essential for assessing the extent of liver disease. Cirrhosis is a contraindication to transplantation of only a kidney, because of elevated morbidity and mortality. A combined as liver-kidney transplantation may be considered. The best treatment of hepatitis infections is preventive: vaccination against the hepatitis B virus and attentive hygiene, especially to prevent nosocomial transmission. Among patients not awaiting transplant, antiviral treatment should be reserved for patients with active or even fibrotic liver disease. For hemodialysis patients awaiting kidney transplant: Alpha interferon is ineffective and poorly tolerated by dialysis patients. Lamivudine is effective and well tolerated, but its long-term efficacy and its optimal effective dose in dialysis patients remain unknown.
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PMID:[Chronic viral hepatitis and kidney failure]. 1829 15


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