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 management of acute HBV infection is supportive. Specific treatment is not indicated for HBV carriers because they often have no evidence of liver injury, and, further, do not respond to currently available therapies. Interferon monotherapy is best indicated for patients with chronic replicating HBV infection and evidence of chronic hepatitis. There is an increased likelihood of clearing HBsAg with interferon monotherapy as compared to lamivudine. Lamivudine is an oral nucleoside analog that is better tolerated than interferon. The clinical situations for its use are far more than interferon monotherapy. Lamivudine should be used in patients with decompensated cirrhosis and also in transplantation, both before and after transplantation. The post-transplant use of hepatitis B immune globulin (HBIG) and lamivudine combination therapy may be better for recipients who are identified in a replicative phase prior to transplantation. Hepatitis B coinfection with one or more viruses, HCV, HDV, or HIV, may occur. Both interferon and lamivudine have been useful in these patients. However, the data are sparse and heterogeneous. Therapy with one or both drugs will have to be tailored to the clinical situation. Combination therapy with immunomodulatory and/or antiviral drugs are what we will be looking toward in the future.
 ...
PMID:Hepatitis B. 1109 30

Hepatitis B is one of the most common infectious diseases in the world. It has been estimated that 350 million people worldwide are chronic hepatitis B virus (HBV) carriers. The global prevalence of chronic HBV infection varies widely, from high ( > 8%, e.g., Africa, Asia and the Western Pacific) to intermediate (2-7% e.g., Southern and Eastern Europe) and low (< 2%, e.g., Western Europe, North America and Australia). The predominant routes of transmission vary according to the endemicity of the HBV infection. In areas of high endemicity, perinatal transmission is the main route of transmission, whereas in areas of low endemicity, sexual contact amongst high-risk adults is predominant. Between one-third and one-quarter of people infected chronically with HBV are expected to develop progressive liver disease (including cirrhosis and primary liver cancer). Although mass vaccination programs have begun to control the spread of HBV infection, therapeutic intervention is the only option for those with established chronic HBV-associated liver disease. Until recently, the only treatment for chronic hepatitis B was the immune modulator, interferon (IFN) alpha. However, IFN alpha treatment has several disadvantages; it is expensive, it must be administered by injection, there are side-effects, and IFN alpha is poorly tolerated. Lamivudine, a nucleoside analogue, is the first effective, and well tolerated, oral treatment for chronic hepatitis B. In conclusion, although we are still some way from eradicating or curing chronic hepatitis B, the advent of lamivudine allows new populations to benefit from therapy and helps to address the global public health problem of hepatitis B.
 ...
PMID:Hepatitis B--an important public health issue. 1121 23

Chronic hepatitis B infection is frequently diagnosed within the genitourinary clinic setting with sexual transmission the commonest route of acquisition in the United Kingdom. Only 3--5% of adults who contract acute hepatitis B will progress to chronic infection, and these individuals can be identified by the presence of hepatitis B surface antigen (HBsAg) in the bloodstream 6 months after infection. Individuals at highest risk of long-term complications such as cirrhosis and hepatocellular carcinoma, carry HBeAg and have high levels of circulating hepatitis B virus (HBV) deoxyribonucleic acid (DNA). Therapy should be targeted towards this group of patients. Two forms of therapy are now licensed for use in chronic hepatitis B infection: interferon-alpha and lamivudine. Seroconversion occurs in 30--40% of patients treated with interferon and treatment is often limited by toxicity. Lamivudine is well tolerated with seroconversion rates of 15--20% at one year, rising with increasing duration of therapy. Long-term monotherapy is limited however by the development of resistance mutations and combination nucleoside therapy is likely to become the treatment of choice in the future. Patients with chronic hepatitis B should be counselled regarding transmission, partner vaccination and alcohol intake and co-infection with other hepatitis viruses should be excluded.
 ...
PMID:The management of chronic hepatitis B infection. 1180 40

Hepatitis B virus (HBV) is a major world health problem and a common cause of cirrhosis and hepatocellular carcinoma. The natural history of HBV varies with many factors, including age of acquisition. Persistent elevation of alanine aminotransferase (ALT) levels and presence of hepatitis B surface antigen for > 6 months after infection suggest chronic HBV. Presence of hepatitis B e antigen (HBeAg) and HBV DNA in serum indicate active disease. Treatment is indicated for chronic active HBV. The aim of treatment is to suppress viral replication and eliminate the virus. Endpoints of treatment are normalization of ALT levels and elimination of HBeAg and HBV DNA from the blood. Available treatments are interferon alfa and lamivudine. Interferon is effective in 25% to 40% of patients, but has serious side effects. Lamivudine is effective in a similar percentage of patients and has fewer side effects; however, it is associated with the emergence of viral mutations and drug-resistant strains.
 ...
PMID:Treatment of hepatitis B. 1150 Nov 92

(1) Chronic hepatitis B is defined by the persistence of circulating HBs antigen for more than 6 months. Between 15 and 25% of chronic HBV carriers die prematurely of complications (mainly cirrhosis and hepatocellular carcinoma). (2) Patients with chronic hepatitis B rarely clear the virus spontaneously, but viral replication ceases in approximately 10% of patients annually, with disappearance of HBe and viral DNA, and emergence of anti-HBe antibodies. (3) Active viral replication and histologically proven liver necrosis are risk factors for progression to cirrhosis. (4) Antiviral treatments have been assessed only in patients with active viral replication. (5) Interferon alfa has been widely tested in the clinical setting. In one trial, in which patients were followed for 7 years, mortality was lower in the treatment group than in untreated controls. (6) Interferon alfa must be injected, and its administration may be followed by adverse effects such as a 'flu-like syndrome (frequently), psychiatric problems and potentially severe thyroid disorders. (7) Interferon alfa monotherapy for 4-6 months (possibly extended to 8-9 months) remains the first-line treatment for chronic hepatitis B. (8) Lamivudine has documented antiviral efficacy but its effect is only temporary in many patients. In the only trial comparing lamivudine with interferon alfa, lamivudine was no more effective than interferon in the short term (on the basis of serological and histological end points), despite a bias in its favour. Trials of lamivudine + interferon alfa in patients who fail to respond to interferon monotherapy have given unfavourable results. (9) Adverse effects are infrequent on lamivudine, but pharmacovigilance is required to assess potential hepatic and pancreatic effects at the dose used in this indication. (10) The long-term effects of lamivudine are unknown, especially on the risks of cirrhosis, hepatocarcinoma and the selection of resistant mutants. (11) Pending further data, lamivudine should be used only in clinical trials and cohort studies.
 ...
PMID:Treatment of chronic hepatitis B: interferon alfa first. 1150 53

Lamivudine treatment of hepatitis B after orthotopic liver transplantation (OLT) is often accompanied by fast viral-resistance formation. Although no clinical data are available, in vitro data indicate that lamivudine-resistant reinfection has a mild course because of defective viral replication. Between 1996 and 1999, a total of 34 patients were treated with lamivudine because of hepatitis B recurrence after OLT. All patients developed reinfection despite long-term passive immunoprophylaxis with hepatitis B immunoglobulin, diagnosed by positive hepatitis B surface antigen and positive hepatitis B virus (HBV) DNA. Before treatment with lamivudine, 21 of these patients underwent a course of famciclovir and developed resistance. Monthly laboratory tests and sequential liver biopsies were performed during the follow-up period. Nineteen of 34 patients (56%) developed lamivudine resistance during the follow-up period of 12 to 49 months. One- and 3-year graft survival rates after the diagnosis of lamivudine resistance were 89% and 66%, respectively. In most cases, lamivudine resistance was associated with high viral replication (3,012 +/- 574 pg/mL 1 month after the diagnosis of lamivudine resistance); however, liver enzyme levels were only moderately elevated (alanine aminotransferase [ALT], 45 +/- 16 U/L). Only 3 patients (15%) showed a rapid increase in ALT level to more than 500 U/L within 3 months after resistance developed. All other patients had mildly elevated liver enzyme levels during the first 6 to 8 months after lamivudine resistance. In the later course, liver enzyme levels increased in most patients. Fourteen patients with elevated transaminase levels were switched to lamivudine plus interferon alfa (n = 8) or lamivudine plus famciclovir therapy (n = 6). This combination was successful in most cases, decreasing HBV DNA and liver enzyme levels. Four patients with lamivudine resistance died during follow-up, only 1 patient because of HBV reinfection. In addition, 2 patients underwent retransplantation because of hepatitis B cirrhosis of the first graft. Compared with historic courses of wild-type recurrence, lamivudine-resistant reinfection is characterized by a milder clinical course. Fulminant cases were not observed; however, in three cases, chronic liver failure developed. The combination of different antivirals diminished viral replication after lamivudine resistance. In the future, new antiviral agents, such as adefovir, might further expand therapeutic options.
 ...
PMID:Occurrence and clinical outcome of lamivudine-resistant hepatitis B infection after liver transplantation. 1169 34

There are two licensed drugs for chronic hepatitis B virus (HBV), interferon alfa and lamivudine, with similar efficacy rates. Lamivudine is less expensive and better tolerated than interferon alfa and is the drug of choice for patients with decompensated cirrhosis and recurrent HBV infection after liver transplantation. The major problem with lamivudine monotherapy has been the emergence of drug-resistant HBV polymerase (YMDD) mutants. Thus, long-term use of lamivudine in other settings remains somewhat controversial. Alternative nucleoside analogues that are active against both wild-type and YMDD-mutant HBV are currently being tested. It is hoped that a combination of one or more of these agents with lamivudine will not only prove more effective than lamivudine alone but also decrease the rate of lamivudine resistance. Preliminary studies suggest that the combination of interferon and lamivudine is associated with an enhanced rate of virologic response when compared with either agent alone. From a theoretical perspective, the combination of interferon with one or more nucleoside analogues may be the most effective way to treat HBV infection in many clinical situations.
 ...
PMID:How will we use the new antiviral agents for hepatitis B? 1182 43

This review updates the treatment of chronic hepatitis B infection. Complete eradication of hepatitis B virus (HBV) is not possible, so the efficacy of treatment has to be assessed by whether it can limit long-term cirrhosis-related complications. We discuss two major groups of treatments--immunomodulators (interferon alfa, thymosin alpha1, therapeutic vaccines) and nucleoside analogues (lamivudine, adefovir, entecavir, emtricitabine, beta-L-2'-deoxythymidine). To date, interferon alfa and lamivudine are the only two agents approved for chronic hepatitis B. Interferon alfa achieves a short-term outcome of around 20-30% loss of HBeAg. The efficacy is lower in Chinese patients, who are immunotolerant to HBV because of acquisition of the disease during early childhood, than in white patients. This difference is further confirmed on long-term follow-up. Interferon alfa does not affect the development of cirrhosis-related complications in Chinese patients, whereas in white patients, the frequency of long-term complications is reduced if interferon alfa is successful in inducing loss of HBeAg. Lamivudine profoundly suppresses viral replication and achieves an HBeAg seroconversion rate similar to that of interferon alfa. It is equally effective in Chinese and white patients because the main antiviral mechanism is through inhibition of reverse transcription of HBV during viral replication. However, long-term lamivudine therapy is associated with emergence of HBV variants, YMDD variants. Newer nucleoside analogues are being extensively investigated by studies in vivo and in vitro. Combination therapy with two or three nucleoside analogues or immunomodulators plus nucleoside analogues will be the future direction of treatment of chronic hepatitis B.
 ...
PMID:Treatment of chronic hepatitis B. 1187 10

Lamivudine therapy for chronic hepatitis and decompensated liver cirrhosis related to the hepatitis B virus (HBV) resulted in improvement of liver function and inhibition of viral replication. Despite emergence of the HBV mutant, e-antigen seroconversion and improvement of liver function may be achieved with continuation of lamivudine therapy. Although hepatic decompensation has been reported in a few cases after the emergence of lamivudine-resistant mutants, fatal cases of non-transplant patients have only rarely been reported in the literature. Here, we describe a patient with HBV-related liver cirrhosis who died after a breakthrough infection with a lamivudine-resistant mutant. Hepatic failure and mortality developed after flare-up of severe hepatitis after 13 months of lamivudine treatment. Emergence of the HBV mutant with substitution of isoleucine for leucine at residue 426 (L4261) in combination with isoleucine for methionine at residue 550 (M5501) was observed at 10 and 13 months of treatment.
 ...
PMID:Fatal hepatic failure after emergence of the hepatitis B virus mutant during lamivudine therapy in a patient with liver cirrhosis. 1191 2

Until recently, interferon monotherapy has been the only available therapeutic option for patients with chronic hepatitis B and hepatitis C. Lamivudine has emerged as another effective first-line therapy for chronic hepatitis B as well as a beneficial treatment option for patients with decompensated hepatitis B cirrhosis. Viral resistance with long-term lamivudine therapy remains a major concern but new data continue to show benefits despite the development of YMDD mutations. Combination therapy with ribavirin and pegylated interferon-alpha has revolutionized the treatment of chronic hepatitis C. The rate of sustained virological response can now be expected to be as high as nearly 50% for genotype 1 and 80% for non-1 genotypes of hepatitis C.
 ...
PMID:Therapeutic advances in the management of hepatitis B and hepatitis C. 1196 81


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>