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)

Chronic HBV infection is a common cause of advanced liver disease that is associated with substantial mortality. Furthermore, chronic hepatitis B was historically a controversial indication for liver transplantation because of a low post-transplant survival, with graft infection being the major contributor to adverse outcomes. The initial use of hepatitis B immune globulin as prophylaxis, followed later by combined therapy with lamivudine, markedly reduced viral recurrence and improved the survival of patients transplanted for acute or chronic hepatitis B with liver failure. Lamivudine alone can also be used for long-term prophylaxis against de novo HBV infection that can be transmitted by organs from donors positive for anti-HBc or anti-HBs. When used in patients with decompensated chronic hepatitis B with cirrhosis, lamivudine has been shown to improve clinical manifestations, prolong pretransplant survival, and defer, or even obviate, the need for transplantation. Despite prophylaxis, viral mutations with breakthrough reinfection may occur and lead to liver failure. The recently approved adefovir dipivoxil, which is active against lamivudine-resistant mutation, and other nucleoside analogs that are in various phases of development, offer hope as rescue therapy for viral recurrence. Other therapeutic alternatives in the future may include gene therapy and immune interventions.
 ...
PMID:Nucleoside analogues and other antivirals for treatment of hepatitis B in the peritransplant period. 1450 26

Morbidity and mortality from co-morbid hepatitis B (HBV) and hepatitis C (HCV) infection in HIV co-infected patients are increasing; hence, the management of HIV and HBV or HCV co-infected individuals is now one of the most challenging clinical management issues. Less than 10% of all HIV-infected patients show markers of chronic HBV infection. Hepatitis B in HIV co-infected patients is characterized by high levels of HBV replication and a high risk for cirrhosis. Treatment of HBV with lamivudine (3TC) remains the best treatment option at this time. Initial results of studies of adefovir or tenofovir, however, demonstrate good antiretroviral efficacy, even in patients with 3TC-resistant HBV. In Europe, it is estimated that approximately 30% of HIV-infected individuals are co-infected with HCV. HIV accelerates HCV liver disease especially when HIV-associated immune deficiency progresses. Within 10-15 years of initial HCV infection, 15-25% of patients who are co-infected with HIV develop cirrhosis compared with 2-6% of patients without HIV infection. With the introduction of pegylated interferon in combination with ribavirin, promising treatment options have become available for HIV/HCV co-infected patients leading to early virological response rates of approximately 50%. The high number of HIV/HCV and HIV/HBV co-infections, as well as the much more unfavorable course of HBV and HCV in these patients, underlines the need to establish treatment strategies for HBV and HCV in HIV co-infected individuals.
 ...
PMID:Management of hepatitis B and C in HIV co-infected patients. 1456 59

Chronic viral hepatitis has emerged as one of the leading causes of morbidity and mortality among HIV-positive patients. These individuals are at risk for aggressive chronic active hepatitis, cirrhosis, and hepatocellular carcinoma, and eventually, death. Currently available therapies for hepatitis B are limited and include interferon-alpha, lamivudine (3TC), and adefovir. Tenofovir (TDF), a recently approved drug for the treatment of HIV, is also active against hepatitis B. We report the case of a HIV-positive patient with liver cirrhosis secondary to chronic hepatitis B virus (HBV) with evidence of resistance to 3TC. The patient was initially accepted as a liver transplant candidate. However, when TDF was added to his treatment, a remarkable virologic and histopathologic improvement was achieved. The patient was subsequently removed from the liver transplant program and has not suffered from any further hepatic complications.
 ...
PMID:Management of chronic hepatitis B in an HIV-positive patient with 3TC-resistant hepatitis B virus. 1458 80

Chronic viral hepatitis is a leading cause of chronic hepatitis, liver cirrhosis, hepatic decompensation and hepatocellular carcinoma worldwide. Here, we will briefly review common indications and current therapies for chronic hepatitis B and C and discuss practical aspects of these therapies. Current therapies for hepatitis C aim at viral eradication. With the introduction of pegylated interferon and ribavirin viral eradication is successful in about 55% of treated patients. The goal of therapy of HBe antigen positive chronic hepatitis B is seroconversion to anti-HBe which can be achieved with interferon alpha in 25-45% of patients. A loss of HBs can be achieved in approximately 10%. Responders proceed significantly less to cirrhosis or hepatocellular carcinoma. Anti-HBe positive patients can be treated with interferon alpha or lamivudine. The former requires longer treatment and the results are disappointing. Lamivudine is a promising agent in the treatment of chronic hepatitis B, but the success is hampered by a high relapse rate and the emergence of viral resistance.
 ...
PMID:[Therapy of viral hepatitis]. 1461 Sep 5

Lamivudine is a nucleoside analogue with potent inhibitory effects on hepatitis B virus (HBV) polymerase/reverse transcriptase activity. The rate of hepatitis B e antigen (HBeAg) seroconversion in a large series of Asian patients treated with lamivudine 100 mg daily for 1 year was only 16% and the incidence of YMDD mutants was 14%. Further analysis of this Asian trial has shown that patients with a pretreatment alanine aminotransferase (ALT) level higher than 5-fold the upper limit of normal (ULN) have a much higher HBeAg seroconversion rate as compared with patients with a pretreatment ALT level <2 x upper limit of normal (64 vs. 5%; p < 0.001). In order to avoid the development of YMDD mutants, we selected 186 patients with acute exacerbation for treatment with lamivudine during 9 months, if possible, and not more than 15 months. They were all seropositive for both hepatitis B surface antigen and HBeAg for more than 6 months and also had serum HBV DNA; 138 (74%) of them were male. HBV genotypes were A in 2 (1%), B in 115 (62%), C in 65 (35%), D in 2 (1%) and F in the remaining 2 (1%). Four patients (2%) had liver cirrhosis. They had mean pretreatment levels of ALT at 608 IU/l (range: 184-2,400 IU/l), total bilirubin at 1.5 mg/dl (0.3-14.8 mg/dl), and HBV DNA at 2,246 pg/ml (0.5-25,903 pg/ml). After a median of 8.2 months (3-15 months) on lamivudine, 96 patients (51%) achieved HBeAg seroconversion, while the other 90 (48%) patients did not. Genotype B was detected comparably frequently in seroconverters and nonconverters (63 vs. 61%). During 1-year follow-up after withdrawal of lamivudine, 56 (58%) of the 96 seroconverters experienced flare-ups with ALT levels elevated higher than 5 x ULN in 50 (89%). Of 90 patients who remained HBeAg-positive, in contrast, 80 (86%) experienced ALT flares (with ALT >5 x ULN in 84%) within 1 year. YMDD mutants did not develop in any of these 186 patients during the course of lamivudine therapy. In conclusion, short-term lamivudine therapy in patients with chronic active hepatitis B can reduce the incidence of YMDD mutants and achieve an acceptable HBeAg seroconversion rate. However, the relapse rate was high (60% during 1-year follow-up). Further study is needed to establish how to improve a sustained HBeAg response.
 ...
PMID:Short-term lamivudine therapy in patients with chronic hepatitis B. 1468 53

Chronic hepatitis B virus (HBV) infection is the major cause of chronic liver disease worldwide. Although the clinical course of HBV infection varies widely, the prognosis of decompensated liver cirrhosis is quite poor and the 5-year survival rate has been estimated to be only 14-35%. While the ultimate treatment of decompensated cirrhosis is orthotopic liver transplantation (OLT), recent studies have suggested that lamivudine can also improve the clinical outcomes in this group of patients. Lamivudine rapidly suppresses HBV replication and can improve several parameters of liver function tests and afford prolonged periods of pretransplantation survival. However, the proportion of clinical improvement as defined by a decrease in Child-Pugh score as well as the prolonged survival rate varied widely from study to study. These discrepancies might result from differences in the severity of cirrhosis at entry, the presence of active viral replication or inflammation, and the proportions of patients who received OLT during the study period. Overall, about half of the patients achieved a clinical improvement with lamivudine therapy. However, data are still lacking on whether lamivudine can prolong survival before OLT and even replace OLT. Most of the deaths or clinical improvement occurred or started to occur within the first 6 months of treatment. Therefore, OLT should be actively considered in patients with risk factors for early mortality or those without clinical improvement within the first 6 months of lamivudine treatment.
 ...
PMID:Lamivudine therapy for decompensated liver cirrhosis related to hepatitis B virus infection. 1468 57

More than 400 million people worldwide are chronically infected by the hepatitis B virus. The virus is responsible for more than 300000 cases of liver cancer every year and for similar numbers of gastrointestinal haemorrhage and ascites. Major breakthroughs have been achieved in diagnosis and treatment of this virus. Hepatitis B vaccine reduces incidence of liver cancer. As with hepatitis C, advances have been made in molecular virology, especially for naturally occurring and treatment-induced mutant viruses. The clinical significance of low viral load and genotypes are also under investigation. Currently available monotherapies-interferon, lamivudine, and adefovir dipivoxil-very rarely eradicate the virus, but greatly reduce its replication, necroinflammatory histological activity, and progression of fibrosis. Lamivudine, and presumably other nucleoside analogues, can reverse cirrhosis of the liver.
 ...
PMID:Viral hepatitis B. 1469 13

Hepatitis B virus (HBV) infection is a serious global health problem, with 2 billion people infected worldwide, and 350 million suffering from chronic HBV infection. The 10th leading cause of death worldwide, HBV infections result in 500 000 to 1.2 million deaths per year caused by chronic hepatitis, cirrhosis, and hepatocellular carcinoma; the last accounts for 320 000 deaths per year. In Western countries, the disease is relatively rare and acquired primarily in adulthood, whereas in Asia and most of Africa, chronic HBV infection is common and usually acquired perinatally or in childhood. More efficacious treatments, mass immunization programs, and safe injection techniques are essential for eliminating HBV infection and reducing global HBV-related morbidity and mortality. Safe and effective vaccines against HBV infection have been available since 1982. The implementation of mass immunization programs, which have been recommended by the World Health Organization since 1991, have dramatically decreased the incidence of HBV infection among infants, children, and adolescents in many countries. However, not all countries have adopted these recommendations and there remains a large number of persons that were infected with HBV prior to the implementation of immunization programs. Antiviral treatment is the only way to reduce morbidity and mortality from chronic HBV infection. Conventional interferon alfa and lamivudine have been the primary treatments to date. Conventional interferon alfa produces a durable response in a moderate proportion of patients but has undesirable side-effects and must be administered subcutaneously three times per week. Lamivudine also produces a response in a modest proportion of patients and causes few side-effects. However, prolonged treatment is often necessary to prevent relapse on cessation of therapy, and continuous treatment can lead to the development of lamivudine resistance. Promising emerging new treatments include adefovir, entecavir and peginterferon alfa-2a (40 kDa).
 ...
PMID:Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. 1499 43

The human immunodeficiency virus (HIV) and the hepatitis B virus share common routes of transmission, and hence, coinfection with these two viruses is common. Chronic hepatitis B does not influence the progression of HIV disease or the response to highly active antiretroviral therapy. It is clear, however, that HIV infection does impact the course of hepatitis B, as higher rates of chronic carriage, lower seroconversion rates, and accelerated progression towards cirrhosis have been observed. Vaccination against hepatitis B is less effective in HIV-infected individuals. Coinfected subjects have a poor response to interferon therapy. Lamivudine is more effective in coinfected subjects but must not be used as monotherapy because of the risk of resistance developing. Combination therapy with lamivudine and tenofovir has shown promise and is currently being investigated in clinical trials, while new drugs and other combinations are in development.
 ...
PMID:Management of hepatitis B in patients coinfected with the human immunodeficiency virus. 1511 69

In conclusion, most patients with CHB have their disease controlled by lamivudine therapy, and those with elevated ALT respond well. The incidence of YMDD-variant increases with duration of treatment, although patients with YMDD still gain clinical benefit from continued lamivudine therapy and seroconversion can still be achieved. Lamivudine has shown efficacy in HBeAg-negative patients and those with decompensated cirrhosis. In long-term use, lamivudine has been found to be well tolerated. Even in patients with YMDD-variant HBV, no increase in hepatic serious adverse events was seen. In patients with decompensated CHB the combination of lamivudine and adefovir dipivoxil showed significant efficacy. After only 24 weeks, clinical improvements in liver function were seen.
 ...
PMID:Therapeutic advances in chronic hepatitis B. 1515 27


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