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 prognosis of decompensated cirrhosis of liver resulting from chronic Hepatitis B Virus (HBV) infection is poor and liver transplantation is the only established mode of treatment. The benefits of treatment with interferon are outweighed by serious side effects and risks of fatal exacerbation of disease activity. Lamivudine rapidly reduces hepatitis B viral DNA in serum to undetectable levels. The purpose of this study was to evaluate effectiveness and safety of Lamivudine treatment in patients with advanced and end stage liver disease caused by Hepatitis B. This was a prospective observational study in which a total of 45 patients, 39 (87.0%) male and 6 (13.0%) female who had viral activity and child pugh score e" 8 were given Lamivudine 100 mg orally once daily. Among them 30 patients completed at least 6 months of therapy, majority (27 patients) showed improvement in liver function with decrease in serum ALT from mean (+/- SD) 118.8 +/- 106.5 to 50.2 +/- 57.1 U/L (p < 0.001), decrease in serum bilirubin from 73.9 +/- 80.5 to 44.7 +/- 62.9 micromol/l (p = 0.129), increase in serum albumin from 26.2 +/- 4.2 to 33.2 +/- 3.4 g/l (p < 0.05), decrease in prothrombin time from 8.3 +/- 4.0 to 3.9 +/- 2.9 seconds prolonged (p < 0.05) and reduction in child pugh score from 11.0 +/- 1.7 to 7.0 +/- 1.3 (p < 0.001). Seroconversion was found in 5 (11.1%) patients on Intention to treat analysis. Among the seroconverted group, 1 (2.2%) patient also lost HBsAg. Six (13.0%) patient had procore mutant virus, 2 (4.4%) of them showed virological response. Therefore, total 7 (15.5%) patients showed virological response by intention to treat analysis. We conclude that inhibition of viral replication with Lamivudine results in a significant improvement of liver function in patients with decompensated cirrhosis of liver due to HBV infection.
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PMID:A study on efficacy of lamivudine therapy in decompensated cirrhosis of liver due to chronic hepatitis B virus infection. 1629 39

Chronic hepatitis B develops in 3 phases: immune tolerance, where viral replication is strong and there is little or no fibrosis; immune activity phase with low viral replication and rapidly developing fibrosis as well as an elevated risk of cirrhosis; low viral replication and remission, with a risk, nonetheless, of reactivation. Antiviral treatment is indicated in patients with moderate or severe levels of either fibrosis or activity (necrotic and inflammatory lesions). Standard interferon treatment produces a prolonged response rate on the order to 20-40%; side effects are frequent but generally mild and reversible when treatment stops. Pegylated interferon (standard interferon conjugated with polyethylene glycol) has substantially better efficacy and comparable tolerance. Lamivudine (a nucleoside analog) has several advantages over interferon: oral administration, excellent tolerance, and rapid antiviral effect. Its principal disadvantage is the frequency of resistant mutations. Adefovir and entecavir have oral administration, are well tolerated and associated with a low incidence of resistance. They induce a sustained response after withdrawal of therapy in only a minority of patients and therefore the treatment needs to be indefinitely administered in the majority of patients.
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PMID:[Treatment of chronic hepatitis B]. 1649 37

Lamivudine is a nucleoside analogue with a potent antiviral activity used as prophylaxis against hepatitis B virus reactivation in patients with chronic HBV infection receiving chemotherapy. No standard guidelines exist, however, for the duration of lamivudine treatment. We report a clinical case of a 56-year-old patient with HBeAg-negative cirrhosis who developed a multiple myeloma. He was treated with lamivudine for 1 year while receiving chemotherapy and a subsequent bone marrow transplant. Complete remission from multiple myeloma was achieved. Four months after lamivudine was withdrawn, he experienced HBV reactivation with jaundice, though no YMDD mutations were detected. The patient rapidly developed fatal decompensation with septicemia and renal failure. In conclusion, this case shows that physicians should avoid discontinuing nucleoside therapy in patients with HBV infection who undergo immunosuppression for concomitant neoplastic conditions.
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PMID:Fatal hepatic decompensation in a bone marrow transplant recipient with HBV-related cirrhosis following lamivudine withdrawal. 1656 68

The Hepatitis B virus (HBV) is a DNA virus that can cause both acute and chronic liver disease in humans. Approximately 350-400 million people are affected worldwide and up to one million deaths occur annually from cirrhosis and hepatocellular carcinoma. When cirrhosis and liver failure develop, the definitive treatment of choice remains orthotopic liver transplantation (OLT). In the past, an unacceptable HBV recurrence rate with a high rate of graft loss was noted. The use of Hepatitis B immunoglobulin (HBIG) has resulted in improved patient and graft survival rates. The addition of the nucleoside analog Lamivudine (LAM) to HBIG has improved these survival curves to an even greater degree. Prolonged use of LAM will almost invariably lead to the development of viral mutations resistant to the drug. There are now several other nucleoside and nucleotide analogs (Adefovir, Entecavir, Tenofovir, and Truvada) available for the clinician to utilize against these resistant strains. It should be possible to prevent recurrence in most, if not all, post-transplant patients and also to significantly reduce viral loads with normalization of transaminases in those who have developed recurrent infection. The antiviral regimen should be robust and minimize the risk of breakthrough mutations. A prudent approach may be the implication of combination antiviral therapy. This review summarizes the efficacy of previous regimens utilized to prevent and treat recurrent HBV following OLT. Particular attention will be paid to the newer nucleoside and nucleotide analogs and the direction for future strategies to treat HBV in the post transplant setting.
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PMID:Prevention and treatment of recurrent Hepatitis B after liver transplantation: the current role of nucleoside and nucleotide analogues. 1660 49

In patients with compensated hepatitis B virus (HBV) cirrhosis, active viral replication correlates significantly with the risk of hepatic flare, decompensation, and the development of hepatocellular carcinoma (HCC). The 5-year survival of patients with compensated cirrhosis was reported to be 80 to 85%, and is significantly lower in patients with replicative HBV. Both interferon and maintenance lamivudine therapy have been shown to reduce the risk of decompensation or HCC and prolong survival in responders. A finite course of interferon is recommended as the first-line agent. For patients who had a contraindication for or who have failed interferon therapy, direct antiviral(s) can be considered for long-term treatment. Once decompensation occurs, mortality increases remarkably. Early treatment with nucleoside analogues should be instituted. Lamivudine therapy is associated with rapid viral suppression, improvement in Child-Pugh scores, and improved survival, but drug resistance is a major problem and is associated directly with a poor clinical outcome. Adefovir or entecavir is preferred in patients with decompensated cirrhosis who require long duration of treatment, due to the lower rate of development of resistance.
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PMID:Hepatitis B virus-related cirrhosis: natural history and treatment. 1667 92

Adefovir dipivoxil is effective against lamivudine-resistant hepatitis B virus (HBV) strains. Whether short-term overlap lamivudine is beneficial remains unknown, particularly in patients with decompensated chronic hepatitis B. We enrolled 30 patients who underwent 48-week adefovir treatment (10 mg daily) for exacerbation of hepatitis B, associated with lamivudine-resistant mutants. Nineteen (63.3%) patients had baseline evidence of hepatic decompensation. Lamivudine was combined for <or=1 month in eight (group I), 2-5 months in 10 (group II) and >or=6 months in 12 (group III). We analysed their serial alanine aninotransferase (ALT) levels, Child-Pugh (CP) score, serum viral load and lamivudine-resistant strains. We found that serum ALT became normalized in 20 (66.7%) and HBV-DNA decreased to <or=100 copies/mL in eight (26.7%) at the end of the 48-week treatment. The log(10) reduction of serum HBV-DNA was significantly smaller in group I patients compared with group II and III patients at week 24 and 48 of treatment [median (range): 3.0 (1.5-5.6) vs 4.5 (1.5-7.4), P = 0.032; and 3.4 (0.9-4.7) vs 5.2 (2.2-7.7), P = 0.008 respectively]. In contrast, the virologic responses at the end of the 48-week therapy were similar between group II and III patients. The improvement in serum ALT and CP score at week 48 was similar irrespective of baseline decompensation, liver cirrhosis and the duration of overlap lamivudine therapy. Our findings suggested that an overlap of lamivudine for >or=2 months might lead to better virological but not biochemical outcomes in patients receiving adefovir for lamivudine-resistance HBV. As our sample size was small and the study was not randomly controlled, further studies are needed.
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PMID:Overlap lamivudine treatment in patients with chronic hepatitis B receiving adefovir for lamivudine-resistant viral mutants. 1684 41

Chronic hepatitis B is a common disease and approximately 20% of infected patients with compensated cirrhosis will decompensate over 5 years. If untreated, the survival of decompensated cirrhosis is poor (15% at 5 years). The extent of hepatitis B virus (HBV) replication, as assessed by serum HBV-DNA level, is a strong predictor of the risk of disease progression and hepatocellular carcinoma. This provides a rationale for antiviral therapy to arrest progression of liver disease. Lamivudine is a pyrimidine analogue that inhibits HBV-DNA reverse transcriptase. It decreases HBV replication, normalises alanine aminotransferase levels and reduces hepatic inflammation and fibrosis in patients with chronic hepatitis B. This article will focus on the use of lamivudine in patients with HBV-cirrhosis. In patients with compensated HBV-cirrhosis, a randomised, placebo-controlled trial has shown that lamivudine significantly reduced the rate of disease progression and hepatocellular carcinoma development over a 3-year period. In patients with decompensated cirrhosis, treatment with lamivudine can produce spectacular improvements of liver function, but the improvement is slow and a clinical benefit is usually not observed until after at least 3-6 months of treatment. A major drawback of lamivudine treatment is the development of resistance, observed in 15-20% of patients after 1 year and up to 70% after 5 years of continued treatment. Thus, patients with HBV-cirrhosis treated with lamivudine should have regular monitoring of serum HBV-DNA levels and prompt institution of additional antiviral therapy if viral breakthrough is observed. Adefovir, tenofovir and entecavir have demonstrated efficacy in patients with lamivudine resistance. In patients with decompensated cirrhosis, in whom the development of resistance can be fatal, combination therapy (such as lamivudine plus adefovir) may prove more effective than monotherapy and this issue needs further study.
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PMID:Lamivudine treatment in patients with chronic hepatitis B and cirrhosis. 1692 9

In this study, the effect of lamivudine therapy on viral suppression, Child-Pugh score, and survival was assessed in patients with decompensated cirrhosis due to precore mutant hepatitis B virus and the results were compared with those for nonreplicative cirrhotic patients. Twenty-three replicative patients who received lamivudine and 15 nonreplicative patients were included and followed up for an average of 23.7+/-13.4 months. At baseline, there were no significant differences between the groups with regard to clinical and biochemical parameters or Child-Pugh scores, except for serum alanine aminotransferase levels (P<0.05) and quantitative hepatitis B virus DNA measurements (P<0.001). Compared to baseline, there was no significant difference in Child-Pugh score in the lamivudine group at the last visit (P=0.202), whereas a marked increase was observed in nonreplicative patients (P=0.002). Mortality rates in the lamivudine and nonreplicative groups were 17.43% and 13.3%, respectively (P=0.556), and there was no difference in survival analysis (P=0.809). Lamivudine therapy stabilizing clinical situation in decompensated cirrhotics with precore mutation makes the natural history of the disease equal with nonreplicative decompensated cirrhotics or even provides some advantages over them.
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PMID:The effectiveness of lamivudine treatment in cirrhotic patients with HBV precore mutations: a prospective, open-label study. 1694 9

Hepatitis B virus (HBV) is one of the major causes of liver disease worldwide, and chronic HBV infection may progress to cirrhosis and hepatocellular carcinoma. Mutations at the active site of DNA polymerase of HBV, tyrosine-methionine-aspartate-aspartate (YMDD) motif, render infected patients resistant to antiviral drug (Lamivudine) therapy. Hence, sensitive and specific methods aimed at detecting the mutants are essential. The purpose of this study was to develop methods for detecting the mutations at YMDD by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR using locked nucleic acid (LNA)-mediated TaqMan probes. The results obtained by these methods were compared with those examined by conventional direct sequencing on serum samples of 77 patients treated with lamivudine. Our results show that both PCR-RFLP and real-time PCR could detect wild type, YMDD, and its mutants, tyrosine-isoleucine-aspartate-aspartate and tyrosine-valine-aspartate-aspartate. In addition, the mixtures of the wild-type virus and its mutants in the serum sample were detected. Importantly, real-time PCR is less time-consuming, and more sensitive for the detection of mixed populations than PCR-RFLP. The real-time PCR with LNA-mediated TaqMan probes is a sensitive, specific and rapid detection method for mutations at the YMDD motif, which will be essential for monitoring patients undergoing lamivudine antiviral therapy.
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PMID:Rapid detection of lamivudine-resistant hepatitis B virus mutations by PCR-based methods. 1696 Mar 47

Chronic hepatitis B is an important public health problem worldwide. In Poland the incidence rate decreased from 40,0 (in the year 1990) to 3,86 (in 2004) per 100,000 inhabitants. The goal of anti-chronic hepatitis B therapy is to prevent the progression of liver disease to cirrhosis which may effect in development of liver failure or HCC. The aims of treatment are: reduction of HBV viral load and normalization of ALT activity. Among HBeAg positive patients important marker is the loss of e antigenemia followed by seroconversion to anti-HBe positivity. Lamivudine is an oral nucleoside analogue with strong antiviral activity against hepatitis B virus. The objective of this study was to analyse the efficacy of lamivudine treatment of chronic hepatitis B patients positive for hepatitis B e antigen (HBeAg). 224 patients were treated in Hospital of Infectious Diseases in Warsaw in the years 2001-2002. Patients were treated for 48 weeks with 100 mg lamivudine once daily (50 mg in case of renal failure). Results obtained at the end of therapy: loss of HBeAg was observed in 33,4% and seroconversion to anti-HBe in 15,1% patients, normalization of ALT activity was noticed in 53,4% patients, inhibition of HBV DNA replication was observed in 37,9% patients. The results are comparable with known randomized clinical trials.
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PMID:[Results of 48 weeks lamivudine treatment of patients with chronic hepatitis B and HBeAg (+)]. 1696 76


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