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)

Fifty patients with chronic HBs antigenemia and Dane particle-associated DNA polymerase and HBeAg in their serum were contrasted to 46 HBsAg positive patients who had neither serum DNA polymerase or HBeAg. The time from acute onset and the duration of antigenemia were longer in patients who were DNA polymerase and HBeAg negative than in those who had both serum markers. Cirrhosis, hypoalbuminemia, and sequelae of chronic liver disease were more common in DNA polymerase, HBeAg negative patients than in those who were positive. These findings are consistent with the hypothesis that active viral replication is an early, albeit prolonged stage in the development of advanced HBsAg-associated liver disease.
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PMID:Dane particle DNA polymerase and HBeAg: impact on clinical, laboratory, and histologic findings in hepatitis B-associated chronic liver disease. 730 91

The hepatitis B virus is a member of an unusual family of noncytopathogenic, hepatotropic DNA viruses--the hepadnaviruses. The complete virus comprises a lipoprotein coat, the hepatitis B surface antigen, enveloping a nucleocapsid core that contains a small, circular DNA molecule. Four open reading frames have been identified on the hepatitis B virus DNA genome. They encode seven proteins, including a hepatitis B virus DNA polymerase molecule with reverse transcriptase activity. The replication of the virus resembles that of retroviruses and occurs predominantly but not exclusively in hepatocytes. Virus variants involving genomic mutations have been identified. Testing for hepatitis B surface antigen permits detection of many but not all acutely infected patients. Diagnosis of acute infection rests on the identification of IgM antibodies to the hepatitis B core antigen. Antibody to hepatitis B surface antigen appears in serum during the convalescent phase of hepatitis B virus infection. It is the neutralizing, protective antibody largely responsible for immunity to reinfection. In persistent infection hepatitis B surface antigen is present, antibody to hepatitis B core antigen is predominantly an IgG antibody, antibody to hepatitis B surface antigen is not detectable or is present in very low titers and viral replication may be active. Persistent infection leads to an asymptomatic carrier state, chronic hepatitis, cirrhosis and hepatocellular carcinoma. No specific treatment exists for acute hepatitis B virus infection. Current data indicate that approximately 50% of adults who have chronic infection achieve virologic, biochemical and histologic remission from treatment with alpha-2b-interferon.
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PMID:Hepatitis B today: clinical and diagnostic overview. 832 12

Among the six species of hepatitis viruses, HBV (hepatitis B virus) and HCV (hepatitis C virus) can induce persistent infection. HBV and HCV are transmitted parenterally, of which maternal transmission and transfusion-associated infection is a major route respectively. We opened the special clinic for carriers detected through blood donation, and followed them at regular intervals for their health care. The prevalence rate of HBV carriers decreased from 3.0% to 1.2% in these 10 years, and that of HCV decreased from 0.9 to 0.4% in these 4 years. Prevalence rate of HBV peaks at 50s and that of HCV peaks at 60s. Due to nearly complete screening of donated blood, post-transfusion hepatitis almost disappeared. HBV vaccine for neonates born from infected mothers reduced the new incidence of HBV carriers. In HBV carriers seroconversion of HBeAg to HBeAb occurs at teens with transient hepatitis and appearance of mutant virus. Ninety percent of the carriers remains healthy for the lifetime but some of them aggravate into chronic hepatitis leading to HCC (hepatocellular carcinoma). In HCV acute infection at adult age succeeds to chronic infection and eventually to liver cirrhosis with sporadic appearance of HCC. On the other hand, less than 50% of HCV carriers seem to be asymptomatic and do not lead to grave disease. In HBV carriers tendency to reject the virus occurs and eventually HBV is cleared in some percentage of the population. In contrast HCV does not tend to be cleared. HBsAb is a defensive antibody. In contrast HCVAb is not a defensive antibody but an infective antibody like HBcAb. DNA polymerase is a good marker of disease state in HBV, and HCV RNA is a good marker of HCV proliferation. Treatment with IFN is sometimes effective for seroconversion in HBV, and for eradication of virus in HCV.
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PMID:[Basic and clinical aspects of hepatitis virus carriers]. 880 69

Hepatitis B virus (HBV) infection is a worldwide public health problem. In France, 150,000 individuals are infected with the HBV. Although many are asymptomatic carriers, about 30% have chronic hepatitis, a condition associated with a risk of cirrhosis and hepatocellular carcinoma. Antiviral treatments, most notably interferon alpha, probably modify the natural history of hepatitis B, decreasing the risk of hepatocellular carcinoma and increasing survival. Nucleoside analogs, particularly lamivudine, have also demonstrated potent antiviral activity, which should however be weighed against the increasing risk over time of mutation development in the YMDD region of the DNA polymerase reverse transcriptase. Antiviral therapy monitoring should include clinical safety evaluations and periodic laboratory tests including blood cell counts, transaminase activities, and serum DNA levels. The improving results provided by antiviral drugs should not deflect attention away from the importance of large-scale hepatitis B immunization of neonates, which has been shown to decrease the incidence of hepatocellular carcinoma in areas with high levels of hepatitis B endemicity.
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PMID:[Hepatitis B: epidemiology, natural history, biology, treatment monitoring]. 1060 72

Hepatitis B virus (HBV) is a small enveloped virus containing partially double-stranded DNA. The DNA and HBV-specific DNA polymerase are surrounded by the HBV core antigen (HBcAg), which in turn is surrounded by a lipoprotein envelope containing the HBV surface antigen (HBsAg). Serum of HBV-infected patients contains complete virus particles, as well as non-infectious spherical or filamentous HBsAg particles. Acute hepatitis is characterized by the appearance of serum HBV markers, including HBsAg and IgM anti-HBc, which then disappear during convalescence. Persistence of HBsAg for more than 6 months indicates a carrier state. Chronic hepatitis develops in 90% of newborns who become infected, compared with 29-40% of children infected and 5-10% of adults infected. The immune status of the infected person also influences the development of chronic hepatitis. Chronic HBV infection can be diagnosed by serology (identification of HBsAg and HBV DNA), biochemistry (elevated aminotransferase levels) and liver biopsy. The last is important to assess the severity of disease, its stage and prognosis, and to exclude other hepatic diseases. The outcome of chronic HBV infection varies between individuals, with estimated 5-year survivals of 97% for chronic persistent hepatitis, 86% for chronic active hepatitis, and 55% for chronic active hepatitis with cirrhosis. Treatment with interferon alpha is effective in up to 40% of cases, but in view of the very large number of infected people worldwide, vaccination to prevent spread of the disease is a more cost-effective option.
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PMID:Clinical course and consequences of hepatitis B infection. 1068 39

Chronic hepatitis B virus (HBV) infection is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Its prevalence approaches 10% in hyperendemic areas, such as southeast Asia, China, and Africa. Although chronic HBV infection is seen less frequently in North America and Europe, an estimated 1.25 million persons in the United States are infected. In the past decade, revolutionary strides have been made toward the treatment of chronic HBV infection. Interferon-alpha was once the only available therapy but has recently been joined by the nucleoside analogues, the most extensively studied of which is lamivudine. Interferon therapy continues to have a role in the treatment of a carefully selected group of patients. Lamivudine therapy, which has less stringent selection criteria, suppresses HBV DNA in almost all treated patients: Seventeen percent to 33% experience loss of hepatitis B e antigen, and 53% to 56% have a histologic response. Extended lamivudine treatment leads to the development of a specific lamivudine-resistant virus with base-pair substitutions at the YMDD locus of the DNA polymerase. Newer nucleoside analogues and other immunomodulator therapies are being investigated. In the future, combination therapy with different classes of agents may yield improved response rates and delay the development of resistance.
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PMID:Chronic hepatitis B virus infection: treatment strategies for the next millennium. 1078 66

Lamivudine has been shown to be an effective therapy for chronic hepatitis B, but resistance to this nucleoside agent is common after prolonged use. Five patients with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 9 to 19 months of treatment. In 4 patients this occurred after liver transplantation and the remaining individual had stable cirrhosis. In each case, resistance was confirmed to be caused by one or more mutations in the HBV-DNA polymerase gene and was associated with active underlying liver disease. The patients were treated with adefovir dipivoxil in a dose of 5 to 30 mg daily. Two to 4 log(10) reductions in HBV-DNA levels were observed in 4 cases, and the fifth patient became negative by quantitative polymerase chain reaction (PCR) after retransplantation in conjunction with hepatitis B immunoglobulin (HBIg). Virologic improvement was associated with stable or declining serum alanine transaminase levels in 4 patients. HBV-DNA suppression has been sustained during a mean treatment period of 13 months (range 11 to 15 months), including 1 patient in whom lamivudine has been discontinued. Mild changes in renal function were observed during treatment in most cases but did not require early discontinuation of the drug. This study provides evidence that adefovir dipivoxil can be an effective treatment for lamivudine-resistant HBV mutants as well as wild-type HBV.
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PMID:Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants. 1086

Hepatitis B virus (HBV) infection is a major cause of chronic liver disease worldwide. Famciclovir is a nucleoside analogue with potent antiviral activity that appears promising in the management of patients with HBV infection. No data exist regarding the safety of nucleoside analogue withdrawal in patients treated for HBV cirrhosis. The authors describe a 41-year-old man with compensated HBV cirrhosis who developed fatal hepatic decompensation due to a rebound in viral replication within six weeks of discontinuing famciclovir therapy. Although several mutations in the HBV DNA polymerase gene have been documented, none has been associated with famciclovir resistance or adverse clinical outcomes. Clinicians should consider the risk of inducing serious flares in hepatic inflammation as a result of abrupt nucleoside analogue withdrawal. Until further data are available regarding the safety of withdrawal of these agents, indefinite treatment may be required in patients with established cirrhosis.
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PMID:Fatal hepatic decompensation in a patient with hepatitis B cirrhosis following famciclovir withdrawal. 1118 39

Breakthroughs during lamivudine therapy were assessed according to hepatitis flares and mutational polymorphism of hepatitis B virus (HBV) infecting patients. Of 42 patients with chronic hepatitis B and positive for hepatitis B e antigen in serum, 13 (30%) harbored HBV mutants with lamivudine resistance after a mean duration of 29 months on lamivudine. The virological breakthrough occurred 14.5 months after the start of lamivudine treatment, and all the patients with it developed breakthrough hepatitis 3 months later. The clinical course of breakthrough hepatitis was self-limited except in one patient who had already developed cirrhosis at the baseline. One year after breakthrough hepatitis, serum ALT, albumin, prothrombin time and platelet counts were maintained well on conventional treatments without resorting to interferon. Major HBV mutants during breakthrough hepatitis were those with M552I in the YMDD motif of viral DNA polymerase/reverse transcriptase in 7 patients (54%), M552I/L528M in 4 patients (31%) and M552V/L528M in 2 patients (15%). There were no patients in whom mutations at nucleotide 529 occurred including the 2 who later developed hepatocellular carcinoma. There was no clear relationship between distinct mutational patterns and clinical courses. Further studies are needed for making out the effects of lamivudine-resistant mutants on clinical outcomes, taking into considerations genotypes of HBV.
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PMID:Subclones of drug-resistant hepatitis B virus mutants and the outcome of breakthrough hepatitis in patients treated with lamivudine. 1468 51

We report a case of fatal liver failure due to reactivation of lamivudine-resistant HBV. A 53-year-old man was followed since 1998 for HBV-related chronic hepatitis. Serum HBV-DNA was 150 MEq/mL (branched DNA signal amplification assay) and ALT levels fluctuated between 50-200 IU/L with no clinical signs of liver cirrhosis. Lamivudine (100 mg/d) was started in May 2001 and serum HBV-DNA subsequently decreased below undetectable levels. In May 2002, serum HBV-DNA had increased to 410 MEq/mL, along with ALT flare (226 IU/L). The YMDD motif in the DNA polymerase gene had been replaced by YIDD. Lamivudine was continued and ALT spontaneously decreased to the former levels. On Oct 3 the patient presenting with general fatigue, nausea and jaundice was admitted to our hospital. The laboratory data revealed HBV reactivation and liver failure (ALT: 1828 IU/L, total bilirubin: 10 mg/dL, and prothrombin INR: 3.24). For religious reasons, the patient and his family refused blood transfusion, plasma exchange and liver transplantation. The patient died 10 d after admission. The autopsy revealed remarkable liver atrophy.
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PMID:Fatal liver failure due to reactivation of lamivudine-resistant HBV mutant. 1516 53


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