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)

Hepatitis B viral (HBV) infection is a major health burden in the Asia-Pacific region. The seriousness of chronic hepatitis B (CHB) is often realized at a late stage. The resultant morbidity and mortality from cirrhosis complications is considerable, with a high human cost. The most affected patients are men aged 40 years or older. Two decades ago, the prognosis for the 300 million "Australia antigen"-positive people (people with chronic HBV infection) was gloomy, with no effective intervention. Twenty years on, research and development have changed their outlook. Chronic hepatitis should now be diagnosed early, at the asymptomatic stage. Proper assessment and judicial introduction of therapy can suppress replication of HBV and resolve liver inflammation, thereby preventing the silent progression of chronic liver disease to end-stage cirrhosis. Interferon (IFN) monotherapy has been available for nearly 20 years, but various limitations restrict its general application. Injection-based therapies are inconvenient, the response rate is low (33% hepatitis B e antigen (HBeAg) seroconversion rate among optimal cases), side-effects are many, and some serious, and the cost is unaffordable for most people. However, in non-cirrhotic patients with mild to moderate disease activity, IFN is still a worthwhile option because the treatment course is shorter, mutation seems less of a problem and most responses are permanent and reduce or abolish late complications. Lamivudine, an oral nucleoside analog with potent antiviral effects, has been approved in many countries. Daily dosing of 100 mg reduces serum HBV-DNA to below detectable levels within 6 weeks. In HBeAg-positive patients, approximately 16% of treated patients seroconverted with the first year. This was associated with significant improvement in liver histology. Long-term treatment induces further HBeAg seroconversion, but overall clinical benefit is undermined by continuous emergence of drug-resistant YMDD mutants. In an Asian multicentre study, 58 patients on 5 years lamivudine therapy showed annual cumulative HBeAg seroconversion rates at 1, 2, 3, 4 and 5 years of 22, 29, 40, 47 and 50%, respectively. The best predictor of response is pretreatment alanine aminotransferase (ALT). Among patients with ALT > 2x the upper limit of normal (ULN), annual HBeAg seroconversion is increased to 38, 42, 65, 73 and 77%, respectively. However, emergence of YMDD mutants occurred at a cumulative rate of 15, 38, 55, 67 and 69%, respectively. The impact of this emergence on disease activity is unpredictable. Thus, while continued disease suppression, or even HBeAg seroconversion, still occurred in some patients, in others hepatitis may relapse and liver failure has been reported despite continuation of lamivudine. While the duration of lamivudine therapy is difficult to define, the best strategy may be to define only active CHB with major ALT elevation (par-ticularly ALT > 5x ULN) for a duration of 1 year or less. Lamivudine can be stopped in responders. The response is durable in approximately 80% of responders. Non-responders should be monitored closely for rebound off treatment. Therapy can be re-instituted if ALT is over 5x ULN. Management of patients with YMDD mutants can be challenging, but there is no clear evidence to recommend stopping or continuing lamivudine, or to add other possible effective agents, such as adefovir dipivoxil. More data are required to help draw up guidelines. Hepatitis B e antigen-negative CHB has been less well studied. Both IFN and lamivudine can suppress disease activity, but permanent responses are few. Without a distinct marker as an end-point for response, the duration of treatment is even more difficult to define. Quantitative polymerase chain reaction for low viral levels may give a clue, but definitive studies are required. Monotherapy is clearly not the answer for the majority of CHB patients with active disease. Combination therapy has the theoretical advantage of additional or synergistic efficacy. Preliminary results on IFN and lamivudine are promising and further clinical trials are ongoing. Emtricitabine (FTC), adefovir dipivoxil, entecavir, BL-thymidine (L-dT), DAPD, clevudine (l-FMAU), thymosin, therapeutic vaccines and various herbal medicines are potential candidates. Antiviral action in conjunction with immune modulation may have a better chance of eradicating HBV and its cccDNA in the hepatocytes as the basis for an eventual successful outcome. The key points are: (i) approved therapeutic agents for chronic hepatitis B (CHB) are IFN, lamivudine and thymosin (in a few countries only); (ii) indications for IFN therapy are viremia in compensated CHB patients with moderately raised ALT; (iii) lamivudine has broader therapeutic indications: it is effective in subgroups of CHB patients with compensated or decompensated liver diseases, but generally works better if patients have raised ALT; (iv) lamivudine has a potent suppressive action on HBV replication, including HBeAg-negative variants, but cannot eliminate cccDNA; this is the reason for the relapse of disease after discontinuing treatment, unless HBeAg seroconversion is obtained; (v) successful use of lamivudine aims at HBeAg seroconversion or profound suppression of HBV-DNA to serum levels of less than 100 000 viral copies/mL, in order to prevent emergence of drug-resistant YMDD mutants (which commences from 6 months onward); (vi) YMDD mutants may cause a flare of hepatitis, resulting in deterioration of liver histology and, occasionally, liver failure; (vii) combination therapy of lamivudine with IFN (standard or pegylated) or other nucleoside analogs should be the next advance. Preliminary data from IFN and lamivudine combination therapy show some promise, but there are conflicting results.
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PMID:Treatment of chronic hepatitis B: case selection and duration of therapy. 1198 21

All patients with HIV infection should be screened for hepatitis B virus (HBV) infection. Preventive HBV vaccination is less effective in HIV-infected patients than in those without HIV infection. Emtricitabine, lamivudine, and tenofovir disoproxil fumarate (tenofovir) each have activity against HIV and HBV. In HBV/HIV-coinfected patients, if HBV or HIV treatment is needed, it should be initiated with tenofovir and emtricitabine or tenofovir and lamivudine as the nucleoside analogue reverse transcriptase inhibitor backbone of a fully suppressive antiretroviral regimen. If HBV treatment is needed and tenofovir cannot be used safely, entecavir is recommended in addition to a fully suppressive antiretroviral regimen. Initiation of treatment for HBV infection is based on the presence of cirrhosis and on HBV DNA level, alanine aminotransferase level, and biopsy results. Current HBV treatments are associated with low functional cure rates. This article summarizes a presentation by Kenneth E. Sherman, MD, PhD, at the IAS-USA continuing education program held in San Francisco, California, in March 2015.
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PMID:Management of the Hepatitis B Virus/HIV-Coinfected Patient. 2651 94