标题: 【转贴】Current Treatment Recommendations for Chronic Hepatitis B in Adults [打印本页] 作者: yongjunchen 时间: 2006-5-14 17:03 标题: 【转贴】Current Treatment Recommendations for Chronic Hepatitis B in Adults Sample TextSample TextSample TextCurrent Treatment Recommendations for Chronic Hepatitis B in Adults
The therapeutic endpoints for hepatitis B treatment are: sustained suppression of HBV replication, as indicated by HBsAg and HBeAg loss; decrease in serum HBV DNA to an undetectable level by a non-PCR-based method; and remission of disease as shown by normalization of ALT and improvement in liver histology.[15] Unfortunately, HBsAg loss rarely occurs and it remains unclear as to what level HBV DNA should be suppressed to prevent relapse after treatment is stopped. Because of recent evidence,[8,35] suggesting disease progression despite HBeAg seroconversion, especially if serum aminotransferases remain in the upper half of the normal range, some experts recommend treating patients with any detectable HBV DNA level if serum ALT is 0.5-2-times the upper limit of normal.[36] However, we believe that the evidence to date does not justify such a broad recommendation, especially given the high costs and unknown long-term consequences of these drugs.
Major predictors of treatment response to interferon-based therapy are female sex, high ALT levels (> 100 U/L or > 526 copies/mL), low HBV DNA levels (< 200 pg/mL or < 600 x 105 copies/mL by slot-blot hybridization [Note: 1 IU = 5.26 copies/mL; 1 pg/mL = 2.83 x 105 copies/mL]), and greater degree of activity on liver biopsy.[37] Infection at birth or early childhood is a negative predictor of response to interferon therapy. For both lamivudine and interferon, pretreatment serum ALT was the strongest determinant for response, indicating that patients with a more vigorous immune response to HBV respond better to antiviral therapy.[23]
Current management recommendations are based on the natural history of HBV infection, but certain patient populations are given special consideration.[15,38] Patients in the asymptomatic immune-tolerant phase should not be routinely treated unless ALT levels fluctuate and there is moderate or severe necroinflammation on liver biopsy. For patients in the immune clearance phase, treatment should be initiated with interferon alfa for 4-12 months, peginterferon for 48 weeks, or for a minimum of 1 year with lamivudine, adefovir, or entecavir. Those with compensated liver disease may spontaneously seroconvert, and thus, treatment should be delayed for 3-6 months, especially in patients with highly elevated ALT values (> 5 times normal). Treatment should also be considered for patients with HBeAg-negative chronic hepatitis B who have high levels of HBV replication (ie, HBV precore mutant) and elevated ALT or moderately severe hepatitis on liver biopsy. Peginterferon alfa, adefovir, or entecavir are the preferred options due to the need for long-term therapy (minimum of 1 year) to achieve a sustained virologic response, although the optimal duration of therapy is unknown.[15]
Due to the lack of efficacy of current treatment regimens, therapy is not recommended for patients in the inactive HBsAg carrier state except in special circumstances (as described below). At present, antiviral treatment of patients with occult HBV infection is also not recommended, because the implications of occult infection remain unclear and there are no data on the use of antiviral treatment.[39]
Patients with decompensated cirrhosis, liver transplantation, acute exacerbations (flares) of chronic hepatitis B, and coinfection with other viruses may require special consideration. Reduced-dosage interferon has been used in patients with well-compensated Child A class cirrhosis. However, flares can occur due to immune-mediated lysis of infected hepatocytes; thus, interferons are contraindicated in decompensated cirrhosis (Child B and C). Lamivudine is therefore recommended for active cirrhosis, but these patients should ideally be managed in specialist centers.[15] YMDD mutants may emerge in this treatment population, leading to reduced efficacy and disease flares, with the associated risk of hepatic decompensation. Given the latter, alternative nucleos[t]ide **ogs with lower rates of resistant mutations, such as adefovir or entecavir, may be considered in cirrhotic patients.
Patients presenting with acute exacerbation, jaundice, and decompensated liver disease have a poor prognosis; lamivudine or other nucleos[t]ide **ogs should be initiated immediately for an indefinite period in these settings.[15,38] Prophylactic lamivudine is also recommended in HBsAg-positive chronic carriers for the duration of immunosuppressive treatment such as cancer chemotherapy, and maintained for 6 months after cessation. In patients undergoing liver transplantation for HBV-related liver disease, antiviral therapy such as lamivudine or adefovir in combination with hepatitis B immune globulin (HBIg) may need to be maintained indefinitely to prevent viral recurrence.[40] Although the nucleos(t)ide **og should be administered indefinitely post transplantation, HBIg (which is extremely costly) may be safely discontinued after the first 2-3 years (although this is not a universal practice).[40] The risk of YMDD mutants with lamivudine therapy remains a management dilemma; thus, adefovir or entecavir treatment may be considered if available. There are insufficient data to provide firm recommendations regarding the management of pregnant patients; patients with concurrent infection with hepatitis C virus, hepatitis delta virus, or HIV; or patients with extrahepatic manifestations.[38]作者: 风中有我 时间: 2006-5-14 17:25
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