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本帖最后由 StephenW 于 2012-8-13 17:55 编辑
http://gut.bmj.com/content/61/Suppl_1/i18.full
[Extracted StephenW]
Gut 2012;61:i18-i24 doi:10.1136/gutjnl-2012-302085
New perspectives in the therapy of chronic hepatitis B
Pietro Lampertico1,
Yun Fan Liaw2
- Author Affiliations
11st Division of Gastroenterology, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy
2Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan
Correspondence to Pietro Lampertico, 1st Division of Gastroenterology, Fondazione Cà Granda IRCCS Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via Francesco Sforza 35, 20122 Milano, Italy; [email protected]
Contributors All authors contributed equally to this work.
Introduction
Since approval of the first nucleos(t)ide analogue (NUC) in 1998, remarkable advances have been made in antiviral treatment of chronic hepatitis B virus (HBV) infection. Both interferon-based therapy and treatment with NUCs have evolved to the stage that pegylated interferon (Peg-IFN) has replaced conventional IFN, and entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have become the first-line oral treatments.1–3 As the therapeutic outcomes are still far from satisfactory, many attempts have been made to optimise antiviral therapy of chronic HBV infection. Along with the evolution of drug therapy, quantitation of hepatitis B surface antigen (HBsAg) has gained popularity as a clinically useful seromarker for assessing the natural course and response to therapy of chronic HBV infection. In addition, the discovery of IL28B polymorphism, which has shed new light on the treatment of hepatic C virus (HCV) infection, has been applied in the study of the response of patients with HBV to IFN regimens. These recent developments are reviewed in this article, focusing on the following topics: IL28B and response to IFN or Peg-IFN therapy; response-guided therapy of Peg-IFN treatment; ETV and TDF in field practice naïve patients.
IL28B as a baseline host factor in the response to IFN- or Peg-IFN-based therapy
IL28B and response of hepatitis B e antigen (HBeAg)-positive patients to IFN- or Peg-IFN-based therapy
IL28B and response of HBeAg-negative patients to IFN- or Peg-IFN-based therapy
Response-guided therapy with Peg-IFN
Stopping rules for HBeAg-positive patients treated with Peg-IFN
Stopping rules for HBeAg-negative patients treated with Peg-IFN
ETV and TDF in field practice naïve patients
Conclusion and perspective
Antiviral therapy of chronic hepatitis B has evolved to the stage of individualised and response-guided approaches. IL28B polymorphisms as host genetic markers and week 12 HBsAg level as an on-treatment viral factor in predicting response to Peg-IFN have recently been studied. Whereas week 12 HBsAg quantitation is of potential clinical application as an on-treatment stopping rule, IL28B polymorphism requires further studies to define its role as a baseline factor. On the other hand, the clinical use of ETV or TDF in real life has confirmed the long-term efficacy and safety of these two first-line NUCs demonstrated in registration trials. In contrast with the earlier 3-year lamivudine study in Asian patients with advanced fibrosis or cirrhosis mostly infected with genotype B and C HBV,46 long-term HBV DNA suppression using ETV seems to be unable to reduce the incidence of HCC in patients mostly infected with genotype D HBV. Perhaps HBV genotype D and old age (median 58 years) are responsible for the high incidence of HCC in the ETV study.40 Further studies in patients with comparable baseline features to the histological control patients are needed to clarify the discrepancies, although HCC is likely to be more efficiently prevented by antiviral therapy that is initiated before the onset of full-blown cirrhosis. Undoubtedly, there is more to learn about ways to further optimise antiviral therapy for chronic hepatitis B.
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发表于 2012-8-13 17:53
