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Perspective

Improving clinical outcomes of chronic hepatitis B virus infection Expert Rev. Gastroenterol. Hepatol. 9(2), 141–154 (2015)

Tung-Hung Su1–3 and Jia-Horng Kao*1–4 1 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te Street, Taipei 10002, Taiwan 2 Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 10002, Taiwan 3 Hepatitis Research Center, National Taiwan University Hospital, 1 Chang-Te Street, Taipei 10002, Taiwan 4 Department of Medical Research, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 10002, Taiwan *Author for correspondence: Tel.: +886 223 123 456; extn. 67307 Fax: +886 223 825 962 [email protected]

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Chronic hepatitis B virus (HBV) infection is a global health problem, leading to cirrhosis, hepatocellular carcinoma (HCC) and liver-related deaths. Universal hepatitis B vaccination is the most cost–effective way to eradicate HBV infection with the remarkable reduction of chronic carriage, neonatal fulminant hepatitis and childhood HCC. The introduction of highly effective antiviral agents, including lamivudine, adefovir dipivoxil, entecavir, telbivudine, tenofovir disoproxil fumarate and pegylated interferons further improve short-, medium- and long-term outcomes of chronic HBV infection, such as ALT normalization, HBV DNA suppression, HBeAg seroconversion, HBsAg seroclearance, fibrosis regression, reduction of cirrhosis, HCC, liver-related deaths and the need for liver transplantation. Above all, sustained and profound viral suppression is the key to improve the clinical outcomes of chronic hepatitis B. KEYWORDS: adefovir dipivoxil • cirrhosis • entecavir • hepatocellular carcinoma • interferon • lamivudine • liver transplantation • telbivudine • tenofovir disoproxil fumarate • vaccination

Hepatitis B virus (HBV) infection is one of the most important global health problems, affecting more than 2 billion people worldwide [1]. Despite the highly effective vaccination against HBV launched since early 1980s [2], there are still more than 240 million people suffering from chronic HBV infection across the world [3], which causes chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) [4]. The clinical course of acute and chronic HBV infection has been extensively studied across a wide range of disease spectrum: from asymptomatic carrier to fulminant hepatitis or acute on chronic liver failure. Since the introduction of five nucleos(t)ide analogs (NAs) including lamivudine, adefovir dipivoxil, entecavir, telbivudine and tenofovir disoproxil fumarate as well as two immunomodulators including conventional and pegylated interferons (Peg-IFN), hepatitis B has become a treatable and controllable disease but it is still not as curable as hepatitis C virus infection. According to the treatment guidelines for chronic hepatitis B (CHB) from the Asian Pacific Association for the Study of the Liver, American Association for the Study of Liver Diseases and European Association for the Study of the Liver, the short-

10.1586/17474124.2015.960398

term treatment goal is alanine aminotransferase (ALT) normalization (biochemical response), hepatitis B e antigen (HBeAg) loss or seroconversion (serological response), HBV DNA negativity (virological response) and improvement of hepatitis activity or fibrosis (histologic response). The medium-term treatment goal is hepatitis B surface antigen (HBsAg) loss/ seroconversion and fibrosis regression, and the long-term goal is reducing liver cirrhosis, HCC, liver-related deaths and the need for liver transplantation (FIGURE 1). Growing lines of evidence have shown the improvement of longterm outcomes after sustained off-therapy or maintained on-treatment viral suppression by interferon or NAs treatment. In this review, the effectiveness of HBV vaccination and the improvement of long-term outcomes of CHB with effective antiviral agents will be summarized and discussed. The natural history of acute hepatitis B & CHB

Because acute HBV infection in adulthood are usually self-limited, fulminant hepatitis only occurs in 1% of patients and less than 5% of acute hepatitis B patients will become chronic carriers afterward [1]. In HBV endemic regions,

 2015 Informa UK Ltd

ISSN 1747-4124

141

Perspective

Su & kao

exacerbation’, and occasionally complicates with hepatic decompensation or even liver failure (0.5%) [10]. During the Transplant need reduction immune clearance phase, about 2–15% of patients have spontaneous HBeAg HCC reduction seroconversion per year [1], most (80%) Cirrhosis reduction occurring before the age of 40 years. In addition, HBV genotype B patients expeHistologic Fibrosis regression response rience more frequent and earlier HBeAg Serological seroconversion than genotype C patients HBsAg seroclearance response [11,12]. HBeAg seroconversion is a mileHistologic Histologic improvement stone in the natural course of chronic response HBV infection, usually conferring clinical Serological HBeAg loss/seroconversion (HBeAg-positive patient only) response remission with favorable long-term outVirological comes. In a previous study on 283 spontaHBV DNA negativity response neous HBeAg seroconverters with a Biochemical ALT normalization median follow-up of 8.6 years, 67% response remained sustained disease remission, Short-term goal Medium-term goal Long-term goal however, 33% experienced HBV reactivation with clinical hepatitis, 8% had newly Treatment start Time developed cirrhosis and HCC eventually Figure 1. Clinical goals of chronic hepatitis B therapy including short-term goals occurred in 2% of them [13]. In addition, (ALT normalization, HBV DNA negativity, HBeAg loss or seroconversion and the SEARCH-B cohort study showed the histologic improvement); medium-term goals (HBsAg seroclearance, fibrosis annual incidence of HBsAg loss was regression) and long-term goals (the reduction of cirrhosis, HCC, transplant 0.62% after HBeAg seroconversion, and need and mortality). ALT: Alanine aminotransferase; HBeAg: Hepatitis B e antigen; HBsAg: Hepatitis B surface serum HBsAg level

Improving clinical outcomes of chronic hepatitis B virus infection.

Chronic hepatitis B virus (HBV) infection is a global health problem, leading to cirrhosis, hepatocellular carcinoma (HCC) and liver-related deaths. U...
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