Twenty‐four‐week clevudine therapy showed potent and sustained antiviral activity in HBeAg‐positive chronic hepatitis B†‡

Yoo, Byung Chul; Kim, Ju Hyun; Chung, Young‐Hwa; Lee, Kwan Sik; Paik, Seung Woon; Ryu, Soo Hyung; Han, Byung Hoon; Han, Ji-Hye; Byun, Kwan Soo; Cho, Mong; Lee, Heon-Ju; Kim, Tae-Hun; Cho, Se-Hyun; Park, Joong-Won; Um, Soon-Ho; Hwang, Seong Gyu; Kim, Young Soo; Lee, Youn-Jae; Chon, Chae Yoon; Kim, Byung-Ik; Lee, Young-Suk; Yang, Jung–Min; Kim, Haak Cheoul; Hwang, Jae Seok; Choi, Sung‐Kyu; Kweon, Young-Oh; Jeong, Sook‐Hyang; Lee, Myung-Seok; Choi, Jong-Young; Kim, Dae‐Ghon; Kim, Yun Soo; Lee, Heon Young; Yoo, Kwon; Yoo, Hee-Won; Lee, Hyo‐Suk

doi:10.1002/hep.21629

Cited by 125 publications

(145 citation statements)

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“…Therefore, clevudine therapy may also be considered for the prevention of liver function deterioration during and after anti-cancer therapy in HBV-related HCC. During 24 weeks of clevudine therapy, the rates of ALT normalization were 68.2% in patients with HBeAg-positive chronic hepatitis B 12 and 74.6% in patients with HBeAg-negative chronic hepatitis B. 13 Our data showed slightly lower rates of ALT normalization, specifically, 62.5% and 66.7% in the CHB/ HCC and CHB groups, respectively.…”

Section: Discussionmentioning

confidence: 50%

“…To date, the results of five clinical trials on clevudine therapy have been published, including phase II studies showing no serious adverse events, including myopathy, after 24 weeks of treatment. 9,12,13,24,25 However, severa l hepatitis B patients develop myopathy during long-term clevudine therapy. 26,27 Moreover, long-term clevudine therapy induces depletion of mitochondrial DNA and leads to mitochondrial myopathy associated with myonecrosis.…”

Section: 16mentioning

confidence: 99%

“…A unique advantageous characteristic of clevudine is prolonged suppression of viral replication even after withdrawal of treatment, which has been demonstrated both in vitro and in vivo. 9,[11][12][13] Clinical effects of clevudine have been reported in patients with HBeAg-positive or -negative chronic hepatitis B. However, current knowledge on the effects of clevudine is insufficient, and the influence of this drug in HBV-related cirrhosis or HCC patients remains to be established.…”

Section: Introductionmentioning

confidence: 99%

“…This relatively small reduction in serum HBV DNA levels may be due to reduced baseline DNA levels and higher rates of lower baseline ALT levels in our study population (Tables 1, 2), compared with those reported previously; 6.6-6.3 vs 8.29-6.92 log 10 copies/mL, 68.5% vs 31.8-26.4% ALT <2X ULN at baseline, respectively. 12,13 Owing to low efficacy, antiviral treatment is not generally recommended to HBV-positive patients with serum HBV DNA levels >20,000 IU/mL and normal or minimally elevated ALT. 19 Careful consideration of the patient age, severity of liver disease, likelihood of response, and potential adverse events is essential prior to initiation of treatment.…”

mentioning

confidence: 99%

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Clinical and Virological Responses to Clevudine Therapy of Hepatocelluar Carcinoma Patients with Chronic Hepatitis B

Woo¹,

Park²,

Lee³

et al. 2011

Gut Liver

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Background/Aims: The clinical effects of clevudine have been reported in patients with chronic hepatitis B virus infections (CHIs). In this investigation, we assessed whether clevudine induced biochemical and virological improvements in hepatocellular carcinoma (HCC) patients with CHI. Methods: Fifty-four patients who received 30 mg clevudine for more than 24 weeks between 2007 and 2009 at the National Cancer Center Hospital, Korea, were enrolled. Among these cases, 39 had HCC (CHI/HCC group) and 15 did not (CHI group). Results: In relation to the CHI group, the CHI/HCC group was older (55.5 years.) and had a higher liver cirrhosis rate (79.5%) (p<0.05). Median changes in serum hepatitis B virus (HBV) DNA levels from baseline at weeks 12, 24, and 36 of treatment in the CHI/HCC group were not signifi cantly different from those of the CHI group (-2.3, -2.7, -2.6 vs -1.7, -1.8, -2.4, respectively). HBV DNA <2,000 copies/mL was achieved in 76.5% of the CHI/HCC group at 24 weeks. Rates of ALT normalization in the CHI/HCC and CHI groups were 62.5% and 66.7%, respectively (p>0.05). Liver function was preserved with clevudine treatment in patients displaying response or stable disease under anti-cancer therapy. Four patients (7.4%) developed viral resistance during clevudine therapy. Among these, one was naïve, and three had previously received antiviral therapy. One CHI/HCC patient (1.9%) discontinued clevudine treatment due to symptomatic myopathy. Conclusions: Our findings clearly indicate that clevudine has comparable antiviral and biochemical effects in patients with CHI and with CHI/HCC and preserves the underlying liver function in HBV-related HCC patients. (Gut Liver 2011;5:82-87) HBV re-activation and chronic hepatitis B exacerbation. In addition, high HBV load prior to chemotherapy has an adverse effect on the survival of HCC patients with chronic HBV infection (CHI). 8 These findings suggest that incorporation of antiviral therapies to reduce the HBV viral load should be considered in the management of HBV-related HCC. Antiviral treatment may render HBV-related HCC patients more tolerant of HCC therapy, ultimately leading to better prognosis. A previous study by our group showed for the first time that lamivudine has comparable antiviral effects in patients with CHI and CHI/HCC and improves underlying liver function in the latter group. MATERIALS AND METHODS PatientsThis study is a retrospective evaluation of 54 CHI patients receiving 30 mg clevudine (Levovir ; Buckwang Pharmaceutical Co., Seoul, Korea) once a day for at least 6 months from August 2007 to February 2009 at the National Cancer Center Hospital (Goyang, Korea). Among the patients, 39 had chronic hepatitis B infection and HCC (CHI/HCC group), and 15 had CHI without HCC (CHI group). Patients with other viral infections, including hepatitis C, D, and human immunodeficiency virus, were excluded. All patients from both groups contained serum HBV DNA >10 5 copies/mL, as assessed using the branched DNA method. Moreover, all patients displayed ser...

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Section: Discussionmentioning

confidence: 50%

Section: 16mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Clinical and Virological Responses to Clevudine Therapy of Hepatocelluar Carcinoma Patients with Chronic Hepatitis B

Woo¹,

Park²,

Lee³

et al. 2011

Gut Liver

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“…Median serum HBV DNA reductions from baseline at week 24 were 5.10 and 0.27 log 10 copies/ml in the clevudine and placebo groups, respectively (P \ 0.0001), with ALT normalization in 68.2 and 17.5%, respectively (P \ 0.0001). A total of 59% of patients in the clevudine group were PCR negative for HBV DNA [129]. Viral suppression in the clevudine group was sustained off therapy, with 2.02 log 10 reduction at week 48 compared with baseline.…”

Section: Clevudinementioning

confidence: 96%

Recent data on treatment of chronic hepatitis B with nucleos(t)ide analogues

Leung

2008

Hepatol Int

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Forty years ago in 1967, Professor Blumberg discovered the Australian Antigen, later known as the hepatitis B surface antigen, and was awarded the Nobel Prize. This discovery enables the diagnosis of hepatitis B virus (HBV) infection and defines its epidemiology. Viral hepatitis B infection affects global health situation, and chronic hepatitis B (CHB) is particularly serious in the Asia-Pacific region. HBV vaccines created the first breakthrough in HBV prevention. Through universal HBV vaccination program for the newborns, promoted since the mid-1980s, the main route that perpetuates chronic infection from mother to child is curbed. Most children and young adults now have immunity against HBV infection. The next breakthrough comes with therapy for CHB. This prevents progression to cirrhosis and hepatocellular carcinoma. Standard interferon therapy with modest efficacy has been largely replaced by therapy with nuclos(t)ide analogues or pegylated interferons alfa-2a and -2b. Lamivudine was approved by the FDA USA in 1998, followed by adefovir dipivoxil in 2002, entecavir in 2005, and telbivudine in 2006. Clevudine, tenofovir, and many promising candidates are in different stages of development and clinical trial. This paper critically reviews recent data published or presented since the APASL Consensus and Guideline Update of 2005. Clinical efficacy mostly in patients with raised serum alanine aminotransferase will be analyzed.

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Anti‐DNAVirus Agents

Holý

Clercq

2010

Burger's Medicinal Chemistry and Drug Discovery

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Anti‐DNA virus agents that are inhibitory to the replication of DNA viruses have been reviewed by Tim Middleton and Rockway in Burger's Medicinal Chemistry, 6th ed., volume 5. Here we will address the various agents effective against these different viruses. For each of the (classes of) compound(s), we will, where applicable, specifically focus on (i) the antiviral compounds that are clinically available; (ii) the antiviral compounds that are under (pre)clinical development; (iii) the mechanism of action of the compounds; (iv) their structure–activity relationship (SAR); (v) resistance that may have arisen; (vi) recent clinical data obtained with the compounds while under development. Previous reviews on antiviral agents have been dealing with “looking back in 2009 at the dawning of antiviral therapy now 50 years ago: an historical perspective,” highlighting the discovery of acyclovir [9‐(2‐hydroxyethoxymethyl)guanine] as a specific antiherpetic agent, “the design of drugs for HIV and HCV,” “HIV drug development: the next 25 years,” “interferons at age 50: past, current, and future impact on biomedicine,” “the way forward in HCV treatment‐finding the right path,” “antiviral treatment of chronic hepatitis B virus infections: the past, the present, and the future,” “antiviral agents active against influenza A viruses,” “the war against influenza: discovery and development of sialidase inhibitors,” “antivirals and antiviral strategies,” and “clinical potential of the acyclic nucleoside phosphonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections.”

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Twenty‐four‐week clevudine therapy showed potent and sustained antiviral activity in HBeAg‐positive chronic hepatitis B†‡

Cited by 125 publications

References 24 publications

Clinical and Virological Responses to Clevudine Therapy of Hepatocelluar Carcinoma Patients with Chronic Hepatitis B

Clinical and Virological Responses to Clevudine Therapy of Hepatocelluar Carcinoma Patients with Chronic Hepatitis B

Recent data on treatment of chronic hepatitis B with nucleos(t)ide analogues

Anti‐DNAVirus Agents

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