Poor durability of lamivudine effectiveness despite stringent cessation criteria: A prospective clinical study in hepatitis B e antigen‐negative chronic hepatitis B patients

Liu, Feng; Wang, Lei; Li, Xiao Ying; Liu, You De; Wang, Jing Bo; Zhang, Zhao Hua; Wang, Yao Zong

doi:10.1111/j.1440-1746.2010.06492.x

Cited by 78 publications

(129 citation statements)

References 22 publications

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“…Few studies have looked at the suitable length of treatment and the results have largely been disappointing. With lamivudine treatment for 2 years and more strict criteria for termination of treatment, the virologic relapse rate was still higher than 50% after 12 months of termination [16][17][18]. Out of 145 patients taking adefovir who were HBV DNA-negative for more than 18 months by PCR, 95 patients (61.4%) underwent virologic relapse as observed by serum HBV DNA >2000 IU/mL.…”

Section: Hbeag-negative Chronic Hbv Infectionmentioning

confidence: 99%

“…Ninetythree percent of all virologic relapse cases occur within 1 year of stopping treatment [19]. However, young patients (20-25 years old) showed a dramatically reduced rate of post-treatment virologic relapse [18,19]. When entecavir was administered to patients for 52 weeks and then stopped, sustained viral suppression was only observed in 48% of patients after 24 weeks [20].…”

Section: Hbeag-negative Chronic Hbv Infectionmentioning

confidence: 99%

“…As the above studies show, the post-treatment relapse rate appears to be approximately 50%, regardless of the suppressive ability of antiviral treatment or the likelihood of drug resistance [16,[18][19][20]22,[24][25][26]. Therefore, it may be important to apply APASL guidelines for stopping antiviral treatments to patients who find long-term treatment financially burdensome or who are experiencing side effects associated with long-term usage of drugs or treatments.…”

Section: Hbeag-negative Chronic Hbv Infectionmentioning

confidence: 99%

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Oral Antiviral Therapy for Chronic Hepatitis B Virus Infection: Is Continuous Treatment Needed?

Lee¹

2014

GHOA

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AbbreviationsNA: Nucleos(T)Ide Analogue; HBV: Hepatitis B Virus; cccDNA: covalently closed circular DNA IntroductionLong-term usage of oral antiviral is highly effective in treating chronic hepatitis B virus (HBV) infection and can effectively suppress HBV proliferation which may prevent the progression of liver fibrosis and the development of HCC after long term use of NAs but cannot completely eradicate the virus. Furthermore, the safety of long-term usage of antivirals is still a concern that needs to be assessed and the increasing cost of antiviral treatments can be a serious financial burden. It is still unclear how long antiviral treatment needs to be continued and how to determine when discontinuation of the treatment is appropriate. The presence of covalently closed circular DNA (cccDNA) in hepatocytes correlates to immune activity and is used as a predictive factor to evaluate sustained viral suppression after termination of antiviral treatment [1]. Unlike pegylated interferon, oral antivirals do not have direct immunomodulatory effects and only temporarily induce a modest increase in immune function. Therefore, oral antiviral treatments are unlikely to provide continued viral suppression after termination. Discussion HBeAg-positive chronic HBV infectionPatients that reach sustained viral suppression (HBV DNA negativity and HBeAg loss or seroconversion) with lamivudine usage show a virologic relapse rate of 15.9-48%, 29-50%, 54-55.7%, and 44-64.8% 1, 2, 3, and 4 years after discontinuation of lamivudine respectively [2][3][4][5][6][7][8]. A considerable number of patients that undergo HBeAg seroconversion upon oral antiviral AbstractPotent nucleos(t)ide analogues (NAs) have improved patient prognosis via suppression of viral load, HBeAg seroconversion and in some cases, HBsAg seroconversion. However, the duration and end point of NA treatment are still debatable. Current international guidelines recommend that discontinuation of NA treatment can be considered when HBeAg seroconversion and undetectable HBV DNA status is maintained for at least 6-12 months for HBeAg-positive patients and undetectable HBV DNA status on 3 separate occasions 6 months apart for HBeAgnegative patients if they have been treated for at least 2 years. Durability of NA, particularly after off-treatment, remains uncertain. A proportion of patients who discontinue NA therapy after HBeAg seroconversion may require retreatment if sustained serological and/or virological response fails and high off-treatment virological relapse can develop in HBeAg-negative patients. Therefore, NA treatment may be continued until HBsAg clearance with or without antibodies to HBsAg, particularly in patients with severe fibrosis or cirrhosis.

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Section: Hbeag-negative Chronic Hbv Infectionmentioning

confidence: 99%

Section: Hbeag-negative Chronic Hbv Infectionmentioning

confidence: 99%

Section: Hbeag-negative Chronic Hbv Infectionmentioning

confidence: 99%

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Oral Antiviral Therapy for Chronic Hepatitis B Virus Infection: Is Continuous Treatment Needed?

Lee¹

2014

GHOA

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“…As this complication is sometimes lethal [8][9][10], it is crucial to determine the optimal conditions for stopping nucleos(t)ide analog therapy, especially for young patients wishing to have children, the avoidance of hyper-resistant viral strains, and regulating medical expenses.…”

mentioning

confidence: 99%

Hepatitis B core-related antigen: a strong indicator for cessation of nucleos(t)ide analog therapy in patients with chronic hepatitis B

Matsumoto

2016

J Gastroenterol

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With successful nucleos(t)ide analog therapy, serum hepatitis B virus (HBV) DNA titer decreases to below detection limit, alanine aminotransferase (ALT) normalizes, and fibrosis of the liver may become improved [1][2][3][4]. The incidence of hepatocellular carcinoma can be decreased as well [5][6][7].However, withdrawal hepatitis frequently occurs after treatment cessation, even in patients with undetectable HBV DNA levels. As this complication is sometimes lethal [8][9][10], it is crucial to determine the optimal conditions for stopping nucleos(t)ide analog therapy, especially for young patients wishing to have children, the avoidance of hyper-resistant viral strains, and regulating medical expenses.Knowledge of intrahepatic HBV replication status is the key to defining the safe conditions for nucleos(t)ide analog therapy cessation. cccDNA level is a suitable indicator for this aim, although frequent liver biopsies are needed. Serum HBV DNA was believed to be a good estimator of cccDNA. However, the correlation of HBV DNA and intrahepatic cccDNA levels is lost under the nucleos(t)ide analog treatment and cannot therefore be adopted [11]. Alternative, non-invasive markers are desired.The possibility of discontinuation of nucleos(t)ide analogs is also affected by the clinical goal, such as no withdrawal hepatitis, no viral relapse, or long-term clinical response. The majority of patients experience viral recurrence during withdrawal, but some will not develop hepatitis or will achieve clinical remission after a hepatitis flare.In this issue, Jung KS et al.[12] report on virological remission (i.e., HBV DNA B2000 IU/ml) over 1 year following cessation of nucleos(t)ide therapy in patients HBeAg-positive or HBeAg-negative at the start of treatment. The virological relapse rate of each group was 57.8 and 54.4 %, respectively. Significantly and independently related factors for virological relapse were age [40 years at the start of nucleos(t)ide therapy and basal HBV DNA level[20,000,000 IU/ml in the HBeAg-positive group, and age [40 years at the start of nucleos(t)ide analog therapy and HB core-related antigen (HBcrAg) level[3.7 log U/ml in the HBeAg-negative group.HBcrAg is an established viral activity marker [13]. HBcrAg levels correlated closely with those of intrahepatic cccDNA, even when HBV DNA became undetectable, during nucleos(t)ide analog therapy [11]. Thus, HBcrAg may represent a non-invasive marker of cccDNA with or without nucleos(t)ide analog therapy. We have also reported that a combination of HBsAg and HBcrAg levels at the end of nucleos(t)ide analog therapy was useful to predict long-term clinical remission [14,15].According to APASL guidelines, the appropriate duration of nucleoside analog administration is unknown, although HBV DNA and HBsAg are suggested as estimators of treatment efficacy [16]. There are no precise criteria for the cessation of nucleos(t)ide analog therapy in the EASL guidelines as well [17]. In the AASLD guidelines, HBsAg loss is regarded as the best predictor of sustained remi...

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“…3 In this issue of the Journal of Gastroenterology and Hepatology, Liu and colleagues reported the relapse rates of 61 HBeAg-negative CHB patients in whom LAM was stopped. 12 These patients were treated for at least 24 months, and had undetectable HBV DNA (<200 IU/mL) and normal ALT levels for at least 18 months. Relapse was defined as HBV DNA Ն2000 IU/mL.…”

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confidence: 99%

To stop or not to stop: The quest for long‐term viral suppression

Fung

Lai

Yuen

2011

J of Gastro and Hepatol

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Poor durability of lamivudine effectiveness despite stringent cessation criteria: A prospective clinical study in hepatitis B e antigen‐negative chronic hepatitis B patients

Abstract: Effectiveness of lamivudine treatment is not durable in HBeAg-negative CHB patients even when stringent cessation criteria are adopted, with the exception of patients aged ≤ 20 years. The ideal end point of lamivudine treatment is clearance of serum HBsAg.

Cited by 78 publications

References 22 publications

Oral Antiviral Therapy for Chronic Hepatitis B Virus Infection: Is Continuous Treatment Needed?

Oral Antiviral Therapy for Chronic Hepatitis B Virus Infection: Is Continuous Treatment Needed?

Hepatitis B core-related antigen: a strong indicator for cessation of nucleos(t)ide analog therapy in patients with chronic hepatitis B

To stop or not to stop: The quest for long‐term viral suppression

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