Long‐term outcome and hepatocellular carcinoma development in chronic hepatitis B or cirrhosis patients after nucleoside analog treatment with entecavir or lamivudine

Kobashi, Haruhiko; Miyake, Yasuhiro; Ikeda, Fusao; Yasunaka, Tetsuya; Nishino, Ken; Moriya, Akio; Kubota, Jyunichi; Nakamura, Shinichiro; Takaki, Akinobu; Nouso, Kazuhiro; Yamada, Gotaro; Yamamoto, Kazuhide

doi:10.1111/j.1872-034x.2011.00785.x

Cited by 42 publications

(48 citation statements)

References 47 publications

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“…The only report which did observe a significantly greater HCC risk reduction with entecavir than with lamivudine is the study by Hosaka et al [26], where no rescue therapy was used (as it was not available for this historical control cohort). Several studies found that HCC development was significantly associated with resistance development, resistanceassociated virologic breakthrough, low genetic barrier drug regimen, and prior lamivudine exposure [37,39,43]. These findings are consistent with earlier results from Liaw et al…”

Section: Discussionsupporting

confidence: 90%

“…After a treatment duration of 4 years, there was no significant difference in the overall HCC incidence between entecavir and lamivudine. However, lamivudine resistance, which developed in 60/127 (47%) lamivudinetreated patients, was associated with a significantly increased risk of HCC (20.3% versus 3.2% at year 5; p=0.04; [39]). A Korean analysis of PS-matched pairs of NA-naive patients treated with entecavir or lamivudine (39% with rescue therapy) found that in the overall study population, and in patients with cirrhosis, the risk of death or transplantation was 50-60% lower with entecavir than with lamivudine (p<0.001) after 3 years of follow-up; however, HCC risk over the same time period was comparable between the two treatments.…”

Section: Hcc Incidence Under Entecavir or Tenofovir Versus Older Nasmentioning

confidence: 95%

“…Four of these studies were from East Asia [26,[39][40][41], two from Turkey [42,43], and one from Greece [38]. The study by Hosaka et al in NA-naive patients also included a comparison between entecavir-treated patients and historical controls receiving lamivudine without any rescue therapy upon resistance (182 PS-matched patients in each group); in non-cirrhotic patients, HCC rates were comparable between entecavir and lamivudine; however, in cirrhotic patients, the HCC incidence was significantly lower with entecavir than with lamivudine (p=0.04) [26].…”

Section: Hcc Incidence Under Entecavir or Tenofovir Versus Older Nasmentioning

confidence: 99%

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Risk of hepatocellular carcinoma in chronic hepatitis B: Assessment and modification with current antiviral therapy

Papatheodoridis

Chan

Hansen

et al. 2015

Journal of Hepatology

421

334

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In the treatment of chronic hepatitis B (CHB), the ultimate goal is preventing hepatitis B virus (HBV)-associated liver disease, including hepatocellular carcinoma (HCC). Recently published studies show that in CHB patients treated with the currently recommended first-line nucleos(t)ide analogs (NAs) entecavir or tenofovir, annual HCC incidences range from 0.01% to 1.4% in non-cirrhotic patients, and from 0.9% to 5.4% in those with cirrhosis. In Asian studies including matched untreated controls, current NA therapy consistently resulted in a significantly lower HCC incidence in patients with cirrhosis, amounting to an overall HCC risk reduction of ∼30%; in non-cirrhotic patients, HCC risk reduction was overall ∼80%, but this was only observed in some studies. For patients of Caucasian origin, no appropriate comparative studies are available to date to evaluate the impact of NA treatment on HCC. Achievement of a virologic response under current NA therapy was associated with a lower HCC risk in Asian, but not Caucasian studies. Studies comparing entecavir or tenofovir with older NAs generally found no difference in HCC risk reduction between agents, except for one study which used no rescue therapy in patients developing lamivudine resistance. Overall, these data indicate that with the current, potent NAs, HCC risk can be reduced but not eliminated, probably due to risk factors that are not amenable to change by antiviral therapy, or events that may have taken place before treatment initiation. Validated pre- and on-therapy HCC risk calculators that inform the best practice for HCC surveillance and facilitate patient counseling would be of great practical value.

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Section: Discussionsupporting

confidence: 90%

Section: Hcc Incidence Under Entecavir or Tenofovir Versus Older Nasmentioning

confidence: 95%

Section: Hcc Incidence Under Entecavir or Tenofovir Versus Older Nasmentioning

confidence: 99%

See 1 more Smart Citation

Risk of hepatocellular carcinoma in chronic hepatitis B: Assessment and modification with current antiviral therapy

Papatheodoridis

Chan

Hansen

et al. 2015

Journal of Hepatology

421

334

View full text Add to dashboard Cite

show abstract

“…As a result, levels of both serum HBV-DNA and transaminase concentrations are rapidly reduced. When viral suppression is prolonged, this can result in histological improvement, including regression of fibrosis [19][20][21][22] , and in patients with HBV-related HCC, liver function has improved [23][24][25][26] . For hepatitis C patients, IFN therapy has previously been the only treatment found to reduce levels of virus.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for deterioration of long-term liver function after radiofrequency ablation therapy

Honda

Seike

Oribe

et al. 2016

WJH

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AIM:To identify factors that influence long-term liver function following radiofrequency ablation (RFA) in patients with viral hepatitis-related hepatocellular carcinoma. METHODS:A total of 123 patients with hepatitis B virus-or hepatitis C virus-related hepatocellular carcinoma (HCC) (n = 12 and n = 111, respectively) were enrolled. Cumulative rates of worsening Child-Pugh (CP) scores (defined as a 2-point increase) were examined. RESULTS:CP score worsening was confirmed in 22 patients over a mean follow-up period of 43.8 ± 26.3 mo. Multivariate analysis identified CP class, platelet count, and aspartate aminotransferase levels as significant predictors of a worsening CP score (P = 0.000, P = 0.011 and P = 0.024, respectively). In contrast, repeated RFA was not identified as a risk factor for liver function deterioration. CONCLUSION:Long-term liver function following RFA was dependent on liver functional reserve, the degree Risk factors for deterioration of long-term liver function after radiofrequency ablation therapy Retrospective Cohort Study ORIGINAL ARTICLEof fibrosis present, and the activity of the hepatitis condition for this cohort. Therefore, in order to maintain liver function for an extended period following RFA, suppression of viral hepatitis activity is important even after the treatment of HCC. Core tip: This study was conducted to identify risk factors for liver function deterioration following radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC) and viral hepatitis. A total of 123 patients with hepatitis B virus-or hepatitis C virusrelated HCC were enrolled. Cumulative rates of worsening Child-Pugh (CP) scores (defined as a 2-point increase) following RFA were examined. CP class, platelet count, and aspartate aminotransferase levels were identified as significant predictors of a worsening CP score. Suppression of viral hepatitis activity with anti-viral therapy is important even after the treatment of HCC in order to maintain liver function following RFA.

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“…Kobashi et al analyzed the HCC incidence among 129 ETV-treated patients and 127 LAM-treated patients (the median observation periods were 2.86 and 5.97 years, respectively). 19 The cumulative incidence rates of HCC at 5 years were 11.8% and 11.7%, respectively (P = 0.680). A large-scale cohort study conducted by Lim et al evaluated the HCC incidence rates among patients receiving ETV or LAM treatment in the propensity scorematched cohort stratified according to the severity of liver disease.…”

Section: Impact Of Nucleos(t)ide Analogue For Hccmentioning

confidence: 99%

The suppressive effect of nucleos(t)ide analogue treatment on the incidence of hepatocellular carcinoma in chronic hepatitis B patients

Hiramatsu

Yamada

Takehara

2016

J of Gastro and Hepatol

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The development of nucleos(t)ide analogues (NA) has influenced hepatitis B virus management. However, the annual incidence rate during NA treatment has been reported to be 0.3-1.2% in non-cirrhosis cases and 1.8-6.0% in cirrhosis cases, indicating that the suppressive effect of NA treatment on hepatocellular carcinoma (HCC) would be insufficient. Past studies, including one randomized control trial that compared lamivudine treatment with placebo, have revealed that NA treatment could suppress the incidence of HCC in patients with advanced fibrosis. However, it remains unknown whether NA treatment can suppress the incidence of HCC in chronic hepatitis patients without advanced fibrosis. The HCC incidence in patients treated with entecavir was similar to that of those treated with lamivudine, although entecavir exhibits a stronger viral suppression than lamivudine. The following risk factors related to the incidence of HCC during NA treatment have been identified: older age, male gender, pre-existing cirrhosis, a family clustering of hepatitis B virus, lower platelet counts, and higher hepatitis B core-related antigens as baseline factors and higher alpha fetoprotein levels as an on-treatment factor. Conversely, the loss of the hepatitis B surface antigen (HBsAg) by interferon or NA was correlated with a lower HCC incidence rate. Because interferon treatment has much more effects on reducing HBsAg levels compared with NA treatment, a combination treatment with NA and pegylated interferon can bring additional reduction of HBsAg levels compared with NA monotherapy. Further study is needed to clarify this.

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Long‐term outcome and hepatocellular carcinoma development in chronic hepatitis B or cirrhosis patients after nucleoside analog treatment with entecavir or lamivudine

Abstract: NA exerted a long-term efficacy and improved hepatic reservation in CHB and cirrhosis. After NA treatment, AFP dropped to lower than 10 ng/mL with marked elevation of specificity, leading to an earlier detection of HCC.

Cited by 42 publications

References 47 publications

Risk of hepatocellular carcinoma in chronic hepatitis B: Assessment and modification with current antiviral therapy

Risk of hepatocellular carcinoma in chronic hepatitis B: Assessment and modification with current antiviral therapy

Risk factors for deterioration of long-term liver function after radiofrequency ablation therapy

The suppressive effect of nucleos(t)ide analogue treatment on the incidence of hepatocellular carcinoma in chronic hepatitis B patients

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