Medication Nonadherence Increases Hepatocellular Carcinoma, Cirrhotic Complications, and Mortality in Chronic Hepatitis B Patients Treated With Entecavir

Kim

et al. 2019

Aliment Pharmacol Ther

Background: It remains unknown whether antiviral treatment for HBeAg-negative chronic hepatitis B (CHB) patients having high viral loads without significant elevation of alanine aminotransferase (ALT) levels would reduce the risks of clinical events. Aim: To compare clinical outcomes of high viral load CHB patients untreated for normal or mildly elevated ALT vs those treated for ALT ≥ 2 upper limit of normal (ULN). Methods: This historical cohort study included 5414 HBeAg-negative CHB patients without cirrhosis at a tertiary hospital in Korea from 2000 to 2013. Inactive phase was defined as serum hepatitis B virus [HBV] DNA < 2000 IU/mL and persistently normal ALT (n = 3572). High viral load (HBV DNA ≥ 2000 IU/mL) patients were classified into three phases by ALT levels: Replicative (persistently normal ALT, n = 900);Mildly active (ALT 1-2ULN, n = 396); and Active (ALT ≥ 2ULN, n = 546) phases. All Active phase patients were treated with nucleos(t)ide analogues. Results:The mean age of the patients was 47 years without a significant difference among the groups. Compared with the treated Active phase group, the untreated Replicative phase group showed a significantly higher risk of hepatocellular carcinoma (HCC; HR 1.76; 95% CI 1.00 -3.10, P = 0.05) and death/transplantation (HR 2.14; 5% CI 1.09 -4.21, P = 0.03) by propensity score-matched analysis. The untreated mildly active phase patients had further increase in risk of HCC and death/ transplantation compared with the treated Active phase group by unadjusted, PSmatched, competing risks, and multivariable-adjusted analyses. Conclusions: Untreated high viral load HBeAg-negative CHB patients without significant ALT elevation had higher risks of clinical events than treated Active phase patients with elevated ALT. S U PP O RTI N G I N FO R M ATI O N Additional supporting information will be found online in the Supporting Information section at the end of the article. How to cite this article: Choi GH, Kim G-A, Choi J, Han S, Lim Y-S. High risk of clinical events in untreated HBeAg-negative chronic hepatitis B patients with high viral load and no significant ALT elevation. Aliment Pharmacol Ther. 2019;50: 215-226. https ://doi.

Section: Discussionmentioning

confidence: 99%

High risk of clinical events in untreated HBeAg‐negative chronic hepatitis B patients with high viral load and no significant ALT elevation

Kim

et al. 2019

Aliment Pharmacol Ther

“…Third, we did not thoroughly investigate patient adherence to antiviral therapy which may have influenced the VR, especially in the ETV group. 20 The strengths of this study were that it was a large-scale, real-world, propensity-matched cohort with >7000 consecutive patients screened, and >3000 patients analysed. In addition, we have performed detailed subgroup analyses which made our data more reliable.…”

Section: Discussionmentioning

confidence: 99%

Comparison of tenofovir and entecavir on the risk of hepatocellular carcinoma and mortality in treatment-naïve patients with chronic hepatitis B in Korea: a large-scale, propensity score analysis

Lee

Kwon

Lee

et al. 2019

Gut

112

157

ObjectiveThe use of tenofovir (TDF) and entecavir (ETV) in patients with chronic hepatitis B (CHB) has led to a decrease in the incidence of hepatocellular carcinoma (HCC) and liver-related events. However, whether there is a difference between the two agents in the extent of improving such outcomes has not been clarified thus far. Therefore, we aimed to compare TDF and ETV on the risk of HCC and mortality.DesignA total of 7015 consecutive patients with CHB who were treated with TDF or ETV between February 2007 and January 2018 at the liver units of the Catholic University of Korea were screened for study eligibility and 3022 patients were finally analysed. Study end points were HCC and all-cause mortality or liver transplantation (LT) within 5 years after the initiation of antiviral therapy. Propensity score matching (PSM) and inverse probability of treatment weighting methods were used.ResultsNo difference was observed between TDF and ETV in the incidence rates of HCC in the entire cohort (HR 1.030; 95% CI 0.703 to 1.509, PSM model, p=0.880) and subgroups of patients with chronic hepatitis and cirrhosis. Also, no difference was observed between TDF and ETV in the incidence rates of all-cause mortality or LT in the entire cohort (HR 1.090; 95% CI 0.622 to 1.911, PSM model, p=0.763), and patients with chronic hepatitis and cirrhosis.ConclusionThis study has demonstrated the clinical outcomes in patients with CHB who received TDF or ETV treatment. There was no difference in the intermediate-term risk of HCC and mortality or LT between the two drugs.

Journal of Viral Hepatitis

“…In addition, we were able to show risk reduction in both cirrhotic and noncirrhotic patients. Shin et al demonstrated the protective effect of entecavir from another aspect by showing the association and a dose‐response relationship between poor compliance to antiviral treatment with adverse outcomes of CHB including HCC, which also reflected the long‐term efficacy of entecavir beyond the initial period of treatment …”

Section: Discussionmentioning

confidence: 99%

A large real‐world cohort study examining the effects of long‐term entecavir on hepatocellular carcinoma and HBsAg seroclearance

Mak

et al. 2019

Real‐world studies examining reduction in risk of hepatocellular carcinoma (HCC) in patients receiving antivirals are limited by the small size of the studies, or by data insufficiency and heterogeneity with short follow‐up duration. We aimed to examine the real‐world long‐term outcome of patients receiving entecavir treatment on HCC incidence and HBsAg seroclearance. The incidence of HCC in 1225 entecavir‐treated patients between 2002 and 2015 was compared with the HCC incidence estimated using the REACH‐B, GAG‐HCC and CU‐HCC scores. Standardized incidence ratios (SIR) were calculated. The impact of entecavir treatment on HBsAg seroclearance was also explored. The median follow‐up of the cohort was 6.6 years, with 66 cases of HCC development. Using the REACH‐B model, the reduction of HCC risk was significant from year 6 onwards with SIR of 0.68 (95% CI 0.535‐0.866) at year 10. In subgroup patients without cirrhosis, consistent risk reduction was observed from the fifth year and the SIR reached 0.51 (95% CI 0.271‐0.704) by year 10. Benefit in cirrhotic patients was demonstrated when using the GAG‐HCC and CU‐HCC score, with the SIR at year 10 being 0.38 (95% CI 0.259‐0.544) and 0.46 (95% CI 0.314‐0.659), respectively. The cumulative rate of HBsAg seroclearance was 5.2%. HBsAg level at third year of treatment and baseline‐to‐3‐year percentage reduction was predictive of subsequent HBsAg seroclearance. In conclusion, long‐term entecavir therapy was associated with significant reduction in the risk of HCC in the real world. However, HBsAg seroclearance rate remained low. Additional therapy may be considered in patients with adverse predictive factors for subsequent HBsAg seroclearance.