Does early on-treatment alanine aminotransferase (ALT) normalization reduce the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B?-A territory-wide study of 21,182 subjects
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AbstractBackground: Alanine aminotransferase (ALT) normalization is considered to be the biochemical response to antiviral treatment. We aimed to evaluate the impact of ALT normalization achieved at different time points after the start of entecavir and/or tenofovir disoproxil fumarate (TDF) treatment, on the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).

Method: We identified a territory-wide cohort of CHB patients who received entecavir and/or TDF for at least 1 year from January 2005 to December 2016 in Hong Kong. Serial on-treatment ALT levels were collected and analyzed. ALT normalization (ALT-N) was defined as the ALT level lower than the upper limit of normal (ULN), which is 30 U/L in males and 19 U/L in females. Early on-treatment ALT-N was defined as ALT-N within 12 months. The primary outcome was HCC based on ICD-9-CM diagnosis codes. Patients with cancers previously or during the first year of treatment were excluded.

Result: 21,182 CHB patients (10,437 with and 10,745 without ALTN at 12 months after antiviral treatment) were identified and followed for a median (interquartile range) of 4.1 (2.4-6.0) years. Patients with or without ALT-N at 12 months differed in gender distribution (76.9% vs. 58.4% male), baseline ALT (58 vs. 61 U/L), baseline serum HBV DNA (4.9 vs. 5.1 log10 IU/mL), proportion of positive hepatitis B e antigen (31.5% vs. 37.1%), proportion of having cirrhosis (8.8% vs. 10.5%) and prevalence of diabetes mellitus (8.1% vs. 9.1%); 509 (2.4%) patients developed HCC. Compared to no ALT-N, ALT-N at 3, 6, 9 and 12 months were associated with a reduced risk of HCC (Figures 1A-D), with adjusted hazard ratios (95% confidence interval [CI]) of 0.55 (0.42-0.71), 0.52 (0.41-0.64), 0.47 (0.38-0.58) and 0.46 (0.37-0.56), respectively (all P<0.001). In contrast, patients with ALT 1 to 2 times the ULN and ALT greater than 2 times the ULN at 12 months were associated with a higher risk of HCC as compared to patients with ALT-N at 12 months, with adjusted hazard ratios (95% CI) of 2.07 (1.67-2.56) and 3.21 (2.32-4.44), respectively, after adjustment for baseline ALT and other important covariates. The cumulative incidence (95% CI) of HCC at 6 years was 2.7% (2.3%-3.2%) in ALT-N at 12 months, 4.6% (4.1%-5.2%) in ALT 1 to 2 times the ULN at 12 months, and 6.0% (4.7%-7.7%) in ALT greater than 2 times the ULN at 12 months (log-rank test, P<0.001) (Figure 2).

Conclusion: Early on-treatment ALT-N can be translated into reduced risk of HCC development in CHB patients having nucleos(t)ide anaolgue treatment. On-treatment ALT above 1 and 2 times the ULN at 12 months were associated with higher risk of HCC.
All Author(s) ListCheuk Fung Yip, Grace Lai Hung Wong, Yee Kit Tse, Henry Lik Yuen Chan, Vincent Wai Sun Wong
Name of ConferenceThe Asian Pacific Association for the Study of the Liver (APASL) 2018 Annual Meeting
Start Date of Conference14/03/2018
End Date of Conference18/03/2018
Place of ConferenceNew Delhi
Country/Region of ConferenceIndia
Proceedings TitleHepatology International
Volume Number12
Issue NumberSuppl 2
PagesS188 - S188
LanguagesEnglish-United Kingdom

Last updated on 2019-21-10 at 15:34