A new screening strategy for varices by liver and spleen stiffness measurement (LSSM) in cirrhotic patients: A randomized trial.

BACKGROUND: Variceal bleeding is a common and life-threatening complication in patients with cirrhosis. Screening with upper endoscopy is recommended but is uncomfortable to patients. Non-invasive assessment with transient elastography for liver/spleen stiffness measurement (LSM and SSM) is accurate in detecting varices. AIMS: To test the hypothesis that a new screening strategy for varices guided by LSM/SSM results (LSSM-guided) is non-inferior to universal endoscopic screening in detecting clinically significant varices in patients with cirrhosis. METHODS: This was a non-inferiority, open-label, randomized controlled trial. Adult patients with known chronic liver diseases, radiological evidence of cirrhosis and compensated liver function. The primary outcome was clinically significant varix diagnosed with upper endoscopy. RESULTS: Between October 2013 and June 2016, 548 patients were randomized to LSSM arm (n = 274) and conventional arm (n = 274) which formed the intention-to-test (ITT) population. Patients in both study arms were predominantly middle-aged men with viral hepatitis-related cirrhosis in 85% of the cases. In the ITT analysis, 11/274 participants in the LSSM arm (4.0%) and 16/274 in the conventional arm (5.8%) were found to have clinically significant varices. The difference between two groups was -1.8% (90% CI, -4.9% to -1.2%, P < .001). The absolute difference in the number of patients with clinically significant varices detected was 5/16 (31.3%) fewer in the LSSM arm. CONCLUSIONS: Non-inferiority of the LSSM-guided screening strategy to the convention approach cannot be excluded by this RCT. This approach should be further evaluated in a cohort of larger sample size with more clinically significant varices.

On-treatment alpha-fetoprotein is a specific tumor marker for hepatocellular carcinoma in patients with chronic hepatitis B receiving entecavir.

UNLABELLED: Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) surveillance, which is criticized as neither sensitive nor specific in active hepatitis and liver cirrhosis. The aim of this study was to determine the performance of AFP as a tumor marker for HCC in entecavir-treated patients with chronic hepatitis B (CHB). This was a retrospective-prospective cohort study of 1,531 entecavir-treated patients under regular HCC surveillance with AFP and ultrasonography. Mean age was 52 ± 12 years; 1,099 (72%) patients were male and 332 (21.7%) had clinical evidence of cirrhosis. At a mean follow-up of 51 ± 13 months, 57 (2.9%) patients developed HCC (median size: 3.3 cm). AFP fluctuated with alanine aminotransferase (ALT) and peaked at the time of starting entecavir, then gradually decreased after. AFP started to increase 6 months before the diagnosis of HCC. The receiver operator characteristic curve (AUROC) of AFP was highest at the time of HCC diagnosis (0.85; 95% confidence interval [CI]: 0.73-0.98) and remained satisfactory at 3 (0.82; 95% CI: 0.73-0.91) and 6 months (0.79; 95% CI: 0.69-0.89) before the diagnosis. Using the conventional AFP cut-off (20 µg/L) at month 0, the sensitivity and specificity to diagnose HCC were 38.6% and 98.9%, respectively. Adopting the lower cut-off value (6 µg/L) of AFP level at month 0, sensitivity was increased to 80.7%, whereas specificity was decreased to 80.4%. CONCLUSION: On-treatment AFP is a specific tumor marker for HCC in CHB patients receiving entecavir therapy. Adopting a lower cut-off value of AFP level at 6 µg/L would significantly increase the sensitivity for HCC detection.

Serum hepatitis B surface antigen kinetics in severe reactivation of hepatitis B e antigen negative chronic hepatitis B patients receiving nucleoside/nucleotide analogues.

BACKGROUND: Kinetics of serum hepatitis B surface antigen (HBsAg) level in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients presented with severe reactivation and received oral antiviral therapy is unknown. We aimed to investigate the kinetics of HBsAg level among these patients. METHODS: HBeAg-negative patients on antiviral therapy with follow-up for 2 years were studied. Those presented with severe reactivation (alanine aminotransferase [ALT] ≥5 times of normal) were compared to those with mild hepatitis. Serum HBsAg level was measured by Elecsys HBsAg II Quant assay (Roche) at baseline and 6-monthly. RESULTS: A total of 192 (74 severe reactivation) patients were studied. Eighty-one (42%), 74 (39%) and 37 (19%) patients were on lamivudine, entecavir and telbivudine, respectively. Forty-four (23%) patients had early HBsAg decline, that is, ≥0.5 log10 reduction, at month 6. Patients with severe reactivation had higher serum baseline ALT (1,415 ±897 versus 73 ±39 IU/l), HBV DNA (6.4 ±1.6 versus 5.2 ±1.2 log10 IU/ml) and HBsAg (3.3 ±1.0 versus 2.9 ±0.6 log10 IU/ml), as well as an earlier HBsAg decline (50% versus 6%; all P<0.001) than those without. The HBsAg change of patients with severe reactivation was higher at months 0-6 (-0.58 ±-1.26 versus -0.01 ±-0.26 log10 IU/ml; P<0.001) but then became comparable from months 6-24 (-0.19 ±-0.60 versus -0.13 ±-0.19 log10 IU/ml; P=0.85), compared to those presented with mild hepatitis. CONCLUSIONS: Patients who presented with severe reactivation of HBeAg-negative hepatitis were more likely to develop early HBsAg decline during antiviral therapy. It may indicate a transient strong immune clearance with rapid initial reduction in serum HBsAg, which cannot be sustained due to a faster clearance of serum HBsAg.