Xieer Liang

Dynamic evaluation of liver stiffness measurement to improve diagnostic accuracy of liver cirrhosis in patients with chronic hepatitis B acute exacerbation.

Summary.  To investigate the dynamic changes of liver stiffness measurement (LSM) by FibroScan® and improve its diagnostic accuracy, we studied patients with chronic hepatitis B undergoing acute exacerbation. Eighty‐nine treatment naïve patients were enrolled, and Fibroscan® was performed every 7–10 days during hospitalization and every 1∼3 months for follow‐up. Haematology and liver functions were tested in parallel. Liver biopsies were performed in 23 patients. A total of 282 LSMs were performed. LSM was positively correlated with both alanine aminotransferase (ALT) (r = 0.321, P < 0.001) and bilirubin levels (r = 0.626, P < 0.001). Mean reduction in LSMs in patients along with ALT or bilirubin normalization was significantly greater than those without ALT or bilirubin nomalization(P = 0.001, P = 0.038, respectively). In 23 patients with initial LSMs in the range usually defined as indicating cirrhosis (i.e.>18.2 kPa), only 5 were diagnosed with cirrhosis by histopathology or ultrasonography. As ALT normalized, LSMs remained over 12.0 kPa in all these 5 patients. However, in 18 other patients without cirrhosis at baseline, LSMs still remained above 12.0kPa in 10 patients and decreased to below 12.0 kPa in the other 8 patients. LSMs decreased in parallel with ALT and bilirubin normalization. LSM performed after ALT and bilirubin nomalization may improve the accuracy in diagnosing cirrhosis in patients with exacerbations of hepatitis B.

Association between vitamin D level and viral load or fibrosis stage in chronic hepatitis B patients from Southern China

The role of vitamin D playing in patients with chronic hepatitis C has been intensively studied. However, studies on the potential interaction between vitamin D level and chronic hepatitis B are still limited. This study aimed to explore whether any association existed between serum vitamin D level and liver histology or virological parameters in patients with chronic hepatitis B infection in Southern China.

Randomized, three-arm study to optimize lamivudine efficacy in hepatitis B e antigen-positive chronic hepatitis B patients

Data about the efficacy of de novo combination therapies, or optimization strategy by adding the other drug based on the virological response at week 24 of low genetic barrier antiviral agents is still limited. This study aimed to compare the efficacy at week 104 of lamivudine monotherapy (MONO), lamivudine plus adefovir dipivoxil (ADV) combination therapy (COMBO), and lamivudine optimization strategy (OPTIMIZE).

Interpretation of liver stiffness measurement based approach for the monitoring of hepatitis B patients with antiviral therapy: a 2-year prospective study

Liver biopsy is not routinely performed in treated chronic hepatitis B. Liver stiffness measurement has been validated for noninvasive liver fibrosis assessment in pretreatment chronic hepatitis B but has not been assessed for fibrosis monitoring during antiviral therapy. Liver stiffness was systemically monitored by Fibroscan® every 6 months in a cohort of patients with hepatitis B receiving antiviral therapy and compared with liver biopsies at baseline and week 104. A total of 534 hepatitis B e antigen‐positive treatment‐naive patients receiving telbivudine‐based therapy with qualified liver stiffness measurement at baseline and week 104 were analyzed, 164 of which had adequate paired liver biopsies. Liver stiffness decreased rapidly (−2.2 kPa/24 weeks) in parallel with alanine aminotransferase (ALT) from 8.6 (2.6‐49.5) kPa at baseline to 6.1 (2.2‐37.4) kPa at week 24. Interestingly, liver stiffness decreased slowly (−0.3 kPa/24 weeks) but continually from week 24 to week 104 (6.1 vs 5.3 kPa, P < .001) while ALT levels remained stable within the normal range. More importantly, liver stiffness declined significantly irrespective of baseline ALT levels and liver necroinflammation grades. From baseline to week 104, the proportion of patients with no or mild fibrosis (Ishak, 0‐2) increased from 74.4% (122/164) to 93.9% (154/164). Multivariate analysis revealed that percentage decline of 52‐week liver stiffness from baseline was independently associated with 104‐week liver fibrosis regression (odds ratio, 3.742; P = .016). Early decline of 52‐week liver stiffness from baseline may reflect the remission of both liver inflammation and fibrosis and was predictive of 104‐week fibrosis regression in treated patients with chronic hepatitis B.

Stepwise application of fibrosis index based on four factors, red cell distribution width–platelet ratio, and aspartate aminotransferase–platelet ratio for compensated hepatitis B fibrosis detection

Fibrosis index based on four factors (FIB‐4) and aspartate aminotransferase–platelet ratio (APRI) were validated with unsatisfactory efficiency. Routine hematology index red cell distribution width–platelet ratio (RPR) had been tried in liver fibrosis detection. This study tries to evaluate the stepwise application of FIB‐4, RPR, and APRI in detecting chronic hepatitis B (CHB) fibrosis.

Effect of hepatitis B virus subgenotype on antiviral response in nucleoside‐treated hepatitis B envelope antigen‐positive patients

Previous studies have reported that hepatitis B virus (HBV) genotype is not a predictor of treatment response with nucleos(t)ide analog therapy. However, the impact of subgenotype on treatment response is unknown. The aim of this study is to identify the effect of HBV subgenotype on treatment response.

Stepwise Application of FIB-4, Red cell distribution width-Platelet Ratio and APRI for Compensated Hepatitis B Fibrosis Detection

Fibrosis index based on four factors (FIB‐4) and aspartate aminotransferase–platelet ratio (APRI) were validated with unsatisfactory efficiency. Routine hematology index red cell distribution width–platelet ratio (RPR) had been tried in liver fibrosis detection. This study tries to evaluate the stepwise application of FIB‐4, RPR, and APRI in detecting chronic hepatitis B (CHB) fibrosis.

Improved performance of quantitative collagen parameters versus standard histology in longitudinal assessment of nonadvanced liver fibrosis for chronic hepatitis B

Monitoring longitudinal nonadvanced fibrosis is a more common scenario in management of chronic hepatitis B (CHB), for which, however, current evaluation methods generally lack sufficient performance. We conducted a proof‐of‐concept study to evaluate the performance of quantitative fibrous collagen parameters (q‐FP) in the assessment. Data sets from a prior CHB trial (NCT00962533) with mostly mild‐to‐moderate fibrosis participants were used for this study. 301 subjects with paired liver biopsies were consecutively included. Of these, 139 subjects were used to establish the test and the rest for internal validation. Fibrosis change between baseline and week 104 of treatment was blindly assessed with q‐FP and was compared with Ishak fibrosis staging. There were 70% and 93% subjects with Ishak F0‐2 at baseline and week 104, respectively. For the test of the subjects, q‐FP and Ishak staging showed no difference in determining the incidence of fibrosis regression (68% vs 67%; difference = 0.7%, P = 1.00). Q‐FP demonstrated that the regression was independently associated with the antiviral efficacy endpoint (OR 3.0, 95% CI 1.4‐6.5, P = .005), but Ishak failed the detection (OR 0.6, 95% CI 0.3‐1.3, P = .24). Moreover, q‐FP directly revealed a higher fibrosis‐resistance to antiviral treatment in virus genotypes C vs B and in males vs females. These results were confirmed in the validation subjects. Additionally, a functional model built on the test subjects showed an accuracy of 82% in stratifying fibrosis reversibility of the validation subjects. In conclusion, q‐FP could have improved efficiency and accuracy in the longitudinal assessment of mild‐to‐moderate CHB fibrosis, indicating a potential alternative to current evaluation methodologies.

395 AGE INFLUENCING LIVER STIFFNESS MEASUREMENTS IN CHINESE MALE GENERAL POPULATIONS

Background: Liver stiffness measurement (LSM) with transient elastography can accurately predict advanced liver fibrosis in treatment-naive chronic hepatitis B (CHB) patients. Its performance to monitor the changes in the severity of liver fibrosis in CHB patients on antiviral treatment is uncertain. Methods: We prospectively studied CHB patients undergoing paired liver biopsy and transient elastography before and at week 48 of antiviral treatment. Based on our previously reported algorithm, advanced liver fibrosis (Metavir F3–4) was excluded by LSM≤6.0 kPa and ≤7.5 kPa while advanced fibrosis was diagnosed by LSM >9.0 kPa and >12.0 kPa for patients with normal and elevated (>1–5 times upper limit of normal) ALT, respectively [Chan et al., J Virol Hepat 2008]. Results: Seventy-one patients (47 on clevudine; 24 on adefovir) were studied. The median change of Metavir fibrosis stage from baseline to week 48 was 0 (range −1 to 1). Seventeen and 11 patients had regression and progression of histologic fibrosis, respectively. The median ALT decreased from 99 IU/l to 33 IU/l (P 10% had decreased, unchanged and increased histologic stages, respectively. Conclusions: LSM could predict advanced fibrosis during antiviral therapy according to the ALT-based algorithm. Decrease in absolute LSM value, which could reflect the effect of ALT normalization, was unreliable to indicate regression of liver fibrosis.

Prevalence of chronic kidney disease in patients with chronic hepatitis B: A cross-sectional survey

Renal safety is a major concern during long‐term antiviral treatment for chronic hepatitis B (CHB). This study aimed to investigate the prevalence of chronic kidney disease (CKD) in patients with CHB that had been treated with antiviral therapy. This was a single‐centre, cross‐sectional study in a real‐life cohort in which all patients received antiviral treatment. Serum creatinine‐based equations from the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) were used to estimate the glomerular filtration rate (GFR). CKD was defined as an eGFR <60 mL/min/1.73 m² or a urinary albumin to creatinine ratio ≥ 3 mg/mmol (defined as albuminuria). Univariate and multivariate analyses were conducted to determine the risk factors of CKD. A total of 1985 patients were included in the analysis from February 2015 to December 2015. The mean age and median duration of antiviral treatment was 42.20 years and 17.05 months, respectively. The overall prevalence of CKD was 7.9% (157/1985), with 44 patients experiencing decreased renal function (eGFR less than 60 mL/min/1.73 m²) and 129 patients with albuminuria. Patients with cirrhosis had a higher prevalence of a decreased GFR (4.3% vs 1.6%, P<.001) and albuminuria (11.1% vs 5.2%, P<.001) than those without cirrhosis. In the multivariate analysis, hypertension (Odds Ratio [OR] 4.564, P<.001), diabetes mellitus (OR 2.688, P<.001) and cirrhosis (OR 1.918, P<.001) were independent factors associated with the presence of CKD. CKD was a clinically significant comorbidity in patients with CHB. Special attention should be paid to cirrhotic patients and patients with the metabolic syndrome.