Chen Y

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.

New classification of liver biopsy assessment for fibrosis in chronic hepatitis B patients before and after treatment

Liver fibrosis is the net result of dynamic changes between fibrogenesis and fibrolysis. Evidence has shown that antiviral therapy can reverse liver fibrosis or even early cirrhosis caused by hepatitis B virus. However, current evaluation systems mainly focus on the severity of, but not the dynamic changes in, fibrosis. Here, we propose a new classification to evaluate the dynamic changes in the quality of fibrosis, namely: predominantly progressive (thick/broad/loose/pale septa with inflammation); predominately regressive (delicate/thin/dense/splitting septa); and indeterminate, which displayed an overall balance between progressive and regressive scarring. Then, we used this classification to evaluate 71 paired liver biopsies of chronic hepatitis B patients before and after entecavir‐based therapy for 78 weeks. Progressive, indeterminate, and regressive were observed in 58%, 29%, and 13% of patients before treatment versus in 11%, 11%, and 78% after treatment. Of the 55 patients who showed predominantly regressive changes on posttreatment liver biopsy, 29 cases (53%) had fibrosis improvement of at least one Ishak stage, and, more interestingly, 25 cases (45%) had significant improvement in terms of Laennec substage, collagen percentage area, and liver stiffness despite remaining in the same Ishak stage. Conclusion: This new classification highlights the importance of assessing and identifying the dynamic changes in the quality of fibrosis, especially relevant in the era of antiviral therapy.(Hepatology 2017;65:1438‐1450)

Model consisting of ultrasonographic and simple blood indexes accurately identify compensated hepatitis B cirrhosis.

Background and Aim:  Several models for significant fibrosis or cirrhosis have been introduced for hepatitis C, but are seldom for hepatitis B. The present study retrospectively evaluates the relationship between ultrasonography, blood tests, and fibrosis stage, and constructs a model for predicting compensated cirrhosis.

Aspartate aminotransferase to platelet ratio index - a reliable predictor of therapeutic efficacy and improvement of Ishak score in chronic hepatitis B patients treated with nucleoside analogues.

ABSTRACT Background No studies have investigated the predictive and monitoring efficacy of aspartate aminotransferase to platelet ratio index in chronic hepatitis B patients undergoing antiviral therapy based on paired Ishak biopsies pre- and post-treatment. We evaluated the efficacy of aspartate aminotransferase to platelet ratio index in monitoring fibrosis improvement in chronic hepatitis B patients treated with nucleoside analogue or interferon. Methods Pre- and post-treatment Ishak fibrosis scores of 86 nucleoside-analogue- and 42 interferon-treated patients were retrospectively analyzed. The area under the receiver operating characteristic curve was calculated. Results In nucleoside-analogue-treated patients, the area under the receiver operating characteristic curve was 0.80 and 0.91 when aspartate aminotransferase to platelet ratio index was used to diagnose fibrosis and cirrhosis, respectively. When the decreased magnitude of aspartate aminotransferase to platelet ratio index was ≥ 0.35, the sensitivity and specificity of predicting fibrosis improvement were 75.8% and 75.0%, respectively. The area under the receiver operating characteristic curve was 0.53 when aspartate aminotransferase to platelet ratio index was used to diagnose fibrosis in 20 interferon-treated patients, while an insufficient patient number in the cirrhosis group prevented the calculation of the area under the receiver operating characteristic curve. The same is true for the remaining 22 interferon-treated patients. Conclusions Our study is the first to demonstrate the aspartate aminotransferase to platelet ratio index as a reliable marker in diagnosing and monitoring fibrosis improvement in nucleoside-analogue-treated patients based on paired Ishak biopsies pre- and post-treatment, but the test is not applicable in interferon therapy.

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.

Optimization of hepatitis B cirrhosis detection by stepwise application of transient elastography and routine biomarkers

Significant inflammation may overestimate liver stiffness and result in false positive diagnosis by transient elastography for chronic hepatitis B (CHB) cirrhosis detection. This study tries to further improve the performance by stepwise combination with routine biomarkers.

Stepwise Application of Transient Elastography and Routine Biomarkers Optimizes Hepatitis B Cirrhosis Detection.

Significant inflammation may overestimate liver stiffness and result in false positive diagnosis by transient elastography for chronic hepatitis B (CHB) cirrhosis detection. This study tries to further improve the performance by stepwise combination with routine biomarkers.

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.

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.