Exclusion criteria were as follows: 1) LSM failure (no valid shots; n=0), 2) invalid LSM [defined as an interquartile Volasertib IC50 range (IQR) to median value ratio (IQR/M) >0.3, success rate <60%, or <10 valid measurements; n=6] [17], 3) a history of hepatic decompensation or antiviral treatment (n=0), 4) co-infection with hepatitis C, hepatitis D, or HIV (n=1), 5) heavy alcohol consumption (>30 g/day for >5 years; n=4), 6) right-sided heart failure, ascites, or pregnancy (n=0), 7) F0�C2 fibrosis stage on LB (n=20), 8) low viral load (<2,000 IU/mL; n=7), 9) LB specimen shorter than 15 mm (n=9), and 10) follow-up loss (n=3) (Figure S1). A total of 50 patients were excluded; the remaining 128 CHB patients showing advanced (��F3) liver fibrosis on LB with a high viral load (HBV DNA ��2,000 IU/L) were selected for the final statistical analysis (Figure S1).
Laboratory tests On the same day as LB and LSM, blood parameters including serum albumin, total bilirubin, alanine aminotransferase (ALT), prothrombin time, platelet count, and alpha-fetoprotein (AFP) were recorded. HBsAg and hepatitis B e antigen (HBeAg) were measured using standard enzyme-linked immunosorbent assays (Abbott Diagnostics, Abbott Park, IL, USA). HBV DNA levels were measured by quantitative PCR assay (Amplicor HBV Monitor Test; Roche Diagnostics, Basel, Switzerland) with a detection limit of 12 IU/mL. The upper normal range of ALT was 40 IU/L. Liver stiffness measurement On the same day as LB, LSM was performed on the right lobe of the liver through the intercostal spaces on patients lying in the dorsal decubitus position with the right arm in maximal abduction [17].
One experienced technician (>10,000 examinations) who was blinded to the patients’ clinical data performed all LSMs. The success rate was calculated by dividing the number of valid measurements by the total number of measurements. IQR was defined as an index of intrinsic variability of LSM corresponding to the interval of LSM results containing 50% of the valid measurements between the 25th and 75th percentiles [14]. LSM scores are expressed as kilopascals (kPa). When LSM showed an IQR/M >0.3, success rate <60%, or <10 valid measurements, it was regarded as invalid and was excluded from the final analysis. Liver biopsy and liver histology evaluation LB specimens were fixed in formalin and embedded in paraffin.
Four-micrometer-thick sections were stained with hematoxylin & eosin and Masson’s trichrome. All liver tissue samples were evaluated by an experienced hepatopathologist who was blinded to the clinical data of the study population, Cilengitide including LSM results. Liver fibrosis and necroinflammation were evaluated semiquantitatively according to the Batts scoring system [18]. Fibrosis was staged on a 0�C4 scale: F0, no fibrosis; F1, portal fibrosis; F2, periportal fibrosis; F3, septal fibrosis; and F4, cirrhosis.