[Show abstract][Hide abstract] ABSTRACT: To explore the predictive value of serum hepatitis B surface antigen (HBsAg) titer and transient elastography in screening for insignificant fibrosis in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients.
We conducted a cross-sectional study of eligible patients treated from March 2012 to May 2013 at the West China Hospital of Sichuan University. Eligible patients underwent liver transient elastography and liver biopsy. We assessed the serum HBsAg level, serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) level, HBV genotypes, liver stiffness measurement (LSM) values by transient elastography, and histological fibrosis staging by METAVIR classification.
A total of 129 consecutive patients were recruited. The LSM value (P<0.001, odds ratio 14.67, 95% CI 0.158-0.551) and log10HBsAg (P=0.045, odds ratio 4.03, 95% CI 0.136-0.976) correlated with a liver fibrosis score <F2, independently. Inverse correlations were found between log10HBsAg and the LSM value (r=-576, P<0.001) and fibrosis staging (r=-374, P<0.001). Patients with a fibrosis score <F2 had a significantly higher log10HBsAg than patients with a fibrosis score ≥F2 among those with an LSM value under 9.4 kPa (4.6±0.7 vs 4.3±0.5, P=0.006). The HBsAg titer achieved an area under the receiver operating characteristic curve of 0.758 (P<0.001, 95% CI 0.631-0.884) in predicting a fibrosis score <F2, with a cut-off value of 10,400 IU/mL, a positive predictive value of 73%, and a negative predictive value of 79%.
In HBeAg-positive patients with an alanine aminotransferase level <2× the upper limit of normal, high serum HBsAg levels can predict a fibrosis score <F2, and a lower HBsAg titer could be supportive of early fibrosis in patients with an LSM value under 9.4 kPa.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the therapeutic efficacy of antiviral combination therapy with pegylated-interferon alpha-2a plus ribavirin (RBV) in patients with autoantibody-positive chronic hepatitis C (CHC) and to investigate the impact of the presence of autoantibodies on the treatment outcome. Eighty-six consecutive CHC patients who underwent a 48-week treatment regimen composed of Peg-IFNa-2a (135 or 180 mug/wk) plus weight-based RBV ( less than or equal to 65 kg, 800 mg/d; 65 to 75 kg, 1000 mg/d; more than or equal to75 kg, 1200 mg/d ). Prior to treatment (baseline) and at end of treatment (EOT; week 48), levels of antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti liver/kidney microsomal antibody type 1 (LKM1), anti-La (SSB), and anti liver cytosolic-1 (LC-1) were detected by indirect immunofluorescence. At baseline, during treatment (weeks 4, 12, 24, and 36), EOT, and 24 weeks after EOT, levels of HCV RNA were assessed by real-time quantitative PCR. Rapid virological response (RVR) was defined as HCV RNA less than 10(3) copy/ml at week 4. Sustained virologic response (SVR) was defined as HCV RNA load below the lower limit of detection at 24 weeks after EOT. Correlation between autoantibodies and treatment-induced reduced HCV RNA load was assessed by univariate analysis of variance or chi-squared tests. Autoantibodies were detected in 24 patients, which included 14 ANA-positive patients, five SMA-positive patients, three LKM1-positive patients, one patient with double-positivity for ANA and SSB, and one patient with double-positivity for ANA and LC-1. The autoantibody-positive patients and autoantibody-negative patients showed similar rates of RVR (70.8% vs. 72.5%, P more than 0.05) and SVR (81.4% vs. 82.2%, P more than 0.05). Antiviral therapy with Peg-IFNa-2a RBV can effectively reduce the HCV RNA load in autoantibody-positive CHC patients; however, the presence of autoantibodies may not be an independent predictor of therapy outcome.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 05/2013; 21(5):345-7.
[Show abstract][Hide abstract] ABSTRACT: Aim:
The accuracy of liver stiffness measurement (LSM) in the diagnosis of liver fibrosis is affected by elevated serum alanine aminotransferase (ALT) levels. The aim of this study was to assess the impact of mild to moderate elevations of ALT on LSM in patients with chronic hepatitis B (CHB) during antiviral therapy.
A total of 58 CHB patients with their ALT levels falling into the range of ×2 to ×10 the upper limit of normal (ULN) were recruited. ALT and LSM values were periodically assessed at baseline and 12, 24 and 48 weeks.
The median ALT levels were 153.5 (76-544), 50.5 (11-475), 36.5 (9-265) and 30 (12-239) IU/L at baseline and 12, 24 and 48 weeks, respectively. The corresponding median value of LSM was 8.8 (3.2-47.3), 6.15 (3.2-31.2), 5.9 (3.1-29.1) and 5.5 (2.8-21.5) kpa. However, after the ALT levels were normalized by the treatment, the values of LSM did not vary significantly (6.1 [3.0-17.7] vs 5.25 [2.8-21.5] kpa, P = 0.381). Pretreatment fibrosis stages of liver biopsies corresponded with LSM after ALT normalization rather than baseline LSM (F0-1, 12/27 vs 23/25, P < 0.001).
The LSM values decreased in parallel with the decline in ALT levels in CHB patients with mild to moderate elevation of ALT. LSM became more accurate when applied to document the liver fibrosis or cirrhosis in CHB patients after the elevated ALT level has been treated to normal level.
Hepatology Research 06/2012; 43(2). DOI:10.1111/j.1872-034X.2012.01068.x · 2.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatocyte nuclear factors 4 alpha (HNF4α) and 3 beta (HNF3β) are members of a group of liver-enriched transcription factors (LETFs) that play important roles in regulating the replication of hepatitis B virus (HBV) and liver inflammation. However, the relationship of the level of HNF4α and HNF3β with the severity of HBV-infected liver diseases is unclear. In this study, liver tissue samples from different types of HBV patients were collected, and HNF4α and HNF3β expression were detected by immunohistochemistry. The expression of HNF4α was significant higher in patients with severe hepatitis B(SHB) than those with chronic hepatitis B(CHB) and liver cirrhosis(LC) (both P < 0.05), but similar between patients with CHB and LC (P > 0.05). And the expression of HNF3β was similar among patients with CHB, LC and SHB (P > 0.05 for all pairwise comparison). This suggests that the expression level of HNF4α was different in patients with different outcome of HBV infection, high expression level of HNF4α may correlate with occurrence of SHB.
[Show abstract][Hide abstract] ABSTRACT: To analyze whether or not the accuracy of liver stiffness measurement (LSM) with transient elastography (FibroScan) for the diagnosis of liver fibrosis influenced by serum alanine aminotransferase (ALT) levels in patients with chronic hepatitis B.
213 consecutive CHB patients who underwent liver biopsy and LSM were enrolled and divided into three groups by the criteria of ALT < 1 x ULN, 1 x ULN ≤ ALT < 2 x ULN and ALT ≥ 2 x ULN. The areas under the receiver operating curve(AUC) were analyzed and the accuracy of FibroScan for the diagnosis of liver fibrosis were detected in the three groups.
Significant correlation existed between the stages of liver fibrosis and LSM (rs = 0.773, 0.889 and 0.412, P < 0.05). AUCs of LSM in all patients for significant fibrosis (F ≥ 2, F0-1 vs F2-4) and cirrhosis (F = 4, F0-3 vs F4) were 0.916 and 0.971 respectively. The accuracy of diagnosis for significant fibrosis and cirrhosis were 84.0% and 93.4% respectively. AUCs of LSM in ALT < 1 x ULN, 1 x ULN ≤ ALT < 2 x ULN and ALT ≥ 2 x ULN groups for significant fibrosis were 0.939, 0.967 and 0.687 respectively. The sensitivity of the three groups was 90.0%, 89.7% and 47.8% respectively. The accuracies of the three groups was 90.5%, 93.9% and 68.4% respectively. The AUC, sensitivity and accuracy of ALT ≥ 2 x ULN group for significant fibrosis were significantly lower than the other two groups. AUCs of LSM in three groups for cirrhosis were 0.970, 0.985 and 0.952 respectively. The sensitivities of the three groups were 93.8%, 100% and 100% respectively. The accuracies of the three groups were 88.9%, 95.9% and 92.1% respectively. The AUCs, sensitivity and accuracy for cirrhosis of the three groups didn't change with elevated ALT.
Transient elastography (FibroScan) is a reasonable noninvasive tool to diagnose significant fibrosis, especially liver cirrhosis in CHB patients. The accuracy of FibroScan for diagnosis of liver cirrhosis may not be influenced by elevated ALT. While in ALT ≥ 2 x ULN group, the accuracy of FibroScan for diagnosis of significant fibrosis was significantly lower as compared to the ALT ≤ 2 x ULN groups.
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 04/2011; 19(4):286-90.
[Show abstract][Hide abstract] ABSTRACT: The FibroScan (FS), the aspartate aminotransferase-to-platelet ratio index (APRI), and the FIB-4 index are simple and inexpensive methods to detect liver fibrosis.
The primary objective was to evaluate the performance of FS for the noninvasive diagnosis of hepatic fibrosis in Western Chinese patients with chronic hepatitis B virus (HBV) infection compared with APRI and FIB-4; the secondary objective was to determine liver stiffness measurement (LSM) cutoff values for the noninvasive diagnosis of significant fibrosis and liver cirrhosis.
Overall, 175 consecutive patients with chronic HBV infection, successful liver biopsy, and alanine aminotransferase levels ≤2× ULN were prospectively studied. Liver fibrosis was graded by an independent pathologist using the METAVIR (F0-F4) classification. APRI and FIB-4 were calculated from laboratory data.
The area under receiver operating characteristics curves (AUROC) for LSM for significant fibrosis (METAVIR F2-3) and cirrhosis (F4) was 0.95 (95% confidence interval, 0.91-0.98) and 0.98 (0.96-0.99), respectively. For the detection of significant fibrosis and cirrhosis, the AUROC of APRI were 0.81 (0.74-0.87) and 0.83 (0.77-0.90); the AUROC of FIB-4 were 0.86 (0.80-0.91) and 0.77 (0.68-0.85). FS optimal cutoff values for the identification of significant fibrosis and cirrhosis were 7.9 and 13.8 kPa, respectively.
FS is a reliable predictor of significant fibrosis and cirrhosis in Western Chinese patients with chronic HBV infection, and is superior to APRI and FIB-4. FS cutoff values could be considered as clinical reference for detecting significant fibrosis and cirrhosis.