Youfu Zhu

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.

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.

Chemokine (C‐X‐C motif) ligand 13 promotes intrahepatic chemokine (C‐X‐C motif) receptor 5+ lymphocyte homing and aberrant B‐cell immune responses in primary biliary cirrhosis

The serologic hallmark of primary biliary cirrhosis (PBC) is the presence of high titer, and specific anti-mitochondrial antibodies (AMA). Interestingly, although there is no global immune defect in patients with PBC, there is widespread dysregulated B cell function, including increased sera levels of IgM and enhanced B cell responses to CpG stimulation. The mechanisms involved in this B cell dysfunction have remained unknown. To address this issue, we focused on identifying the frequencies of B cell subsets in patients with PBC and the mechanisms that lead to B cell dysregulation, including the relationships with CXCR5+CD4+T cells. Herein we report that elevations of both serum and intrahepatic IL-21 were found in patients with PBC and, in particular, promoted B cell proliferation, STAT3 phosphorylation and AMA production in vitro. More importantly, upon stimulation with rPDC-E2, CXCR5+CD4+T cells in PBC produced higher levels of IL-21 than healthy controls. Additionally, sorted CXCR5+CD4+T cells increased production of AMA by autologous CD19+B cells. Indeed, elevated expression of intrahepatic CXCL13, a key chemokine of CXCR5+ cells, was uniquely found within the portal tracts in PBC, accompanied by infiltrates of CD4+, CXCR5+, CD19+, and CD38+ cells. In conclusion, CXCL13 promotes aggregation of CD19+B cells and CXCR5+CD4+T cells, which directs the aberrant AMA response via IL-21. These data have implications for potential immunotherapy and also reflect the unique lymphoid biology in the liver of PBC.The serological hallmark of primary biliary cirrhosis (PBC) is the presence of high titer and specific antimitochondrial antibodies (AMAs). Although there is no global immune defect in patients with PBC, there is widespread dysregulated B‐cell function, including increased sera levels of immunoglobulin M and enhanced B‐cell responses to cytosine‐phosphate‐guanine stimulation. The mechanisms involved in this B‐cell dysfunction have remained unknown. To address this issue, we focused on identifying the frequencies of B‐cell subsets in patients with PBC and the mechanisms that lead to B‐cell dysregulation, including the relationships with chemokine (C‐X‐C motif) receptor 5 (CXCR5)+CD4+T cells. Herein, we report that elevations of both serum and intrahepatic interleukin‐21 (IL‐21) were found in patients with PBC and, in particular, promoted B‐cell proliferation, signal transducer and activator of transcription 3 phosphorylation and AMA production in vitro. More important, upon stimulation with recombinant E2 subunit of pyruvate dehydrogenase complex, CXCR5+CD4+T cells in PBC produced higher levels of IL‐21 than healthy controls. Additionally, sorted CXCR5+CD4+T cells increased production of AMAs by autologous CD19+B cells. Indeed, elevated expression of intrahepatic chemokine (C‐X‐C motif) ligand 13 (CXCL13), a key chemokine of CXCR5+ cells, was uniquely found within the portal tracts in PBC, accompanied by infiltrates of CD4+, CXCR5+, CD19+, and CD38+ cells. Conclusion: CXCL13 promotes aggregation of CD19+B cells and CXCR5+CD4+T cells, which directs the aberrant AMA response by IL‐21. These data have implications for potential immunotherapy and also reflect the unique lymphoid biology in liver of PBC. (Hepatology 2015;61:1998‐2007)

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.

Tailored regimen of interferon alpha for HBeAg‐positive chronic hepatitis B: a prospective controlled study

Summary.  The response to interferon‐alpha treatment of patients with chronic hepatitis B under the current protocol is not satisfactory. The aim of this study was to try an alternative approach to improve treatment outcome. Of 374 HBeAg‐positive patients, 127 of them received 5 million units of interferon‐alpha thrice weekly for 6 months and constituted the control group, while 247 in the study group received the same dosage but the duration of treatment was tailored. The study protocol provided for continuation of treatment if HBV DNA levels were continuously decreasing. The treatment ended when viral, antigenic and biochemical endpoints were reached or when HBV DNA levels were no longer decreasing. The median length of tailored treatment was 10 (range 6–24) months. The end‐of‐treatment response rates were 39.3% and 23.6% (P = 0.002), and after 12‐month, follow‐up, the sustained response rates were 40.5% and 28.3% (P = 0.013) in the study and control groups, respectively. Excluding the patients who dropped out, 228 and 115 completed a median of 40‐ and 44‐month‐long follow‐up; the long‐term response was thus 45.3% and 33.1% (P = 0.014) in the respective groups. Interferon‐alpha treatment tailored in length demonstrated significantly increased efficacy in patients with chronic hepatitis B.

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.

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.