Xiaoning Wu

Expression of extracellular matrix genes in cultured hepatic oval cells: an origin of hepatic stellate cells through transforming growth factor beta?

Background: Hepatic oval cells, progenitor cells in the liver, can differentiate into hepatocytes and bile duct cells both in vitro and in vivo. Although hepatic stellate cells are another important cell component in the liver, less attention has been focused on the relationship between hepatic oval cells and hepatic stellate cells.

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)

Thymosin alpha-1 treatment in chronic hepatitis B

Introduction: Stimulating a successful host immune response may be a promising helpful therapy to achieve elimination of hepatitis B virus (HBV) infection in chronic hepatitis B (CHB). Thymosin α-1 (Tα-1), as an immunomodulatory agent, can enhance T-cell response in CHB patients and has been widely studied either alone or in combination with nucleos(t)ide analogs. This editorial reviews these articles to present the efficacy of Tα-1 in CHB. Areas covered: English and Chinese articles in MEDLINE, EMBASE, the Cochrane Controlled Trial Registry, Chinese periodical full-text database of science and technology, Chinese periodical full-text database and Wan-fang database by thesis search were collected and reviewed. Expert opinion: In CHB, Tα-1monotherapy is effective in suppressing viral replication compared with untreated control or conventional interferon. Most of the combination therapy of Tα-1 plus either lamivudine or IFN-α showed better effects on HBV DNA suppression and HBeAg seroconversion. Presently, clinical studies of Tα-1 combined with entecavir on the treatment of HBV-cirrhosis are ongoing.

Increasing Newly Diagnosed Rate and Changing Risk Factors of HCV in Yanbian Prefecture, a High Endemic Area in China

Background The newly diagnosed rate of HCV infection is increasing in China. However, the risk factors have not been fully identified. Here, a survey was performed in Yanbian Prefecture, a high-endemic area in China. Methods We identified newly diagnosed HCV infection in 2007–2011, using the local National Disease Supervision Information Management System from the Chinese Center for Disease Control and Prevention. We determined the risk factors using a case-control survey by questionnaire. Results Yanbian Prefecture had a rapid increase in the yearly newly diagnosed rate of HCV infection from 32.6 to 72.1/100.000 from the year 2007 to 2011. People aged 50–64 years had a high HCV infection of 43.4%, but only 0.3% of cases were reported in those aged less than 20 years. Cosmetic treatment, family history, blood transfusion, and dental treatment were independent risk factors for HCV infection. Unexpectedly, cosmetic treatments [odd ratio (OR) = 5.15, 95% confidence interval (CI) = 2.31–11.48, P = 0.00] and family history (OR = 4.68, 95% CI = 2.67–8.75, P = 0.00) showed a higher risk than the conventional risk factors of blood transfusion (OR = 4.49, 95% CI = 1.95–10.37, P = 0.001) and dental treatment (OR = 2.98, 95% CI = 1.42–6.25, P = 0.00). To further analyze the intrafamilial transmission, we found that spouses of HCV patients had an increased risk for acquiring HCV (OR = 5.75, 95% CI: 1.94–17.07), without significant association between either HCV RNA viral load (P = 0.29) or genotype (P = 0.43). Conclusions HCV infection was increased in Yanbian Prefecture. Cosmetic treatment was a higher risk factor than medical procedure. HCV infection had a clear family clustering phenomenon, especially between spouses.

Baseline Hepatitis B Virus DNA Level is a Promising Factor for Predicting the 3 (rd) Month Virological Response to Entecavir Therapy: A Study of Strict Defined Hepatitis B virus Induced Cirrhosis.

Background: Cirrhosis is a common complication of chronic hepatitis B. It remains unclear if viral and biochemical parameters at baseline affect virological response to entecavir and therefore warrant investigation. In the present study, we aimed to evaluate the efficacy of entecavir therapy by monitoring virological response at the end of the 3rd month of treatment and try to figure out whether baseline factors could help predict it in a cohort of hepatitis B virus (HBV) compensated cirrhosis patients and to determine the cut-off value of a predicting parameter. Methods: A total of 91 nucleos(t)ide-naïve patients with HBV induced cirrhosis (compensatory stage) were enrolled in a prospective cohort. HBV DNA and alanine aminotransferase (ALT) were tested at baseline and monitored every 3–6 months after starting therapy. Results: Of all 91 patients, the median follow-up time was 12 (9–24) months. Overall, 64 patients (70.3%) achieved virological response in the 3rd month. Univariate analysis showed that the 3rd month virological response can be predicted by baseline HBV DNA levels (P < 0.001, odds ratio [OR]: 2.13, 95% confidence interval [CI]: 1.44–3.15), ALT value (P = 0.023, OR: 1.01, 95% CI: 1.00–1.01) and hepatitis B e antigen (HBeAg) negativity (P = 0.016, OR: 0.30, 95% CI: 0.11–0.80). Multiple regression analysis showed baseline HBV DNA level was the only parameter related to full virological response. Higher baseline HBV DNA strata indicated a higher probability that HBV DNA remains detectable at the 3rd month (P = 0.001). Area under receiver operating characteristic curve for determining the 3rd month virological response by baseline HBV DNA was 77.6% (95% CI: 66.7–85.2%), with a best cut-off value of 5.8 log10. Conclusions: Baseline HBV DNA, HBeAg negativity, and ALT were independent factors contributing to virological response at the 3rd month. Further, multiple regression showed that HBV DNA level was the only parameter predicting full virological response as early as the 3rd month, in this cirrhosis cohort.

Two patterns of alanine aminotransferase increase to predict long-term viral response in chronic hepatitis B patients: virus- or host-induced?

BACKGROUND Serum alanine aminotransferase (ALT) increase is a well-known phenomenon during interferon treatment for chronic hepatitis B. However, little is known about these increases during nucleoside/nucleotide treatment and the effects on long-term clinical outcomes. METHODS A total of 170 treatment-naive hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients were treated with a nucleoside/nucleotide analogue for at least 2 years and followed up for 1 more year post-treatment. Clinical characteristics were detected and analysed at baseline and at every 3-month interval. RESULTS Two patterns of ALT increase, virus- and host-induced, were detected. Virus-induced increases were characterized by a rapid increase in serum ALT and HBV DNA typically after 2 years of treatment, and were more common than host-induced ALT increases (15.9% versus 6.5%; P<0.05) with a median ALT increase of 5.7-fold the upper limit of normal (ULN). Host-induced ALT increases were characterized by moderately increased ALT (median 2.5-fold ULN) with a slow decrease in HBV DNA that occurred mainly in the first year of treatment (63.6%). Most importantly, host-induced increases were associated with favourable long-term treatment outcomes in HBV DNA undetectable rate (82% versus 0%), HBeAg seroconversion (82% versus 7%) and histological improvement. Moreover, interferon-γ-expressing T-helper cells were increased in patients with host-induced ALT increases. CONCLUSIONS Two patterns of ALT increases may occur during nucleoside/nucleotide analogue treatment. Host induced ALT increases, accompanied by decreased HBV DNA, lead to better long-term clinical outcomes.

On-treatment changes of liver stiffness at week 26 could predict 2-year clinical outcomes in HBV-related compensated cirrhosis

It is unclear whether liver stiffness measurement (LSM) dynamic changes after anti‐HBV treatment could predict the risk of liver‐related events (LREs), particularly in patients with HBV‐related compensated cirrhosis.

Effective viral suppression is necessary to reduce hepatocellular carcinoma development in cirrhotic patients with chronic hepatitis B: Results of a 10-year follow up

Abstract High viral load is an independent risk factor for development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Antiviral therapy can reduce but not eliminate the risk of HCC. The aim of this study was to identify the risk factors for HCC development in CHB patients during antiviral therapy. CHB patients with HBV DNA level ≥104 copies/mL, with or without compensated cirrhosis receiving adefovir were followed up every 6 months for 10 years (2004–2014). The primary endpoint was the development of HCC. The cumulative incidence and risk factors of HCC were evaluated by the Kaplan-Meier method and multivariate Cox proportional hazards models. At baseline, 28 of the 120 patients (23.3%) were cirrhotic. One patient developed HCC within 1 year, and therefore 119 patients were analyzed. At the end-point of follow-up, 59.7% (71/119) patients achieved virological remission (VR). Overall, 16 patients developed HCC, giving a 10-year cumulative incidence of 15.73%. Multivariate analysis showed that cirrhosis at baseline and failure to achieve VR were significant risk factors for HCC. The 10-year incidence of HCC was significantly higher in cirrhotic than noncirrhotic patients (43.16% vs. 7.05%, P < .0001). For cirrhotic patients, the 10-year incidence of HCC was significantly higher in patients without VR than those with VR (62.24% vs. 27.78%, P = .0139). Cirrhosis at baseline and failure to achieve VR during antiviral therapy were significant risk factors for HCC development in CHB patients. Effective viral suppression is necessary to reduce HCC development in cirrhotic CHB patients.

A Meta-Analysis of the Efficacy of Interferon Monotherapy or Combined with Different Nucleos(t)ide Analogues for Chronic Hepatitis B.

Background: The aim of the present study was to compare the efficacy of interferon (IFN) with or without different nucleos(t)ide analogues (NAs). Methods: The PubMed, Wan Fang and CNKI databases were searched to identify relevant trials up to May 2015. Meta-analysis was performed with Review Manager 5.0. The stability and reliability were evaluated by publication bias tests. Results: Fifty-six studies fulfilled the criteria for the meta-analysis. Compared with IFN monotherapy, combination therapy were superior in HBV DNA undetectable rate (Risk Ratio (RR) = 1.55, 95% confidence interval (CI): 1.44–1.66, p < 0.00001), HBeAg and HBsAg loss rate (RR = 1.38, 95% CI: 1.22–1.56, p < 0.00001; RR = 1.69, 95% CI: 1.03–2.78, p = 0.04, respectively) at the end of week 48 treatment. Sub-analysis showed the RRs of virological response for entecavir (ETV), adefovir (ADV), and lamivudine (LAM) were 1.64, 1.61 and 1.52, respectively; RRs of HBeAg loss rate were 1.34, 1.71 and 1.34, respectively. However, at the end of follow-up, IFN plus NAs therapy was better than IFN monotherapy only in terms of HBV DNA undetectable rate (p = 0.0007). Conclusions: Combination therapy was better than IFN monotherapy in virological and serological responses at the end of treatment. After follow-up, only HBV DNA undetectable rate was superior for combination therapy.

Hepatitis B virus directly promotes collagen I expression of LX-2 cells without infection in vitro.

Aim:  To investigate direct effects of hepatitis B virus (HBV) on collagen type I in vitro.