Guiqiang Wang

Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon α-2a and ribavirin

Background and Aim:  The therapeutic effect of pegylated interferon (peg‐IFN)‐α‐2a combination with ribavirin on patients with chronic hepatitis C virus (HCV) infection is dependent on the rapidity of the virological response. The aim of this study was to investigate the predictive value of rapid virological response (RVR) and early virological response (EVR) on sustained virological response (SVR) in HCV patients treated with peg‐IFN‐α‐2a and ribavirin.

Prediction of the prognosis in patients with acute-on-chronic hepatitis using the MELD scoring system

Aim:  To predict prognosis in patients with acute‐on‐chronic hepatitis (AOCH) using the model for end‐stage liver disease (MELD) scoring system and to study the effects of age, sex, etiology, low serum sodium, and persistent ascites on MELD.

A pilot randomized controlled trial of dual-plasmid HBV DNA vaccine mediated by in vivo electroporation in chronic hepatitis B patients under lamivudine chemotherapy.

Summary.  A DNA vaccine against the hepatitis B virus (HBV), enhanced by IL‐2/IFN‐γ fusion protein expression from a plasmid construct and mediated by in vivo electroporation, was evaluated in a total of 39 HBeAg‐positive patients with chronic hepatitis B (CHB). The six of 39 patients with a serum alanine aminotransferase (ALT) value of 1–2 times upper limit of normal (ULN) were assigned to the open‐label arm (Group01) receiving vaccine monotherapy; the remaining 33 patients with an ALT of more than two times ULN were enroled to the randomized and controlled arm (Group02) receiving lamivudine (LAM) monotherapy (LAM+placebo) or combined therapy (LAM+DNA vaccine) in 1:2 ratio. In Group01, a significant elevation of HBV‐specific IFN‐γ‐secreting T‐cell counts in comparison with baseline was observed. In Group02, the proportion of patients with HBV DNA suppression was higher with LAM+DNA vaccine than with LAM monotherapy at each visit time point after the final injection of DNA vaccine at week 36, revealing a significant difference between the two groups (P = 0.03) at week 60. The incidence of dual‐site mutations of rtM204/I/S+rtL180M was significantly lower (P = 0.03) with an identified lower virological breakthrough (VBT) rate (P = 0.03) in patients receiving LAM+DNA vaccine than LAM monotherapy, accompanied with a significant higher positive T‐cell response rate in patients receiving LAM+DNA vaccine (P = 0.03). In conclusion, this study provides evidence that HBV DNA vaccination is safe and immunologically effective, and that the HBV‐specific T‐cell responses induced by DNA vaccination under LAM chemotherapy showed a correlation with the suppression of viral replication in patients with CHB.

Response to pioglitazone treatment is associated with the lipoprotein lipase S447X variant in subjects with type 2 diabetes mellitus

To investigate the influence of the S447X variant in lipoprotein lipase (LPL) gene on the response rate to therapy with the thiazolidinedione pioglitazone. A total of 113 diabetic patients were treated with pioglitazone 30 mg for 10 weeks. Response to the pioglitazone treatment was defined by either a >10% relative reduction in fasting blood glucose (FBG) or a more than 1% decrease in glycosylated haemoglobin (HbA1c) values after 10 weeks of pioglitazone treatment. The genotypes were determined by polymerase chain reaction–restriction fragment length polymorphism method. Using the criteria >10% relative reduction in FBG after 10 weeks of pioglitaone treatment, responder frequency to pioglitazone treatment in S447S genotype group is significantly higher than S447X genotype group. Meanwhile, the S447X genotype conferred a statistically significant 0.538‐fold reduction in response rate to pioglitazone treatment relative to the S447S genotype. Moreover, pioglitazone treatment has significantly beneficial effects on serum lipid profile and blood pressure in S447S genotype carriers. The S447X variant in LPL gene may be a cause for therapy modification by pioglitazone.

Quantitative hepatitis B core antibody level is a new predictor for treatment response in HBeAg-positive chronic hepatitis B patients receiving peginterferon.

A recent study revealed that quantitative hepatitis B core antibody (qAnti-HBc) level could serve as a novel marker for predicting treatment response. In the present study, we further investigated the predictive value of qAnti-HBc level in HBeAg-positive patients undergoing PEG-IFN therapy. A total of 140 HBeAg-positive patients who underwent PEG-IFN therapy for 48 weeks and follow-up for 24 weeks were enrolled in this study. Serum samples were taken every 12 weeks post-treatment. The predictive value of the baseline qAnti-HBc level for treatment response was evaluated. Patients were further divided into 2 groups according to the baseline qAnti-HBc level, and the response rate was compared. Additionally, the kinetics of the virological and biochemical parameters were analyzed. Patients who achieved response had a significantly higher baseline qAnti-HBc level (serological response [SR], 4.52±0.36 vs. 4.19±0.58, p=0.001; virological response [VR], 4.53±0.35 vs. 4.22±0.57, p=0.005; combined response [CR], 4.50±0.36 vs. 4.22±0.58, p=0.009)). Baseline qAnti-HBc was the only parameter that was independently correlated with SR (p=0.008), VR (p=0.010) and CR(p=0.019). Patients with baseline qAnti-HBc levels ≥30,000 IU/mL had significantly higher response rates, more HBV DNA suppression, and better hepatitis control in PEG-IFN treatment. In conclusion, qAnti-HBc level may be a novel biomarker for predicting treatment response in HBeAg-positive patients receiving PEG-IFN therapy.

Rapid downregulation of programmed death‐1 and interferon‐γ‐inducible protein‐10 expression is associated with favourable outcome during antiviral treatment of chronic hepatitis B

The dynamics of programmed death‐1 (PD‐1) as well as cytokine/chemokine expression and its correlation with virological response in patients with chronic hepatitis B (CHB) is unclear. This study was conducted in 29 treatment‐naïve patients undergoing telbivudine treatment for 52 weeks. The results showed that PD‐1 expression on both CD4+ and CD8+ T cells was positively correlated with hepatitis B virus (HBV) DNA levels (r = 0.621, P < 0.0001; r = 0.548, P = 0.002, respectively), and in virological responders, this decrease was directly correlated with a decrease in HBV DNA levels (r = 0.664, P = 0.002; r = 0.572, P = 0.01, respectively). Furthermore, at the end of 52 weeks, in virological responders, the decreased rate in the frequency of PD‐1+ CD8+ T cells was significantly higher than in non‐virological responders (58.3% vs 25.7%, P = 0.001), and at weeks 24 and 52, in virological responders, PD‐1 expression on CD4+ and CD8+ T cells was lower than in non‐virological responders (P = 0.01 and P = 0.035; P < 0.0001 and P < 0.0001, respectively). In 34 cytokines/chemokines detected in serum, IP‐10 expression was positively correlated with viral load, level of ALT and PD‐1 expression on CD8+ and CD4+ T cells at baseline (r = 0.36, P = 0.055, r = 0.635, P < 0.0001, r = 0.414, P = 0.026, and r = 0.402, P = 0.030, respectively). Moreover, the decrease in IP‐10 in serum directly correlated with a decrease in ALT levels (r = 0.751, P < 0.0001). At weeks 24 and 25, IP‐10 expression was significantly lower than baseline in virological responders (both P = 0.005); however, this was not observed in nonresponders. Based on the above findings, PD‐1 and IP‐10 may be used as predictors for virological response, and blockade of their pathway may improve the outcome of patients with CHB.

Telbivudine treatment is associated with high hepatitis B e antigen seroconversion and immune modulatory effects in chronic hepatitis B patients.

Chronic hepatitis B (CHB) is characterized by an impaired immune response to hepatitis B virus. Among the nucleos(t)ides used in CHB treatment, telbivudine is associated with the highest rates of hepatitis B e antigen (HBeAg) seroconversion rates, which are similar to those observed with pegylated interferon (PegIFN). Besides direct antiviral effect, modulation of the immune system may be an additional benefit for telbivudine‐treated patients. Indeed, there is much clinical data indicating an IFN‐like behaviour for telbivudine in contrast to other oral nucleos(t)ides, such as high HBeAg seroconversion, similar hepatitis B surface antigen (HBsAg) decline and biphasic viral kinetics. Clinical studies, animal models and in vitro studies suggest that both the innate and adaptive immune system responses contribute to high HBeAg seroconversion during telbivudine treatment through modulation of the function and/or expression of CD4+/CD8+ T cells, Th1/Th2, Treg, PD‐1/PD‐L1, Th17, IL‐21 and TFH. The results described in this review suggest that the antiviral effect of telbivudine may be attributable not only to direct suppression of hepatitis B virus, but also to immunoregulatory effects. Hypothetically, telbivudine shares some common signal pathways with IFN.

Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus? An Economic Analysis Using Real-World Data

Background Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions. Methods A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable. Results Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US

Diagnostic value of circulating cell-free DNA levels for hepatocellular carcinoma

21,612. It varied by economic regions. The probability of cost-effectiveness was 18% and 47% for treatment-naive and experienced patients, and it ranged from 15% in treatment-naïve patients in Central-China to 64% in treatment-experienced patients in Eastern-China. The price of 12-week sofosbuvir/ledipasvir treatment needs to be reduced by at least 81% to US

Phase IIb trial of in vivo electroporation mediated dual-plasmid hepatitis B virus DNA vaccine in chronic hepatitis B patients under lamivudine therapy

18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US