240-week entecavir maleate treatment in Chinese chronic hepatitis B predominantly genotype B or C.

This study aimed to evaluate the efficacy and safety of entecavir(ETV) versus ETV maleate in Chinese patients with chronic hepatitis B(CHB). This was a randomized, double-blind, double-dummy, controlled, multicentre study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A) or 0.5 mg/day ETV maleate (group B), then, all patients received treatment with 0.5 mg/day ETV maleate from week 49 onwards. Patients were regularly followed up. Serum hepatitis B virus (HBV) markers were detected. Adverse events (AE) were recorded. The primary endpoint was the decline in HBV DNA in each group at the end of treatment. Secondary endpoints included the rate of HBV DNA below the lower limit of detection (LLOD) (20 I U/ml) at the end of treatment, the rate of hepatitis B e antigen (HBeAg) loss, the rate of HBeAg seroconversion and serum alanine aminotransferase (ALT) normalization. One hundred and thirty-seven (71 in group A) patients with HBeAg-positive CHB and 46 (21 in group A) patients with HBeAg-negative CHB completed the 240-week treatment and follow-up. Baseline characteristics were well balanced between the two groups. For the HBeAg-positive CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.67 log10 IU/ml vs. B: by 6.74 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA (<20 IU/ml) at Week 240 were similar between groups (A:91.55% vs. B:87.88%; p > .05). Both groups achieved similar HBeAg seroconversion rates at week 240 (A:26.98% vs. B:20.97%; p > .05). Both groups achieved similar normalization of ALT (A:87.32% vs. B:83.61%; p > .05) at Week 240 (p > .05). For the HBeAg-negative CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.05 log10 IU/ml vs. B: by 6.10 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA at Week 240 were similar between groups (A:100% vs. B:100%). Both groups achieved similar normalization rates (A:90.91% vs. B: 95.45%; p > .05) of ALT at Week 240 (p > .05). In conclusion, long-term ETV maleate treatment was safe and efficient in Chinese CHB predominantly of genotype B or C.

[Analysis of a randomized, double-blind, double-dummy, controlled, multicenter study confirmed the similar therapeutic efficacies of entecavir maleate and entecavir for treatment of HBeAg-positive chronic hepatitis B].

OBJECTIVE: To evaluate the efficacy and safety of entecavir maleate (ETV) versus ETV in Chinese patients with hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB). METHODS: The patient population of this previously published randomized, double-blind, double-dummy, controlled, multicenter study was expanded by patients in the 0.5 mg/day ETV maleate group (total n = 110) and patients in the 0.5 mg/day ETV group (total n = 108). At treatment weeks 12, 24 and 48, hepatitis B virus (HBV) DNA levels were measured by the Roche Cobas Ampliprep/Cobas Taqman PCR assay. Adverse events (AE) were recorded. RESULTS: As in the original analysis, the two treatment groups showed similar characteristics at baseline. In addition, the results for the all therapeutic effects showed identical trends to the results obtained in the original analysis, including the statistically similar effects of ETV and ETV maleate treatment-induced decreases in mean HBV DNA level at weeks 12, 24, and 48 (ETV: by 4.28, 5.00, and 5.53 log10 IU/ml vs. ETV maleate: by 4.46, 4.99, and 5.51 log10 IU/ml, respectively; all vs. baseline P more than 0.05), achievement of undetectable levels of serum HBV DNA ( less than 20 IU/ml) at week 48 (ETV: 38.18% vs. ETV maleate: 35.19%; P more than 0.05), HBeAg loss rates at week 48 (ETV: 10.91% vs. ETV maleate: 12.96%; P more than 0.05), HBeAg seroconversion rates at week 48 (ETV: 7.77% vs. ETV maleate: 10.38%; P more than 0.05), normalization of alanine aminotransferase at week 48 (ETV: 75.47% vs. ETV maleate: 82.86%; P more than 0.05), and overall incidence of AE (ETV: 18.02% vs. ETV maleate: 17.43%; P more than 0.05). CONCLUSION: Performing analysis of the therapeutic efficacies of entecavir maleate versus entecavir with a larger study population confirmed our original findings of similar efficacy and safety profiles for these two drugs in patients with HBeAg-positive CHB.

[A randomized, double-blind, double-dummy, controlled, multicenter study of entecavir maleate versus entecavir for treatment of HBeAg-negative chronic hepatitis B: results at week 48].

OBJECTIVE: To evaluate the efficacy and safety of entecavir (ETV) maleate versus ETV in Chinese patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). METHODS: This was a randomized, double-blind, double-dummy, controlled, multicenter study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A; n = 26) or 0.5 mg/day ETV maleate (n = 31). Hepatitis B virus (HBV) DNA levels were measured at weeks 12, 24, and 48 by the Roche Cobas Ampliprep/Taqman PCR assay. Adverse events (AE) were recorded. RESULTS: Baseline characteristics were similar between the two groups. At weeks 12, 24, and 48, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 4.24, 4.61 and 4.88 log10 IU/mL vs. B: 4.01, 4.50 and 4.99 log10 IU/mL, respectively; all P more than 0.05). Patients who achieved undetectable levels of serum HBV DNA (less than 20 IU/mL) at week 48 were similar in the two groups (A: 69.23% vs. B: 80.65%; P more than 0.05). Both groups achieved similar normalization of ALT at week 48 (A: 96.00% vs. B: 83.87%; P more than 0.05). The overall AE incidence was similar for the two groups (A: 22.22% vs. B: 9.38%; P more than 0.05). CONCLUSION: Entecavir maleate and entecavir showed similar efficacy and safety in patients with HBeAg-negative CHB.

The Emerging Role of Branched-Chain Amino Acids in Liver Diseases.

Chronic liver diseases pose a substantial health burden worldwide, with approximately two million deaths each year. Branched-chain amino acids (BCAAs)-valine, leucine, and isoleucine-are a group of essential amino acids that are essential for human health. Despite the necessity of a dietary intake of BCAA, emerging data indicate the undeniable correlation between elevated circulating BCAA levels and chronic liver diseases, including non-alcoholic fatty liver diseases (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC). Moreover, circulatory BCAAs were positively associated with a higher cholesterol level, liver fat content, and insulin resistance (IR). However, BCAA supplementation was found to provide positive outcomes in cirrhosis and HCC patients. This review will attempt to address the contradictory claims found in the literature, with a special focus on BCAAs' distribution, key signaling pathways, and the modulation of gut microbiota. This should provide a better understanding of BCAAs' possible contribution to liver health.

One hundred and ninety-two weeks treatment of entecavir maleate for Chinese chronic hepatitis B predominantly genotyped B or C.

BACKGROUND: Entecavir (ETV) is a potent and selective nucleotide analog with significant activity against hepatitis B virus (HBV). ETV maleate is a derivative compound of ETV and was reported to have an efficacy and safety profile that is comparable to ETV (Baraclude) when used in Chinese patients with chronic hepatitis B (CHB) in phase III clinical trials (Clinical Trials.gov number, NCT01926288) at weeks 48, 96, and 144. AIM: To investigate the antiviral potency and safety of ETV maleate at week 192 in Chinese CHB patients predominantly genotyped B or C. METHODS: In this double-blind study, we randomly assigned patients to receive 0.5 mg/d ETV (Group A) or ETV maleate (Group B) (ratio, 1:1), each with a placebo tablet for 48 wk. Then, all patients received open-label treatment with 0.5 mg/d ETV maleate starting at week 49. The primary efficacy endpoint was the reduction in HBV DNA levels from baseline. Secondary endpoints included the proportion of patients with undetectable HBV DNA (< 20 IU/mL), serologic response, serum alanine aminotransferase (ALT) normalization and development of resistance mutations. RESULTS: Two hundred eighteen patients who were hepatitis B e antigen (HBeAg) positive and 57 who were HBeAg negative were analyzed and predominantly presented with genotype B (49.82%) or C (48.73%). For the HBeAg-positive CHB patients, the mean HBV DNA level decrease (6.61 Log10 IU/mL vs 6.69 Log10 IU/mL, P > 0.05), viral suppression with HBV DNA < 20 IU/mL (83.33% vs 79.17%, P > 0.05) and HBeAg seroconversion (28.77% vs 20.00%, P > 0.05) occurred similarly between Groups A and B at week 192. However, there was a significant difference in the proportion of patients with normal ALT levels (91.14% vs 78.38%, P < 0.05). For the HBeAg-negative CHB patients, no significant difference was found between Groups A and B at week 192 in terms of reductions in HBV DNA levels from baseline (6.05 Log10 IU/mL vs 6.03 Log10 IU/mL, P > 0.05), percentages of patients who achieved undetectable HBV DNA (100% vs 100%, P > 0.05) and rates of ALT normalization (95.65% vs 100.00%, P > 0.05). Safety and adverse event profiles were similar between Groups A and B. Two HBeAg-positive patients in Group A and 5 in Group B developed genotypic resistance to ETV. CONCLUSION: Long-term ETV maleate treatment for up to 192 wk is effective and safe in Chinese CHB patients predominantly genotyped as B or C.

Human immune repertoire in hepatitis B virus infection.

Hepatitis B virus (HBV) infection is a public health threat that affects 257 million people worldwide and can progress to liver cirrhosis, liver failure, and hepatocellular carcinoma. The HBV antigen- induced adaptive immune response plays an important role in HBV clearance. Immune repertoire sequencing (IRS) has been used to investigate the molecular mechanisms behind the immune system, find novel ways to treat HBV infection, and evaluate the genetic responses and immune characteristics of individuals infected by HBV or immunized by HBV vaccine. This review summarizes the human immune repertoire analysis methodology, and the application of the IRS in the prediction of HBV infection progression, treatment, and vaccination.

Tenofovir disoproxil fumarate in Chinese chronic hepatitis B patients: Results of a multicenter, double-blind, double-dummy, clinical trial at 96 weeks.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is a prodrug of a nucleotide analogue. As an antiviral drug, TDF has been proposed in the first-line treatment of chronic hepatitis B (CHB). Qingzhong, a brand name of TDF, commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd., and Viread, another brand name of TDF, commercialized by GlaxoSmithKline, have both been approved by the State Food and Drug Administration, China. AIM: To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB patients. METHODS: This trial was registered at ClinicalTrials.gov with the identifier number of NCT02287857. A total of 330 Chinese CHB patients, among which 232 were hepatitis B e antigen (HBeAg)-positive, were included in this 5-year-long, multicenter, double-blinded, double-dummy, randomized-controlled, non-inferiority phase III trial. The participants were initially randomized into two groups: Group A (n = 161), in which the participants received 300 mg Qingzhong once a day for 48 wk; and Group B, in which the participants received 300 mg Viread once a day for 48 wk. Starting from week 49, all the participants in Groups A and B received 300 mg Qingzhong once a day until the 96th week. In this study, the primary endpoint was the decrease in plasma level of hepatitis B virus (HBV) DNA at the 96th week, while the secondary endpoints were suppression of HBV replication, alanine aminotransferase (ALT) normalization, HBeAg loss, and HBeAg seroconversion rates. RESULTS: For the participants with HBeAg-positive CHB, the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B (5.77 vs 5.73 log10 IU/mL, P > 0.05) at the 96th week. In addition, similar percentages of HBeAg-positive participants in the two groups exhibited undetectable levels of HBV DNA, HBeAg loss, and HBeAg seroconversion (71.05% vs 77.97%, 31.00% vs 27.27%, and 20.22% vs 15.79%, respectively, in Group A vs Group B; P > 0.05). For the participants with HBeAg-negative CHB, the decrease in mean HBV DNA level relative to the baseline value was also comparable between Groups A and B (4.46 vs 4.70 log10 IU/mL, P > 0.05) at the 96th week. In addition, similar percentages of HBeAg-negative participants in the two groups exhibited undetectable levels of HBV DNA (87.23% vs 94.12% in Group A vs Group B, respectively; P > 0.05). Finally, similar percentages of CHB patients (HBeAg-positive or HBeAg-negative) in the two groups exhibited normalization of ALT (80.14% vs 84.57% in Group A vs Group B, respectively; P > 0.05), and similar incidences of adverse events were observed (106 vs 104 in Group A vs Group B, respectively; P > 0.05). CONCLUSION: Both Qingzhong and Viread are effective and safe in the treatment of Chinese CHB patients according to the results of our clinical trial.

[Comparison of lamivudine or interferon monotherapy and sequential therapy in chronic hepatitis B: a random controlled trial].

OBJECTIVE: To compare the efficacy and safety of lamivudine or interferon monotherapy and sequential therapy in HBeAg positive chronic hepatitis B patients. METHODS: A total of 225 patients with HBeAg positive chronic hepatitis B were randomized into 3 groups: sequential group (group A, 83 patients), lamivudine group (group B, 89 patients) and interferon group (group C, 53 patients). Group A was administrated with lamivudine 100 mg/d for 32 week, and 5 million units of interferon alpha 2b injected subcutaneously every other day lasting for 24 week were added since week 25. Group B was administrated with lamivudine 100 mg/d for 48 week. Group B was injected with 5 million units of interferon alpha 2b subcutaneously every other day for 24 week. All subjects were followed up for 24 week. Serum HBV DNAs were measured quantitatively by PCR. HBV mutations were analyzed by PCR-RFLP. RESULTS: For groups A, B and C, baseline HBV DNAs were 7.8±1.0, 7.9±1.1 and 8.0±0.9 log10 copies/mL, respectively, P>0.05. Baseline ALTs were 167.5 (99.0, 267.8), 134.0 (101.0,275.0) and 131.0 (99.0, 192.8)U/L, respectively, P>0.05. At the end of the treatment, HBV DNA decrease rates for groups A, B and C were 78.2%, 87.8% and 78.4% (P>0.05), respectively. At the end of the follow-up, HBV DNA decrease rates for groups A, B and C were 54.4%, 63.6% and 66.7% (P>0.05), respectively. At the end of the treatment, group B (83.5%, P<0.05) achieved the highest response rate and group C achieved the lowest (39.6%, P<0.05). At the end of the follow-up, the response rates for groups A, B and C were 36.2%, 54.4% and 42.1% (P>0.05), respectively. YMDD motif mutation rate in group A was lower than that of group B (10.5% vs 26.9%, P<0.05) at the end of the treatment. CONCLUSION: Sequential therapy decreased hepatitis B virus mutation. But no efficacy advantages were found in sequential therapy than in lamivudine or interferon monotherapy.

Chinese guidelines on the management of liver cirrhosis (abbreviated version).

Based on reviews of the literature and experts' consensus, the Chinese Society of Hepatology developed guidelines for the diagnosis and treatment of liver cirrhosis, in order to improve clinical practice. In addition to what has been covered in previously published guidelines on the management of cirrhosis complications, these guidelines add new sections and provide updates. The guidelines emphasize the early diagnosis of the cause and assessment of complications. Comprehensive treatments including etiological treatment and complication management should be initiated immediately. In addition, regular monitoring, especially surveillance of hepatocellular carcinoma, is crucial for managing patients.

[A clinical study of viral dynamic change in patients with hepatitis B e antigen positive chronic hepatitis B by lamivudine treatment].

OBJECTIVE: To observe viral dynamic change in patients with HBeAg positive chronic hepatitis B by lamivudine treatment. METHODS: A multi-center clinical trial. Both outpatients and inpatients with HBeAg positive chronic hepatitis B have been administrated lamivudine 100 mg/d for 24 weeks. To detect the hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels of the baseline, 12 hours, 1 day, 2 days, 3 days, 1 week, 2 weeks, 4 weeks, 12 weeks, 24 weeks after lamivudine treatment by real time polymerase chain reaction (PCR). To estimate the parameters of viral dynamics through regression analysis. RESULTS: 172 patients were enrolled, 145 male, 30.8 +/- 9.7 (16 - 65) years old. Significant decrease of HBV DNA level occurred 12 hours after administration, the average decrease was 0.45 lg(copies/ml), maximum was 3.86 lg(copies/ml), 4 patients decreased not less than 2 lg(copies/ml). On day 2 and 7, the average decrease was 1.20 lg(copies/ml) and 2.01 lg(copies/ml), maximum was 4.41 lg(copies/ml) and 5.79 lg(copies/ml), respectively. Then HBV DNA level continued decreasing until week 24. 24-week administration of lamivudine cause 4.10 lg(copies/ml) decrease of HBV DNA averagely and 6.68 lg(copies/ml) mostly. Half life of free virion was 2.57 days. Half life of infected hepatocyte was 63.0 days. CONCLUSION: Lamivudine could rapidly decrease the HBV DNA level of patients with HBeAg positive chronic hepatitis B rapidly.

A randomized, double-blind, double-dummy, controlled, multicenter study of Qingzhong (tenofovir disoproxil fumarate) versus Viread for the treatment of chronic hepatitis B: First-stage results at week 48.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been widely recommended as a first-line antiviral agent to treat chronic hepatitis B (CHB). Qingzhong and Viread, formulations of TDF commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd and GlaxoSmithKline, respectively, have both been approved by the State Food and Drug Administration, China. This study analyzed the efficacy and safety of these 2 TDF agents in Chinese patients with CHB. METHODS: In this multicenter, randomized, double-blind, double-dummy, noninferiority phase 3 clinical trial (ClinicalTrials.gov identifier: NCT02287857), 330 Chinese patients with CHB [hepatitis B envelope antigen-positive (HBeAg) (+): 232] were randomly assigned to receive Qingzhong (group A: 161 patients) or Viread (group B: 169 patients) 300 mg once daily for 48 weeks. Subsequently, all patients were administered Qingzhong 300 mg once daily from week 49 to week 240. The primary end point was the degree of decline of plasma hepatitis B virus (HBV) DNA levels at week 48 and the secondary endpoints were viral suppression, normalization of alanine aminotransferase (ALT) levels, hepatitis B surface antigen (HBsAg)/HBeAg loss or seroconversion, and virological breakthrough. RESULTS: Among patients with CHB who were HBeAg (+), the mean HBV DNA titer decreased similarly between the groups at week 48. The percentages of patients who achieved undetectable HBV DNA were similar between the groups (85.11% and 82.35% in groups A and B, respectively) and similar losses of HBeAg and HBeAg seroconversion rates were achieved. Moreover, for patients with CHB who were HBeAg (-), reductions in HBV DNA were similar. Among all patients with CHB, the rates of normalization of ALT and the loss of HBsAg were similar. The overall incidence of adverse events was comparable between the groups. CONCLUSION: In conclusion, the 48-week administration of Qingzhong showed noninferior efficacy and safety profiles compared to Viread in Chinese patients with CHB.

[The histopathologic and clinical analysis of viral chronic hepatitis patients with negative serological viral markers].

OBJECTIVE: To analyze the histopathological and clinical features of viral chronic hepatitis patients with negative serological viral markers. METHODS: 62 hepatitis patients with negative serological markers were assayed with serological viral hepatitis markers, liver function test and liver biopsies were enrolled in the study. Serum HBV DNA of HBV cases was analyzed by PCR. Liver specimens were examined by immunohistochemistry for HBsAg and HBcAg. RESULTS: The fit rate of histopathological diagnosis with clinical diagnosis is 53.2%, the fit rate is 69.1% in moderate chronic hepatitis group. The immunohistochemistry showed that HBsAg and/or HBeAg positive rate was 45.2%, 53.6% had moderate chronic hepatitis and 25% had mild hepatitis. 13 (46.4%) had G1 hepatitis, 10 (35.7%) had G2 hepatitis, 3 (10.8%) had G3 hepatitis and 2 (7.1%) had G4 hepatitis, and serum HBV DNA positive rate was 35.7%. There were no differences in HBV DNA levels between different hepatitis group and fibrosis stage group (P > 0.05). There were no differences in all indexes between HBV DNA negative group and HBV DNA positive group (P > 0.05). There were no differences in all indexes between HBV patients and other patients (P > 0.05). CONCLUSION: Occult HBV infection may account for a high proportion of the cases with chronic hepatitis of unknown etiology. Most patients are chronic mild hepatitis, but they still have HBV replication and can progress to liver cirrhosis. Serum PCR test, liver biopsy and immunohistochemistry are helpful for the diagnosis.

Effects of HRT and water temperature on nitrogen removal in autotrophic gravel filter.

Organic Carbon added to low ratio of carbon to nitrogen (C/N ratio) wastewater to enhance heterotrophic denitrification performance might lead to higher operating costs and secondary pollution. In this study, sodium thiosulfate (Na2S2O3) was applied as an electron donor for a gravel filter (one kind of constructed wetland) to investigate effects of hydraulic retention time (HRT) and water temperature on the nitrate removal efficiency. The results show that with an HRT of 12 h, the average total nitrogen (TN) removal efficiencies were 91% at 15-20 °C and 18% at 3-6 °C, respectively. When HRT increased to 24 h, the average TN removal increased accordingly to 41% at 3-6 °C, suggesting denitrification performance was improved by extended HRT at low water temperatures. Due to denitrification, 96% of added nitrate nitrogen (NO3(-)-N) was converted to nitrogen gas, with a mean flux of nitrous oxide (N2O) was 0.0268-0.1500 ug m(-2) h(-1), while 98.86% of thiosulfate was gradually converted to sulfate throughout the system. Thus, our results show that the sulfur driven autotrophic denitrification constructed wetland demonstrated an excellent removal efficiency of nitrate for wastewater treatment. The HRT and water temperature proved to be two influencing factors in this constructed wetland treatment system.

Relationship between virological response and FIB-4 index in chronic hepatitis B patients with entecavir therapy.

AIM: To investigate whether long-term low-level hepatitis B virus (HBV) DNA influences dynamic changes of the FIB-4 index in chronic hepatitis B (CHB) patients receiving entecavir (ETV) therapy with partial virological responses. METHODS: We retrospectively analyzed 231 nucleos(t)ide (NA) naïve CHB patients from our previous study (NCT01926288) who received continuous ETV or ETV maleate therapy for three years. The patients were divided into partial virological response (PVR) and complete virological response (CVR) groups according to serum HBV DNA levels at week 48. Seventy-six patients underwent biopsies at baseline and at 48 wk. The performance of the FIB-4 index and area under the receiver operating characteristic (AUROC) curve for predicting fibrosis were determined for the patients undergoing biopsy. The primary objective of the study was to compare the cumulative probabilities of virological responses between the two groups during the treatment period. The secondary outcome was to observe dynamic changes of the FIB-4 index between CVR patients and PVR patients. RESULTS: For hepatitis B e antigen (HBeAg)-positive patients (n = 178), the cumulative probability of achieving undetectable levels at week 144 was 95% and 69% for CVR and PVR patients, respectively (P < 0.001). In the Cox proportional hazards model, a lower pretreatment serum HBV DNA level was an independent factor predicting maintained viral suppression. The cumulative probability of achieving undetectable levels of HBV DNA for HBeAg-negative patients (n = 53) did not differ between the two groups. The FIB-4 index efficiently identified fibrosis, with an AUROC of 0.80 (95%CI: 0.69-0.89). For HBeAg-positive patients, the FIB-4 index was higher in CVR patients than in PVR patients at baseline (1.89 ± 1.43 vs 1.18 ± 0.69, P < 0.001). There was no significant difference in the reduction of the FIB-4 index between the CVR and PVR groups from weeks 48 to 144 (-0.11 ± 0.47 vs -0.13 ± 0.49, P = 0.71). At week 144, the FIB-4 index levels were similar between the two groups (1.24 ± 0.87 vs 1.02 ± 0.73, P = 0.06). After multivariate logistic regression analysis, a lower baseline serum HBV DNA level was associated with improvement of liver fibrosis. In HBeAg-negative patients, the FIB-4 index did not differ between the two groups. CONCLUSION: The cumulative probabilities of HBV DNA responses showed significant differences between CVR and PVR HBeAg-positive CHB patients undergoing entecavir treatment for 144 wk. However, long-term low-level HBV DNA did not deteriorate the FIB-4 index, which was used to evaluate liver fibrosis, at the end of three years.

Promoting hepatic growth factor in the treatment of heavy type hepatitis and severe chronic hepatitis: a multicenter clinical study.

BACKGROUND: The mortality rate of heavy type hepatitis is high. No special treatment is available except general treatment. This multicenter clinical study was designed to observe the safety and efficacy of promoting hepatic growth factor (PHGF) in the treatment of heavy type hepatitis and severe chronic hepatitis. METHODS: 347 patients with heavy type hepatitis and 324 with severe chronic hepatitis were subjected to administration of 120 microg of PHGF per day for 4 weeks on the basis of general treatment. Those who were being effectively treated would last additional 2 to 4 weeks. Blood routine, urine routine, blood urea nitrogen (BUN), blood creatinine (Cr), blood ammonia, alpha fetoprotein (AFP), electrolyte, alanine transaminase (ALT), aspartate transaminase (AST), serum total bilirubin (TBIL), serum direct bilirubin (DBIL), prothrombin time activity (PTA), total protein (TP) and albumin (ALB) were detected in the patients before treatment, 2 weeks after treatment, and at the end of the treatment. Any side-effect would be recorded. RESULTS: In the patients with severe chronic hepatitis, the total effective rate of the treatment was 88.9%. The levels of ALT, AST and TBIL decreased significantly (P<0.001), whereas those of PTA and ALB increased significantly (P<0.001), and the level of AFP increased slightly. In patients with heavy type hepatitis, the total effective rate of this treatment was 78.4%, and patients at different stage showed different results. The total effective rates of patients with early, medium and terminal stage heavy type hepatitis were 89.9%, 84.8% and 27.5%, respectively. No severe side-effect was shown. CONCLUSION: PHGF is effective and safe in the treatment of patients with heavy type hepatitis and severe chronic hepatitis. But it should be administered early in patients with heavy type hepatitis so as to get better curative effects.

[Construction of HLA-A2-peptide tetramer and application in HBV/HCV infection].

OBJECTIVE: To construct HBV and HCV-specific HLA-A2-peptide tetramers, and to direct clinical therapy. METHODS: Recombinant class I HLA-A2 heavy chains and beta-2 M were produced in Escherichia coli cells transformed with pBV220 vectors. Only the extracellular domain of class I heavy chain was expressed, following modification by replacement of the C-terminal domain with a substrate sequence for BirA biotinylation. HLA-A2-BSP was folded in the presence of beta-2 microglobulin and a specific peptide to form a peptide-MHC complex. The MHC complexes were biotinylated using purified BirA enzyme. Biotinylated MHC-peptide complexes were purified. Tetramers were generated by mixing biotinylated protein complex with streptavidin-PE at a molar ratio of 4:1. Then analysis of stained PBMCs was performed using FACScan and CellQuest software. RESULTS: The expression levels of pBV220-HLA-A2-BSP and beta-2M were 46% and 48% of total bacterial proteins estimated from SDS - PAGE, respectively. And they were mainly located in the insoluble fraction of the cell as inclusion bodies and the proportion were about 85% and 90%, respectively. The purity of pBV220-HLA-A2-BSP and beta-2M was above 95% analyzed by SDS-PAGE, and the concentration of pBV220-HLA-A2-BSP and beta-2M was about 1.5 g/L and 1.2 g/L, respectively. Using the constructed HLA-A2-peptide tetramer to detect the HBV/HCV-specific CTL, the HBV-specific CD8(+) frequencies were 1.84% and 0.02% - 0.68% of the total CD8(+) T cells in acute and chronic HBV hepatitis, respectively. As an additional control, an HLA-A2/HCV tetramer was tested in the acute and chronic HBV hepatitis. The frequencies never exceeded 0.02% of the total CD8(+) T cell number. Similar low levels of background staining were also detected in the HLA-A2(+) or A2(-) healthy control. The HCV-specific CD8(+) frequency was 0.02 - 0.72% of the total CD8(+) T cells in chronic HCV hepatitis. The same frequencies of control were detected. CONCLUSION: High-efficient expressions of HLA-A0201-BSP and beta-2m proteins lay a good foundation for further expression and purification in prokaryotic system and constructing MHC class I-peptide tetramer complexes to study the function of CTLs. Especially, using these two HBV and HCV-specific tetramer can detect the frequencies of the HBV/HCV-specific CD8(+) T cells directly in vitro.

Can antidepressants prevent pegylated interferon-α/ribavirin-associated depression in patients with chronic hepatitis C: meta-analysis of randomized, double-blind, placebo-controlled trials?

BACKGROUND: Antidepressants are effective in treating interferon-α/ribavirin (IFN-α/RBV)-associated depression during or after treatment of chronic hepatitis C (CHC). Whether antidepressant prophylaxis is necessary in this population remains under debate. METHODS: Comprehensive searches were performed in Medline, Embase, Cochrane Controlled Trials Register and PubMed. Reference lists were searched manually. The methodology was in accordance with the 2009 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) Statement. RESULTS: We identified six randomized, double-blind, placebo-controlled trials involving 522 CHC patients treated with pegylated (PEG)-IFN-α plus RBV. The antidepressants used were escitalopram, citalopram, and paroxetine, which are selective serotonin reuptake inhibitors (SSRIs). The rates of depression (17.9% vs. 31.0%, P = 0.0005), and rescue therapy (27.4% vs. 42.7%, P<0.0001) in the SSRI group were significantly lower than those in the placebo group. The rate of sustained virological response (SVR) (56.8% vs. 50.0%, P = 0.60) and drug discontinuation (18.7% vs. 21.1%, P = 0.63) in the SSRI group did not differ significantly to those in the placebo group. In terms of safety, the incidence of muscle and joint pain (40.8% vs. 52.4%, P = 0.03) and respiratory problems (29.3% vs. 40.1%, P = 0.03) were lower, but the incidence of dizziness was significantly higher (22.3% vs. 10.2%, P = 0.001) in the SSRI group. CONCLUSION: Prophylactic SSRI antidepressants can significantly reduce the incidence of PEG-IFN-α/RBV-associated depression in patients with CHC, with good safety and tolerability, without reduction of SVR.