[Assessment Value of Short-Term Prognosis of Six Predictive Models for Patients with Acute-on-Chronic Liver Failure Treated with Artificial Liver Support System].

Objective: To apply 6 predictive models on acute-on-chronic liver failure (ACLF) patients treated with artificial liver support system (ALSS), and to compare their assessment values for the short-term prognosis of patients. Methods: A total of 258 ACLF patients who underwent ALSS therapy between January 2018 and December 2019 were selected from the ALSS clinical database established by West China Hospital, Sichuan University, and their clinical data and 90-day prognosis information were collected. Cox proportional hazards model was used to estimate the association between the six predictive models, including Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH ACLF), European Association for the Study of the Liver--Chronic Liver Failure-Consortium (CLIF-C) ACLF, CLIF-C Organ Failure (OF), Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) ACLF, Model for End-Stage Liver Disease (MELD) and Simplified MELD (sMELD), and 90-day mortality, which included death or receiving liver transplantation. The area under the receiver operating characteristic (ROC) curve ( AUC), Harrell's C-index and Brier scores were calculated and compared to evaluate the predictive power. Results: A total of 258 ACLF patients were enrolled. Of these patients, who had a mean age of (46.2±11.7) years old, 37 (14.3%) patients were female, 202 (78.3%) patients had a diagnosis of liver cirrhosis, and 107 (41.5%) patients died during the 90-day follow-up period. The six predictive models all yielded higher scores for patients who died than those for patients who survived (all P<0.001). The six predictive models were all independent risk factors for the short-term prognosis of ACLF patients treated with ALSS (all adjusted hazard ratio [HR]>1, all P<0.001). The AUC (0.806, 95% confidence interval [CI]: 0.753-0.853) and Harrell's C-index (0.772, 95% CI: 0.727-0.816) of COSSH ACLF were much higher than those of the five other predictive models (all AUCs<0.750, P<0.01; all Harrell's C-indices<0.750, P<0.001). The Brier score of COSSH ACLF was 0.18 (95% CI: 0.15-0.20). The 90-day mortality of patients defined as having low risk, moderate risk, and high risk according to the risk stratification of COSSH ACLF were 22.2%, 56.3%, and 90.2%, respectively. Conclusion: The COSSH ACLF could more accurately predict short-term prognosis in ACLF patients who received ALSS therapy, and could facilitate clinical decision-making.

Simple non-invasive scoring systems and histological scores in predicting mortality in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: There is debate among the hepatology community regarding the simple non-invasive scoring systems and histological scores (even it was developed for histological classification) in predicting clinical outcomes in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether the presence of simple non-invasive scoring systems and histological scores could predict all-cause mortality, liver-related mortality, and liver disease decompensation (liver failure, cirrhosis, hepatocellular carcinoma, or decompensated liver disease). METHODS: The pooled hazard ratio of prognostic factors and incidence rate per 1000 person-years in patients with NAFLD was calculated and further adjusted by two different models of handling the duplicated data. RESULTS: A total of 19 longitudinal studies were included. Most simple non-invasive scoring systems (Fibrosis-4 Score, BARD, and aspartate aminotransferase-to-platelet ratio index ) and histological scores (NAFLD activity score, Brunt, and "steatosis, activity, and fibrosis" ) failed in predicting mortality, and only the NAFLD fibrosis score > 0.676 showed prognostic ability to all-cause mortality (four studies, 7564 patients, 118 352 person-years followed up, pooled hazard ratio 1.44, 95% confidence interval [CI] 1.05-1.96). The incidence rate per 1000 person-years of all-cause mortality, liver-related mortality, cardiovascular-related mortality, and liver disease decompensation resulted in a pooled incidence rate per 1000 person-years of 22.65 (14 studies, 95% CI 9.62-53.31), 3.19 (7 studies, 95% CI 1.14-8.93), 6.02 (6 studies, 95% CI 4.69-7.74), and 11.46 (4 studies, 95% CI 5.33-24.63), respectively. CONCLUSION: Non-alcoholic fatty liver disease fibrosis score showed promising prognostic value to all-cause mortality. Most present simple non-invasive scoring systems and histological scores failed to predict clinical outcomes.

Long-term follow-up of HCV patients with sustained virological response after treatment with pegylated interferon plus ribavirin.

BACKGROUND: The progress of liver diseases may not stop after viral eradication. This study aimed to provide data on long-term prognosis of patients with hepatitis C virus (HCV) infection who underwent pegylated interferon plus ribavirin (PR) regimen and achieved a sustained virological response 24 weeks post-treatment (SVR24). METHODS: Responders to the PR regimen in our hospital from January 2011 to June 2014 were enrolled and prospectively followed up. Baseline characteristics were profiled. The incidence of hepatocellular carcinoma (HCC), progression of liver disease (increase in liver stiffness or occurrence of decompensated complication), and HCV recurrence was all monitored. The accumulative and annualized incidence rates (AIRs) of these adverse events were analyzed, and the risk factors were also examined. RESULTS: In total, 151 patients reached a median follow-up time of 103 weeks. Among them, two had an incidence of HCC during the surveillance with AIR of 0.68% (95% CI: 0.00-1.63%). Six patients showed progression of liver disease with AIR of 2.05% (95% CI: 0.42%-3.68%). Three patients who had risky behaviors encountered HCV reinfection. The cirrhotic patients faced higher risk of poor prognosis than non-cirrhotic patients, including HCC and progression of liver disease (AIR: 6.17% vs. 1.42%, P = 0.039). CONCLUSIONS: The incidence of HCC and progression of liver disease was evident in PR responders during the long-term follow-up period, but the risk level was low. Cirrhotic responders were more vulnerable to develop HCC post SVR24 compared with non-cirrhotic ones. HCV recurrence was rare in responders with SVR24 who had corrected their risky behaviors.

Correlation between the suppressor of cytokine signaling-1 and 3 and hepatitis B virus: possible roles in the resistance to interferon treatment.

BACKGROUND: The suppressor of cytokine signaling family (SOCS) is an important negative regulator in the JAK-STAT signaling pathway. This study was designed to explore the correlation between SOCS-1, 2 and 3, Hepatitis B Virus (HBV) and interferon (IFN), and the relationship between SOCS and IFN therapeutic efficacy. METHODS: Four types of mouse models were established. Mice were administered with HBV replicative plasmid pHBV4.1 and IFN inducer Poly IC (Group A), pHBV4.1 (Group B), Poly IC (Group C) and saline (Group D), respectively. Liver tissues were harvested from the mice and SOCS expression was determined. Meanwhile, patients with chronic hepatitis B (CHB) were treated with pegylated interferon α-2b for 24-48 weeks. Liver biopsy was collected and the baseline SOCS expression was determined. Serum assay was performed for efficacy evaluation and correlation analysis. RESULTS: In animal studies, the expression level of SOCS-1 and 3 was found in the descending order of B, A, C and D. The difference between Group B and D suggested that HBV could induce SOCS. The difference between Group A and C suggested that HBV could still induce SOCS with up-regulated endogenous IFN. The difference between Group C and D suggested that ploy IC could induce SOCS, while the difference between Group B and A suggested that Poly IC might have a stronger inhibition effect for SOCS. There was no difference in SOCS-2 expression. In clinical studies, eight of twenty-four enrolled patients achieved either complete or partial therapeutic response. The expression of both SOCS-1 and 3 was higher in CHB patients than in normal controls. The baseline HBV-DNA level was positively correlated with SOCS-1 and 3. The age, viral genotype, HBVDNA, SOCS-1 and SOCS-3 were found to be related to IFN efficacy. CONCLUSION: HBV could induce both SOCS-1 and 3 expression regardless of endogenous IFN level. Elevated IFN could directly up-regulate SOCS-1 and 3 expression, but it could also indirectly down-regulate SOCS-1 and 3 expression by inhibiting HBV replication. HBV might play a more important role in the SOCS up-regulation than IFN, a possible reason why patients with high HBV viral load encounter poor efficacy of IFN treatment.

Impact of mild to moderate elevations of alanine aminotransferase on liver stiffness measurement in chronic hepatitis B patients during antiviral therapy.

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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

The positive rates of hepatitis B surface antibody in youth after booster vaccination: a 4-year follow-up study with large sample.

BACKGROUND: Hepatitis B virus (HBV) infection is still a public issue in the world. Hepatitis B vaccination is widely used as an effective measure to prevent HBV infection. This large-sample study aimed to evaluate the positive rates of hepatitis B surface antibody (anti-HBs) in youth after booster vaccination. METHODS: A total of 37788 participants were divided into two groups according to the baseline levels of anti-HBs before booster vaccination: the negative group (anti-HBs(-)) and the positive group (anti-HBs(+)). Participants were tested for anti-HBs levels after receiving a booster vaccine at 1 and 4 years. RESULTS: The positive rates of anti-HBs were 34.50%, 73.80% and 67.32% before booster vaccination at 1 and 4 years after vaccination, respectively. At 4 years after the booster vaccination, the positive rates of 13-18 years were 47.54%, which was the lowest level among all youth age groups. In the anti-HBs(-) group, the positive conversion rates of anti-HBs were 74.62% at 1 year after receiving a booster vaccine, and 67.66% at 4 years after vaccination. In the anti-HBs(+) group, the positive maintenance rates of anti-HBs were 70.16% after 1 year, and 66.66% after 4 years. Compared with the baseline anti-HBs (+) group, the positive rates of the baseline anti-HBs(-) group were higher at 1 and 4 years after receiving the booster vaccine. CONCLUSION: The positive rates of anti-HBs declined over time, especially the positive maintenance rates were the lowest at age of 13-18 years.

Mutations in basal core promoter is associated with significant fibrosis in both HBeAg positive and negative treatment-naïve chronic hepatitis B.

AIM: Assessment of liver fibrosis is important for the decision of whether to administrate antiviral treatment in chronic Hepatitis B (CHB) patients. The objective was to investigate the relationship between clinical factors and fibrosis, identify predictors of significant fibrosis in Chinese CHB patients. METHODS: Two hundred and seventy-four treatment-naïve CHB patients (208 HBeAg-positive and 66 HBeAg-negative) who performed transient elastography were consecutively included. We assessed ALT, HBsAg, HBeAg, HBV-DNA, HBV genotype and precore (PC)/basal core promoter (BCP) variants and liver stiffness measurement (LSM) values. RESULTS: One hundred and nine patients (39.78%) had significant fibrosis (F≥2, include those with liver cirrhosis). On univariate analysis, significant fibrosis was associated with older age (P<0.001), high ALT levels (P=0.003), lower HBsAg levels (P<0.001), lower HBV DNA levels (P<0.001), HBeAg negative (P<0.001), presence of BCP (P<0.001) and combined BCP/PC mutations (P=0.001). Multivariate logistic regression analysis showed that the strongest independently associated predictors of significant fibrosis (F≥2) were the presence of HBV BCP mutations (P<0.001) and older age (P<0.001), followed by presence of lower HBsAg (P<0.001), higher ALT levels (P=0.006), PC mutations (P=0.011). The diagnostic accuracy of the combination (age, ALT, HBsAg, BCP/PC variants) model with an area under the receiver-operating characteristic curve of 0.819 (cut-off value was 0.349, P<0.001, 95% CI 0.731-0.914) in predicting significant fibrosis. CONCLUSIONS: We identified four independent risk factors (age, ALT, HBsAg, HBV BCP/PC variants) in predicting significant fibrosis. HBV BCP variants was the strongest predictor of significant fibrosis. The combination of these four variables may facilitate the assessment and management of fibrosis in HBV infected patients.

Serum hepatitis B core-related antigen is a satisfactory surrogate marker of intrahepatic covalently closed circular DNA in chronic hepatitis B.

Recently, hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. This study aimed to investigate whether serum quantitative HBcrAg (qHBcrAg) was a satisfactory surrogate marker of intrahepatic covalently closed circular DNA (cccDNA). A total of 139 patients with liver biopsy were enrolled, consisting of 59 patients in immune tolerance (IT) phase, 52 patients in immune clearance (IC) phase, 18 patients in low-replication (LR) phase, and 10 patients in reactivation phase. All patients in IC phase have received entecavir (ETV) therapy, and 32 of them undergone a second liver biopsy at 24 months. Among those patients, qHBcrAg was strongly correlated with intrahepatic cccDNA, which is superior to that of qHBsAg and HBV DNA. And similar findings were also observed in patients in IT, IC, LR and reactivation phases. Among the 32 ETV-treated patients with a second liver biopsy in IC phase, the decline of intrahepatic cccDNA was accompanied by changes in both qHBcrAg and qHBsAg. However, as compared to qHBsAg, the change of qHBcrAg was more strongly associated with intrahepatic cccDNA-decline. In summary, serum qHBcrAg should be a satisfactory surrogate of intrahepatic HBV cccDNA in CHB patients.

Plasma Apolipoprotein A-V Predicts Long-term Survival in Chronic Hepatitis B Patients with Acute-on-Chronic Liver Failure.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition, and the lipid metabolism disorder is common in the development of this disease. This prospective observational study aimed to define the characteristics of plasma apolipoprotein A-V (apoA-V) in long-term outcome prediction of HBV-ACLF, and a total of 330 HBV-ACLF patients were included and followed for more than 12 months. In this cohort, the 4-week, 12-week, 24-week and 48-week cumulative mortality of HBV-ACLF was 18.2%(60/330), 50.9%(168/330), 59.7%(197/330) and 63.3%(209/330), respectively. As compared to survivors, the non-survivors had significantly lower concentrations of plasma apoA-V on admission. Plasma apoA-V concentrations were positively correlated with prothrombin time activity (PTA), and negatively correlated with interleukin-10, tumor necrosis factor-α, and iMELD scores. Though plasma apoA-V, PTA, total bilirubin(TBil) and blood urea nitrogen(BUN) were all independent factors to predict one-year outcomes of HBV-ACLF, plasma apoA-V had the highest prediction accuracy. And its optimal cutoff value for one-year survival prediction was 480.00 ng/mL, which had a positive predictive value of 84.68% and a negative predictive value of 92.23%. In summary, plasma apoA-V decreases significantly in non-survivors of HBV-ACLF, and it may be regarded as a new predictive marker for the prognosis of patients with HBV-ACLF.

Quantitative intrahepatic HBV cccDNA correlates with histological liver inflammation in chronic hepatitis B virus infection.

BACKGROUND: The aim of this study was to determine the role of baseline hepatitis B virus (HBV) forming covalently closed circular DNA (HBV cccDNA) in liver inflammation in patients infected with HBV with serum alanine aminotransferase (ALT) levels under two times the upper limit of normal (2×ULN). METHODS: After liver biopsy and serum virological and biochemical marker screening, patients diagnosed with chronic HBV infection with serum ALT levels under 2×ULN and histological liver inflammation of less than grade G2 were prospectively recruited into this study. Recruitment took place between March 2009 and November 2010 at the Center of Infectious Disease, Sichuan University. Patient virological and biochemical markers, as well as markers of liver inflammation, were monitored. RESULTS: A total of 102 patients were recruited and 68 met the inclusion criteria; the median follow-up was 4.1 years (range 3.9-5.2 years). During follow-up, 41 patients (60.3%) exhibited signs of inflammation. Baseline HBV cccDNA >1 copy/cell (odds ratio 9.43, p=0.049) and liver inflammation grade ≥G1 (odds ratio 5.77, p=0.046) were both independent predictors of liver inflammation. CONCLUSIONS: A higher baseline intrahepatic HBV cccDNA level may increase the risk of liver inflammation. Further investigations will be required to validate HBV cccDNA as an intrahepatic virological marker of patients who require extended outpatient management.

Hepatitis B virus infection in Chinese patients with hepatitis C virus infection: prevalence, clinical characteristics, viral interactions and host genotypes: a nationwide cross-sectional study.

OBJECTIVES: Little is known about hepatitis B virus (HBV) infection in patients with hepatitis C virus (HCV) infection in China. This study aimed to evaluate the prevalence, clinical characteristics, viral interactions and host genotypes of HBV/HCV dual infection compared with HCV monoinfection. STUDY DESIGN: A cross-sectional study. SETTING: China. PARTICIPANTS AND METHODS: 997 patients with HCV from 28 university-affiliated hospitals in China were enrolled in this research. Patients were divided into two subgroups. RESULTS: The prevalence of HBV infection in patients with HCV was 4.11% (41/997). The age-specific prevalence of HBsAg was 0.70%, 3.97% and 5.85% in groups aged 18-30, 30-50 and >50 years old (p=0.057), respectively. Patients with HBV/HCV dual infection and patients with HCV monoinfection had similar HCV viral loads (5.80±0.89 vs 5.83±1.00 log10 IU/mL, p=0.904). The dominant HCV genotype was 1b in both groups (53.65% vs 56.90%, p=0.493). The protective C allele in IL-28B (rs12979860) was also the dominant allele type in both patient groups (85.36% vs 83.99%, p=0.814). Patients with HBV/HCV dual infection had a higher ratio of liver cirrhosis and hepatic decompensation than patients with HCV monoinfection (39.02% vs 17.69%, p=0.001; 31.70% vs 12.13%, p=0.001). CONCLUSIONS: The HBV burden was moderate in HCV-infected patients in China. Liver cirrhosis was more common in patients with HBV/HCV dual infection, suggesting the need for closer monitoring of dual-infected individuals. TRIAL REGISTRATION NUMBER: NCT01293279; Post-results.

Low Ratio of Treg to Th17 Cells After 36 Weeks of Telbivudine Therapy Predict HBeAg Seroconversion.

Changes of Treg/Th17 cells ratio and their associated cytokines have some correlations with an immune modulatory effect of Telbivudine treatment. The aim of our study was to investigate the role of the dynamic ratio of Treg/Th17 cells in the mechanism of LdT therapy and their relationships with the clinical responses. We detected the frequency and cytokines production of Treg and Th17 cells in 28 hepatitis B envelope antigen (HBeAg)-positive CHB patients at 0, 12, 24, 36, 48, and 96 weeks after initial LdT therapy. LdT could upregulate the frequency of Th17 cells and Th17 cells associated cytokines, downregulated the frequency of Treg cells and level of TGF-ß, which leads to the decrease of Treg/Th17 ratio in HBeAg-positive CHB patients. Treg/Th17 ratio at treatment week 36 could independently predict HBeAg seroconversion in the first 2 years of Telbivudine treatment. Telbivudine therapy can decrease Treg/Th17 ratio, which may predict HBeAg seroconversion during treatment.

The predictive value of early indicators for HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients with Telbivudine treatment for 104 weeks.

PURPOSE: Through an observation on HBeAg-positive chronic hepatits B (CHB) patients in Telbivudine (LDT) treatment for 104 weeks, we tried to explore valuable early predictors for HBeAg seroconversion during the treatment. MATERIALS AND METHODS: A prospective study lasting for 104 weeks was conducted, and the patients enrolled were administered with LDT 600 mg daily. The medical evaluation went every 12 weeks, then the age distribution, baseline ALT level, early HBVDNA, HBsAg and HBeAg levels at baseline, week 12 and 24 as well as the decrease of the three indicators at week 12 and 24 were analyzed for their predictive values for HBeAg seroconversion at week 104. RESULT: Thirty-three patients finished the observation. All patients got ALT normalisation and 28 patients (84.84%) got complete virological response (HBV DNA<291 copies/ml) at week 104. Poor virological response and virologic breakthrough was observed in two (6.06%) and three patients (9.09%), respectively. Nine patients (27.27%) got HBeAg seroconversion. HBeAg levels and its decrease levels at week 12 and 24 showed significant differences between patients with and without HBeAg seroconversion. And the HBsAg levels at week 12 and 24 showed tendencies of significant differences in two groups. HBeAg level at week 24 was confirmed related to its longer term seroconversion in regression analysis. The patients with HBeAg level<2.1 S/CO at week 24 would be more possible to get HBeAg seroconversion at week 104, with sensitivity, specificity, positive and negative predictive value of 95.83%, 88.89%, 95.8% and 88.9%, respectively. CONCLUSION: Good efficacy of long-term LDT treatment in biological and virological response and its advantage in serological response was confirmed again in our study. The HBeAg level at week 24 showed significant value in prediction for HBeAg seroconversion at week 104 compared to other serological markers in the early period.

Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load.

BACKGROUND AND AIMS: To evaluate the antiviral response of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients who had baseline high viral load (HVL), defined as having hepatitis B virus (HBV) DNA>9log 10 copies/mL, after 96weeks of entecavir (ETV) treatment. METHODS: A total of 99 HBeAg-positive CHB patients (50 with HVL and 49 with non-HVL) were treated with ETV monotherapy for 96weeks. RESULTS: Virological response (VR) (HBVDNA<300copies/mL) was achieved in 42%, 62%, 68% of HVL patients and in 67.34%, 85.71%, 85.71% of non-HVL patients at weeks 48,72,96, respectively. The VR rates of the HVL group were lower than those of the non-HVL group (P=0.006, P=0.007, and P=0.037). In the HVL group, a total of 30 patients had HBV DNA<1000copies/mL at week 48 and those patients had a 93.3% chance of achieving VR at week 96, whereas the patients who had HBV DNA levels>1000copies/mL at week 48 only had a 30% chance to achieve VR at week 96. Among the 96weeks of treatment, one patient had virological breakthrough in the HVL group and this patient had HBVDNA>1000copies/mL at week48. The rates of biochemical responses (BR) and HBeAg seroconversion (SR) were similar between the HVL group and non-HVL group at weeks 48 and 96. CONCLUSION: The baseline HVL was a negative predictor of virological response in CHB patients with ETV monotherapy. For those HVL patients treated by ETV with poor VR, which defined as HBVDNA>1000copies/mL at week48, the treatment strategies need to be adjusted.

Serum hepatitis B surface antigen titer and transient elastography in screening for insignificant fibrosis in HBeAg-positive chronic hepatitis B patients.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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

Biological characteristics of the A1762T/G1764A mutant strain of hepatitis B virus in vivo.

The double nucleotide, A1762T and G1764A exchange (TA mutation), in the hepatitis B virus (HBV) genome basal core promoter (BCP) region is a common viral mutation in patients with chronic HBV infection. This mutation is located in the binding site of hepatocyte nuclear factor 4 (HNF4), and a number of liver­enriched transcription factors are involved in the regulation of HBV transcription and replication. The aim of the present study was to investigate the biological characteristics of the HBV strain with this mutation, and the effect of HNF4 inhibition on the replication of this strain in vivo. The results indicated that in vivo the HBV strain with the TA mutation supported a higher level of pregenomic RNA transcription and HBV DNA replication, compared with the wild­type strain. Furthermore, the concentration of serum HBeAg in the TA mutant group was lower than that in the wild­type strain. Following treatment of the mice with entecavir (ETV) or tenofovir disoproxil fumarate (TDF), the transcription and replication levels of wild­type and mutant strains were reduced. In the groups treated with TDF, the inhibition effect was more marked. In hepatocytes in which HNF4 expression was specifically inhibited, the level of 3.5 kb mRNA of HBV was reduced compared with that in mouse cells with normal HNF4 expression, and HBV DNA replication levels were also reduced to a greater extent. Furthermore, following liver­specific knockdown of HNF4, the reduction in variant virus expression was greater than that of the wild­type virus. In conclusion, the replication capacity of HBV with the TA mutation was increased, and the mutation was associated with a reduction in serum HBeAg levels. This mutant strain remained sensitive to ETV and TDF, and HNF4 supported a higher replication level of TA mutant HBV in vivo.

Prolonged Combination Therapy is More Effective than Monotherapy in Management of Chronic Hepatitis B Patients With Sustained Virological Response: An Experience From a 'Real-World' Clinical Setting.

BACKGROUND: Little is known about the duration of combination therapy for patients with chronic hepatitis B (CHB) and suboptimal response to nucleos(t)ide analogues(NAs) monotherapy. OBJECTIVES: This study aimed to assess whether monotherapy could be used for treatment of CHB patients, who poorly responded to Adefovir Dipivoxil (ADV) but obtained good responses after at least 12-month lamivudine (LAM) or telbivudine (LdT) add-on therapy. PATIENTS AND METHODS: Forty-five patients were enrolled, and the baseline time-point was determined according to enrollment data. Twenty-six patients chose to continue combination therapy (LAM+ADV or LdT+ADV, Group A) and 19 patients switched to single-drug maintenance therapy (LAM or LdT or ADV, Group B). RESULTS: There were no significant differences between two groups in baseline characteristics (P > 0.05). At 12th month, sustained virological response rate was greater in group A compared to group B (96.2% vs. 47.4%, P < 0.001), and the rates of NAs-associated resistance were 0% in group A and 15.8% in group B. Alanine aminotransferase normalization rate was also significantly higher in group A compared with group B (92.3% vs. 36.8%, P < 0.001). Among hepatitis positive patients with Be antigen (HBeAg)-, 40% (4/10) in group A and 9.1% (1/11) in group B achieved HBeAg seroconversion at the 12th month. Of patients in group B with positive-HBeAg before the previous combination therapy and detectable HBV DNA at 6 months of previous combination therapy were associated with high risks of viral relapse after switching to single-drug maintenance therapy. CONCLUSIONS: Prematurely switching to single-drug maintenance therapy would be resulted in viral relapse, and prolonged combination therapy was effective to maintain sustained responses for patients with initial suboptimal response to ADV.

Treatment of HCV patients before and after renal transplantation.

CONTEXT: Patients with end-stage renal disease can easily acquire a hepatitis C virus (HCV) infection via several ways. An HCV infection is difficult to treat after renal transplantation due to the conflicting actions of immunosuppressant therapy to maintain the function of the transplanted kidney and viricidal interferon (IFN) or ribavirin (RBV) treatment. Antiviral therapy requires great caution to avoid the complex and potentially fatal pharmacological effects. In this review, we examined clinical challenges and potential solutions for this specific scenario. EVIDENCE ACQUISITIONS: We searched Pubmed (NLM), LISTA (EBSCO), Web of Science (TS). The management of patients on waiting list, the indications and regimens about treatment were studied. RESULTS: More than forty papers about this topic were found, including seven small clinical trials. International consensus has been reached to test patients awaiting renal transplantation. HCV detection after renal transplantation warrants careful consideration of when to initiate antiviral therapy. Treatment will begin immediately if deteriorating liver function increases the risk for loss of renal function. The choice of regimen depends on the patient's renal function and is individualized under close observation. The immunosuppressive regimen will be adjusted accordingly before antiviral therapy is initiated. CONCLUSIONS: The effects of modified antiviral therapy on these patients varies because of individual characteristics and disease state, and also because of the difficulty associated with conducting a large clinical trial to obtain statistically sound conclusions. The management before transplantation is important and when antiviral therapy needs to start, careful consideration of risks and benefits is needed before initiating this type of treatment.