Chinese guidelines on the management of ascites in cirrhosis : Chinese Society of Hepatology, Chinese Medical Association.

In 2023, Chinese Society of Hepatology of Chinese Medical Association convened a panel of experts to update the Chinese guidelines on the management of ascites and associated complications in cirrhosis which was launched in 2017 and renamed this guidelines as "Guidelines on the Management of Ascites in Cirrhosis." This comprehensive resource offers essential recommendations for the diagnosis and treatment of cirrhotic ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome.

SEU2-Net: multi-scale U2-Net with SE attention mechanism for liver occupying lesion CT image segmentation.

Liver occupying lesions can profoundly impact an individual's health and well-being. To assist physicians in the diagnosis and treatment of abnormal areas in the liver, we propose a novel network named SEU2-Net by introducing the channel attention mechanism into U2-Net for accurate and automatic liver occupying lesion segmentation. We design the Residual U-block with Squeeze-and-Excitation (SE-RSU), which is to add the Squeeze-and-Excitation (SE) attention mechanism at the residual connections of the Residual U-blocks (RSU, the component unit of U2-Net). SEU2-Net not only retains the advantages of U2-Net in capturing contextual information at multiple scales, but can also adaptively recalibrate channel feature responses to emphasize useful feature information according to the channel attention mechanism. In addition, we present a new abdominal CT dataset for liver occupying lesion segmentation from Peking University First Hospital's clinical data (PUFH dataset). We evaluate the proposed method and compare it with eight deep learning networks on the PUFH and the Liver Tumor Segmentation Challenge (LiTS) datasets. The experimental results show that SEU2-Net has state-of-the-art performance and good robustness in liver occupying lesions segmentation.

A dataset of low-carbon energy transition index for Chinese cities 2003-2019.

Cities are at the heart of climate change mitigation as they account for over 70% of global carbon emissions. However, cities vary in their energy systems and socioeconomic capacities to transition to renewable energy. To address this heterogeneity, this study proposes an Energy Transition Index (ETI) specifically designed for cities, and applies it to track the progress of energy transition in Chinese cities. The city-level ETI framework is based on the national ETI developed by the World Economic Forum (WEF) and comprises two sub-indexes: the Energy System Performance sub-index, which evaluates the current status of cities' energy systems in terms of energy transition, and the Transition Readiness sub-index, which assesses their socioeconomic capacity for future energy transition. The initial version of the dataset includes ETI and its sub-indexes for 282 Chinese cities from 2003 to 2019, with annual updates planned. The spatiotemporal data provided by the dataset facilitates research into the energy transition roadmap for different cities, which can help China achieve its energy transition goals.

Histopathological Features Predicting Long-term Clinical Outcomes in Patients with Vanishing Bile Duct Syndrome.

Background and Aims: The clinicopathological features and long-term outcomes of patients with vanishing bile duct syndrome (VBDS) have yet to be elucidated. The study aims to investigate these features and identify factors associated with poor prognosis. Methods: This multicenter retrospective study recruited patients with liver biopsy-proven VBDS who were followed up at five hospitals in northern China from January 2003 to April 2022. Clinical and pathological data at time of biopsy were reviewed. Clinical outcomes including cirrhosis, decompensation events, liver transplantation (LT), and liver-related death were recorded. Cox regression analysis was used to identify the risk factors associated with poor outcomes. Results: A total of 183 patients were included. The median age was 47 years, with 77.6% being women. During a median follow-up of 4.8 years, 88 patients developed compensated or decompensated cirrhosis, 27 died, and 15 received LT. Multivariate Cox regression analysis showed that hepatocellular cholestasis (HR 2.953, 95% CI: 1.437-6.069), foam cells (HR 2.349, 95% CI: 1.092-5.053), and advanced fibrosis (HR 2.524, 95% CI: 1.313-4.851) were independent predictors of LT or liver-related deaths. A nomogram formulated with the above factors showed good consistency with a concordance index of 0.746 (95% CI: 0.706-0.785). Conclusions: Nearly half of VBDS patients studied progressed to end-stage liver disease and 23% of them had LT or liver-related death within two years of diagnosis. Hepatocellular cholestasis, foam cells and advanced fibrosis rather than the degree of bile duct loss or underlying etiologies were independently associated with poor prognosis in VBDS patients.

Boosting photocatalytic synchronous production of H2 coupled with acetone over Co doped Cu3P quantum dots/ZnIn2S4 nanosheets p-n nanojunction.

Photocatalysis provides a new way for synchronous H2 production and organic synthesis at normal temperature and pressure, usually, water and organic substrate function as sources of hydrogen protons and organic products, which are complex and limited by two half-reactions. Employing alcohols as reaction substrates to simultaneously produce H2 and valuable organics in a redox cycle is worthy studying, to which catalyst design at atomic level holds the key. In this paper, Co elements doped Cu3P (CoCuP) quantum dots (QDs) are prepared and coupled with ZnIn2S4 (ZIS) nanosheets to form a 0D/2D p-n nanojunction which can effectively boost aliphatic and aromatic alcohols activation to simultaneously produce H2 and corresponding ketones (or aldehydes). The optimal CoCuP/ZIS composite demonstrated the highest activity for dehydrogenation of isopropanol to acetone (17.77 mmol⋅g-1⋅h-1) and H2 (26.8 mmol⋅g-1⋅h-1), which was 2.40 and 1.63 times higher than that of Cu3P/ZIS composite, respectively. Mechanistic investigations revealed that such high-performance originated from the accelerated electron transfer of the formed p-n junction and the thermodynamic optimization caused by the Co dopant which was the active site of oxydehydrogenation as a prerequisite step for isopropanol oxidation over the surface of the CoCuP/ZIS composite. Besides that, coupling of the CoCuP QDs can lower the dehydrogenation activation energy of isopropanol to form a key radical intermediate of (CH3)2CHO* for improving the activity of simultaneous production of H2 and acetone. This strategy provides an overall reaction strategy to obtain two meaningful products (H2 and ketones (or aldehydes)) and deeply explores the integrated redox reaction of alcohol as substrate for high solar-chemical energy conversion.

A case report of hepatitis B virus reactivation 19 months after cessation of chemotherapy with rituximab.

A 72-year-old woman presented to our hospital with elevation of serum transaminases. Her blood tests showed the hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) negative. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were given for the diffuse large B-cell lymphoma. She didn't receive anti- hepatitis B virus (HBV) drug for the isolated HBcAb positive. HBV reactivation confirmed based on the serum HBV DNA detectable until 19 months after stopping R-CHOP regimen. HBV DNA became undetectable after 4 weeks therapy with Tenofovir alafenamide fumarate (TAF). Serum transaminases went down to normal 3 months later after receiving TAF. HBV reactivation is a substantial risk for patients with isolated HBcAb positive receiving rituximab-containing chemotherapy without anti- HBV drug. Regular monitoring with a frequency of 1-3 months is the basis for timely diagnosis and treatment of HBV reactivation. Serum transaminases abnormalities may be the initial manifestation of HBV reactivation.

Exploration of immune infiltration and feature genes in viral hepatitis-associated liver fibrosis using transcriptome data.

Background: Immune cells play an essential role in virus-induced liver fibrosis. However, the underlying mechanisms remain unclear. In this study, we systematically explored immune cell infiltration and feature genes to provide new insights into viral hepatitis-associated liver fibrosis. Methods: The expression datasets GSE14323, GSE33650, GSE6764 (for testing), and GSE84044 (for validation) were downloaded from the Gene Expression Omnibus (GEO) database. Immune cell infiltration was assessed using the CIBERSORT algorithm, and characteristic subgroups were obtained using least absolute shrinkage and selection operator (LASSO) regression and Wilcoxon test. The association between feature genes and immune-infiltrating cells was explored using Spearman's correlation analysis. R software and IBM SPSS Statistics were utilized for data analysis and visualization. Results: We identified 10 differential immune cells between viral hepatitis-associated liver fibrosis and non-fibrosis, including naive B cells, plasma cells, resting CD4+ memory T cells, T follicular helper (Tfh) cells, regulatory T (Treg) cells, M0-M2 macrophages, and resting and activated mast cells. Six feature genes were identified: STAT1, CXCL10, PTPRC, IFIT3, OAS2, and MX1. They also differed significantly in the subgroups of non-fibrosis, mild to moderate fibrosis and severe fibrosis. Both the feature genes and immune cells were verified in the validation group. All the genes were positively associated with macrophages M1 and negatively associated with macrophages M2. Conclusions: The six feature genes may be involved in viral hepatitis-associated liver fibrosis by promoting the polarization of macrophages from M0 to M1 and inhibiting their conversion to M2. Thus, these genes may serve as potential therapeutic targets.

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.

Dimensional-matched two dimensional/two dimensional TiO2/Bi2O3 step-scheme heterojunction for boosted photocatalytic performance of sterilization and water splitting.

A Step-scheme (S-scheme) heterojunction can regulate the directional migration of powerful photogenerated carriers and realize high photocatalytic activity. Herein, we propose a novel dimensional matched S-scheme photocatalyst comprising of two-dimensional (2D) TiO2 nanosheets and 2D Bi2O3 nanosheets for environmental and energy applications, such as water sterilization and water splitting. X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance, in-situ irradiated XPS and theoretical calculations provided strong evidence that the photocarrier migration in the TiO2/Bi2O3 composite followed the S-scheme mode, which efficiently prevented the recombination of powerful photocarriers, thereby enabling the heterojunction with a strong redox ability for producing abundant reactive oxygen species. The tight and large 2D/2D interface minimized the distance of photocarrier migration to further extend the lifetime of useful photocarriers (active radicals for sterilization and photoelectrons for H2 generation). The 2D/2D TiO2/Bi2O3 heterojunction demonstrated an improved photocatalytic antibacterial performance with complete inactivation of 4.63 × 107 CFU mL-1Escherichia coli cells within 6 h in water. In addition, the heterojunction displayed a H2 generation rate of 12.08 mmol h-1g-1 through water splitting process. This study provides a potential bifunctional photocatalyst for minimizing the adverse impact of pollution on the environment.

A Multicenter Real-World Study Evaluating the Hepatoprotective Effect of Polyene Phosphatidylcholine Against Chronic Hepatitis B.

Background: Polyene phosphatidylcholine (PPC) has been widely used to treat liver diseases in China. However, there is a lack of post-marketing evidence demonstrating its liver-protective efficiency among patients infected with hepatitis B virus (HBV). This study analyzed the multicenter real-world data to compare the effectiveness of PPC with those of magnesium isoglycyrrhizinate (IsoMag) and glutathione (GSH) in patients with liver injury. Methods: This study comprised the real-world data analysis of a multicenter, retrospective observational cohort. The data were retrieved from the Cooperative Registry of the Hospital Prescription in China between 1 October 2018, and 30 September 2019. A growth curve analysis was performed to compare the effects of different treatments on liver function longitudinally for up to 30 days after treatment commencement. In addition, the dose effect of the PPC treatment was investigated. Results: The final cohort included 6,052 patients with approximately 8% infected with HBV (N = 471). There were 1,649, 1,750, and 2,653 patients in the PPC, GSH, and IsoMag groups, respectively, with an average age of 53.9 years. In patients with HBV infection, the PPC treatment was associated with a significant decline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (slopes: -3.7, 95% CI, -6.0 to -1.5 U/L/day; -2.4, 95% CI, -4.5 to -0.3 U/L/day, respectively). However, there were no significant differences in the effects among the three groups. In patients without HBV infection, the PPC treatment decreased ALT, AST, γ-glutamyl transferase (GGT), and albumin levels (-5.2, 95% CI, -5.8 to -4.5 U/L/day; -3.5, 95% CI, -4.2 to -2.7 U/L/day; -4.9, 95% CI, -6.2 to -3.7 U/L/day, -0.07, 95% CI, -0.09 to -0.04 g/L/day, respectively) and showed a stronger effect on lowering ALT levels than GSH (-2.6, 95% CI, -3.3 to -1.8 U/L/day, p < 0.05), as well as a stronger effect on lowering GGT levels than IsoMag (-1.4, 95% CI, -2.4 to -0.4 U/L/day, p < 0.05). PPC had no impact on prothrombin activity levels in patients with or without HBV infection. High-dose PPC exhibited a stronger effect on lowering ALT and AST levels than low-dose PPC. Conclusion: This was the first real-world multicenter study to demonstrate that PPC efficiently lowers ALT and AST levels in patients with liver diseases regardless of the status of HBV infection. PPC treatment showed a comparable or better effect compared with GSH and IsoMag treatments. High-dose PPC resulted in a stronger effect than low-dose PPC.

T-Cell Receptor ß Chain and B-Cell Receptor Repertoires in Chronic Hepatitis B Patients with Coexisting HBsAg and Anti-HBs.

Antibodies in response to antigens are related to the immune repertoire of T- and B-cell receptors. However, some patients with chronic hepatitis B (CHB) have coexisting HBsAg and anti-HBsAg antibodies (anti-HBs) that cannot neutralize HBV. We attempted to investigate the repertoires that produce this response in CHB patients. The T-cell receptor ß chain (TRB) and B-cell receptor (BCR) repertoires of peripheral blood genomic DNA were analyzed using MiXCR. T-cell receptor (TCR) cluster analysis was carried out by clusTCR, and motifs prediction was selected by Multiple Em for Motif Elicitation (MEME). A total of 76 subjects were enrolled, including 26 HBsAg and anti-HBs coexisting patients with CHB (DP group), 25 anti-HBs single-positive healthy people (SP group), and 25 CHB patients (CHB group). The clone length of BCR in 39, 90 was significantly different among these groups (p = 0.005, 0.036). The motif "CASSLG" in the DP group was significantly higher than SP and CHB groups and may relate to coexistence, and the motif "GAGPLT" was only shown in the SP group and may relate to anti-HB expression. These provide important insights into vaccine development and CHB treatment.

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.

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.

Dynamics of Hepatitis B Virus Pregenomic RNA in Chronic Hepatitis B Patients With Antiviral Therapy Over 9 Years.

Serum hepatitis B virus pregenomic RNA (HBV pgRNA) is a potential biomarker that is correlated with covalently closed circular DNA. The long-term dynamics of HBV pgRNA in patients with chronic hepatitis B need to be explored. One hundred naïve nucleos(t)ide analog-treated patients with chronic hepatitis B were enrolled to analyze the dynamics of HBV pgRNA over 9 years. The positive rates of HBV pgRNAs declined gradually and showed biphasic kinetics. Serum HBV pgRNA levels in patients treated with entecavir became negative later than those treated with adefovir or lamivudine. Patients who remain positive for HBV pgRNA after 9 years of treatment may have higher viral transcription efficiencies. The reverse transcription efficiency of hepatitis B e-antigen (HBeAg)-positive patients was higher than that of HBeAg-negative patients at baseline and showed no difference after 24-week nucleos(t)ide analog treatment. The trajectory of serum HBV pgRNA-negative transformation differs in patients with different characteristics. Long-term dynamic monitoring of serum HBV pgRNA levels has significance in hepatitis B treatment.

Evaluation of the association of a variant in PNPLA3 and TM6SF2 with fibrosis progression in patients with chronic hepatitis C infection after eradication: A retrospective study.

The relationship of single nucleotide polymorphisms (SNPs) in patatin-like phospholipase domain containing 3 (PNPLA3) rs738409, transmembrane 6 superfamily member 2 (TM6SF2) rs58542926, and membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs641738 with outcomes in patients with hepatitis C infection (HCV) is unclear. This study aimed to evaluate the association of PNPLA3, TM6SF2, and MBOAT7 with the baseline fibrosis stage and progression of liver fibrosis after HCV eradication with direct antiviral agents (DAAs). A total of 171 patients who received the DAAs at the Peking University First Hospital between June 2015 and June 2020 were included in the retrospective cohort. Transient elastography was used to determine liver stiffness measurements (LSMs) at the baseline, the end of treatment (EOT), 24 weeks after treatment (W24), and the last follow-up (LFU) visit. We used the QIAamp Blood Mini Kit (Qiagen) for whole blood genomic DNA extraction and polymerase chain reaction for PNPLA3, TM6SF2, and MBOAT7 amplification of the target gene. The PNPLA3 rs738409 SNP was associated with the baseline fibrosis stage in multivariate logistic regression analysis adjusted for other factors, and the adjusted odds ratio (OR) for advanced fibrosis (≥F3) at baseline was 2.52 (95% confidence interval[CI] = 1.096-5.794, p = 0.03). The G and GG alleles were predictive of advanced fibrosis (OR = 1.98, 95% CI = 1.021-4.196, p = 0.015; OR = 3.12, 95% CI = 1.572-6.536, p = 0.005). Similarly, the OR of TM6SF2 rs58542926 at baseline was 2.608 (95% CI = 1.081-6.29, p = 0.033). T and TT alleles were predictive of advanced fibrosis (OR = 2.3, 95% CI = 1.005-5.98, p = 0.007; OR = 3.05, 95% CI = 1.32-6.87, p = 0.001). After adjustment, the MBOAT7 rs641738 T plus TT alleles were not independently associated with the baseline fibrosis stage (95% CI = 0.707-2.959, p = 0.312). At the EOT, there were 35 patients and 136 patients in the fibrosis improvement and fibrosis non-improvement group, respectively. Logistic regression analysis showed that the G allele in PNPLA3 rs738409 was associated with fibrosis progression (OR = 2.47, 95% CI = 1.125-5.89, p = 0.003). The GG alleles were predictive of fibrosis progression (OR = 2.95, 95% CI = 1.35-6.35, p = 0.005). Similarly, the ORs of the T and TT alleles in TM6SF2 rs58542926 for fibrosis progression were 1.82 and 2.21, respectively (95% CI = 1.006-5.373, p = 0.045; 95% CI = 1.18-5.75, p = 0.01). At the W24 visit, we found that there was an association between the G allele in PNPLA3 rs738409 and fibrosis progression (OR = 2.218, 95% CI = 1.095-5.631, p = 0.015). Moreover, GG alleles were also predictive for fibrosis progression (OR = 2.558, 95% CI = 1.252-5.15, p = 0.008). Similarly, the OR of T allele and TT alleles in TM6SF2 rs58542926 for fibrosis progression was 2.056 and 2.652 (95% CI = 1.013-5.592, p = 0.038; 95% CI = 1.25-5.956, p = 0.015). For additional affirmation, we surveyed fibrosis progression utilizing the Cox proportional hazards model. G and GG alleles in PNPLA3 rs738409 were associated with an increased risk of progression to advanced fibrosis in multivariate model (hazard ratio [HR]1.566, 95% CI = 1.02-2.575, p = 0.017; and HR2.109, 95% CI = 1.36-3.271, p = 0.001, respectively). Besides, T and TT alleles in TM6SF2 rs58542926 were associated with an increased risk of progression to advanced fibrosis in multivariate model (HR = 1.322, 95% CI = 1.003-1.857, p = 0.045; and HR = 1.855, 95% CI = 1.35-2.765, p = 0.006, respectively). In contrast, rs641738 in MBOAT7 did not show a significant trend in the univariate and multivariate models. The PNPLA3 CG/GG SNP at rs738409 and TM6SF2 CT/TT SNP at rs58542926 were associated with the baseline fibrosis stage and fibrosis progression after HCV eradication with DAAs.

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.

Predictive Nomograms for Clinical Outcomes in Hepatitis B-Related Cirrhosis Patients Receiving Antiviral Therapy.

OBJECTIVE: Many scores have been constructed to predict liver-related events in chronic hepatitis B, while most of them are based on baseline clinical parameters. The objective of this study was to develop nomograms based on on-treatment improvement in established scores to predict clinical outcomes in patients with hepatitis B virus (HBV)-related cirrhosis who are receiving antiviral therapy. METHODS: The Cox proportional hazards regression model was used. Nomograms were constructed for the prediction of liver-related events, hepatocellular carcinoma (HCC), and liver-related mortality risk during long-term antiviral therapy. RESULTS: A total of 277 treatment-naive patients with HBV-associated cirrhosis were enrolled from January 2010 to December 2013. After a median follow-up of 63.3 months, 95 patients developed liver-related events, including 59 patients with liver-related death. Multivariate Cox analysis showed that the albumin-bilirubin score at year 1 was an independent predictor of liver-related events, liver-related mortality, and HCC. Age, decompensation, and delayed virological remission were independent factors for liver-related mortality. Age was also a risk factor for liver-related events. The concordance index values of event-nomogram, mortality-nomogram, and HCC-nomogram were 0.742 (95% confidence interval [CI], 0.691~0.793), 0.799 (95% CI, 0.748~0.850), and 0.613 (95% CI, 0.540~0.686), respectively. The calibration plots showed an agreement between the predicted and observed incidences, which indicates good calibration of the model of event-nomogram and mortality-nomogram. CONCLUSION: The nomograms achieved an optimal preoperative prediction of liver-related events, mortality, and HCC development in patients with HBV-related cirrhosis receiving antiviral therapy. These findings may help to identify high-risk patients for further optimal surveillance and intervention strategies.

Clinical Aspects of Gut Microbiota in Hepatocellular Carcinoma Management.

Liver cancer, predominantly hepatocellular carcinoma (HCC), is the third leading cause of cancer-related deaths worldwide. Emerging data highlight the importance of gut homeostasis in the pathogenesis of HCC. Clinical and translational studies revealed the patterns of dysbiosis in HCC patients and their potential role for HCC diagnosis. Research on underlying mechanisms of dysbiosis in HCC development pointed out the direction for improving the treatment and prevention. Despite missing clinical studies, animal models showed that modulation of the gut microbiota by probiotics may become a new way to treat or prevent HCC development.

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.

Direct antiviral agent treatment leads to rapid and significant fibrosis regression after HCV eradication.

Limited data are currently available regarding fibrosis progression after hepatitis C virus (HCV) eradication. The goal of the present study was to evaluate the effects of HCV eradication on liver stiffness measurements (LSMs), aspartate aminotransferase/platelet ratio index (APRI) scores, fibrosis-4(FIB-4) scores, chitinase-3-like protein 1 (CHI3L1) levels and Golgi protein 73 (GP73) levels in patients with chronic hepatitis C (CHC). One hundred and two patients who received direct antiviral agents (DAAs) therapy at Peking University First Hospital participated in the present study. Clinical information and serum samples were collected at baseline, at the end of treatment (EOT), and at the weeks 12, 24 and 48 after treatment (W12, W24 and W48, respectively). Of the 102 patients, 51 had mild-to-moderate fibrosis (F1/F2), and 51 had advanced fibrosis (F3/F4). The LSMs improved for all patients at the EOT, with observed changes of 2.85 kPa, and the decrease continued to W12. However, a more pronounced improvement was noted for the advanced fibrosis (F3/F4) patients, with a change of 3.6 kPa from baseline to the EOT. Significant decreases between the baseline and EOT measurements were observed in the APRI and FIB-4 scores [0.64 (0.39-1.21) vs. 0.35 (0.26-0.52), p<0.001; 2.53 (1.30-3.91) vs. 1.87 (0.89-2.5), p<0.001], after which the values decreased until W12, with no significant difference observed. Serum CHI3L1 and GP73 levels were profoundly decreased at the EOT compared with those at baseline [134.07 (154.49) vs. 103.75 (98.04), p=0.025; 98.24 (64.76) vs. 88.91 (50.89), p=0.002]. DAA treatments could significantly improve liver fibrosis of CHC patients as evidenced by decreased liver stiffness, APRI scores and FIB-4 scores. Improvements in liver fibrosis markers (especially serum CHI3L1 and GP73) were prominent in patients with advanced fibrosis, indicating that serum CHI3L1 and GP73 could be noninvasive markers for monitoring fibrosis in CHC patients. Significance Statement The prospective cohort evaluated the effect of direct antiviral agents (DAAs) on fibrosis regression after hepatitis C virus (HCV) eradication of Chinese people in the real-world study. This study highlighted that rapid and significant fibrosis regression rather than reduction in inflammation was achieved with DAA treatment, and this regression could be detected as early as the end of treatment. We found the serum CHI3L1 and GP73 levels can be used to monitor changes in fibrosis in CHC patients.