The effects of low-dose IL-2 on Th17/Treg cell imbalance in primary biliary cholangitis mouse models.

BACKGROUND/AIMS: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The imbalance of Th17/Treg cells has been reported in PBC patients. Low-dose IL-2 can alleviate disease severity through modulating CD4 + T cell subsets in patients with autoimmune diseases. Hence, the present study aimed to examine the effects and mechanism of low-dose IL-2 in PBC mouse models. METHODS: PBC models were induced in female C57BL/6 mice by two immunizations with 2OA-BSA at two-week intervals, and poly I: C every three days. PBC mouse models were divided into the IL-2 treated and untreated groups and low-dose IL-2 was injected at three different time points. Th17 and Tregs were analyzed by flow cytometry, and the related cytokines were analyzed by ELISA. Liver histopathology was examined by H&E and immunohistochemical staining. RESULTS: Twelve weeks after modeling, the serum AMA was positive and the ALP was significantly increased in PBC mouse models (P<0.05). The pathology showed lymphocyte infiltration in the portal area, damage, and reactive proliferation of the small bile duct (P<0.05). The flow cytometric showed the imbalance of Th17/Treg cells in the liver of PBC mouse models, with decreased Treg cells, increased Th17 cells, and Th17/Treg ratio (P < 0.05). After the low-dose IL-2 intervention, biochemical index and liver pathologies showed improvement at 12 weeks. Besides, the imbalance of Th17 and Treg cells recovered. Public database mining showed that Th17 cell differentiation may contribute to poor response in PBC patients. CONCLUSION: Low-dose IL-2 can significantly improve liver biochemistry and pathology by reversing the imbalance of Th17 and Treg cells, suggesting that it may be a potential therapeutic target for PBC.

HBV pregenome RNA as a predictor of spontanous HBeAg seroconversion in HBeAg-positive chronic hepatitis B patients.

BACKGROUND: Previous studies have indicated that HBV pregenome RNA (HBV pgRNA) could predict HBeAg seroconversion among the chronic hapatitis B (CHB) patients treated with pegylated interferon (Peg-IFN) or nucleos(t)ide analogues (NAs). However, the data about the prediction of HBV pgRNA for spontaneous HBeAg seroconversion is limited. METHODS: One hundred thirteen CHB patients with HBeAg-positive in the immune active phase were followed up for 76 weeks without antiviral treatment. Based on the laboratory test results of liver function, HBeAg, anti-HBe, and HBV DNA at week 76, patients were assigned to two groups: spontaneous HBeAg seroconversion (group A, n = 18) and non-spontaneous HBeAg seroconversion group. Among the latter group, 36 patients were selected as controls (group B, n = 36). RESULTS: At week 12, between group A and group B, there was a significant difference in the level of HBV pgRNA (group A 6.35 ± 1.24 log10 copies/ml and group B 7.52 ± 0.79 log10 copies/ml, P = 0.001), and the difference enlarged at week 28. The receiver operating characteristic curves (AUROCs) of the HBV pgRNA level and the ∆HBV pgRNA at week 28 were 0.912 (P = 0.001, 95% CI: 0.830-0.994), and 0.934 (P = 0.001, 95% CI: 0.872-0.996), respectively. The optimal cutoffs of HBV pgRNA and the reduction from baseline (∆HBV pgRNA) at week 28 for spontaneous HBeAg seroconversion prediction were 5.63 log10 copies/ml and 1.85 log10 copies/ml, respectively. The positive predictive value and negative predictive value of HBV pgRNA and ∆HBV pgRNA at week 28 were 86.7% and 87.2%, 87.5% and 89.5%, respectively. And the combination of the HBV pgRNA level and the HBV pgRNA decreased could provide better prediction. CONCLUSIONS: HBV pgRNA is a sound predictor for spontaneous HBeAg seroconversion among the CHB patients in immune active phase. Dynamic monitoring of HBV pgRNA is helpful for clinical treatment decision.

Lower end of treatment HBsAg and HBcrAg were associated with HBsAg loss after nucleos(t)ide analog cessation.

BACKGROUND: Since hepatitis B surface antigen (HBsAg) loss is rarely achieved with nucleos(t)ide analog (NA) treatment, most patients require life-long NA treatment. Previous studies have shown that some patients remain virologically responsive even after NA cessation. However, there is still controversy surrounding whether NA discontinuation increases the HBsAg loss rate. Therefore, this study aimed to assess the cumulative rate of HBsAg loss and identify the predictors of HBsAg loss after NA discontinuation. METHODS: This multicenter prospective study included HBV e antigen (HBeAg)-positive patients without cirrhosis from 12 hospitals in China who met the inclusion criteria. The enrolled patients stopped NA and were followed up with clinical and laboratory assessments every 3 months for 24 months after NA cessation or until clinical relapse (CR) occurred. RESULTS: Overall, 158 patients were classified into two groups. Group A included patients with HBsAg positivity at NA cessation (n = 139), and Group B included patients with HBsAg negativity at NA cessation (n = 19). In Group A, the 12-month and 24-month cumulative rates of HBsAg loss were4.3%and 9.4%, respectively. End of treatment (EOT) HBsAg (hazard ratio (HR) = 0.152, P < 0.001) and EOT hepatitis B core-related antigen (HBcrAg) (HR = 0.257, P = 0.001) were associated with HBsAg loss. The areas under the receiver operating characteristic curves for EOT HBsAg and HBcrAg levels were 0.952 (P < 0.001) and 0.765 (P < 0.001), respectively. Patients with EOT HBsAg ≤ 135 IU/mL (59.2% vs. 1.3%, P < 0.001) or HBcrAg ≤ 3.6 logU/mL (17% vs. 5.4%, P = 0.027) had a higher 24-month cumulative HBsAg loss rate. In Group B, none of the patients experienced virological relapse after NA cessation. Only 1 (5.3%) patient had HBsAg reversion. CONCLUSIONS: EOT HBsAg ≤ 135 IU/mL or HBcrAg ≤ 3.6 logU/mL can be used to identify patients with a higher likelihood of HBsAg loss after NA cessation. Patients with HBsAg negativity after NA cessation have favorable clinical outcomes, and HBsAg loss was durable in most cases.

IP10 and Anti-HBc can Predict Virological Relapse and HBsAg Loss in Chronic Hepatitis B Patients after Nucleos(t)ide Analog Discontinuation.

INTRODUCTION: To assess predictive ability of serum interferon-inducible protein 10 (IP10) and hepatitis B core antibody (anti-HBc) levels for virological relapse (VR) and hepatitis B surface antigen (HBsAg) loss after nucleos(t)ide analog (NA) discontinuation. METHODS: In this multicenter prospective study, overall 139 patients were followed up for 24 months after NA discontinuation. RESULTS: End of treatment (EOT) IP10 and anti-HBc were 29.2 (5.1-66.4) pg/mL and 193.6 (136.9-221.4) IU/mL. EOT IP10 and anti-HBc were independent predictors for VR and HBsAg loss in Cox regression analysis. Cumulative rates of VR in patients with EOT IP10 > 26.99 pg/mL was 31.9% (vs. 70.1%, hazard ratio [HR] 2.998, p < 0.001). Cumulative incidences of VR in patients with EOT anti-HBc ≤141.35 IU/mL was 49.1% (vs. 60.6%, HR 2.99, p < 0.001). Cumulative probabilities of VR was 16.7% in patients with EOT IP10 > 26.99 pg/mL plus anti-HBc ≤141.35 IU/mL (vs. 73.6%, HR 6.464, p < 0.001). Cumulative probabilities of HBsAg loss in patients with EOT IP10 > 93.5 pg/mL was 46.2% (vs. 4.7%, HR 10.94, p < 0.001). Cumulative probabilities of HBsAg loss in patients with EOT anti-HBc ≤78.42 IU/mL were 47.1% (vs. 5%, HR 12.27, p < 0.001). Patients with EOT IP10 > 93.5 pg/mL plus anti-HBc ≤78.42 IU/mL had the highest 24-month cumulative HBsAg loss rate (53.8% vs. 4%, HR 16.83, p < 0.001). CONCLUSION: High EOT IP10 and low EOT anti-HBc levels were related to both lower risk of VR and higher probability of HBsAg loss.

Recombinant human thrombopoietin increases platelet count in severe thrombocytopenic patients with hepatitis B-related cirrhosis: Multicentre real-world observational study.

Patients with hepatitis B-related cirrhosis complicated with thrombocytopenia have a higher risk of bleeding, which may lead to higher mortality. We aimed to explore the efficacy and safety of recombinant human thrombopoietin (rhTPO) in the treatment of hepatitis B-related cirrhosis complicated with severe thrombocytopenia. Patients with hepatitis B-related compensated liver cirrhosis complicated with severe thrombocytopenia were divided into four groups according to the treatment method for thrombocytopenia. Platelet counts, the appearance of bleeding symptoms and adverse events were evaluated during the observation period. Also during the observational period, the platelet counts in the prednisone group, rhTPO group and prednisone plus rhTPO group were higher than those in the no treatment group. Patients without splenomegaly reacted better to rhTPO. Fewer bleeding events of grade 2 or worse were observed in the three treatment groups compared to the no treatment group. The platelet counts at baseline and treatment with rhTPO and/or prednisone were factors associated with bleeding events of grade 2 or worse in multivariate analysis. There could be a potential advantage for the use of rhTPO plus prednisone based on higher platelet counts and fewer bleeding events. Treatment with rhTPO was more effective in patients without splenomegaly.

Combining the HBcrAg decline and HBV mutations predicts spontaneous HBeAg seroconversion in chronic hepatitis B patients during the immune clearance phase.

To assess predictive ability of hepatitis B virus (HBV) markers and genome mutations for spontaneous hepatitis B e antigen (HBeAg) seroconversion. A total of 113 chronic hepatitis B (CHB) patients were followed up for 76 weeks without antiviral treatment. Baseline basal core promoter (BCP) and precore mutations were detected and serum hepatitis B surface antigen (HBsAg), HBeAg, hepatitis B core-related antigen (HBcrAg), and HBV DNA levels were serially quantified. Eighteen patients experienced spontaneous HBeAg seroconversion (Group A), and the remaining 95 patients did not experience spontaneous HBeAg seroconversion (Group B). At Week 28, HBsAg (p = 0.03) and HBcrAg (p = 0.01) levels were significantly different between Groups A and B. Reduced HBsAg (p = 0.02) and HBcrAg (p < 0.01) levels from baseline to Week 28 were significantly different between two groups. Multivariate logistic regression showed that lower HBcrAg (odds ratio [OR] = 1.02, p = 0.03) levels at Week 28, and HBcrAg levels with sharp decrease at Week 28 (OR = 0.19, p = 0.02) were related with spontaneous HBeAg seroconversion. The areas under the receiver operating characteristic curve (AUROC) showed that reduction in HBcrAg levels from baseline to Week 28 (0.93, p = 0.001, 95% CI: 0.74-1.08) have excellent prediction value. The mutation frequencies of A1574T (51.11% vs. 18.18%, p = 0.001), G1862A (30.00% vs. 13.03%, p = 0.001), G1896A (27.22% vs. 5.45%, p = 0.001), and C1913G (32.78% vs. 12.73%, p = 0.001) in Group A were significantly higher than Group B. Baseline A1574T, G1862A, G1896A, and C1913G mutations and HBcrAg levels with a sharp decrease at Week 28 were associated with spontaneous HBeAg seroconversion.

Hepatitis E virus infection after haploidentical haematopoietic stem cell transplantation: incidence and clinical course.

Hepatitis E virus (HEV) is increasingly found to cause hepatitis in allogeneic haematopoietic stem cell transplantation (HSCT) patients. However, little is known about HEV infection in patients receiving haploidentical HSCT (haplo-HSCT). Here, we retrospectively evaluate the incidence and clinical course of HEV infection in haplo-HSCT patients. From January 2014 to July 2017, 177 patients with unexplained elevated transaminases after receiving haplo-HSCT at Peking University Institute of Haematology were screened for HEV using HEV serology. HEV RNA was assessed in blood samples when HEV-IgG and/or IgM antibodies were positive. Acute HEV infection was identified in 7 patients (3·9%), 1 of whom had developed a chronic HEV infection. The median time from haplo-HSCT to HEV infection was 17·5 (range, 6-55) months. HEV infection was confirmed by the presentation of anti-HEV IgM + anti-HEV IgG (rising) (n = 5) or HEV-RNA + anti-HEV IgM + anti-HEV IgG (n = 2). None of the patients died of HEV infection directly: 2 patients with HEV infection died showing signs of ongoing hepatitis, and 5 patients cleared HEV with a median duration of HEV infection of 1·5 (range, 1·0-5·7) months. In conclusion, HEV infection is a rare but serious complication after haplo-HSCT. We recommend screening of HEV in haplo-HSCT.

Effect of abstinence from alcohol on survival of patients with alcoholic cirrhosis: A systematic review and meta-analysis.

AIM: To address the questions of whether abstinence improves survival of patients with alcoholic cirrhosis (AC) and how long it takes for the effect to be significant. METHODS: A systematic review and a meta-analysis are performed to assess the effect of abstinence on the survival of patients with AC. RESULTS: Seven cohort studies involving 1235 patients with AC were included. No differences were found in 0.5-year survival (hazard ratio [HR] = 0.48, 95% confidence interval [CI] = 0.23-1.03, P = 0.06) and 1-year survival (HR = 0.58, 95% CI = 0.32-1.03, P = 0.06) between the abstinent and continue drinking groups. However, differences were found in 1.5-year survival (HR = 0.51, 95% CI = 0.33-0.81, P = 0.004), 2-year survival (HR = 0.55, 95% CI = 0.38-0.78, P = 0.0008), 2.5-year survival (HR = 0.54, 95% CI = 0.38-0.77, P = 0.0005), 3-year survival (HR = 0.54, 95% CI = 0.40-0.74, P = 0.0001), 3.5-year survival (HR = 0.56, 95% CI = 0.44-0.73, P < 0.00001), 4-year survival (HR = 0.60, 95% CI = 0.48-0.73, P < 0.00001), 4.5-year survival (HR = 0.61, 95% CI = 0.49-0.76, P < 0.0001) and 5-year survival (HR = 0.63, 95% CI = 0.52-0.76, P < 0.00001) between the two groups. CONCLUSION: Alcohol abstinence does improve the survival of patients with AC, and it takes at least 1.5 years of alcohol abstinence before a statistically significant difference in survival can be observed between the abstinent and the continue drinking groups.

GSDMD induces hepatocyte pyroptosis to trigger alcoholic hepatitis through modulating mitochondrial dysfunction.

BACKGROUND: Mechanisms and consequences of Gasdermin D (GSDMD) activation in alcoholic hepatitis (AH) are unclear. In the present study, we investigated whether GSDMD induces hepatocyte pyroptosis by regulating mitochondrial dysfunction in AH. RESULTS: Liver damage in AH mice was assessed by HE staining, serum levels of AST, ALT, TC, and TG. The levels of IL-1ß, IL-18, LDH, inflammasome-associated proteins and hepatocyte death were assessed to determine pyroptosis. Mitochondrial dysfunction was assessed through various parameters including mitochondrial DNA (mtDNA) levels, ROS generation, mitochondrial membrane potential, ATP contents, levels of mitochondrial function-related proteins and morphological changes of mitochondria. AH induced gasdermin D (GSDMD) activation, leading to increased protein expression of N-terminal GSDMD (GSDMD-N), NLRP3, and Caspase 11 in liver tissues. Downregulation of GSDMD alleviated alcohol-induced hepatocyte pyroptosis. Alcohol also causes mitochondrial dysfunction in hepatocytes in AH, which was improved by inhibiting GSDMD. Furthermore, enhancing mitochondrial function suppressed alcohol-induced hepatocyte pyroptosis. Further, knockdown of GSDMD or dynamin-related protein 1 (Drp1) improved AH-induced liver injury, accompanied by a decrease in hepatocyte pyroptosis. CONCLUSION: GSDMD induces hepatocyte pyroptosis by modulating mitochondrial dysfunction during AH-induced inflammation and liver injury. These findings may pave the way to develop new therapeutic treatments for AH.

O-carboxymethyl chitosan in biomedicine: A review.

O-carboxymethyl chitosan (O-CMC) is a chitosan derivative produced through the substitution of hydroxyl (-OH) functional groups in glucosamine units with carboxymethyl (-CH2COOH) substituents, effectively addressing the inherent solubility issues of chitosan in aqueous solutions. O-CMC has garnered significant interest due to its enhanced solubility, elevated viscosity, minimal toxicity, and advantageous biocompatibility properties. Furthermore, O-CMC demonstrates antibacterial, antifungal, and antioxidant characteristics, rendering it a promising candidate for various biomedical uses such as wound healing, tissue engineering, anti-tumor therapies, biosensors, and bioimaging. Additionally, O-CMC is well-suited for the fabrication of nanoparticles, hydrogels, films, microcapsules, and tablets, offering opportunities for effective drug delivery systems. This review outlines the distinctive features of O-CMC, offers analyses of advancements and future potential based on current research, examines significant obstacles for clinical implementation, and foresees its ongoing significant impacts in the realm of biomedicine.

Characteristics of alcoholic liver disease and predictive factors for mortality of patients with alcoholic cirrhosis.

BACKGROUND: Alcoholic liver disease is one of the major chronic liver diseases worldwide. The aim of the study was to describe the clinical characteristics of alcoholic liver disease and to compare the predictive values of biochemical parameters, complications, Child-Turcotte-Pugh score, model for end-stage liver disease (MELD) score and discriminant function score for the mortality of in-hospital or 3-month after discharge of patients with alcoholic cirrhosis (AC). METHODS: A retrospective record review and statistical analysis were performed on 205 consecutive patients with the discharge diagnosis of alcoholic liver disease. Three models were used to predict the mortality of patients with AC. The number of variceal hemorrhage, infection, hepatic encephalopathy and hepatocellular carcinoma was analyzed as "numbers of complications". Model 1 consisted of creatinine, white blood cell count, international normalized ratio and "numbers of complications". Model 2 consisted of MELD score. Model 3 included "numbers of complications" and MELD score. RESULTS: The risk of developing AC was significant for patients with alcohol consumption of higher than 80 g/d (OR=2.807, P<0.050) and drinking duration of longer than 10 years (OR=3.429, P<0.028). The area under curve for predicting in-hospital mortality of models 1, 2 and 3 was 0.950, 0.886 and 0.911 (all P<0.001), respectively. The area under curve for predicting the 3-month mortality of models 1, 2 and 3 was 0.867, 0.878 and 0.893 (all P<0.001), respectively. CONCLUSIONS: There is a dose-dependent relationship between alcohol consumption and the risk of developing AC. MELD score has a better predictive value than Child-Turcotte-Pugh or discriminant function score for patients with AC, and model 1 or 3 is better than model 2.

[Virus spectrum features of adult influenza-like fever in outpatients].

OBJECTIVE: To analyze the results of detection on respiratory virus of influenza-like illness ( ILI ) in Beijing from June 2010 to February 2012 and understand the virus spectrum of adult influenza-like fever. METHODS: A total of 502 swabs were collected and 279 throat swabs tested for 12 respiratory viruses with multiplex reverse transcription-polymerase chain reaction (RT-PCR). And 413 swabs were tested for pH1N1 by virus isolation influenza viruses. And the data were statistically analyzed. RESULTS: One or two viruses were detected in 26.9% (75/279) of the samples. Influenza A virus (FLU-A) accounted for 85.3% of positive samples and 22.9% (64/279) of ILI tested. The positive rate of other viruses was less than 3.0 %. The positive rates among the following subtypes were: 2.7% (11/413) for pH1N1, 2.4% (10/413) for H3 and 6.5% (27/413) for FLU-B. FLU-A was the predominant virus during the 2010-2011 influenza season and the positive rate peaked in January 2011 in Beijing and north China. FLU-B was the primary virus during the 2011-2012 influenza season and the positive rate peaked in January and February 2012. There was a significant reduction in the incidence of ILI in 2010 and 2011 when compared with 2009. During the 2009-2012 influenza seasons, the incidence peaked in December 2009, January 2011 and January and February 2012 in Beijing. CONCLUSIONS: Exposure to pH1N1 had no impact on typical influenza seasonal peaks. Influenza virus was the predominant virus of adult influenza-like fever cases after the pandemic period of influenza A (H1N1) 2009 and the positive rate peaked in January and February during the 2009-2012 influenza seasons.

eALT-F: A New Non-Invasive Staging Method to Identify Medium to High-Risk Patients with HCC from Ultra-High HBV Viral Load Population - China, 2010-2023.

Background: The objective of this study was to examine the clinical characteristics of individuals with ultra-high hepatitis B virus (HBV) viral load and develop a novel staging method for chronic hepatitis B (CHB) that can more effectively identify patients with medium to high hepatocellular carcinoma (HCC) risk. Methods: A total of 2,118 patients with HBV DNA >1×107 IU/mL who visited Peking University People's Hospital between January 2010 and March 2023 were enrolled retrospectively. Clinical data from the first visit were obtained and analyzed. The traditional phases and new 'eALT-F' stages were compared to evaluate the risk of HCC. Results: In the overall patients, more than one-third of the patients were under 30 years old. Additionally, a small proportion of older people (>60 years) also had ultra-high HBV viral load (4.3%). 9.1% and 6.7% of individuals with ultra-high HBV viral load showed FIB-4>3.25 and aMAP≥50, respectively. In the traditional stages of CHB, which are based on HBeAg and alanine aminotransferase (ALT) [the upper limit of normal (ULN) ALT level at 40 IU/L for both men and women], regardless of phase, a certain proportion of patients were at risk of developing HCC (4.1%, 6.4%, 25.0%, and 20.3%). However, in the new 'eALT-F' stages, which are based on HBeAg, ALT (the ULN of ALT level at 30 IU/L for men and 19 IU/L for women), and/or FIB-4 levels (>1.45), aMAP≥50 was only observed in chronic hepatitis patients with positive or negative HBeAg (6.4% and 22.1%, respectively). Conclusions: The 'eALT-F' staging method, based on HBeAg, ALT (males: the ULN of ALT was 30 IU/L, females: 19 IU/L) and/or FIB-4 levels, was more effective in identifying medium to high-risk patients with HCC from patients with ultra-high HBV viral load than the traditional staging methods.

Treatment of ursodeoxycholic acid with glucocorticoids and immunosuppressants may improve the long-term survival rate in primary biliary cholangitis patients.

Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease. The clinical effectiveness of ursodeoxycholic acid (UDCA) plus glucocorticoids and/or immunosuppressants remains controversial in PBC patients. The study aimed to compare the efficacy of monotherapy and combination therapy in patients with PBC and to assess the factors affecting the efficacy. In this retrospective study, 266 patients diagnosed with PBC were divided into monotherapy group (UDCA), double therapy group (UDCA plus glucocorticoids or immunosuppressants), and triple therapy group (UDCA plus glucocorticoids and immunosuppressants) according to different treatments. Demographic characteristics, immune parameters, biochemistry profiles, and other indicators were evaluated at baseline, 6 months, and 1 year following treatment. The prognosis was evaluated using the Paris II standard. The liver transplant-free survival at 3, 5, 10, and 15 years was predicted by GLOBE score. All statistical analyses were conducted using SPSS (version 24) software (SPSS Inc, Chicago, IL). The long-term survival rate of the triple therapy group was significantly improved compared with the monotherapy group (P = .005). In addition, multivariate analysis showed that abnormal platelet count, alkaline phosphatase, and albumin levels were risk factors for poor response. When IgG levels were elevated but below twice the upper limit of normal, the clinical benefit was not significant compared with monotherapy (P > .05). Compared with monotherapy and double therapy, triple therapy may improve the long-term survival rate of PBC patients. Abnormal platelet count, alkaline phosphatase, and albumin levels were associated with a poor prognosis.

Combination therapy of ursodeoxycholic acid and glucocorticoid and (or) immunosuppressant in patients with primary biliary cholangitis: A meta-analysis.

BACKGROUND/OBJECTIVES: Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune cholestasis liver disease. There were many studies comparing a combination of glucocorticoids and/or immunosuppressants to a single UDCA therapy in PBC patients, while the literature demonstrated divergent finds. To evaluate the effectiveness of ursodeoxycholic acid (UDCA) combined with glucocorticoids and (or) immunosuppressants on biochemistry, immunology, histology, clinical symptoms, and adverse reactions of PBC from the perspective of evidence-based medicine. MATERIALS AND METHODS: PubMed, web of science, the Cochrane Library, EMBASE databases were searched to collect clinical randomized trials and self-control studies of UDCA combined with glucocorticoids and (or) immunosuppressants and UDCA monotherapy in the treatment of PBC. The retrieval time is from the establishment of the database to August 2020. Two reviewers independently screened literature, extracted data and evaluated the bias of included studies. Revman 5.3 software was used for meta-analysis. RESULTS: Six studies including 201 patients were included. The meta-analysis found that the combination therapy can improve some biochemical indexes, immunological indexes, and clinical symptoms of patients with PBC. However, combination therapy has no significant improvement in other biochemical indicators which respond to liver and bile duct damage, such as ALT, GGT, and ALB. Besides, the improvement of liver histology is limited, and the incidence of adverse events is higher. CONCLUSION: Overall, the combination therapy showed no improvement in key biochemical parameters and limited improvement in liver pathology. Besides, the side effects were more serious. Therefore, in the current treatment regimen, it is not recommended for PBC patients.

HBeAg-positive patients with HBsAg < 100 IU/mL and negative HBV RNA have lower risk of virological relapse after nucleos(t)ide analogues cessation.

BACKGROUND: Nucleos(t)ide analogues (NAs) cessation is not widely practiced and remains a controversial, but highly relevant subject in patients infected with hepatitis B virus (HBV). We aimed to explore the related factors for safe NAs cessation. METHODS: This is a multicenter prospective cohort study. Overall, 139 initially HBV e antigen (HBeAg)-positive patients meeting the stopping criteria were included in 12 hospitals in China. Enrolled patients ceased NAs and were followed up every 3 months for 24 months or until clinical relapse (CR). RESULTS: The 24 month cumulative rates of virological relapse (VR), CR, HBeAg reversion and HBV surface antigen (HBsAg) loss were 50.4, 24.5, 11.5 and 9.4%, respectively. Patients with end of treatment (EOT) HBsAg < 100 IU/mL plus negative HBV RNA had the lowest 24 month cumulative VR rate (5 vs 58%, p < 0.001). EOT HBsAg ≥ 2 log10 IU/mL [odds ratio (OR) = 6.686, p = 0.006], EOT positive HBV RNA (OR = 3.453, p = 0.008) and EOT hepatitis B core-related antigen (HBcrAg) ≥ 4log U/mL (OR = 3.702, p = 0.002) were found to independently predict the risk of VR. To predict VR, the area under the receiver-operating characteristic (AUROC) value of the EOT HBsAg < 100 IU/mL plus EOT HBV RNA negative was 0.698 (p < 0.001), which was higher than other parameters alone or combinations. CONCLUSIONS: NAs cessation is suitable only for a small and selected patients. An EOT HBsAg < 100 IU/mL and EOT negative HBV RNA identified a patient with low risk of off-treatment VR.

Correlation analysis of hepatitis C virus core antigen and low viral loads: Can core antigen replace nucleic acid test?

Value of hepatitis C virus (HCV) core antigen (cAg) test has been controversy in patients with low HCV loads for its lower sensitivity. We assessed correlation between HCV-cAg and HCV RNA in serum samples with low viral loads and analyzed the performance of HCV-cAg assay in determining diagnosis and treatment outcomes in chronic hepatitis C patients. Both HCV RNA and HCV-cAg were detected for 2298 serum samples. Correlation analysis was performed between the two tests. Receiver operating characteristics (ROC) curve was used to assess value of HCV-cAg test in determining diagnosis and response outcomes at the different HCV RNA thresholds. The two tests were correlated very well, and moreover, correlation in the low viral load group was higher than that in the high viral load group (r value: 0.901 and 0.517). Positive agreement of HCV-cAg ≥ 3 fmol/L was as high as 97.0% for HCV RNA ≥ 1000 IU/mL, and its negative agreement for HCV RNA < 15 IU/mL was up to 98.9% in all samples. Area under ROCs ranged from 0.939 to 0.992, regardless of HCV RNA thresholds. When lower limit of detection of HCV RNA was 15, 100 or 1000 IU/mL, positive predictive value of HCV-cAg was 96.8%, 98.8% or 92.4%, and its negative predictive value was 87.0%, 89.9% or 98.3%, respectively, on the basis of different cutoff values. High-sensitivity HCV-cAg detection may likely replace HCV RNA to confirm the existence of HCV and to guide the treatment of chronic HCV infection.

Alcohol consumption analysis among patients with liver disease in China.

BACKGROUND: Alcohol consumption has been observed to be a contributing factor in liver damage. However, very few studies have tried to decipher the correlation between patients with liver disease and alcohol consumption. Therefore, this study was planned to determine the prevalence of alcohol consumption among patients with liver disease, and to evaluate the risk factors, liver diseases, and chronic medical conditions associated with alcohol drinking. METHODS: A cross-sectional study was conducted among patients with liver disease in 30 provinces, autonomous regions, and municipalities across China. All participants answered the questionnaire, which led to the calculation of Alcohol Use Disorders Inventory Test (AUDIT) score for each patient. Based on this score, low-risk drinkers, hazardous drinkers, and harmful drinkers were defined as having AUDIT score of <8, between 8 and 15, and ≥16, respectively. RESULTS: A total of 1489 participants completed the questionnaire. Based on this information, 900 (60.44%) participants were classified as alcohol drinkers. Among these, 8.66% were ex-drinkers, 22.10% were low-risk drinkers, 17.13% were hazardous drinkers, and 12.56% were harmful drinkers. Further investigation of the association between alcohol consumption and other baseline characteristics of patients with liver disease revealed that usually men <40 years old, participants having higher family annual income, having college degree or higher education, living alone, having higher body mass index (BMI), current smokers, and ex-smokers had significant association with higher risk of alcohol consumption. In addition, among the 18.07% of the participants with cirrhosis, it was observed that risk of cirrhosis increased with higher alcohol consumption. Furthermore, harmful drinkers showed greater odds of hypertension and heart diseases, while hazardous drinkers and harmful drinkers, both had greater odds of hyperlipidemia. CONCLUSIONS: Overall our analyses indicated that among the patients with liver disease in China, there was high rate of alcohol consumption and dependence. Alcohol consumption usually associated with men <40 years old, higher family income, education level, living alone, high BMI, and smoking. Increased alcohol consumption not only increased the risk of cirrhosis, but also enhanced the risk of hypertension, heart diseases, and hyperlipidemia.

Combined prednisone and levothyroxine improve treatment of severe thrombocytopenia in hepatitis B with compensatory cirrhosis accompanied by subclinical and overt hypothyroidism.

The aim of the present study was to investigate the relationship between hypothyroidism and thrombocytopenia in hepatitis B-related compensatory liver cirrhosis and to determine whether treatment with levothyroxine and prednisone is superior in a multicenter, open-label, observational study in China. In total, 125 consecutive hepatitis B-related compensated liver cirrhosis patients with severe thrombocytopenia accompanied by hypothyroidism were included. The patients were divided into four groups according to treatment strategy: a control group (n=29), a prednisone group (n=25), a levothyroxine group (n=32) and a prednisone plus levothyroxine group (n=39). Severe thrombocytopenia was more prevalent in hepatitis B-associated compensatory liver cirrhosis patients with hypothyroidism than in euthyroid patients (29.6% vs. 14.7%, P<0.05). Combination treatment with prednisone and levothyroxine decreased the risk of bleeding and improved platelet recovery compared to control treatment and treatment with either prednisone or levothyroxine alone. The platelet count before therapy, serum thyroid stimulating hormone and combination treatment with prednisone and levothyroxine were associated with bleeding events. Therefore, the present study suggests that hypothyroidism is associated with severe thrombocytopenia in hepatitis B-associated compensatory liver cirrhosis. Treatment with prednisone plus levothyroxine may present a novel approach in these patients.

Efficacy of Real-world Entecavir Therapy in Treatment-naïve Chronic Hepatitis B Patients.

BACKGROUND:: Entecavir (ETV) has been shown to be effective in randomized controlled trials in highly selected patients with hepatitis B virus (HBV) infection. This study aimed to evaluate the efficacy of ETV in chronic hepatitis B (CHB) patients in the real-world setting. METHODS:: A total of 233 treatment-naïve, CHB patients who received at least 12 months of ETV treatment were included in this retrospective study. Rates of virological response (VR), hepatitis B s antigen (HBsAg) loss, hepatitis B e antigen (HBeAg) clearance/seroconversion, virological breakthrough, cirrhosis, and hepatocellular carcinoma were evaluated. RESULTS:: Of 233 patients, 175 patients were male, with mean age of 43 years old, and 135 patients were HBeAg positive. The mean baseline levels of serum alanine aminotransferase and HBV DNA in all patients were 230 U/L and 6.6 log 10 IU/ml, respectively. The mean follow-up period was 28 months. The cumulative rates of achieving VR increased from 3.4% at 3 months to 94.4% at 60 months. Primary nonresponse occurred in 3 (1.3%) patients. Partial VR (PVR) occurred in 61 (26.2%) patients at 12 months. The baseline serum HBV DNA level (hazard ratio [HR], 2.054; P < 0.001) was an independent risk factor for PVR. HBsAg loss did not occur. The cumulative rates of HBeAg clearance increased from 2.2% at 3 months to 28.2% at 60 months. PVR was the significant determinant of HBeAg clearance (HR, 0.341; P = 0.026). Age (HR, 1.072; P = 0.013) and PVR (HR, 5.131; P = 0.017) were the significant determinants of cirrhosis. CONCLUSIONS:: ETV treatment was effective for HBV DNA suppression in this study, but HBsAg loss and HBeAg clearance/seroconversion rates were lower compared with previous clinical trials. PVR was associated with HBeAg clearance and cirrhosis.