The Albumin-Bilirubin Score as a Predictor of Liver-Related Mortality in Primary Biliary Cholangitis with Compensated Cirrhosis.

BACKGROUND: Although several prognostic scores have been reported to correlate with the prognosis of primary biliary cholangitis (PBC) patients, there are limited tools to predict the prognosis of PBC with compensated cirrhosis. This study aimed to evaluate the prognostic performance of the albumin-bilirubin (ALBI) score in PBC patients with compensated cirrhosis. METHODS: We conducted a retrospective longitudinal study of 219 patients with compensated PBC cirrhosis to evaluate the prognostic performance of the ALBI using Cox regression model, receiver operating characteristic (ROC) curve, and Kaplan-Meier method. RESULTS: During follow-up, a total of 19 subjects (8.7%) met the primary endpoint of liver-related death or liver transplantation (LT). Patients who died/underwent LT have higher ALBI score (-1.06 vs. -2.06, p < 0.001) at baseline than those who survived. ALBI score (hazard ratio: 15.011, 95% confidence interval [CI]: 5.045-44.665, p < 0.001) was associated with an increase in liver-related mortality or LT. ALBI score had the best discriminative capacity to predict the 5-year liver-related mortality (area under the ROC curve: 0.871, 95% CI [0.820, 0.913]) compared with other prognostic scores. The ROC curve showed that the best cut-off value of ALBI score was -1.47, with 90.0% sensitivity and 76.6% specificity. Also, the probability of transplant-free survival decreased with increasing ALBI grade (log-rank p = 0.003). The 5-year transplant-free survival rates of patients in grade 1, grade 2, and grade 3 were 100.0%, 96.4%, and 89.4%, respectively. CONCLUSION: ALBI score is a simple and effective predictive factor estimating the clinical outcome of patients with compensated PBC cirrhosis and provides better prognostic performance compared with other prognostic scores.

TR score: A noninvasive model to predict histological stages in patients with primary biliary cholangitis.

Introduction: The aim of this study was to develop a noninvasive prediction model for histological stages in PBC that is simple, easy to implement, and highly accurate. Methods: A total of 114 patients with PBC were included in this study. Demographic, laboratory data and histological assessments were collected. The independent predictors of histological stages were selected to establish a noninvasive serological model. The scores of 22 noninvasive models were calculated and compared with the established model. Results: This study included 99 females (86.8%) and 15 males (13.2%). The number of patients in Scheuer's stage 1, 2, 3 and 4 was 33 (29.0%), 34 (29.8%), 16 (14.0%), and 31 (27.2%), respectively. TBA and RDW are independent predictors of PBC histological stages. The above indexes were used to establish a noninvasive model-TR score. When predicting early histological change (S1) or liver fibrosis and cirrhosis (S3-S4), the AUROC of TR score were 0.887 (95% CI, 0.809-0.965) and 0.893 (95% CI, 0.816-0.969), higher than all of the other 22 models included in this study. When predicting cirrhosis (S4), its AUROC is still as high as 0.921 (95% CI, 0.837-1.000). Conclusion: TR score is an easy, cheap and stable noninvasive model, without complex calculation formulas and tools, and shows good accuracy in diagnosing the histological stages of PBC.

96-Week Treatment of Tenofovir Amibufenamide and Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients.

Background and Aims: Tenofovir amibufenamide (TMF) is a novel phosphoramidated prodrug of tenofovir with noninferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate (TDF) in 48 weeks of treatment. Here, we update 96-week comparison results. Methods: Patients with chronic hepatitis B were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks. The virological suppression was defined as HBV DNA levels <20 IU/mL at week 96. Safety was evaluated thoroughly with focusing on bone, renal, and metabolic parameters. Results: Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations. Noninferior efficacy was maintained in the pooled population, while it was first achieved in patients with HBV DNA ≥7 or 8 log10 IU/mL at baseline. Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted, while a smaller decline of which was seen in the TMF group than in the TDF group (p=0.01). For bone mineral density, patients receiving TMF displayed significantly lower reduction levels in the densities of spine, hip, and femur neck at week 96 than those receiving TDF. In addition, the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend. Conclusions: TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles (NCT03903796).

Finite-Time Thermodynamic Modeling and Optimization of Short-Chain Hydrocarbon Polymerization-Catalyzed Synthetic Fuel Process.

The short-chain hydrocarbon polymerization-catalyzed synthetic fuel technology has great development potential in the fields of energy storage and renewable energy. Modeling and optimization of a short-chain hydrocarbon polymerization-catalyzed synthetic fuel process involving mixers, compressors, heat exchangers, reactors, and separators are performed through finite-time thermodynamics. Under the given conditions of the heat source temperature of the heat exchanger and the reactor, the optimal performance of the process is solved by taking the mole fraction of components, pressure, and molar flow as the optimization variables, and taking the minimum entropy generation rate (MEGR) of the process as the optimization objective. The results show that the entropy generation rate of the optimized reaction process is reduced by 48.81% compared to the reference process; among them, the component mole fraction is the most obvious optimization variable. The research results have certain theoretical guiding significance for the selection of the operation parameters of the short-chain hydrocarbon polymerization-catalyzed synthetic fuel process.

Performance Analysis of a Solar Heating Ammonia Decomposition Membrane Reactor under Co-Current Sweep.

Ammonia is an excellent medium for solar thermal chemical energy storage and can also use excess heat to produce hydrogen without carbon emission. To deepen the study of ammonia decomposition in these two fields, finite-time thermodynamics is used to model a solar-heating, co-current sweeping ammonia decomposition membrane reactor. According to the needs of energy storage systems and solar hydrogen production, five performance indicators are put forward, including the heat absorption rate (HAR), ammonia conversion rate (ACR), hydrogen production rate (HPR), entropy generation rate (EGR) and energy conversion rate (ECR). The effects of the light intensity, ammonia flow rate, nitrogen flow rate and palladium membrane radius on system performances are further analyzed. The results show that the influences of the palladium membrane radius and nitrogen flow rate on reactor performances are very slight. When the light intensity is increased from 500 W/m2 to 800 W/m2, the ACR, EGR, HAR and HPR increase obviously, but the ECR decreases by 14.2%. When the ammonia flow rate is increased by 100%, the ECR, EGR and HPR increase by more than 70%, the HAR increases by 15.6% and the ACR decreases by 12.9%. At the same time, the ammonia flow rate needs to be adjusted with the light intensity. The results can provide some guiding significance for the engineering application of ammonia solar energy storage systems and solar hydrogen production.

The impact and role of hepatic hydrothorax in the prognosis of patients with decompensated cirrhosis: A retrospective propensity score-matched study.

Background and aims: Hepatic Hydrothorax (HH) is one of the complications in patients with decompensated cirrhosis and its impact and role in the prognosis of patients with decompensated cirrhosis are not yet clear. Thus, this study aimed to determine the role of HH in patients with decompensated cirrhosis and the long-term impact on their mortality. Materials and methods: A retrospective study analyzed 624 patients with ascites without pleural effusion in decompensated cirrhosis and 113 patients with HH. Propensity scores were calculated based on eight variables, and the HH and non-HH groups were matched in a 1:1 ratio. The effect and role of HH on the prognosis of patients with decompensated cirrhosis was analyzed using the Kaplan-Meier method and Cox proportional hazards regression model. Results: A total of 737 patients were included. Out of 113 HH patients, 106 could be matched to 106 non-HH patients. After matching, baseline characteristics were well-balanced. The multifactorial Cox proportional hazards model indicated that hepatic encephalopathy and HH were independent risk factors affecting prognostic survival in patients with decompensated cirrhosis (P < 0.01), with risk ratios and 95% confidence intervals (CI) of 2.073 (95% CI: 1.229-3.494, P < 0.01) and 4.724 (95% CI: 3.287-6.789, P < 0.01), respectively. Prognostic survival was significantly worse in the HH group compared to patients in the non-HH group, with mortality rates of 17.9, 30.1, and 59.4% at 6 months, 1 year, and 2 years in the HH group, compared to 0.9, 3.8, and 5.6% in the non-HH group, respectively. The estimated median survival time was 21 (95% CI: 18-25) months in the HH group and 49 (95% CI: 46-52) months in the non-HH group (P < 0.001). Conclusion: Hepatic hydrothorax is significantly associated with higher mortality in patients with decompensated cirrhosis and is a highly negligible independent decompensated event affecting their prognosis.

Analysis of clinical features and prognostic factors in patients with hepatic hydrothorax: a single-center study from China.

BACKGROUND: The clinical features and factors affecting the prognostic survival of hepatic hydrothorax (HH) are currently unknown. METHODS: We conducted a retrospective cohort study of 131 patients with HH using the Kaplan-Meier method and Cox proportional hazards regression analysis to assess factors influencing the prognosis of HH. RESULTS: A total of 131 patients were enrolled: the male to female ratio was 80:51 (1.59:1), and the mean age was 52.76 ± 11.88 years. Hepatitis B cirrhosis was the main cause of HH, and abdominal distention and dyspnea were the most common clinical signs. Ascites was present in varying amounts in all patients and was the most common decompensated complication, with pleural effusions mostly seen on the right side (107/131; 82%), followed by the left side (16/131; 12%) and bilateral effusions (8/131; 6%). For overall survival without transplantation, the estimated median survival time was 21 (95% confidence interval [CI]:18-25) months, and survival rates at 6 months, 1 year, and 2 years were 77.2%, 62.4%, and 29.7%, respectively. After controlling for covariates that were associated with liver-related mortality in the univariate analysis, males (hazard ratio [HR]: 1.721, 95% CI: 1.114-2.658, P = 0.005) and combined hepatic encephalopathy (HR: 2.016, 95% CI: 1.101-3.693, P = 0.001) were found to be associated with an increase in liver-related mortality. CONCLUSIONS: In this cohort of HH patients without liver transplantation, male sex and hepatic encephalopathy were associated with a higher risk of liver-related death.

Thermodynamic Optimization of Ammonia Decomposition Solar Heat Absorption System Based on Membrane Reactor.

In this paper, an ammonia decomposition membrane reactor is applied to a solar heat absorption system, and thermodynamic optimization is carried out according to the usage scenarios. First, a model of an ammonia decomposition solar heat absorption system based on the membrane reactor is established by using finite time thermodynamics (FTT) theory. Then, the three-objective optimization with and the four-objective optimization without the constraint of the given heat absorption rate are carried out by using the NSGA-II algorithm. Finally, the optimized performance objectives and the corresponding design parameters are obtained by using the TOPSIS decision method. Compared with the reference system, the TOPSIS optimal solution for the three-objective optimization can reduce the entropy generation rate by 4.8% and increase the thermal efficiency and energy conversion rate by 1.5% and 1.4%, respectively. The optimal solution for the four-objective optimization can reduce the heat absorption rate, entropy generation rate, and energy conversion rate by 15.5%, 14%, and 8.7%, respectively, and improve the thermal efficiency by 15.7%. The results of this paper are useful for the theoretical study and engineering application of ammonia solar heat absorption systems based on membrane reactors.

Ecological Function Analysis and Optimization of a Recompression S-CO2 Cycle for Gas Turbine Waste Heat Recovery.

In this paper, a recompression S-CO2 Brayton cycle model that considers the finite-temperature difference heat transfer between the heat source and the working fluid, irreversible compression, expansion, and other irreversibility is established. First, the ecological function is analyzed. Then the mass flow rate, pressure ratio, diversion coefficient, and the heat conductance distribution ratios (HCDRs) of four heat exchangers (HEXs) are chosen as variables to optimize cycle performance, and the problem of long optimization time is solved by building a neural network prediction model. The results show that when the mass flow rate is small, the pressure ratio, the HCDRs of heater, and high temperature regenerator are the main influencing factors of the ecological function; when the mass flow rate is large, the influences of the re-compressor, the HCDRs of low temperature regenerator, and cooler on the ecological function increase; reasonable adjustment of the HCDRs of four HEXs can make the cycle performance better, but mass flow rate plays a more important role; the ecological function can be increased by 12.13%, 31.52%, 52.2%, 93.26%, and 96.99% compared with the initial design point after one-, two-, three-, four- and five-time optimizations, respectively.

Serum qAnti-HBc combined with ALT and HBsAg predicts significant hepatic inflammation in HBeAg-positive immune active patients.

BACKGROUND AND AIM: Quantitative hepatitis B core antibody (qAnti-HBc) level has been reported to predict significant liver inflammation in treatment-naïve chronic hepatitis B patients. However, little evidence has been revealed that qAnti-HBc alone or with other serum parameters in predicting moderate to severe hepatic inflammation in HBeAg-positive immune active patients treated with entecavir (ETV). METHODS: A total of 142 patients with HBeAg-positive immune active hepatitis were recruited in our study. Serum liver biochemistry, qAnti-HBc, hepatitis B virus markers, and liver inflammation were evaluated during 48-week ETV treatment. The association between liver inflammation grades and serum markers was systematically analyzed. RESULTS: The patients with moderate to severe inflammation (≥ G2) had a significantly higher level of qAnti-HBc compared with those with no to mild liver inflammation patients (< G2). The levels of qAnti-HBc and alanine transaminase (ALT) were positively correlated with hepatic inflammation grades, and qAnti-HBc had a better correlation than ALT, whereas HBsAg was negatively correlated with hepatic inflammation grades before treatment. After 48-week ETV treatment, no correlation was observed between hepatic inflammation grades and qAnti-HBc, ALT, or HBsAg. The combination of qAnti-HBc, ALT, and HBsAg had better performance in predicting significant liver inflammation (≥ G2) than qAnti-HBc alone or its combination with ALT. CONCLUSION: Serum qAnti-HBc levels were positively correlated with hepatic inflammation grades before treatment, but no positive correlation between them was observed after 48-week treatment. The level of qAnti-HBc combined with ALT and HBsAg may serve as a more reliable marker for identifying significant liver inflammation before treatment in HBeAg-positive immune active patients.

The prognostic value of antibodies to gp210 among patients with primary biliary cholangitis in Northeast China.

BACKGROUND: Whether the anti-gp210 antibody can be used as a biomarker in patients with primary biliary cholangitis (PBC) remains controversial. AIMS: We aimed to investigate the association between anti-gp210 antibodies and prognosis in ursodeoxycholic acid (UDCA)-treated PBC patients. METHODS: We conducted a retrospective cohort study of 180 UDCA-treated PBC patients to assess the prognostic value of anti-gp210 antibodies using the Kaplan-Meier method and Cox proportional hazard regression analysis. RESULTS: Of the patients included in our analysis, 50 (27.8%) were anti-gp210 positive, and 130 (72.2%) were anti-gp210 negative. The incidence of liver-related death or transplantation was more common in the anti-gp210 + group (22.0 vs. 9.2%, P=0.022). The five-year transplant-free survival rates of anti-gp210-positive patients vs. anti-gp210-negative patients were 77.0% and 90.3%, respectively. We found that the probability of transplant-free survival was significantly lower in the anti-gp210-positive patients than in the anti-gp210-negative patients (log-rank P=0.004). After adjusting for potential confounders using multivariable Cox regression model, positivity for anti-gp210 antibody (hazard ratio: 4.619, 95% confidence interval: 1.895-11.261, P=0.001) was found to be independently associated with an increase in liver-related mortality or transplantation. CONCLUSION: In this cohort of UDCA-treated PBC patients, positivity for anti-gp210 antibody was independently associated with a higher risk of liver-related death or transplantation.

A rare case report of iatrogenic Cushing syndrome caused by direct anti-hepatitis C virus therapy with sofosbuvir/velpatasvir.

RATIONALE: Sofosbuvir/velpatasvir (SOF/VEL) is a combination of direct-acting antivirals with pan-genotypic activity that is used to treat chronic hepatitis C virus infection. This was a fixed-dose regimen. SOF is a nucleotide nonstructural 5B polymerase inhibitor and VEL is an nonstructural 5A inhibitor. Side effects of this agent on the endocrine system, particularly iatrogenic Cushing syndrome (ICS), are uncommon. Here, we present a case of ICS with significantly low serum adrenocorticotropic hormone and cortisol levels caused by SOF/VEL. PATIENT CONCERNS: A 49-year-old Asian woman with chronic hepatitis C and cirrhosis presented with a round face, fat thickening at the clavicle and back of the neck, mild facial edema, facial congestion, skin ulceration on the hands, central obesity, acne, and general status changes after 3 months of treatment with SOF/VEL (400 mg/dose, 1/day). DIAGNOSES: The patient's serum adrenocorticotropic hormone and cortisol levels dropped significantly, and her normal rhythm vanished, with no visible aberrant lesions on computed tomography or across the abdomen. The patient was diagnosed with ICS. OUTCOMES: Symptoms improved after withdrawing SOF/VEL and taking low-dose oral hydrocortisone. Thus, the SOF/VEL was suspected to be an offender. To our knowledge, this is the first time that SOF/VEL has been linked to ICS. LESSONS: Hepatologists and primary care physicians treating hepatitis C virus should be more aware of this uncommon adverse event so that direct-acting antiviral therapy can be stopped sooner if it recurs. The findings of this study emphasize the importance of collaboration between hepatologists and endocrinologists in co-management of complications.

Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B.

BACKGROUND: Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF). AIM: To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB). METHODS: We performed a randomised, double-blind, non-inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities. RESULTS: We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non-inferiority criterion was met in all analysis sets. In the HBeAg-positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAg-negative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip (P < 0.001) and spine (P < 0.001), and a smaller increase in serum creatinine at week 48 (P < 0.05). Other safety results were similar between groups. CONCLUSION: TMF was non-inferior to TDF in terms of anti-HBV efficacy and showed better bone and renal safety. (NCT03903796).

Serum HBV RNA correlated with intrahepatic cccDNA more strongly than other HBV markers during peg-interferon treatment.

BACKGROUND: Serum hepatitis B virus RNA (HBV RNA) has been reported to be a surrogate marker of intrahepatic cccDNA during nucleos(t)ide analogs therapy. However, in HBeAg-positive patients treated with peg-interferon (peg-IFN), whether HBV RNA is superior to other HBV markers in reflecting cccDNA profile is still unclear. METHODS: Serum HBV RNA, HBcrAg, HBV DNA, and HBsAg were longitudinally assessed among 30 HBeAg-positive patients during 48-week peg-IFN treatment. Besides, intrahepatic cccDNA was detected at baseline and week 48 respectively. Then, the individual correlations between HBV RNA, HBcrAg, HBV DNA, HBsAg, and cccDNA were statistically analyzed. RESULTS: HBV RNA levels decreased more rapidly in patients with HBeAg seroconversion than those without HBeAg seroconversion. Among all patients, cccDNA correlated better with HBV RNA than with HBcrAg, HBV DNA, and HBsAg at baseline. After 48 weeks peg-IFN treatment, cccDNA still correlated more strongly with HBV RNA than other HBV markers. Further analysis indicated that in patients with HBeAg seroconversion cccDNA strongly correlated with HBV RNA and HBcrAg, whereas not correlate with HBV DNA and HBsAg. While in patients without HBeAg seroconversion, cccDNA highly correlated with HBV RNA and HBV DNA, moderately correlated with HBcrAg, and not correlated with HBsAg. CONCLUSION: Compared to HBcrAg, HBV DNA, and HBsAg, serum HBV RNA correlated more strongly with intrahepatic cccDNA levels before and after 48-week peg-IFN treatment. The level of serum HBV RNA may be a superior surrogate marker in reflecting the intrahepatic cccDNA profile in HBeAg-positive patients during peg-IFN treatment. Trial registration ClinicalTrials, NCT03546530. Registered 1 January 2015. https://clinicaltrials.gov/ct2/results?cond=&term=NCT03546530 .

Herb-induced autoimmune-like hepatitis associated with Xiang-tian-guo (Swietenia macrophylla seeds): A case report and literature review.

RATIONALE: Drug-induced liver injury (DILI) has a relatively low incidence, whereas the incidence of herb-induced liver injury (HILI) is still under investigation. As a special type of DILI, the diagnosis of drug-induced autoimmune-like hepatitis presents a persistent challenge, because this condition has partial characteristics of both DILI and autoimmune hepatitis (AIH), such as a certain history of medication use and histology that similar is to AIH. Thus, the differential diagnosis between DILI and AIH can be confusing. PATIENT CONCERNS: A 67-year-old woman taking xiang-tian-guo for 6 months was admitted to our hospital with a complaint of experiencing jaundice for 2 weeks. DIAGNOSIS: A liver biopsy exhibited interface inflammation, foam cells, and "rosette" -like hepatocytes. She was diagnosed with herb-induced liver injury (hepatocellular and acute), a RUCAM score of 7 (probable), a severity for grade 4 liver injury, and accompanied autoimmune-like changes. INTERVENTIONS: The patient was instructed to cease the administration of suspicious drugs. The patient also received liver protection and albumin transfusion. OUTCOMES: After 25 days of hospitalization, the patients aminotransferase levels returned to normal. No recurrence was observed after the administration of the treatments and a close follow-up. LESSONS: We must to be vigilant about the safety of xiang-tian-guo as a herbal medicine. When faced with the difficulty of distinguishing between AIH and DILI, long-term follow-up observations for recurrence can aid clinicians in making a judgment.

Safety and pharmacokinetics of a biosimilar of denosumab (KN012): Phase 1 and bioequivalence study in healthy Chinese subjects.

BACKGROUND: KN012 is a proposed biosimilar candidate for the reference drug denosumab, with the brand name Prolia®. This study explored the tolerance, variability, and pharmacokinetics (PK) of denosumab and its biosimilar in healthy Chinese subjects. RESEARCH DESIGN AND METHODS: A randomized, double-blind, parallel, two-arm study was performed to analyze the bioequivalence of denosumab biosimilar (60 mg) compared with denosumab. RESULTS: The PK properties of denosumab biosimilar were similar to those of denosumab. When denosumab biosimilar was compared to denosumab, the geometric mean ratios (GMRs) of Cmax, AUC0-t, and AUC0-∞ were 98.74%, 102.54%, and 102.18%, respectively, and the 90% confidence interval was observed to be within 80-125%. The inter-subject variability ranged from 31.4% to 34.6%. Five subjects in the denosumab biosimilar group and one subject in the denosumab group were positive for anti-drug antibodies (ADAs) and negative for neutralizing antibodies (NAbs). Adverse reactions were observed in 100% (52 subjects) and 94.0% (47 subjects) of the subjects in the denosumab biosimilar and denosumab groups, respectively. Reductions in the blood calcium and phosphate levels were the most common adverse reactions. CONCLUSION: The PK characteristics were comparable for the denosumab biosimilar and denosumab groups. Their safety profiles were also similar. TRIAL REGISTRATION: : The trial is registered at the Chinese Clinical Trial website (http://www.chinadrugtrials.org.cn/index.html #CTR20181231).

Association of interleukin-6 gene polymorphisms with the risk of hepatocellular carcinoma: An up-to-date meta-analysis.

BACKGROUND: This study was aimed to evaluate the association between interleukin-6 (IL-6) gene polymorphisms and the risk of hepatocellular carcinoma (HCC) in a meta-analysis. METHODS: A literature search was performed for case-control studies published during May, 1993 to May, 2020 focusing on IL-6 gene polymorphisms (-174G > C, -572G > C, and -597G > A) and HCC susceptibility by using PubMed, Cochrane Database, EMBASE, Web of science, and China National Knowledge Infrastructure. From 128 full-text articles, 11 were included in this meta-analysis. I index was used to assess heterogeneity and Newcastle-Ottawa Scale was utilized for quality assessment. RESULTS: For IL-6 -174G > C polymorphism, in codominant (GG vs CC: odds ratios [OR] = 2.78, 95% confidence intervals [CI] = 1.25-6.19, P = .01, I = 16%) and recessive (GG+GC vs CC: OR = 2.76, 95% CI = 1.29-5.90, P = .009, I = 3%) models, IL-6 -174G>C polymorphism was significantly associated with the risk of HCC. In dominant (GG vs CC+GC: OR = 1.80, 95% CI = 0.92-3.54, P = .09, I = 86%) and allele (G vs C: OR = 1.49, 95% CI = 0.95-2.32, P = .08, I = 68%) models, IL-6 -174G>C polymorphism had no impact on the risk of HCC. However, in non-Italian Caucasian population, IL-6 -174G>C polymorphism was significantly related to the occurrence of HCC in both dominant (GG vs CC+GC: OR = 3.26, 95% CI = 2.29-4.65, P < .00001, I = 0%) and allele (G vs C: OR = 2.48, 95% CI = 1.48-4.15, P = .0006) models. Such correlations also could be observed when healthy individuals were selected as controls. For IL-6 -572G>C and -597G>A polymorphisms, no significant association was observed in all models, regardless of the source of control and population subgroups. No publication bias could be calculated when Begg and Egger tests were employed. CONCLUSION: This meta-analysis indicated that IL-6 -174G>C polymorphism was significantly related with the risk for HCC, especially in non-Italian Caucasian population. No significant association was observed for the correlation between IL-6 -572G>C and -597G>A polymorphisms and HCC susceptibility.

Clinical significance of IgG antimitochondrial M2 antibody levels in primary biliary cholangitis: A single center study from China.

BACKGROUND AND OBJECTIVE: The relationship between antimitochondrial antibody (AMA) levels and the severity or prognosis of primary biliary cholangitis (PBC) is unclear. This study explored the clinical significance of serum IgG antimitochondrial M2 antibody (IgG-M2) levels. METHODS: From 2008 to 2017, a retrospective analysis was conducted with PBC patients who had available quantitative values of serum IgG-M2 levels obtained with ELISA based on triple expression hybrid clones. The patients were divided into two groups based on high and low concentrations of IgG-M2. Baseline parameters, the incidence of adverse events, and prognosis were compared. RESULTS: Among the 530 PBC patients, the levels of albumin, cholinesterase, hemoglobin, fibrinogen and triglycerides and the red blood cell count were significantly lower in the high-concentration group than in the low-concentration group (n = 263, 49.6%). The red cell distribution width (RDW) and levels of serum immunoglobulin (Ig) G, IgM and IgA were significantly higher in the high-concentration group than in the low-concentration group. Spearman's correlation analysis suggested that the correlation between the above baseline indicators and IgG-M2 levels was statistically significant but weak (r < 0.2, P < 0.05). In total, 203 patients were followed up, of whom 87 (42.9%) were in the high-concentration group. During the median follow-up period of 52 months (range: 28-75), 121 (59.6%) experienced hepatic decompensation, and 37 (18.2%) died or underwent liver transplantation. There was no significant difference in the incidence of complications or survival (log-rank test: P = 0.079) between the two groups. One year after ursodeoxycholic acid (UDCA) treatment, the two groups had similar responses. In addition, the levels of IgG-M2 did not fluctuate significantly during treatment. CONCLUSION: IgG-M2 levels were not related to the disease severity, prognosis or efficacy of UDCA. The levels of IgG-M2 did not change significantly during treatment.

Validation of the GALAD Model and Establishment of GAAP Model for Diagnosis of Hepatocellular Carcinoma in Chinese Patients.

PURPOSE: GALAD is a statistical model for estimating the likelihood of having hepatocellular carcinoma (HCC) based on gender, age, AFP, AFP-L3, and PIVKA-II. We aimed to assess its performance and build new models in China, where hepatitis B virus (HBV) is the leading etiology of HCC. PATIENTS AND METHODS: We built the GALAD-C model with the same five variables in GALAD, and the GAAP model with gender, age, AFP, and PIVKA-II, using logistic regression based on 242 patients with HCC and 283 patients with chronic liver disease (CLD). We also collected 50 patients with other malignant liver tumors (OMTs) and 50 healthy controls (HCs). A test dataset (169 patients with HCC and 139 with CLD) was used to test the performance of GAAP. RESULTS: The GALAD-C and GAAP models achieved comparable performance (area under the receiver operating characteristic curve [AUC], 0.922 vs 0.914), and both were superior to GALAD, PIVKA-II, AFP, and AFP-L3% (AUCs, 0.891, 0.869, 0.750, and 0.711) for discrimination of HCC from CLD for the entire dataset. The AUCs of the GALAD, GALAD-C and GAAP models were excellent for the hepatitis C virus (HCV) subgroup (0.939, 0.958 and 0.954), and for discrimination HCC from HCs (0.988, 0.982, and 0.979), but were relatively lower for the HBV subgroup (0.855, 0.904, and 0.894), and for HCC within Milan Criteria (0.810, 0.841, and 0.840). They were not superior to AFP (0.873) for discrimination of HCC from OMT (0.873, 0.809, and 0.823). GAAP achieved an AUC of 0.922 in the test dataset. CONCLUSION: GALAD was excellent for discrimination of HCC from CLD in the HCV subgroup of a cohort of Chinese patients. The GAAP and GALAD-C models achieved better performance compared with GALAD. These three models exhibited better performance in patients with an HCV etiology than those with HBV.

Efficacy of a combination of HBV RNA and HBeAg in predicting HBeAg seroconversion in patients treated with entecavir for 144 weeks.

BACKGROUND: In some previous studies, serum hepatitis B virus RNA (HBV RNA) was proposed as an HBV viral marker during therapy. However, the dynamic change of HBV RNA, the correlation of HBV RNA with cccDNA, and the combination of HBV RNA with known HBV markers in predicting entecavir (ETV) treatment outcome in the same cohort are rarely reported. METHODS: A total of 111 HBeAg-positive patients were enrolled in our study. The dynamic changes of serum HBV RNA and the correlation of HBV RNA with other HBV markers were investigated in the early treatment period of 144-week ETV treatment. Intrahepatic cccDNA was detected at baseline and week 48. Receiver operating characteristic analyses were used to identify HBV RNA levels associated with HBeAg seroconversion. RESULTS: The serum HBV RNA levels decreased more rapidly in patients with HBeAg seroconversion than those without HBeAg seroconversion. The levels of HBV RNA decreased slower compared with the serum HBV DNA, irrespective of whether the patients achieved HBeAg seroconversion or not. Although the serum HBV RNA was positively correlated with cccDNA at baseline among all patients, no significant correlation was observed in the patients with HBeAg seroconversion at week 48 (r=0.094, P=0.588). The area under the receiver operating characteristic (AUROC) of HBV RNA and HBeAg at week 24 was 0.754 and 0.800, respectively. The AUROC of the HBV RNA and HBeAg combination had a higher value (AUROC=0.821). CONCLUSIONS: The level of HBV RNA at week 24 was a powerful predictor of HBeAg seroconversion in HBeAg-positive patients after 144-week ETV treatment, while the combination of HBV RNA and HBeAg was superior to HBV RNA alone in predicting HBeAg seroconversion.