Objective　This study aims to investigate and compare the clinical characteristics and prognostic factors among primary liver cancer (PLC) patients who had hepatitis B virus (HBV)-induced cirrhosis associated with liver cancer, alcoholic cirrhosis associated with liver cancer, or both HBV and alcoholic cirrhosis associated with liver cancer. 　　　Methods　Inpatients diagnosed with PLC admitted to the First Affiliated Hospital of Fujian Medical University between January 2010 and September 2020 were enrolled and divided into three groups based on the etiology. The follow-up period ends in October 2024. Survival analyses were performed using Kaplan-Meier curves, univariate analysis, and multivariate Cox regression. Results　During the study period, 45 cases of alcoholic cirrhosis associated liver cancer (ALD group), and 71 cases of hepatitis B combined with alcoholic cirrhosis associated liver cancer (HBV+ALD group) were enrolled. At the same time, 73 patients with hepatitis B cirrhosis associated liver cancer (HBV group) during the same period were randomly selected with a ratio of about 1∶1.5, totaling 189 cases. And 183 (96.8%) of the patients were male and 6 (3.2%) were female. The age was (55.93±10.20) years. 109 deaths (57.7%) were recorded. The median survival times were 12 months for the entire cohort, 55 months for HBV group, 36 months for ALD group and 11 months for HBV+ALD group. And the 10-year death rate was 42.5% in HBV group, compared to 66.7% in ALD group and 67.6% in HBV+ALD group. In this study, 93 patients chose either the surgical resection or the radiofrequency ablation as their treatments. The recurrence rate was 69.9%, the median recurrence time was 8 months and the median overall survival time was 39 months. Univariate Cox regression identified that etiology of HBV and ALD, alpha-fetoprotein (AFP)>1 200 ng/mL, Child-Pugh class B and C, Barcelona Clinic Liver Cancer (BCLC) stages of C and D and curative therapies such as surgery and radiofrequency ablation were significantly correlated with overall survival (all P<0.05). Multivariate Cox regression revealed that patients with both HBV and ALD (HR=1.750，95%CI: 1.107-2.765，P=0.017), AFP>1 200 ng/mL (HR=1.649，95%CI: 1.060-2.564，P=0.027), and BCLC stages of C and D (HR=3.404，95%CI: 2.254-5.142，P<0.001) were independent risk factors of mortality in PLC patients with cirrhosis. Conclusions　Among HBV, ALD and HBV+ALD groups, the HBV+ALD group had the shortest median survival time and the highest overall mortality rate, suggesting that alcohol consumption and HBV infection may accelerate the progression of PLC with cirrhosis and worsen its prognosis. HBV infection combined with alcoholic consumption, AFP>1 200 ng/mL, and BCLC stages of C and D were independent risk factors for mortality in PLC patients with cirrhosis.

Objective:To evaluate the accuracy and practicability of hepatocellular carcinoma prediction score (PAGE-B) and modified hepatocellular carcinoma prediction score (mPAGE-B) in predicting the development of hepatocellular carcinoma in patients with hepatitis B virus (HBV)-associated liver cirrhosis and received nucleos(t)ide analogue (NA) treatment.Methods:From June 2009 to December 2014, at Department of Hepatology, the First Affiliated Hospital of Fujian Medical University, the clinical data of 707 patients with HBV-associated liver cirrhosis and received NA treatment were retrospectively collected, and the patients were followed up. The risk factors of development of hepatocellular carcinoma were analyzed. PAGE-B (including platelet count, age, gender), mPAGE-B (including platelet count, age, gender and albumin), Child-Turcotte-Pugh (CTP) score and aspartate aminotransferase to platelet ratio index (APRI) were compared in area under receiver operator characteristic curve (AUROC) for predicting the occurrence of hepatocellular carcinoma within 5 years. Risk stratification analysis was carried out for mPAGE-B and PAGE-B. Multivariate Cox regression analysis, receiver operator characteristic curve, Mann-Whitney U test and Kaplan-Meier method were used for statistical analysis. Results:The age of 707 patients was (46.7±12.2) years old, including 567 males (80.2%) and 140 females (19.8%). The positive rate of hepatitis B e antigen was 56.4% (399/707). The scores of PAGE-B, mPAGE-B, CTP and APRI were 15.90±4.24, 12.39±3.58, 6.88±2.15 and 1.80 (0.85, 3.79), respectively. The overall follow up time was (38.14±20.97) months and the incidence of hepatocellular carcinoma was 8.1% (57/707). The results of multivariate Cox regression analysis showed that advanced age, low platelet count and quantitative reduction of HBV DNA were independent risk factors of development of hepatocellular carcinoma (Wald=20.44, 5.64 and 9.25; HR(95% confidence interval (95% CI) 1.056(1.031 to 1.081), 0.994(0.989 to 0.999) and 0.769(0.649 to 0.911); P<0.001, =0.018 and 0.002). The AUROCs (95% CI) of PAGE-B, mPAGE-B, CTP score and APRI for predicting the occurrence of hepatocellular carcinoma within 5 years were 0.708 (0.639 to 0.778), 0.724 (0.657 to 0.778), 0.576 (0.500 to 0.652) and 0.516 (0.443 to 0.589), respectively. There were no statistically significant differences in AUROCs for predicting the occurrence of hepatocellular carcinoma within 5 years between mPAGE-B and PAGE-B, between APRI and CTP score (both P>0.05). The AUROC for predicting the occurrence of hepatocellular carcinoma within 5 years of CTP score was less than those of PAGE-B and mPAGE-B, and the differences were statistically significant ( Z=3.00 and 3.79; P=0.003, <0.001). The AUROC for predicting the occurrence of hepatocellular carcinoma within 5 years of APRI was less than those of PAGE-B and mPAGE-B, and the differences were statistically significant ( Z=4.75 and 5.46, both P<0.001). There were 51 cases (7.2%), 394 cases (55.7%) and 262 cases (37.1%) in the low-risk (<10) group, medium-risk (10 to 17) group and high-risk (>17) group as assessed by PAGE-B. The incidence of hepatocellular carcinoma was 0(0/51), 4.8% (19/394) and 14.5% (38/262), respectively the annual average incidence of hepatocellular carcinoma was 0, 1.6% and 5.5%, respectively, the 5-year cumulative incidence of hepatocellular carcinoma was 0, 7.3% and 31.3%, respectively. The 5-year cumulative incidence of hepatocellular carcinoma of high-risk group was higher than those of medium-risk group and low-risk group (log-rank test=19.27, P<0.001). There were 97 cases (13.7%), 246 cases (34.8%) and 364 cases (51.5%) in the low-risk group (<9), medium-risk group (9 to 12) and high-risk group (>12) as assessed by mPAGE-B. The incidence of hepatocellular carcinoma was 2.1% (2/97), 3.7% (9/246) and 12.6%(46/364), the annual average incidence of hepatocellular carcinoma was 0.6%, 1.1% and 4.7%, respectively, the 5-year cumulative incidence of hepatocellular carcinoma was 2.4%, 5.1% and 26.7%, respectively. The 5-year cumulative incidence of hepatocellular carcinoma of high-risk group was higher than those of medium-risk group and low-risk group (log-rank test value=18.64, P<0.001). Conclusions:Both PAGE-B and mPAGE-B can predict the occurrence of hepatocellular carcinoma within 5 years in patients with HBV-associated liver cirrhosis treated with antiviral therapy, identify liver cirrhotic patients at high risk of development of hepatocellular carcinoma and guide clinicans to use more efficient screening strategies.

A case of Gilbert syndrome (GS) with a heterozygous mutation in the gene is reported. The patient had no symptoms except for recurrent sclera icterus since childhood. Laboratory examinations revealed an elevated unconjugated bilirubin. Biliary obstruction, hemolysis and other diseases that might cause jaundice were excluded. *28 and c.211G>A heterozygous mutations in gene were found, which may be another type of mutation causing GS in Chinese population.
Asian Continental Ancestry Group ; Bilirubin ; Gilbert Disease ; genetics ; Glucuronosyltransferase ; genetics ; Heterozygote ; Humans ; Mutation

The circadian clock is a generator of self-sustaining physiological and behavioral rhythms, which can be guided by external environmental factors, so as to synchronize biological behaviors with external environmental changes. The modern lifestyles make the human body incapable of synchronization to the external time with the circadian rhythm, and thus form a social jet lag. Non-alcoholic fatty liver disease (NAFLD) is a disorder closely related to metabolic abnormalities. The circadian clock is closely related to metabolic abnormalities and NAFLD and changes among them may be involved with feeding mode and ingredients, sleeping time, and intestinal flora. Molecules associated with the circadian clock are expected to become potential drugs for the treatment of NAFLD. This article mainly reviews the latest research progress of circadian clock and NAFLD.

Objective To investigate the relationship between Toxoplasma gondii (T.gondii) infection and metabolic syndrome (MS).Methods A total of 20 577 patients who received serum test of anti-T.gondii IgG antibody in the National Health and Nutrition Examination Survey ( NHANES) of the United States from 2009 to 2014 were collected to analyze the clinical features of anti-T.gondii IgG antibody positive patients , and to compare metabolic related indicators in the antibody IgG positive and negative groups .The independent sample t-test, chi-square test, and logistic regression analysis were used to explore the risk factors of MS . Results A total of 2 746 participants were positive for the T.gondii antibody (13.34%), with a higher prevalence of male (14.44%vs 12.27%, χ2 ＝15.99, P＜0.01).Meanwhile, the prevalence of T.gondii increased with age and body mass index (BMI) (χ2 ＝979.98 and 50.85,respectively, both P＜0.01).Among the 2 191 patients with MS, 449 (20.49%) patients were positive for T.gondii.While 2 297 (12.49%) patients were anti-T.gondii positive in 18 386 non-MS patients.The difference was statistically significant (χ2 ＝78.504, P＜0.01).Age (t＝-37.37), BMI (t＝-4.28), glycosylated hemoglobin (t＝-11.81), fasting blood glucose (t＝-9.38), triacylglycerol (t＝-6.32), cholesterol (t＝-7.16), serum uric acid (t＝-5.25) and serum creatinine (t＝-7.69) in the seropositive group were all higher than those in the seronegative group (all P＜0.01).After adjusting for age and gender , the prevalence of T.gondii was an independent risk factor for MS (odds ratio [OR]＝1.147,P＝0.023).Conclusions BMI, blood lipids, blood uric acid and blood glucose are significantly increased in patients with T.gondii infection.T.gondii infection is an independent risk factor for MS.

Objective: To investigate the correlation between interleukin-6 (IL-6) single nucleotide polymorphism (SNP) and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Methods: Patients with chronic hepatic diseases diagnosed as HBV infection in the Hepatology Center of the First Affiliated Hospital of Fujian Medical University from July 2012 to March 2018 were divided into HBV-ACLF and non-ACLF group. SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) was determined by the improved multi-temperature ligase detection reaction (imLDRTM) technique. Simultaneously, case data were reviewed with the 3-months followed up survival condition of the ACLF group. Normally distributed data were expressed as arithmetic means and SDs, and t-test was adopted. Data with skewed distribution were expressed as medians with interquartile range, and were measured by non-parametric test. Multivariate logistic regression analysis was used to analyze the relative risk of genetic polymorphism and HBV-ACLF as well as the relationship between IL-6 SNPs with the occurrence and prognosis of HBV-ACLF. Results: Four hundred patients were included in the study, with 122 (30.5%) in the HBV-ACLF and 278 (69.5%) in the non-ACLF group. There were significant differences in total bilirubin, albumin, and white blood cell count, percentage of neutrophils, platelet count, alanine aminotransferase, aspartate aminotransferase, prothrombin time and international standardized ratio, creatinine and the model for end-stage liver disease score between the two groups (P < 0.001). The genotype of IL-6 genes (rs1800795, rs1800797, rs2069827, and rs2069830) of all subjects showed no mutation or the mutation rate under 1%. There was no significant difference in the genotype of IL-6 (rs1524107, rs2069837, rs2069840 and rs2069845) between the two groups (P > 0.05). Multivariate logistic regression analysis showed that the SNPs in the above four loci of IL-6 gene was not associated with HBV-ACLF risk, nor had significant correlation with the 3-months prognosis. Conclusion The SNP genotyping of eight loci in IL-6 gene (rs1524107, rs1800795, rs1800797, rs2069827, rs2069830, rs2069837, rs2069840 and rs2069845) is unrelated to the occurrence and short-term prognosis of HBV-ACLF.

Objective To investigate the correlation between interleukin-6(IL-6)single nucleotide polymorphism(SNP)and the occurrence and prognosis of hepatitis B virus-associated acute-on-chronic liver failure(HBV-ACLF).Methods Patients with chronic hepatic diseases diagnosed as HBV infection in the Hepatology Center of the First Affiliated Hospital of Fujian Medical University from July 2012 to March 2018 were divided into HBV-ACLF and non-ACLF group.SNP genotyping of eight loci in IL-6 gene(rs1524107,rsl800795,rsl 800797,rs2069827,rs2069830,rs2069837,rs2069840 and rs2069845)was determined by the improved multi-temperature ligase detection reaction(imLDRTM)technique.Simultaneously,case data were reviewed with the 3-months followed up survival condition of the ACLF group.Normally distributed data were expressed as arithmetic means and SDs,and t-test was adopted.Data with skewed distribution were expressed as medians with interquartile range,and were measured by non-parametric test.Multivariate logistic regression analysis was used to analyze the relative risk of genetic polymorphism and HBV-ACLF as well as the relationship between IL-6 SNPs with the occurrence and prognosis of HBV-ACLF.Results Four hundred patients were included in the study,with 122(30.5%)in the HBV-ACLF and 278(69.5%)in the non-ACLF group.There were significant differences in total bilirubin,albumin,and white blood cell count,percentage of neutrophils,platelet count,alanine aminotransferase,aspartate aminotransferase,prothrombin time and international standardized ratio,creatinine and the model for end-stage liver disease score between the two groups(P<0.001).The genotype of IL-6 genes(rsl800795,rsl800797,rs2069827,and rs2069830)of all subjects showed no mutation or the mutation rate under 1%.There was no significant difference in the genotype of IL-6(rs 1524107,rs2069837,rs2069840 and rs2069845)between the two groups(P > 0.05).Multivariate logistic regression analysis showed that the SNPs in the above four loci of IL-6 gene was not associated with HBV-ACLF risk,nor had significant correlation with the 3-months prognosis.Conclusion The SNP genotyping of eight loci in IL-6 gene(rs 1524107,rs1800795,rs1800797,rs2069827,rs2069830,rs2069837,rs2069840 and rs2069845)is unrelated to the occurrence and short-term prognosis of HBV-ACLF.

Objective To investigate the association between interleukin-22 (IL-22) single nucleotide polymorphisms (SNPs) and the prognosis of hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF).Methods The patients with HBV-ACLF from the First Affiliated Hospital of Fujian Medical University were retrospectively studied.Seven SNP genotypes of IL-22 gene,including rs2227478,rs2227491,rs1179251,rs1179249,rs2227473,rs2227484,and rs11611206,were detected using imLDRTM multiple SNP typing kit and the distribution features of SNP genotypes were described.The relationship between the distribution of SNP genotypes and alleles and the prognosis of ACLF was analyzed.Comparison of genotypes and allele frequencies between groups were performed by chi-square test of R × C table or Fisher's exact tests.Binary logistic regression analysis was used to analyze whether IL-22 gene polymorphisms was an independent prognostic factor for patients with ACLF.Results A total of 122 patients with HBV-ACLF were included in this study.Ninety-two (75.1％) were male and 30 (24.59 ％) were female.Patients were stratified as survival group (90 cases) and non-survival group (32cases) according to the Results of three months follow-up.The genotype distribution of rs2227484 of IL-22 gene was significantly different between the two groups (x2=6.128,P=0.033).The A allele frequency in the non-survival group (15.6％) was significantly higher than that in the survival group (5.6％) with statistically significance (OR=0.318,95％ CI=0.126-0.804,P=0.012).There was no significant difference in the other six SNP genotypes of IL-22 gene between the two groups (all P＞0.05).However,binary logistic regression showed that rs2227484 of IL-22 gene was not an independent risk factor for the short-term mortality in HBV-ACLF patients (adjusted OR=3.102,95％ CI:0.939-10.250,P=0.063).Conclusions The A allele and AA genotype of rs2227484 of IL-22 gene may be associated with a short-term prognosis in patients with HBV-ACLF.

Objective To explore the dynamic expressions and clinical significance of toll-like receptor 4 (TLR4)/microRNA (miRNA)-181a in the pathogenesis of hepatic fibrosis (HF) in patients with chronic hepatitis B (CHB) .Methods CHB patients underwent liver biopsy for fibrosis staging HF (S) .Real-time polymerase chain reaction (PCR) was used to detect the expressions of miRNA-181a in both serum and liver tissue and the expression of TLR4 mRNA in liver tissue .Western blot was used to detect the expression of TLR4 protein in liver tissue . The fibrosis-4 (FIB-4 ) index and aspartate aminotransferase-to-platelet ratio index (APRI ) were calculated for noninvasive evaluation of fibrosis staging .One-way ANOVA ,Mann-Whitney U test ,spearman correlation analysis and receiver operating characteristic (ROC) curve were used for statistical analysis .Results Forty CHB patients were includedin this study ,including 7 with S0 ,6 with S1 ,14 with S2 ,7 with S3 and 6 with S4 .Serum levesl of miRNA-181a (2-ΔΔCt ) in paitents with S0-4 were 1 .00 ± 0 .00 ,0 .68 ± 0 .08 ,1 .60 ± 0 .43 ,2 .32 ± 0 .40 , and 1 .81 ± 0 .22 ,respectively ,showing an overall upward trend (F=207 .242 ,P< 0 .01) and a positive correlation with the severity of HF (r= 0 .754 , P< 0 .01) .The expressions of miRNA-181a ,TLR4 mRNA and TLR4 protein in liver tissues showed an overall increasing trend from S 0 to S4 (F=207 .242 , 110 .390 and 57 .030 ,respectively ,all P<0 .01) .The expression of miRNA-181a in liver tissue showed a positive correlation with both the expression of TLR4 protein in liver tissue and the severity of HF (r=0 .673 and 0 .911 ,respectively ,both P< 0 .01) .There was no significant difference of APRI scores between the severe (S3-4) and non-severe (S0-2) HF groups (Z= -1 .401 ,P>0 .05) .The serum level of miRNA-181a was superior to FIB-4 index for evaluation of the severe HF (S3-4) ,with areas under the ROC curve (AUROC ) of 0 .887 and 0 .695 , respectively , and accuracy of 85 .0％ and 60 .0％ , respectively .Conclusions miRNA-181a may be involved in the regulation of TLR4 signaling pathway so that to affect the progression of HF in CHB patients ,which may be a potential new target for the prevention and early treatment of HF and a non-invasive serum marker for evaluation of HF .

Objective To investigate the relationship between hepatic steatosis and virological markers in patients with chronic hepatitis B (CHB ) during immune clearance (IC ) phase.Methods Pathology proven CHB patients in IC phase were collected from the Liver Center of the First Affiliated Hospital of Fujian Medical University from January 2009 to October 2016 .Patients were divided into non-to mild fatty liver (F0 －F1) group and moderate to severe fatty liver (F2 －F4) group according to the liver steatosis degree .The relationship between liver steatosis and virological markers in serum was compared .The measurement data were analyzed using independent sample t test ,and the count data were analyzed by chi-square test .Results A total of 298 patients were included ,including 237 males (79 .5%) and 61(20 .5%) females ,and the average age was (32 .4 ± 10 .3) years old .The 23 .5%(70／298) of these patients had liver steatosis .A total of 273 (91 .6%) cases were in F0－F1 group ,and the remaining 25 (8 .4%) cases were in F2 －F4 group.The patients in F2 － F4 group had higher body mass index ([25.90 ± 2.70] vs [21 .68 ± 2.90] kg／m2) ,serum triglyceride ([1.52 ± 0.77] vs [1.11 ± 0.55] mmol／L) and cholesterol ([4 .88 ± 1 .15] vs [4 .33 ± 0 .92] mmol／L) than F0－F1 group ,and the differences were all statistically significant (t＝ －7 .007 ,－2 .667 ,and －2 .751 ,respectively ,all P＜0 .05).In addition , the serum levels of HBsAg and HBV DNA in F2 －F4 group were also significantly higher than F0 －F1 group (t＝ －3 .291 and －2 .831 ,respectivelt ,both P＜0 .01).According to the grading of inflammation and fibrosis ,the differences of HBsAg and HBV DNA levels between F0 －F1 group and F2 －F4 group were statistically significant only in patients with more severe inflammation (t＝ －2 .738 and －2 .135 , respectively ,both P＜0 .05) or less severe fibrosis (t＝ －2 .258 and －2 .333 ,respectively ,both P＜0 .05).Conclusion Among CHB patients experiencing immune clearance ,serum HBsAg and HBV DNA levels are positively correlated with the severity of hepatic steatosis ,and this phenomenon is closely related to the degree of liver inflammation.