Hepatitis D virus dual-infection among Chinese hepatitis B patient related to hepatitis B surface antigen,hepatitis B virus DNA and age

The screening practices for hepatitis D virus(HDV)are diverse and nonstandardized worldwide,and the exact prevalence of HDV is uncertain.AIM To estimate HDV prevalence and investigate viral marker quantity trends in patients with hepatitis D.METHODS We collected 5594 serum samples from patients with hepatitis B in Jilin Province,China(3293 males and 2301 females,age range of 2 to 89 years).We then conducted tests for hepatitis B surface antigen(HBsAg),hepatitis B Virus(HBV)DNA,anti-hepatitis D antigen(HDAg),and HDV RNA.RESULTS We found that the prevalence of anti-HDAg and HDV RNA among hepatitis B patient were 3.6%(3.2-4.2%)and 1.2%(0.9-1.5%),respectively,87.69%of hepatitis D patients were 51-70 years old.HDV infection screening positive rate of patients with HBV DNA levels below 2000 IU/mL(2.0%)was higher than those above 2000 IU/mL(0.2%).Among anti-HDAg positive patients,the HDV RNA positive rate was positively correlated with the HBsAg level and anti-HDAg level.There was a weak correlation between HBsAg and anti-HDAg levels among hepatitis D patients.CONCLUSION Our study highlights the importance of considering multiple factors when assessing the severity of HDV infection,comprehensive evaluation of patients’clinical and laboratory parameters is necessary for proper diagnosis and treatment.

Growing burden of alcoholic liver disease in China: A review

Explosive economic growth and increasing social openness in China over the last30 years have significantly boosted alcohol consumption, and consequently, the incidence of alcoholic liver disease(ALD) in China has increased. Because the epidemiologic and clinical features of ALD in the Chinese population may differ from those of the Caucasian population, this review describes the epidemiology,pathogenesis, genetic polymorphisms, diagnosis, and treatment of ALD in the Chinese population. This updated knowledge of ALD in China provides information needed for a global understanding of ALD and may help in the development of useful strategies for reducing the global ALD burden.

Daclatasvir plus asunaprevir in treatment-na?ve patients with hepatitis C virus genotype 1b infection

AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assigned(3:1) to receive 24 wk of treatment with d UAL(daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period(immediate treatment arm) or following 12 wk of matching placebo(placebodeferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12(SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin(70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in d UAL-treated patients compared with placebo patients during the first 12 wk(doubleblind phase), and during 24 wk of d UAL in both arms combined.RESULTS In total, 207 patients were randomly assigned to immediate(n = 155) or placebo-deferred(n = 52) treatment. Most patients were Asian(86%), female(59%) and aged < 65 years(90%). Among them, 13% had cirrhosis, 32% had IL28 B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/m L. Among patients in the immediate treatment arm, SVR12 was achieved by 92%(95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate(70%). SVR12 was largely unaffected by cirrhosis(89%), age ≥ 65 years(92%), male sex(90%), baseline HCV RNA ≥ 6 million(89%) or IL28 B non-CC genotypes(96%), although SVR12 was higher among patients without(96%) than among those with(53%) baseline NS5 A resistanceassociated polymorphisms(at L31 or Y93 H). during the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving d UAL. during 24 wk of d UAL therapy(combined arms), the most common adverse events(≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities(alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued d UAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths.CONCLUSION d UAL was well-tolerated during this phase 3 study, and SVR12 with d UAL treatment(92%) exceeded thehistorical SVR rate for peg-interferon plus ribavirin of 70%.

Iron metabolism disorders in patients with hepatitis B-related liver diseases

AIM To investigate the relationship between levels of iron metabolism markers and hepatitis B virus(HBV)-related chronic liver diseases.METHODS This case-control study with 318 participants included 78 cases of chronic hepatitis B, 85 cases of HBV-related liver cirrhosis, 77 cases of HBV-related hepatocellular carcinoma, and 78 healthy controls. Markers of iron metabolism were detected in participants. Hematological and biochemical parameters and HBV-DNA were assessed. Child-Pugh grade and Barcelona Clinic Liver Cancer stage were determined for each hepatocellular carcinoma patient. Perls' staining was performed on liver sections. The SPSS program was used for all statistical analyses, and statistical significance was considered if a P-value < 0.05.RESULTS Significantly higher serum ferritin and lower serum hepcidin levels were detected in all groups of HBV-infected patients compared with healthy controls. Serum iron, total iron binding capacity, and serum transferrin levels were significantly lower in patients with cirrhosis and hepatocellular carcinoma, whereas the hepcidin level was higher than that in chronic hepatitis B patients. Correlation analysis indicated that serum hepcidin was negatively correlated with HBV-DNA load(P < 0.01). Serum ferritin and transferrin saturation levels increased proportionally to the extent of liver cirrhosis and poorer Child-Pugh scores(P < 0.05). The decreased serum iron and transferrin saturation levels were significantly correlated with a smaller hepatocellular carcinoma tumor burden according to Barcelona Clinic Liver Cancer staging. Liver histology showed a clearly increasing trend in iron deposition in the liver tissues with increased fibrosis, which became prominent at stages 3(severe liver fibrosis) and 4(cirrhosis). CONCLUSION Iron metabolism disorders occur in patients with HBVrelated liver diseases. The serum markers of iron metabolism disorders vary in different stages of HBV-related liver diseases.

Liver failure associated with benzbromarone:A case report and review of the literature

BACKGROUND Benzbromarone is a uricosuric agent that reduces proximal tubular reabsorption of uric acid.Because of hepatotoxicity,it has been withdrawn from the market in Europe.Recently,some benefit-risk assessments of benzbromarone suggest that benzbromarone has greater benefits than risks,and the application of benzbromarone in the treatment of gout and hyperuricemia is still under debate.CASE S UMMARY A 39-year-old man was admitted to the hospital for icterus and nausea,and he was treated with benzbromarone(100 mg/d)for 4 mo because of hyperuricemia He had a 10-year history of beer drinking(alcohol:about 28 g/d).Laboratory data showed severe liver injury and serious coagulation dysfunction;tests for autoimmune antibodies,viral hepatitis,and human immunodeficiency virus were negative.Despite administration of liver function-protecting drugs and efficient supportive treatment,the patient deteriorated quickly after hospitalization and developed grade Ⅱ encephalopathy within a few days.The patient accepted continuous plasma exchange six times;however,his condition did not improve.Based on suggestions from multidisciplinary consultation,the patient underwent liver transplantation 26 d after admission.Liver specimen pathology results showed massive necrosis consistent with drug-induced liver injury,supporting the diagnosis of acute liver failure associated with benzbromarone.The patient recovered quickly thereafter.CONCL USION This case highlights that clinicians should be on the alert for the severe hepatotoxicity of benzbromarone.Before prescribing benzbromarone,physicians should evaluate the high-risk factors that may lead to liver injury and provide suggestions for monitoring benzbromarone’s hepatotoxicity during treatment.

Serum hepatitis B core-related antigen as a surrogate marker of hepatitis B e antigen seroconversion in chronic hepatitis B

BACKGROUND Quantitative hepatitis B core-related antigen(qHBcrAg)has a better correlation with intrahepatic hepatitis B virus(HBV)covalently closed circular DNA(cccDNA)than HBV DNA or hepatitis B e antigen(HBeAg),but data are still lacking for its clinical application.AIM The aim was to investigate serum qHBcrAg levels in patients with chronic hepatitis B and assess the correlation of serum qHBcrAg with pregenomic RNA(pgRNA),cccDNA,and HBeAg seroconversion.METHODS This study was a secondary analysis of patients who underwent percutaneous liver biopsy between July 2014 and June 2019 in two multicenter randomized controlled clinical trials of peginterferon vs nucleos(t)ide analog(NUC)-based therapy(NCT03509688 and NCT03546530).Serum qHBcrAg,pgRNA,HBV DNA,hepatitis B core antigen,HBeAg,liver cccDNA,and HBV DNA were measured.The correlations of serum qHBcrAg with other biomarkers were analyzed.RESULTS A total of 139 patients were included.The mean qHBcrAg levels were 5.32±1.18 log10 U/mL at baseline and decreased during treatment(all P<0.0001).Serum qHBcrAg levels were positively correlated with pgRNA(r=0.597,P<0.0001)and cccDNA(r=0.527,P<0.0001)levels.The correlation of serum qHBcrAg level and intrahepatic HBV DNA levels at baseline was weak but significant(r=0.399,P<0.0001).HBcrAg predicted HBeAg seroconversion,with areas under the receiver operating characteristics curve of 0.788 at 24 wk and 0.825 at 48 wk.Log HBcrAg at wk 24 and 48 was independently associated with HBeAg seroconversion[odds ratio(OR)=2.402,95%confidence interval(CI):1.314-4.391,P=0.004;OR=3.587,95%CI:1.315-9.784,P=0.013].CONCLUSION Serum HBcrAg levels were correlated with HBV virological markers and could be used to predict HBeAg seroconversion.

Association between polymorphisms of the APOBEC3G gene and chronic hepatitis B viral infection and hepatitis B virusrelated hepatocellular carcinoma

AIM to determine the relationship between five A3 G gene single nucleotide polymorphisms and the incidence of hepatitis B virus(HBV) infection and hepatocellular carcinoma(HCC). METHODS this association study was designed as a retrospective study, including 657 patients with chronic HBV infection(CHB) and 299 healthy controls. All subjects were ethnic Han Chinese. Chronic HBV-infected patients recruited between 2012 and 2015 at the First Hospital of Jilin University(Changchun) were further classified into HBV-related HCC patients(n = 287) and non-HCC patients(n = 370). Frequency matching by age and sex was performed for each group. Human genomic DNAwas extracted from whole blood. Gene polymorphisms were identified using a mass spectroscopic method.RESULTS there were no significant differences between the genotype and allele frequencies of the rs7291971, rs5757465 and rs5757463 A3 G gene polymorphisms, and risk of CHB and HBV-related HCC. the AG genotype and G allele for rs8177832 were significantly related to a decreased risk of CHB(OR = 0.67, 95%CI: 0.47-0.96; OR = 0.69, 95%CI: 0.50-0.95, respectively) and HCC(OR = 0.53, 95%CI: 0.34-0.84; OR = 0.58, 95%CI: 0.39-0.87, respectively). A significant relationship was found between rs2011861 computed tomography, tt genotypes and increased risk of HCC(OR = 1.69, 95%CI: 1.02-2.80; OR = 1.82, 95%CI: 1.08-3.06, respectively). Haplotype analyses showed three protective and four risk haplotypes for HCC. Also, one protective haplotype was found against CHB.CONCLUSION this study indicates that the A3 G rs8177832 polymorphism is associated with a decreased risk of CHB infection and HCC, while the rs2011861 polymorphism is associated with an increased risk of HCC.

Serum metabolic profiling of targeted bile acids reveals potentially novel biomarkers for primary biliary cholangitis and autoimmune hepatitis

BACKGROUND Primary biliary cholangitis(PBC)and autoimmune hepatitis(AIH)are two unexplained immune diseases.The golden standard for diagnosis of these diseases requires a liver biopsy.Liver biopsy is not widely accepted by patients because of its invasive nature,and atypical liver histology can confuse diagnosis.In view of the lack of effective diagnostic markers for PBC and AIH,combined with the increasingly mature metabolomics technologies,including full-contour metabolomics and target.AIM To determine non-invasive,reliable,and sensitive biochemical markers for the differential diagnosis of PBC and AIH.METHODS Serum samples from 54 patients with PBC,26 patients with AIH and 30 healthy controls were analyzed by Ultra-high performance liquid chromatographytandem mass spectrometry serum metabolomics.The metabolites and metabolic pathways were identified,and the metabolic changes,metabolic pathways and inter-group differences between PBC and AIH were analyzed.Fifteen kinds of target metabolites of bile acids(BAs)were quantitatively analyzed by SRM,and the differential metabolites related to the diagnosis of PBC were screened by receiver operating characteristic curve analysis.RESULTS We found the changes in the levels of amino acids,BAs,organic acids,phospholipids,choline,sugar,and sugar alcohols in patients with PBC and AIH.Furthermore,the SRM assay of BAs revealed the increased levels of chenodeoxycholic acid,lithocholic acid(LCA),taurolithocholic acid(TLCA),and LCA+TLCA in the PBC group compared with those in the AIH group.The levels of BAs may be used as biomarkers to differentiate PBC from AIH diseases.The levels of glycochenodeoxycholic acid,glycochenodeoxycholic sulfate,and taurodeoxycholic acid were gradually elevated with the increase of Child-Pugh class,which was correlated with the severity of disease.CONCLUSION The results demonstrated that the levels of BAs could serve as potential biomarkers for the early diagnosis and assessment of the severity of PBC and AIH.

Isolated elevated aspartate aminotransferase in an asymptomatic woman due to macro-aspartate aminotransferase: A case report

BACKGROUND Macro-aspartate aminotransferase(AST), a macroenzyme, is a high-molecular mass complex formed by self-polymerization or association with other serum components that are difficult for the kidney to clear, leading to the isolated elevation of serum AST activity. Cases of macro-AST formation are rare, with only 3 published in the English language literature up to September 2019 in China. In this paper, we present a case in which an asymptomatic woman with persistent isolated elevated AST was confirmed as having macro-AST by the polyethylene glycol precipitation method.CASE SUMMARY A 34-year-old woman was referred to our clinic for elevated AST levels with normal levels of other liver-associated enzymes on November 12, 2018. Her AST level of liver function test had been abnormal for 7 mo before she came to the clinic. The patient was asymptomatic with a normal physical examination. There was no relevant family history and no alcohol consumption or smoking. She had a several-month history of traditional Chinese medical taking and had stopped it 1 year prior. The laboratory tests in our clinic showed only the elevation of AST(89.5 U/L) with no other significant abnormalities. We performed the precipitation technique with polyethylene glycol to confirm the presence of macro-AST. Then for almost a year, her AST level still fluctuated in the abnormal range.CONCLUSION This case highlights that clinical physicians should be familiar with this rare condition of persistent isolated AST elevation due to the presence of macro-AST to avoid unnecessary investigation and patient anxiety.

Determination of the upper cut-off values of serum alanine aminotransferase and aspartate aminotransferase in Chinese

AIM:To determine the upper cut-off values of serumalanine aminotransferase(ALT)and aspartate aminotransferase(AST)in a Northern Chinese population.METHODS:A total of 3769 subjects in Jilin Province Northeast China were stratified to determine the potential factors affecting serum ALT and AST levels.The upper cut-off values of serum ALT and AST in these subjects were determined using receiver operating characteristic analysis and their sensitivity and specificity were evaluated.RESULTS:Stratification analysis revealed that serum ALT and AST levels were associated with gender,alcohol consumption,serum cholesterol and triglyceride levels,and body mass index.The upper cut-off values of serum ALT and AST were 22.15 U/L and 25.35 U/L for healthy men and 22.40 U/L and 24.25 U/L for healthy women,respectively.The new cut-off values had a higher sensitivity,but a slightly lower specificity than the current standards.CONCLUSION:Our results indicate that the new upper cut-off values of serum ALT and AST are markedly lower than current standards and may be valuable for the evaluation of liver function.

Elevated soluble 4-1BB is associated with serum markers of hepatitis B virus in patients with chronic hepatitis B

BACKGROUND Previous studies have suggested that the costimulatory molecule 4-1BB plays pivotal roles in regulating immunity during chronic viral infection.However,up to now,there are few studies about 4-1BB in chronic hepatitis B(CHB).AIM To clarify this issue,we report our comprehensive study results on the expression levels of 4-1BB in patients with CHB.METHODS From September 2018 to June 2019,a total of 64 patients with CHB were recruited from the Department of Hepatology,The First Hospital of Jilin University.Peripheral blood samples were collected from 52 treatment-naïve and 12 entecavir-treated patients with CHB as well as 37 healthy donors(including 24 healthy adults and 13 healthy children).The levels of soluble 4-1BB(s4-1BB)in plasma were measured by ELISA.4-1BB mRNA expression in peripheral blood mononuclear cells was detected by real-time quantitative PCR.RESULTS The s4-1BB levels in the plasma of patients with CHB were significantly higher than those in healthy adults(94.390±7.393 ng/mL vs 8.875±0.914 ng/mL,P<0.001).In addition,the s4-1BB level in plasma was significantly increased in patients with a higher viral load and a disease flare up.However,there were no significant differences between treatment-naïve and entecavir-treated patients.Interestingly,among treatment-naïve patients with CHB,the levels of s4-1BB in plasma had a significant positive correlation with hepatitis B surface antigen,hepatitis B virus DNA,hepatitis B e antigen,and triglyceride levels(r=0.748,P<0.001;r=0.406,P=0.004;r=0.356,P=0.019 and r=-0.469,P=0.007,respectively).The 4-1BB mRNA expression was higher in the peripheral blood mononuclear cells of patients with CHB than in the peripheral blood mononuclear cells of healthy adults,but the difference was not statistically significant.CONCLUSION These results suggest that the levels of s4-1BB may be associated with pathogenesis of hepatitis B virus and therefore may be a promising biomarker for disease progression.

Association of Estrogen Receptor Gene Polymorphisms and Primary Biliary Cirrhosis in a Chinese Population： A Case- Control Study

Background： Primary biliary cirrhosis （PBC） is a chronic and slowly progressive cholestatic liver disease characterized by destruction of the interlobular bile ducts and a striking female predominance, The aim of this study was to identity associations between estrogen receptor （ESR） gene polymorphisms with the risk of developing PBC and abnormal serum liver tests in a Chinese population. Methods： Thirty-six patients with PBC （case group） and 35 healthy individuals （control group） from the First Hospital of Jilin University were studied. Whole genomic DNA was extracted from all the participants. Three single-nucleotide polymorphisms （rs2234693~ rs2228480, and rs3798577） from ESR1 and two （rs1256030 and rs1048315） from ESR2 were analyzed by a pyrosequencing method. Demographic data and liver biochemical data were collected. Results： Subjects with the T allele at ESR2 rs1256030 had 1.5 times higher risk of developing PBC than those with the C allele （odds ratio [OR] = 2.1277, 95% confidence interval [CI] = 1.1872-4.5517）. Haplotypes TGC of ESRI rs2234693, rs2228480, and rs3798577 were risk thctors for having PBC. The C allele at ESRI rs2234693 was associated with abnormal alkaline phosphatase （OR 5.2469, 95% CI = 1.3704-20.0895） and gamma-glutamyl transferase （OR = 3.4286, 95% CI = 1.0083-13.6578） levels in PBC patients. Conclusions： ESR2 rs1256030 T allele may be a significant risk factor for the development of PBC. Screening for patients with gene polymorphisms may help to make early diagnoses in patients with PBC.