Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B: A meta-analysis.

BACKGROUND: Although hepatitis B virus infection is the leading cause of chronic liver injury globally, nonalcoholic fatty liver disease (NAFLD) is gradually gaining attention as another major chronic liver disease. The number of patients having chronic hepatitis B (CHB) with concomitant hepatic steatosis has increased. AIM: To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB. METHODS: Relevant English studies were systematically searched across PubMed, EMBASE, Web of Science, and Cochrane Library until October 2023. Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included. RESULTS: Of the 2502 retrieved studies, 11 articles were finally included. Biochemical response until 48 wk (OR = 0.87, 95%CI: 0.50-1.53, P = 0.000) and 96 wk (OR = 0.35, 95%CI: 0.24-0.53, P = 0.24) and virological response until 96 wk (OR = 0.80, 95%CI: 0.43-1.49, P = 0.097) were lower in patients with hepatic steatosis than in patients with CHB alone. CONCLUSION: Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update.

Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. Currently, the diagnosis of DILI still follows the strategy of exclusion. Therefore, a detailed history taking and a thorough and careful exclusion of other potential causes of liver injury is the key to correct diagnosis. This guideline was developed based on evidence-based medicine provided by the latest research advances and aims to provide professional guidance to clinicians on how to identify suspected DILI timely and standardize the diagnosis and management in clinical practice. Based on the clinical settings in China, the guideline also specifically focused on DILI in chronic liver disease, drug-induced viral hepatitis reactivation, common causing agents of DILI (herbal and dietary supplements, anti-tuberculosis drugs, and antineoplastic drugs), and signal of DILI in clinical trials and its assessment.

Biliary sepsis complication with congenital hepatic fibrosis: an unexpected outcome.

BACKGROUND: CHF (Congenital hepatic fibrosis) is a rare hereditary disease characterized by periportal fibrosis and ductal plate malformation. Little is known about the clinical presentations and outcome in CHF patients with an extraordinary complication with biliary sepsis. Our case described a 23-year-old female diagnosed as CHF combined with biliary sepsis. Her blood culture was positive for KP (Klebsiella pneumoniae), and with a high level of CA19-9 (> 1200.00 U/ml, ref: <37.00 U/ml). Meanwhile, her imaging examinations showed intrahepatic bile duct dilatation, portal hypertension, splenomegaly, and renal cysts. Liver pathology revealed periportal fibrosis and irregularly shaped proliferating bile ducts. Whole-exome sequencing identified two heterozygous missense variants c.3860T > G (p. V1287G) and c.9059T > C (p. L3020P) in PKHD1 gene. After biliary sepsis relieved, her liver function test was normal, and imaging examination results showed no significant difference with the results harvested during her biliary sepsis occurred. CONCLUSION: The diagnosis of CHF complicated with biliary sepsis in the patient was made. Severely biliary sepsis due to KP infection may not inevitably aggravate congential liver abnormality in young patients. Our case provides a good reference for timely treatment of CHF patients with biliary sepsis.

Alleviated symptoms of SARS-CoV-2 Omicron variant infection in chronic hepatitis B patients with immune control.

The impact of hepatitis B virus (HBV) infection on the progression of coronavirus disease 2019 (COVID-19) disease remains controversial. We aimed to investigate whether pre-existing chronic HBV (CHB) infection and therapy with anti-HBV nucleos(t)ide analogs (NAs) influence the clinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. In this study, clinical information was collected via a questionnaire from patients with COVID-19, and their clinical symptoms were quantitatively assessed for comparative analyses. Additionally, hepatitis B-related laboratory data were collected for CHB patients. Propensity score matching (PSM) was used to minimize confounding biases. A total of 785 patients with COVID-19 were included in the cohort, of which 387 were identified as being infected with CHB infection and they were categorized as being in the immune control or clearance phase. After PSM, the CHB group (n = 222) had a shorter duration of fever and disease course, milder clinical symptoms, and lower incidence of pneumonia than the non-CHB group (n = 222) after Omicron variant infection (p < 0.05). After the adjustment of confounding factors, CHB patients showed a lower risk of prolonged fever, severe clinical symptoms, and pneumonia (p < 0.05). However, there were no statistically significant differences in the clinical symptoms and incidence of pneumonia between CHB patients who received and did not receive NAs, or CHB patients who received tenofovir disoproxil fumarate and entecavir (p > 0.05). In conclusion, our findings suggest that the crosstalk of anti-HBV immunity may contribute to the alleviated symptoms of SARS-CoV-2 Omicron variants infection in the CHB patients, independent of anti-HBV NA therapy.

PROS1 variant c.1574C>T p.Ala525Val causes portal vein thrombosis with protein S deficiency.

BACKGROUND: Protein S (PS) is a vitamin K-dependent plasma glycoprotein, and the deficiency of PS increases the risk of venous thromboembolism (VTE). PS deficiency has been found in 1.5-7% of selected groups of thrombophilic patients. However, the reported PS deficiency patients with portal vein thrombosis are scarce. CASE REPORT AND RESULTS: Our case described a 60-year-old male patient presented portal vein thrombosis with protein S deficiency. Imaging findings of the patient revealed extensive thrombosis involving the portal vein and superior mesenteric vein. His medical history revealed lower extremity venous thrombosis 10 years ago. The level of PS activity was greatly reduced (14%, reference: 55-130%). Acquired thrombophilia caused by antiphospholipid syndrome, hyperhomocysteinemia, or malignancy were excluded. Whole exome sequencing revealed a heterozygous missense variation c.1574C>T, p.Ala525Val in the PROS1 gene. The in-silico analysis of the variant was performed by SIFT and PolyPhen-2. The results showed that the variant is a pathogenic and likely pathogenic variation respectively (SIFT, -3.404; PolyPhen-2, 0.892), the amino acid substitution A525V is presumed to result in unstable PS protein which is degraded intracellularly. Mutation site of the proband and his family members was validated by Sanger sequencing. CONCLUSION: According to the clinical manifestation, imaging findings, protein S level, and the genetic results, a diagnosis of portal vein thrombosis with PS deficiency was made. To the best of our knowledge, our case is the second reported PS deficiency patient caused by PROS1 c.1574C>T, p.Ala525Val variant in Asia, and the case is also the only reported case with PROS1 c.1574C>T, p.Ala525Val variant presents portal vein thrombosis.

Is fatigue related to the severity of liver inflammation in patients with chronic liver disease? A cross-sectional study.

OBJECTIVES: Fatigue is common in patients with chronic liver disease; however, its pathogenesis is unclear. This study aimed to provide insights into the pathogenesis of chronic liver disease-related fatigue by assessing the relationship between fatigue and the degree of inflammation in chronic liver disease. DESIGN: We performed a cross-sectional study of 1374 patients with pathologically proven chronic liver disease diagnosed at the Affiliated Hospital of Hangzhou Normal University in Hangzhou, China. SETTING: Primary single-centre study. PARTICIPANTS: One thousand three hundred and seventy-four patients with liver biopsy-proven chronic liver disease. INTERVENTIONS: The patients were divided into fatigue and non-fatigue groups according to the Chronic Liver Disease Questionnaire. Propensity score matching was used to match the baseline features of the patients in the two groups. PRIMARY AND SECONDARY OUTCOME MEASURES: Liver steatosis, ballooning, inflammation and fibrosis were measured according to the pathological results of liver biopsy. Fatigue was measured using the Chronic Liver Disease Questionnaire. RESULTS: Of the 1374 patients, 262 (19.67%) experienced fatigue. There were 242 and 484 patients with and without fatigue, respectively, who were successfully matched for sex, age and classification of chronic liver disease by propensity score matching. After matching, the fatigue group showed higher liver enzyme levels, inflammation grades and fibrosis stages than the non-fatigue group (p<0.05). Multivariate analysis showed that age (OR: 2.026; p=0.003), autoimmune liver disease (OR: 2.749; p=0.002) and active inflammation (OR: 1.587; p=0.003) were independent risk factors for fatigue after adjusting for confounders. The OR of the risk for fatigue increased in a stepwise manner with increasing inflammation grade in young-aged and middle-aged patients (p<0.05). This tendency was not observed in elderly patients (p>0.05). CONCLUSION: Patients with chronic liver disease were burdened by fatigue, which increased progressively with rising liver inflammation severity in young-aged and middle-aged rather than elderly patients.

Blood pressure stratification for predicting liver fibrosis risk in metabolic dysfunction associated fatty liver disease.

INTRODUCTION AND OBJECTIVES: The optimal blood pressure (BP) range for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) is currently unknown. This study aimed to explore the relationship between stratified BP levels and MAFLD progression. PATIENTS AND METHODS: The data of adults who underwent yearly health check-ups were screened to establish both a cross-sectional and a 6-year longitudinal cohort of individuals with MAFLD. BP was classified into the following categories optimal, normal, high-normal, and hypertension. Liver fibrosis was diagnosed with fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase-to-platelet ratio index (APRI). RESULTS: A total of 10,232 individuals were included in the cross-sectional cohort. In the MAFLD population, individuals with liver fibrosis had significantly higher BP levels and hypertension prevalence (P < 0.001) than those without. Furthermore, liver fibrosis score was significantly associated with BP levels (P < 0.001). In the 6-year longitudinal cohort of 3661 individuals with MAFLD without liver fibrosis, the incidence rates of liver fibrosis increased with increasing BP levels as follows optimal=11.20%, normal=13.90%, high-normal=19.50%, hypertension=26.20% (log-rank 22.205; P < 0.001). Cox regression analysis showed that both baseline high-normal BP (hazard ratio [HR], 1.820; P=0.019) and hypertension (HR, 2.656; P < 0.001) were predictive of liver fibrosis. CONCLUSIONS: BP stratification may be useful in predicting the progression of MAFLD. Individuals having MAFLD with concurrent hypertension or high-normal BP are at a higher risk of liver fibrosis. These findings may provide a criteria for early intervention of MAFLD to prevent liver fibrosis.

Chlamydia psittaci pneumonia complicated with organizing pneumonia: A case report and literature review.

A patient with pneumonia had a fever for 2 weeks. After the initial anti-infection treatment failed, he was diagnosed with C. psittaci pneumonia complicated with organizing pneumonia, through next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) and lung biopsy. He was treated with antibiotics and corticosteroids for 2 months.

The aberrant upregulation of exon 10-inclusive SREK1 through SRSF10 acts as an oncogenic driver in human hepatocellular carcinoma.

Deregulation of alternative splicing is implicated as a relevant source of molecular heterogeneity in cancer. However, the targets and intrinsic mechanisms of splicing in hepatocarcinogenesis are largely unknown. Here, we report a functional impact of a Splicing Regulatory Glutamine/Lysine-Rich Protein 1 (SREK1) variant and its regulator, Serine/arginine-rich splicing factor 10 (SRSF10). HCC patients with poor prognosis express higher levels of exon 10-inclusive SREK1 (SREK1L). SREK1L can sustain BLOC1S5-TXNDC5 (B-T) expression, a targeted gene of nonsense-mediated mRNA decay through inhibiting exon-exon junction complex binding with B-T to exert its oncogenic role. B-T plays its competing endogenous RNA role by inhibiting miR-30c-5p and miR-30e-5p, and further promoting the expression of downstream oncogenic targets SRSF10 and TXNDC5. Interestingly, SRSF10 can act as a splicing regulator for SREK1L to promote hepatocarcinogenesis via the formation of a SRSF10-associated complex. In summary, we demonstrate a SRSF10/SREK1L/B-T signalling loop to accelerate the hepatocarcinogenesis.

Alagille syndrome caused by NOTCH2 mutation presented atypical pathological changes.

BACKGROUND: Alagille syndrome (ALGS) is a rare multisystem disorder caused by mutations in the JAG1 or NOTCH2 gene. However NOTCH2 gene mutations were rarely found in the Alagille patients. Little is known about the clinical and pathological profiles about Alagille patients with NOTCH2 mutation. CASE REPORT: Our case described a 16-year-old female patient manifesting as recurrent jaundice and abnormal liver function from the second week of her birth. She presented a butterfly vertebrae and typical facial features including a prominent forehead, deep-set eyes, a pointed chin, and a straight nose with bulbous tip. Pathogenic heterozygous c.5857 C > T variant in NOTCH2 gene was found. Her liver biopsy featured by a disorder liver structure with cholestasis and fibrosis in portal area, which is different from typical bile duct paucity reported in JAG1 deficient patients. RESULTS: A diagnosis of ALGS was made. The patient was treated with ursodeoxycholic acid and compound embryonic bovine liver extract tablets and infusion of human serum albumin to improve her clinical and pathological symptoms. CONCLUSION: Since Alagille patients with NOTCH2 mutations have been rarely reported, our case will highlight the clinical and pathological profiles of these patients.

Successful treatment of infantile hepatitis B with lamivudine: A case report.

BACKGROUND: How to treat infantile hepatitis B virus (HBV) infection remains a controversial issue. The nucleoside analogue lamivudine (LAM) has been approved to treat children (2 to 17 years old) with chronic hepatitis B. Here, we aimed to investigate the benefit of LAM treatment in infantile hepatitis B. CASE SUMMARY: A 4-mo-old infant born to a hepatitis B surface antigen (HBsAg)-positive woman was found to be infected by HBV during a health checkup. Liver chemistry and HBV seromarker tests showed alanine aminotransferase of 106 U/L, HBsAg of 685.2 cut-off index, hepatitis B "e" antigen of 1454.0 cut-off index, and HBV DNA of > 1.0 × 109 IU/mL. LAM treatment (20 mg/d) was initiated, and after 19 mo, serum HBsAg was entirely cleared and hepatitis B surface antibody was present. The patient received LAM treatment for 2 years in total and has been followed for 3 years. During this period, serum hepatitis B surface antibody has been persistently positive, and serum HBV DNA was undetectable. CONCLUSION: Early treatment of infantile hepatitis B with LAM could be safe and effective.

Effects of Deposition and Annealing Temperature on the Structure and Optical Band Gap of MoS2 Films.

In this study, molybdenum disulfide (MoS2) film samples were prepared at different temperatures and annealed through magnetron sputtering technology. The surface morphology, crystal structure, bonding structure, and optical properties of the samples were characterized and analyzed. The surface of the MoS2 films prepared by radio frequency magnetron sputtering is tightly coupled and well crystallized, the density of the films decreases, and their voids and grain size increase with the increase in deposition temperature. The higher the deposition temperature is, the more stable the MoS2 films deposited will be, and the 200 °C deposition temperature is an inflection point of the film stability. Annealing temperature affects the structure of the films, which is mainly related to sulfur and the growth mechanism of the films. Further research shows that the optical band gaps of the films deposited at different temperatures range from 0.92 eV to 1.15 eV, showing semiconductor bandgap characteristics. The optical band gap of the films deposited at 200 °C is slightly reduced after annealing in the range of 0.71-0.91 eV. After annealing, the optical band gap of the films decreases because of the two exciton peaks generated by the K point in the Brillouin zone of MoS2. The blue shift of the K point in the Brillouin zone causes a certain change in the optical band gap of the films.

SNGH16 regulates cell autophagy to promote Sorafenib Resistance through suppressing miR-23b-3p via sponging EGR1 in hepatocellular carcinoma.

OBJECTIVE: Tumor cells could acquire drug resistance through cell autophagy. This study aimed to explore the role of SNHG16 in sorafenib-resistant HCC cells and its mechanism with miR-23b-3p. METHODS: The sorafenib-resistant Hep3B cell model was established. The SNHG16 and miR-23b-3p gene expressions were determined in normal HCC and sorafenib-resistant HCC tissues. Detection of the expression of SNHG16 and miR-23b-3p and its respective correlation with survival rate were performed. Target genes to SNHG16 and miR-23b-3p were predicted, and verified by dual-fluorescent reporter assay. The effects of SNHG16 and miR-23b-3p on SNHG16, miR-23b-3p, EGR1 expression, viability, apoptosis as well as LC3II/LC3 expression in Hep3B and Hep3B/So cells were detected by qRT-PCR, CCK-8, flow cytometry, and western blot. In in vivo studies, the NOD/SCID mice model was established to explore the effects of Hep3B and Hep3B/So cells with inhibited SNHG16 or miR-23b-3p on tumor size, EGR1 expression, and autophagy. RESULTS: High SNHG16 expression in HCC-resistant tissues and low miR-23b-3p expression in all HCC tissues were detected, and the two were negatively correlated. Low SNHG16 and high miR-23b-3p were related to a high survival rate of HCC patients. Moreover, SNHG16 overexpression promoted Hep3B/So cell viability and autophagy, suppressed apoptosis by inhibiting miR-23b-3p expression through up-regulating EGR1, however, the effect of si-SNHG16 was opposite. In in vivo studies, miR-23b-3p inhibitor suppressed the high sorafenib sensitivity in Hep3B/So cells caused by SNHG16 silencing through promoting viability, autophagy, and suppressing apoptosis. CONCLUSION: SNHG16 promotes Hep3B/So cell viability, autophagy, and inhibits apoptosis to maintain its resistance to sorafenib through regulating the expression of miR-23b-3p via sponging EGR1.

Analysis of the UGT1A1 Genotype in Hyperbilirubinemia Patients: Differences in Allele Frequency and Distribution.

OBJECTIVE: The spectrum of UDP-glucuronyl transferase A1 (UGT1A1) variants in hereditary unconjugated hyperbilirubinemia varies markedly between different ethnic populations. This study evaluated the UGT1A1 genotypes in hyperbilirubinemia patients from southeastern China. METHODS: We enrolled 60 patients from southeastern China (44 men and 16 women; age range: 3-76 years) with unconjugated hyperbilirubinemia and performed genetic analysis of the UGT1A1 gene by direct sequencing. RESULTS: For patients with Gilbert syndrome, 85% (47/55) harbored pathogenic variants of UGT1A1⁎60. Both UGT1A1⁎28 and UGT1A1⁎81 were detected in the promoter region of UGT1A1. Additionally, 83% (20/24) of patients with Gilbert syndrome heterozygous for UGT1A1⁎60 had an association with heterozygous variation of UGT1A1⁎28 or UGT1A1⁎81, while 91% (21/23) of Gilbert syndrome patients homozygous for UGT1A1⁎60 had biallelic variations of UGT1A1⁎28 and UGT1A1⁎81. We detected 213 UGT1A1 allelic variants, including six novel variations, with the most frequent allele being the UGT1A1⁎60, followed by UGT1A1⁎28 and UGT1A1⁎6. All of the patients showed multiple sites of variants in UGT1A1; however, variation number was not associated with bilirubin levels (P>0.05). CONCLUSIONS: The spectrum of UGT1A1 variants in southeastern Chinese patients was distinct from other ethnic populations. Our findings broaden the knowledge concerning traits associated with UGT1A1 variants and help profile genotype-phenotype correlations in hyperbilirubinemia patients.

Role of MicroRNAs in the Development of Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease.

Hepatocellular carcinoma (HCC) is a prevalent liver malignancy that can be developed from nonalcoholic fatty liver disease (NAFLD). Numerous pathophysiological alterations, including insulin resistance, specific cytokine release, oxidative stress, and mitochondrial damage, are involved in the transition of NAFLD to cirrhosis and HCC. MicroRNAs, as post-transcriptional modulators, play a critical role in the pathogenesis of NAFLD-related HCC by regulating lipid metabolism, glucose homeostasis, cell proliferation, apoptosis, migration, and differentiation. This review summarizes the current progress of microRNAs in the risk and prognosis of NAFLD-related HCC. Anat Rec, 302:193-200, 2019. © 2018 Wiley Periodicals, Inc.

Meta-analysis of DNA methylation biomarkers in hepatocellular carcinoma.

DNA methylation is an epigenetic mechanism in the pathogenesis of hepatocellular carcinoma (HCC). Here, we conducted a systematic meta-analysis to evaluate the contribution of DNA methylation to the risk of HCC. A total of 2109 publications were initially retrieved from PubMed, Web of Science, Cochrane Library, Embase, CNKI and Wanfang literature database. After a four-step filtration, we harvested 144 case-control articles in the meta-analysis. Our results revealed that 24 genes (carcinoma tissues vs adjacent tissues), 17 genes (carcinoma tissues vs normal tissues) and six genes (carcinoma serums vs normal serums) were significantly hypermethylated in HCC. Subgroup meta-analysis by geographical populations showed that six genes (carcinoma tissues vs adjacent tissues) and four genes (carcinoma tissues vs normal tissues) were significantly hypermethylated in HCC. Our meta-analysis identified the correlations between a number of aberrant methylated genes (p16, RASSF1A, GSTP1, p14, CDH1, APC, RUNX3, SOCS1, p15, MGMT, SFRP1, WIF1, PRDM2, DAPK1, RARß, hMLH1, p73, DLC1, p53, SPINT2, OPCML and WT1) and HCC. Aberrant DNA methylation might become useful biomarkers for the prediction and diagnosis of HCC.

AKT/mTOR signaling pathway is involved in salvianolic acid B-induced autophagy and apoptosis in hepatocellular carcinoma cells.

Chinese medicines are emerging as an attractive new generation of anticancer drugs. Here, we explored the impact of salvianolic acid B (Sal B), the major water-soluble compounds of Danshen, on apoptosis and autophagy of human hepatocellular carcinoma cells (HCC). We also investigated the related molecular mechanisms. We found that Sal B exhibits potent ability to inhibit HCC cells viability in a concentration-dependent manner, and to induce apoptosis via the mitochondrial apoptosis pathway. Additionally, Sal B could also induce autophagy. Furthermore, pretreatment with the autophagy inhibitor chloroquine or 3-methyladenine showed the potential in attenuating the apoptosis rate induced by Sal B. Mechanistically, Sal B treatment inhibited the AKT/mTOR signaling cascade in vitro. Overexpression of AKT abolished the effects of Sal B on HCC cells, suggesting a critical role of the AKT/mTOR signaling pathway in Sal B-induced biological effects. Our results indicated that the mitochondrial pathway was involved in Sal B-induced apoptosis of HCC cells. Moreover, the AKT/mTOR signaling pathway was involved in Sal B-induced autophagy, which promoted apoptosis. This study may provide a promising strategy for using Sal B as a chemotherapeutic agent for patients with HCC.

MEK-ERK inhibition potentiates WAY-600-induced anti-cancer efficiency in preclinical hepatocellular carcinoma (HCC) models.

The search for novel anti-hepatocellular carcinoma (HCC) agents is important. Mammalian target of rapamycin (mTOR) hyper-activation plays a pivotal role in promoting HCC tumorigenesis and chemoresistance. The current preclinical study evaluated the potential anti-HCC activity by a potent mTOR kinase inhibitor, WAY-600. We showed that WAY-600 inhibited survival and proliferation of HCC cell lines (HepG2 and Huh7) and primary human HCC cells. Caspase-dependent apoptosis was activated by WAY-600 in above HCC cells. Reversely, caspase inhibitors largely attenuated WAY-600's lethality against HCC cells. At the signaling level, WAY-600 blocked mTOR complex 1/2 (mTORC1/2) assemble and activation, yet activated MEK-ERK pathway in HCC cells. MEK-ERK inhibitors, PD-98059 and MEK-162, or MEK1/2 shRNA significantly potentiated WAY-600's cytotoxicity in HCC cells. Further studies showed that WAY-600 intraperitoneal (i.p.) administration in nude mice inhibited p-AKT Ser-473 and displayed significant anti-cancer activity against HepG2 xenografts. Remarkably, co-administration of MEK-162 further potentiated WAY-600's anti-HCC activity in vivo. These preclinical results demonstrate the potent anti-HCC activity by WAY-600, either alone or with MEK-ERK inhibitors.

[Clinical significance of serum HBsAg levels, HBsAg/HBV DNA ratio, and association with liver inflammation activity in HBeAg-positive chronic hepatitis B].

OBJECTIVE: To study the clinical significance of hepatitis B surface antigen (HBsAg) levels and HBsAg/hepatitis B virus (HBV) DNA ratio in relation to liver inflammation in HBeAg-positive chronic hepatitis B (CHB). METHODS: One hundred and fifty-three Chinese patients with chronic HBV infection with HBeAg-positive status were enrolled in the study.Quantitative measurements were made for HBsAg levels by immunoassay (Architect HBsAg QT by Abbott Diagnostic) and HBV DNA by real-time fluorescence quantitative PCR.Levels of liver function markers were measured by standard methods.Liver biopsy specimens were obtained from all patients and used to score the histology (liver inflammation) activity index (HAI) and grade (G) the extent of necroinflammation.Statistical correlation analysis was performed to determine the association of HBsAg titre or HBsAg/HBV DNA ratio with the various parameters of liver injury. RESULTS: HBsAg titre and HBsAg/HBV DNA ratio were significantly correlated (r =0.578, P less than 0.0001).A significant positive correlation (r =0.642, P less than 0.0001) was found between HBsAg titre and HBV DNA load, and a significant negative correlation was found between the HAI and HBsAg (r =-0.389, P less than 0.0001) and HBsAg/HBV DNA ratio (r =-0.307, P=0.000l).A significant positive correlation was found between alanine aminotransferase (ALT) level and the HAI (r =0.480, P less than 0.0001).Patients with G less than 2 necroinflammation had significantly higher HBsAg titre and HBsAg/HBV DNA ratio than patients with G more than or equal to 2 necroinflammation (both P less than 0.01) but similar levels ofHBV DNA.Generation of a receiver operating characteristic curve using G more than or equal to 2 as the positive index provided the following area under the curve (AUC) values:HBsAg titre, 0.700; HBsAg/HBV DNA ratio, 0.672; ALT level, 0.713.When the random chance AUC was 0.5, all levels of AUC were statistically significant (Pless than 0.001).HBsAg titre (sensitivity =76.92%) was more sensitive than ALT level (sensitivity =76.92%), and HBsAg/HBV DNA ratio (specificity =81.33%) was more specific than ALT level (specificity =81.33%).Youden's index for comprehensive evaluation using ALT was higher than those for HBsAg titre or HBsAg/HBV DNA ratio.When HBsAg and ALT were considered in parallel, the sensitivity increased to 94.08% and specificity rose to 85.60%. CONCLUSION: HBsAg titre, HBsAg/HBV DNA ratio and ALT levels can be used as the index for judging the degree of liver inflammation in HBeAg-positive CHB patients.Higher sensitivity and specificity are attained when HBsAg and ALT are used in series or parallel.