Antigen-negative Chronic Hepatitis Research Articles

WED-188 - Higher risk of disease progression in the gray zone relative to hepatitis B e antigen negative chronic hepatitis B infection

WED-188 - Higher risk of disease progression in the gray zone relative to hepatitis B e antigen negative chronic hepatitis B infection

SAT-168 - Safety, pharmacokinetics, and antiviral activity of the next-generation hepatitis B core inhibitor ABI-H3733 in patients with hepatitis B e antigen negative chronic hepatitis B infection: preliminary results from a randomized, blinded, Phase 1b study

SAT-168 - Safety, pharmacokinetics, and antiviral activity of the next-generation hepatitis B core inhibitor ABI-H3733 in patients with hepatitis B e antigen negative chronic hepatitis B infection: preliminary results from a randomized, blinded, Phase 1b study

Correlation Between Quantitative Hepatitis B Surface Antigen and Hepatitis B Virus Deoxyribonucleic Acid Levels in Hepatitis B e Antigen-Positive and Hepatitis B e AntigenNegative Chronic Hepatitis B Patients.

This study aimed to analyze the relationship between quantitative hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid in hepatitis B e antigen-positive and hepatitis B e antigen-negative chronic hepatitis B patients and to determine the best cut-off value for quantitative hepatitis B surface antigen to predict high hepatitis B virus deoxyribonucleic acid levels (≥2000 IU/mL). Ninety-seven sera from chronic hepatitis B patients were collected in this study. Hepatitis B virus deoxyribonucleic acid levels were quantified by real-time polymerase chain reaction. Quantitative hepatitis B surface antigen and hepatitis B e antigen levels were determined by two-site sandwich chemiluminescence immunoassay. Alanine transaminase levels were measured by the International Federation of Clinical Chemistry-approved methods. A significant correlation between quantitative hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid levels was observed in hepatitis B e antigen-positive group (r = 0.453, P = .002), but not in hepatitis B e antigen-negative group (r = 0.117, P = .454). No significant correlation between quantitative hepatitis B surface antigen and alanine transaminase was found in the hepatitis B e antigen-positive group (r = 0.521, P = .241). However, a significant correlation was shown between quantitative hepatitis B surface antigen and alanine transaminase levels in the hepatitis B e antigen-negative group (r = 0.455, P = .001). The best cut-off value of quantitative hepatitis B surface antigen for predicting high hepatitis B virus deoxyribonucleic acid levels was 3.422 × 103 IU/mL. Correlation between quantitative hepatitis B surface antigen and hepatitis B virus deoxyribonucleic acid levels is significant in the hepatitis B e antigen-positive group. Quantitative hepatitis B surface antigen can be used to predict high hepatitis B virus deoxyribonucleic acid levels in the hepatitis B e antigen-positive group.

Lower frequency of MDSCs was significantly related to functional cure in CHB patients treated with peginterferon.

Myeloid-derived suppressor cells (MDSCs) and CD4+ regulatory T cells (Tregs) expand during chronic hepatitis B virus (HBV) infection and inhibit antiviral immunity. However, the relationship between antiviral effect and the frequencies of those immune suppressive cells after pegylated interferon α-2a (PegIFNα-2a) therapy is not clearly understood. This study aimed to investigate the contribution of monocytic MDSCs (mMDSCs) and CD4+ Tregs to functional cure (HBsAg seroclearance) after PegIFNα-2a therapy and evaluate the effect of PegIFNα-2a therapy on these cells. Flow cytometry analysis was performed along with longitudinal immune monitoring of 97 hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) patients receiving PegIFNα-2a weekly for 48 weeks. The frequencies of mMDSCs and CD4+ Tregs increased in all HBV patients, and they were higher in the HBsAg persistence group than in the HBsAg seroclearance group. A significant decline in the frequency of mMDSCs was found in patients who realized functional cure after PegIFNα-2a treatment. In contrast, the frequency of CD4+ Tregs in both the HBsAg seroclearance and persistence groups significantly increased. Multivariate analyses indicated that the baseline serum HBsAg levels (p < .001) and mMDSCs frequency (p=.027) were independently associated with the HBsAg clearance, and the combined marker (HBsAg plus mMDSCs) displayed the highest specificity (93.1%) than any other markers in predicting HBsAg seroclearance. These results suggest that a poor response to PegIFNα-2a treatment in CHB patients may be related to the frequencies of immune suppressive cells, while the therapeutic targeting of these cells might be effective in boosting anti-HBV immunity.

STAT1 is associated with NK cell dysfunction by downregulating NKG2D transcription in chronic HBV-infected patients

PurposeNatural killer (NK) cells are key players in the immune system, however, the exact mechanism of NK cell dysfunction during HBV infection remains poorly defined. MethodsHepatitis B envelope antigen-negative (HBeAg-, n = 19) chronic hepatitis B infection (CHB) patients, HBeAg-positive (HBeAg+, n = 20) CHB patients, HBV-related hepatocellular carcinoma (HBV-HCC, n = 12) patients and healthy blood donors (HD, n = 20), were enrolled in our study. The phenotype and function of the corresponding NK cells of these subjects were then determined. NK cells were cocultured with HBV to assess whether HBV influences the activation of STAT1. Receptors, proliferation, apoptosis rate, and cytotoxicity of NK-92 cells were detected after STAT1 overexpression and knockdown. The relationship between STAT1 and NKG2D promoter was determined by luciferase assay. ResultsThe levels of NKG2D and STAT1 were the lowest in the HBV-HCC group compared with the HD group, followed by the HBeAg+ group and then the HBeAg- group, respectively. Interestingly, STAT1 levels were positively correlated with NKG2D expression and HBeAg status. Furthermore, STAT1 directly bound to the NKG2D promoter to regulate the transcription and expression of NKG2D. Finally, the results also suggested that knockdown of STAT1 can inhibit proliferation, increase apoptosis rate of NK-92 cells and impair cytotoxicity of NK-92 cells. ConclusionSTAT1 is correlated with NK cell dysfunction by downregulating NKG2D transcription in HBV-infected patients. Our findings demonstrate that STAT1 is an important and positive regulator of NK cells, which could provide a potential immunotherapy target for CHB.

The Role of Off-Therapy Viral Kinetics in the Timing and Severity of Flares in Hepatitis B e Antigen–Negative Patients

Hepatitis B flare occurs earlier and is more severe in patients stopping tenofovir (TDF) compared with entecavir (ETV). This study investigated relationship between hepatitis B virus (HBV) kinetics, onset timing, and the severity of flares. Hepatitis B e antigen-negative chronic hepatitis B patients who developed off-ETV or off-TDF hepatitis flare were recruited. Their HBV kinetics and the severity of flares were compared between patients with early (<6 months) and late (between 6 and 24 months) flares. Propensity score matching was performed at 1:1 adjusting for age, sex, cirrhosis, and end-of-treatment (EOT) hepatitis B surface antigen between off-ETV and off-TDF flares. After propensity score matching, 76% and 15% of each 107 off-TDF and off-ETV patients, respectively, developed early flare. A much steeper HBV DNA upsurge (ΔHBV DNA/month) was observed in off-TDF than off-ETV flares (2.12 vs 0.73 log10 IU/mL; P < .01). Greater ΔHBV DNA/month correlated with earlier timing and higher peak alanine aminotransferase levels of flares. ΔHBV DNA/month ≥2.5 log10 IU/mL was an independent factor for severe off-TDF flare, and ≥1 log10 IU/mL was a predictor for severe off-ETV flares. Greater HBV DNA upsurge rate (ΔHBV DNA/month) ≥1 log10 IU/mL is a key factor for an earlier onset and more severe flare. More frequent ΔHBV DNA/month ≥1 log10 IU/mL in off-TDF than off-ETV flares may explain why off-TDF flare mostly occurred early and was more severe. More stringent monitoring in those with ΔHBV DNA/month ≥1 log10 IU/mL at flare, especially ≥2.5 log10 IU/mL in early off-TDF flares, is important for timely retreatment to prevent decompensation.

HBeAg-Negative/Anti-HBe-Positive Chronic Hepatitis B: A 40-Year-Old History.

Hepatitis B “e” antigen (HBeAg) negative chronic hepatitis B (CHB), 40 years since discovery in the Mediterranean area, has become the most prevalent form of HBV-induced liver disease worldwide and a major health care burden caused by HBV infection. A great deal of knowledge accumulated over the last decades provides consistent evidence on the bimodal dynamics of the expression of structural and non-structural forms of the viral core proteins which associate with different virologic and clinic–pathologic outcomes of HBV infection. In absence of serum HBeAg, the presence and persistence of HBV replication causes and maintains virus-related liver injury. Thus, in clinical practice it is mandatory to screen HBV carriers with HBeAg-negative infection for the early diagnosis of HBeAg-negative CHB since antiviral therapy can cure HBV-induced liver disease when started at early stages.

THU311 - Limited value of HBV-RNA levels for the prediction of relapse after discontinuation of nucleos (t)ide analogue therapy in HBe antigen negative chronic hepatitis B patients

THU311 - Limited value of HBV-RNA levels for the prediction of relapse after discontinuation of nucleos (t)ide analogue therapy in HBe antigen negative chronic hepatitis B patients

Cost-effectiveness of combination antiviral treatment with extended duration for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B in China.

BackgroundHepatitis B surface antigen clearance or seroconversion is rarely achieved for patients using nucleoside analogs or pegylated interferon alpha monotherapy approaches. Several recent studies have confirmed the benefit of a combination of these two approaches for selected chronic hepatitis B patients. However, few reports have investigated long-term outcomes or health economic evaluation for hepatitis B surface antigen clearance. The aim of this study was to perform a cost-effectiveness analysis of the long-term use of this combination strategy among selected hepatitis B e antigen-negative patients.MethodsDrawing on experience in China, we used a Markov model to simulate disease progression among a population of hepatitis B e antigen-negative chronic hepatitis B patients with surface antigen levels of ≤1,000 IU/mL through a discrete series of health states. We compared nucleoside analog monotherapy to the combination strategy over a prolonged period. We measured lifetime costs, quality-adjusted life-years and incremental cost-effectiveness ratios.ResultsThe combination therapy produced 15.8 quality-adjusted life-years, and cost US dollars (USD) 45,032 per patient. The monotherapy gave 13.9 quality-adjusted life-years, and had a cost of USD 52,064. The incremental cost-effectiveness ratio of the monotherapy (USD −3,755 per quality-adjusted life-year) did not obtain extended dominance over combination therapy. The most cost-effective option was combination therapy among patients with hepatitis B surface antigen levels of ≤10 IU/mL, which had the lowest calculated cost of USD 35,318 and most quality-adjusted life-years (16.7).ConclusionsA long-term combination treatment strategy for selected hepatitis B e antigen-negative chronic hepatitis B patients may prolong quality-adjusted life-years compared with nucleoside analog monotherapy. Chronic hepatitis B patients with a hepatitis B surface antigen level of ≤10 IU/mL were the most cost-effective population under this strategy.

Naïve hepatitis B e antigen-negative chronic hepatitis B patients are at risk of carotid atherosclerosis: A prospective study.

BACKGROUNDThere is an increased risk of atherosclerosis in patients with chronic hepatitis C or human immunodeficiency virus, but there is scarce data on hepatitis B virus infection. The hypothesis of this study is that hepatitis B virus infection increases the risk of carotid plaques and subclinical atherosclerosis in naïve hepatitis B e antigen (HBeAg) negative subjects.AIMTo assess the rate of carotid plaques and subclinical atherosclerosis in naïve HBeAg negative subjects in comparison with a cohort of healthy controls.METHODSProspective case-control collaborative study conducted in two tertiary hospitals. Four hundred and two subjects prospectively recruited at the outpatient clinic were included from May 2016 to April 2017: 201 naïve HBeAg-negative hepatitis B virus-infected [49 chronic hepatitis B (CHB) and 152 inactive carriers(ICs)] and 201 healthy controls. Anthropomorphic and metabolic measures, liver stiffness and carotid Doppler ultrasound were performed. Subclinical atherosclerosis was established on an intima-media thickness increase of ≥1.2 mm and/or the presence of carotid plaques. Normally distributed quantitative variables were compared with the Student t test and those with a non-normal distribution with the Mann-Whitney U test. Categorical variables were compared between groups using the χ2 or Fisher exact test.RESULTSCarotid plaques were found more often in CHB (32.7%) than ICs (17.1%) or controls (18.4%) (P = 0.048). Subclinical atherosclerosis was also increased in CHB (40.8%) vsICs (19.1%) or controls (19.4%) (P = 0.003). No differences in the risk of atherosclerosis were observed between controls and ICs. The factors independently associated with the presence of carotid plaques were age [odds ratio(OR) 1.43, P < 0.001] and CHB (OR 1.18, P = 0.004) and for subclinical atherosclerosis, age (OR 1.45, P < 0.001), CHB (OR 1.23, P < 0.001) and diabetes (OR 1.13, P = 0.028). In the subset of young subjects (< 50 years), carotid plaques (12.5% vs 1.1%, P = 0.027) and subclinical atherosclerosis (12.5% vs 2.2%, P = 0.058) were more frequent among CHB than ICs.CONCLUSIONUntreated HBeAg-negative CHB is an independent risk factor for carotid plaques and subclinical atherosclerosis, while ICs present a similar risk to controls.

The role of quantitative HBsAg in the natural history of e antigen-negative chronic hepatitis B: A Tunisian prospective study

Background/AimsDuring the natural course of Chronic Hepatitis B (CHB) infection, differentiation between inactive carrier (IC) and HBeAg negative CHB is a subject of ongoing debate. We studied the role of hepatitis B surface antigen (HBsAg) level as a means of differentiating between CHB and IC in a group of untreated chronic HBeAg-negative HBV-infected patients. StudyA total of 115 HBeAg negative carriers were enrolled and followed up for>12 months; 78 as inactive carriers (IC), and 37 as active carriers (AC). Among ACs, patients were categorized according to the highest rate of viral load: AC1 (n=23), active carriers with persistent HBV-DNA<20,000 IU/mL; AC2 (n=14), active carriers with HBV-DNA>20,000 IU/mL. ResultsHBsAg levels were higher in AC compared to IC patients (1607 IU/ml vs. 225 IU/ml respectively, P=0.001). Among the AC group, the 23 AC1 cases had HBsAg levels significantly lower than the 14 AC2 patients (1756 IU/mL vs. 3327 IU/mL respectively; P<10-3). HBsAg showed weak correlation with HBV-DNA in the whole cohort (r=0.44, P<0.01). The suggested cutoff value of HBsAg titer to differentiate between the two groups was 938 IU/mL. Combined single-point quantification of HBsAg (938 IU/mL) and HBV DNA (2000 IU/mL) identified IC with 87.2% specificity and 91.7% positive predictive value. ConclusionThis study confirms the predictability of a one-time combined HBsAg and HBV DNA measurement for true inactive carriers requiring neither strict follow-up nor antiviral treatment.

A Retrospective Single-Center Study in which Hepatitis B e Antigen Negative Chronic Hepatitis B Patients' Treatment of Nucleos(t)ide Analogues are Discontinued

A Retrospective Single-Center Study in which Hepatitis B e Antigen Negative Chronic Hepatitis B Patients' Treatment of Nucleos(t)ide Analogues are Discontinued

De novo combination antiviral therapy in e antigen-negative chronic hepatitis B virus-infected paediatric patients with advanced fibrosis.

To date, studies that focus on treatment of e antigen-negative chronic hepatitis B virus-infected children with advanced fibrosis are extremely limited. This puts these patients at risk of rapid disease progression. Our study aimed to investigate the efficacy of combination antiviral therapy in this population. We prospectively enrolled treatment-naı̈ve paediatric patients between 1year and 12years of age who had e antigen-negative chronic hepatitis B and histologically proven advanced fibrosis.All patients received de novo combination therapy with lamivudine (LAM) and interferon-α (IFN) for 12months and then were clinically followed up. The main outcome measure was rate of serum hepatitis B surface antigen (HBsAg) loss at month 12 of treatment. A total of 14 paediatric patients were enrolled, including 9 boys and 5 girls. All patients achieved undetectable HBV DNA levels at month 9 of treatment. A total of 5 patients (35.7%) achieved HBsAg loss at month 12 and finally developed HBsAg seroconversion. Four patients who did not clear HBsAg underwent second liver biopsy, and histological evaluation revealed significant improvements in all of them. As a serum fibrosis marker, aspartate aminotransferase-to-platelet ratio index after 12-month treatment in the 14 patients showed a significant improvement compared with that at baseline (P=.0021). No serious adverse events were observed during the study. Combination antiviral therapy is beneficial to e antigen-negative chronic hepatitis B virus-infected paediatric patients with advanced fibrosis. Further studies with larger cohorts are required.

A randomized controlled trial of pegylated interferon-alpha with tenofovir disoproxil fumarate for hepatitis B e antigen-negative chronic hepatitis B: A 48-week follow-up study

BackgroundRecent studies report incongruent finds regarding the addition of pegylated interferon -alpha (Peg- IFNα) to nucleos(t)ide analogues. This study was designed to compare the efficacy of Peg- IFNα and tenofovir disoproxil fumarate (TDF) combination therapy with each of the treatments separately. MethodsIn this open-label, randomized clinical trial, treatment-naive hepatitis B e antigen (HBeAg)-negative patients were randomly assigned to three treatment groups: Group A: Peg- IFNα (180 mcg/week) with TDF (300 mg/day); Group B: TDF (300 mg/day); and Group C: Peg- IFNα (180 mcg/week). The intervention spanned 48 weeks and patients were followed up every 12 weeks. The primary end-point was HBV DNA load <20 IU/mL. ResultsGroups A, B and C each comprised of 22, 23 and 22 patients, respectively. The number of patients with HBV DNA suppression in group A was significantly higher compared to groups B and C (P = 0.034). No significant difference was observed in the normalization trends of serum ALT levels between the three groups (P = 0.082). At week 48, combination therapy was significantly more effective in suppressing HBV DNA concentration to below the level of detection than TDF monotherapy (OR = 2.1, 95%CI: 1.18–4.15; P = 0.034). Furthermore, a comparison between monotherapy arms revealed that both interventions had similar effects on the overall outcome (OR = 1.24, 95%CI: 1.02–5.8; P = 0.062). ConclusionA Peg- IFNα and TDF combination therapy resulted in improved virologic response and was safe in HBeAg negative patients. Monotherapy with Peg-IFNα or TDF procured limited benefits in comparison. Trial registrationThis study was registered in the Iranian Registry of Clinical Trials (IRCT20181113041635N1).

Baseline and kinetics of serum hepatitis B virus RNA predict response to pegylated interferon-based therapy in patients with hepatitis B e antigen-negative chronic hepatitis B.

Serum hepatitis B virus (HBV) RNA has emerged as a novel biomarker of treatment response. This study aimed to investigate the role of this marker in predicting long-term outcome of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) receiving pegylated interferon (PEG-IFN)-based therapy. Serial serum samples from 91 patients with HBeAg-negative CHB previously treated with PEG-IFN alone or combined with entecavir in a randomized trial were retrospectively analysed. HBV RNA quantification was examined by droplet digital PCR. At the end of 3years post-treatment follow-up, maintained virological response (MVR, HBV DNA<2000IU/mL), and hepatitis B surface antigen (HBsAg) clearance were achieved in 37.4% (34/91) and 7.7% (7/91), respectively. Baseline serum HBV RNA concentrations correlated with HBV DNA and covalently closed circular DNA but did not correlate with HBsAg levels. Multiple regression analysis showed that pre-treatment HBV RNA and HBsAg were independently associated with MVR and HBsAg clearance. Baseline HBV RNA (cut-off 2.0 log10 copies/mL) had a positive predictive value (PPV) and a negative predictive value in predicting MVR of 80.8% and 80.0%, respectively. At the same cut-off value, PPV and NPV for predicting HBsAg clearance were 30.8% and 95.4%, respectively. At week 12 during therapy, HBV RNA level≥2 log10 copies/mL displayed high NPVs of achieving MVR and HBsAg clearance (95% and 100%, respectively). In conclusion, the measurement of HBV RNA prior to PEG-IFN-based therapy could identify patients with high probability of MVR. In addition, HBV RNA kinetics may serve as a promising "stopping rule" in patients infected with HBV genotypes B or C.

Characteristics of an Outpatient Cohort with HBeAg-Negative Chronic Hepatitis B.

BACKGROUND:Patients with hepatitis Be antigen-negative chronic hepatitis B (HBeAg-negative CHB), and patients’ inactive carriers (IC) have similar laboratory and serologic characteristics and are not always easy to distinguish.AIM:To characterise hepatitis Be antigen (HBeAg) negative chronic hepatitis B cohort based on their laboratory and virology evaluations at one point of time.METHODS:A prospective non-randomized study was conducted on 109 patients with HBeAg negative chronic hepatitis B treated as outpatients at the Clinic for Infectious Diseases and Febrile Conditions. All patients underwent laboratory and serology testing, quantification of HBV DNA and HBs antigen (qHBsAg).RESULTS:A group of 56 patients were inactive carriers (IC), and 53 patients had HBeAg-negative CHB (AH). The mean values of ALT, HBV DNA and qHBsAg in IC were 29.13 U/L; 727.95 IU/ml and 2753.73 IU/ml respectively. In the AH group, the mean values of ALT, HBV DNA and quantitative HBsAg were 50.45 U/L; 7237363.98 IU/ml and 12556.06 IU/ml respectively. The serum value of ALT was more influenced by qHBsAg than HBV DNA in both IC and AH groups (R = 0.22 vs R = 0.15) (p > 0.05).CONCLUSION:patients with inactive and active HBeAg-negative CHB have similar laboratory and serology profile. It is necessary to combine analysis of ALT, HBV DNA and qHBsAg for better discrimination between patient’s IC and patient with HBeAg-negative CHB.

SAT-189-GCAC1809-1812TTCT a novel viral quadruple mutation is strongly associated with basal core promotor double mutation and viral load in Hepatitis B e antigen negative chronic hepatitis B virus infected patients

SAT-189-GCAC1809-1812TTCT a novel viral quadruple mutation is strongly associated with basal core promotor double mutation and viral load in Hepatitis B e antigen negative chronic hepatitis B virus infected patients

Baseline HBsAg levels associated with HBsAg loss in HBeAg-negative chronic hepatitis B infection with persistently normal alanine aminotransferase

We aimed to assess the long-term outcomes of e antigen-negative chronic hepatitis B (CHB) infection with low hepatitis B virus (HBV) DNA level (< 200 IU/mL) and persistently normal alanine aminotransferase (PNALT) and to explore the factors associated with the results. This retrospective cohort study enrolled consecutive baseline CHB patients with PNALT from January 2005 to June 2008. In total, 252 e antigen-negative CHB patients with PNALT and low HBV DNA level (< 200 IU/mL) were enrolled, of whom 188 were eligible for this analysis. Among the 188 patients, 131 were followed up more than twice per year and 57 were followed up at least once per year, with a median follow-up period of 102 (73-123) months. Of 188 patients, 16 had HBV DNA level of > 200 IU/mL and PNALT, 164 had HBV DNA level of < 200 IU/mL and PNALT and 8 had HBV DNA level of > 200 IU/mL and elevated ALT level, of which 3 used an antiviral drug during follow-up. Twelve of 164 experienced HBsAg loss. Cox regression analysis suggested that baseline HBsAg levels were associated with HBsAg loss in patients after follow-up, especially the baseline HBsAg levels of < 200 IU⁄mL, which is a risk factor for HBsAg loss. The AUC of baseline HbsAg level in the e antigen-negative CHB group was 0.772 (cutoff value 426, P < 0.001). The cumulative probability of HBsAg loss in the HBsAg < 400 IU/L group was 20% (7/35), which ws higher than that in the HBsAg ≥ 400 IU/L group (3.88%; 5/129; X2 = 11.75, P = 0.0006). The e antigen-negative CHB infection with low HBV DNA level (< 200 IU/mL) and PNALT will progress to chronic hepatitis, although the probability of its occurrence is low. Spontaneous HBsAg loss may not occur frequently because the manifested cumulative probability of HBsAg loss was higher in the HBsAg < 400 IU/L group than in the HBsAg ≥ 400 IU/L group.

Paediatric chronic hepatitis B virus infection: are children too tolerant to treat?

Guidelines for managing the hepatitis B (HB) virus infection in children are still evolving. We aimed to assess the eligibility of children with HB virus infections for treatment based on the current guidelines. This observational study took place in 2016 and focused on children with isolated chronic HB infections, who attended the paediatric hepatology units at two centres in Egypt. We recruited all treatment-naïve children aged one year to 18 years who had completed at least 12 months of follow-up. The study comprised 103 children aged between 1.5-18 years. Of these, 51 (50%) had the HB e antigen-positive chronic infection, 28 (27%) had the HB-negative chronic infection, 11 (11%) had the HB e antigen-positive chronic hepatitis and none had the HB e antigen-negative chronic hepatitis. The remaining 13 (12%) children did not fulfil the criteria for chronic HB definitions. Only two of the children were candidates for treatment: both had HB e antigen-positive chronic hepatitis and had undergone liver biopsies. Only two of the 103 children with chronic HB were eligible for treatment according to the current guidelines and every measure should be taken to prevent the HB virus infection in children.

Polycystic kidney and hepatic disease 1 gene mutations in von Meyenburg complexes: Case report

Von Meyenburg complexes (VMCs) are a rare type of ductal plate malformation. We herein report two Chinese families with VMCs, and the suspicious gene mutation of this disease. Proband A was a 62-year-old woman with abnormal echographic presentation of the liver. She received magnetic resonance imaging (MRI) examination and liver biopsy, and the results showed she had VMCs. Histologically proved hepatocellular carcinoma was found 1 year after the diagnosis of VMCs. Proband B was a 57-year-old woman with intrahepatic diffuse lesions displayed by abdominal ultrasonography. Her final diagnoses were VMCs, congenital hepatic fibrosis, and hepatitis B surface e antigen-negative chronic hepatitis B after a series of examinations. Then, all the family members of both proband A and proband B were screened for VMCs by MRI or ultrasonography. The results showed that four of the 11 family members from two families, including two males and two females, were diagnosed with VMCs. DNA samples were extracted from the peripheral blood of those 11 individuals of two VMCs pedigrees and subjected to polymerase chain reaction amplification of the polycystic kidney and hepatic disease 1 (PKHD1) gene. Two different mutation loci were identified. Heterozygous mutations located in exon 32 (c.4280delG, p.Gly1427ValfsX6) in family A and exon 28 (c.3118C>T, p.Arg1040Ter) in family B were detected. We speculate that PKHD1 gene mutations may be responsible for the development of VMCs.