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Noninvasive methods for assessing hepatic fibrosis are clinically necessary. This study aims to explore HBV markers correlated with liver fibrosis and capable of diagnosing significant fibrosis and predicting fibrosis regression. Seventy‐four HBeAg‐positive chronic hepatitis B (CHB) patients were enrolled and started on entecavir or adefovir therapy. Serum HBV RNA, HBV DNA, HBsAg and hepatitis B core‐related antigen (HBcrAg) levels were measured at baseline and during treatment. Liver fibrosis was assessed at baseline and month 60 by liver biopsy. Fibrosis regression was defined as Ishak fibrosis score decreased ≥1‐point. At baseline, HBsAg, HBcrAg and HBV RNA levels had a stronger correlation with Ishak fibrosis score (r = −.441, p =.002; r = −.469, p =.001; r = −.398, p =.001) than APRI and FIB‐4 (r =.321 p =.006; r =.371, p =.001). HBsAg >4 log10 IU/ml plus HBcrAg >7 log10 IU/ml or HBsAg >4 log10 IU/ml plus HBV RNA >5 log10 copies/ml exhibited the same excellent diagnostic ability for significant fibrosis with the AUROC of 0.857. After 60 months of antiviral treatment, 66.7% of patients who suffered significant fibrosis at baseline achieved fibrosis regression, and an HBV RNA decline from baseline to month 6 greater than 0.63 log10 copies/ml could predict the fibrosis regression at month 60. In conclusion, serum HBsAg, HBcrAg and HBV RNA are potential markers for predicting significant liver fibrosis. HBV RNA measurement would be particularly useful for monitoring hepatic fibrosis changes in HBeAg‐positive CHB patients. [ABSTRACT FROM AUTHOR]

This study evaluated the predictive value of serum HBV DNA, HBV RNA, HBcrAg, HBsAg, intrahepatic HBV DNA and cccDNA for HBeAg clearance and seroconversion during long‐term treatment with nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B (CHB). A single centre, prospective cohort of CHB patients was used for this study. Serum HBV RNA levels were retrospectively measured at baseline, 6, 12, 24, 36, 48, 60, 72 and 84 months post‐NAs treatment. Serum HBsAg and HBcrAg levels were quantified at baseline, month 6, 60 and 72. Histological samples from liver biopsy at baseline and month 60 were analysed for intrahepatic HBV DNA and cccDNA. Eighty‐three HBeAg‐positive patients were enrolled with a median follow‐up time of 108 months (range 18–138 months). Of them, 53 (63.86%) patients achieved HBeAg clearance, and 37 (44.58%) achieved HBeAg seroconversion. Cox multivariate analysis showed that only baseline HBV RNA was independently associated with HBeAg clearance and seroconversion (<5.45 log10copies/mL, HR = 5.06, 95% CI: 1.87–13.71, p =.001; HR = 3.38, 95% CI: 1.28–8.91, p =.01). The independent association with HBeAg clearance and seroconversion remained for HBV RNA levels at month 6 (<4.72 log10copies/mL, HR = 4.16, 95% CI: 1.61–10.72, p =.003; HR = 6.52, 95% CI: 1.85–22.94, p =.003) and month 12 (<4.08 log10 copies/mL, HR = 3.68, 95% CI: 1.96–6.90, p <.001; HR = 2.79, 95% CI: 1.31–5.94, p =.008). The AUCs of baseline HBV RNA for predicting the HBeAg clearance (0.83, 95% CI: 0.70–0.96, 0.83, 95% CI: 0.70–0.96 and 0.82, 95% CI: 0.69–0.95 respectively) and seroconversion (0.89, 95% CI: 0.77–1.00; 0.81, 95% CI: 0.66–0.95 and 0.84, 95% CI: 0.71–0.98 respectively) at month 36, 60 and 84 were higher than those of HBV DNA, HBsAg and HBcrAg. In conclusion, lower serum HBV RNA at baseline, month 6 and 12 post‐NAs treatment could predict HBeAg clearance and seroconversion during long‐term NAs treatment. [ABSTRACT FROM AUTHOR]

Background: With the global pandemic of obesity and nonalcoholic fatty liver disease (NAFLD), the incidence of cirrhosis associated with nonalcoholic steatohepatitis (NASH) has greatly increased. This study aimed to evaluate the efficacy and safety of bariatric surgery in obese cirrhotic patients. Methods: PubMed, EMBASE, and the Cochrane Library were searched for relevant studies. Effectiveness outcomes were weight loss, remission of comorbidities, and improvement in liver function. Safety outcomes were procedural complications and mortality. Results: A total of 15 studies were included in this meta-analysis. Patients with compensated cirrhosis lost weight significantly after surgery, and the percentage of excess weight loss was 60.44 (95% CI, 44.34 to 76.55). Bariatric surgery resulted in remission of NAFLD in 57.9% (95% CI, 27.5% to 88.3%), T2DM in 58.4% (95% CI, 48.4% to 68.4%), hypertension in 53.1% (95% CI, 43% to 63.3%), dyslipidemia in 59.8% (95% CI, 41.1% to 78.5%) of patients with cirrhosis. Bariatric surgery reduced the levels of alanine aminotransferase and aspartate aminotransferase. The incidence of surgical complications in patients with cirrhosis was about 19.2% (95% CI, 11.7% to 26.6%), which was higher than that in patients without cirrhosis (OR 2.67 [95% CI, 1.26 to 5.67]). Patients with cirrhosis had an overall mortality rate of 1.3%, and the mortality rates for compensated cirrhosis and decompensated cirrhosis were 0.9% and 18.2%, respectively. Conclusions: Bariatric surgery is effective for weight loss, remission of comorbidities, and reversal of liver damage. Although cirrhotic patients have a higher risk of complications and death, bariatric surgery is relatively safe for well-compensated cirrhosis. [ABSTRACT FROM AUTHOR]

Background and Aim: This single‐arm, open‐label, multicenter, phase 3 trial evaluated the efficacy and safety of seraprevir, an hepatitis C virus (HCV) nonstructural protein 3/4A (NS3/4A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic HCV infection without cirrhosis. Methods: Treatment‐naive or interferon‐experienced adult patients without cirrhosis were treated with a universal, combinational regimen of seraprevir 100 mg, twice daily and sofosbuvir 400 mg, once daily, for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response at week 12 after treatment (SVR12). Results: Overall, 205 patients with genotype 1 HCV infection without cirrhosis were enrolled from 23 sites, 202 of whom completed the full treatment and post‐treatment course and 3 discontinued follow‐up. In total, 27 patients (13.2%) were interferon experienced. SVR12 was achieved by 201 out of 205 (98.0% [95% CI, 95.1%, 99.5%]) patients, 100.0% of patients with genotype 1a, and 98.0% of genotype 1b. In the other exploratory study, SVR 12 was achieved by 100% patients with genotype 2 (n = 21), genotype 3 (n = 7), and genotype 6 (n = 8). The majority of adverse events were mild to moderate and transient and did not require a specific medical intervention. Conclusions: The all‐oral, ribavirin‐free regimen of seraprevir and sofosbuvir is an effective and well‐tolerated treatment option for Chinese patients mono‐infected with HCV, including those with a history of interferon treatment. [ABSTRACT FROM AUTHOR]

Background & Aim: An affordable, pangenotypic regimen remains as an unmet medical need for chronic hepatitis C patients in China. This single‐arm, open‐label, multicenter, phase 3 trial evaluated the efficacy and safety of coblopasvir, a pangenotypic non‐structural protein 5A (NS5A) inhibitor, combined with sofosbuvir for treating Chinese patients with chronic hepatitis C virus (HCV) infection. Methods: Treatment‐naïve and interferon‐experienced adult patients, including those with advanced fibrosis (F3) or compensated cirrhosis (F4), were treated with a universal, combinational regimen of coblopasvir 60 mg and sofosbuvir 400 mg, once daily, for 12 weeks. The primary efficacy endpoint was sustained virological response at post‐treatment week 12 (SVR12). Results: Overall, 371 patients (men, 51%; age, 47 ± 11 years; genotype 1a < 1%, 1b 48%, 2a 26%, 3a 6%, 3b 7% and 6 12%) were enrolled from 19 sites. Fifty‐one patients (14%) had F3, 39 patients (11%) had F4 and 39 patients (11%) were interferon experienced. The overall SVR12 was 97% (95% CI, [94%, 98%]) for the full analysis set and was equal to or above 90% for all predefined subsets. Ten patients (3%) experienced virological relapse and two patients did not complete follow‐up. No adverse events (AEs) occurred at a frequency ≥5%, and the most often reported AEs (≥1%) were neutropenia and fatigue. The majority of AEs were mild to moderate and transient without specific medical intervention. Conclusions: The universal, pangenotypic combo of coblopasvir plus sofosbuvir is an efficacious and safe treatment for Chinese patients monoinfected with HCV of genotype 1, 2, 3 and 6, including those with compensated cirrhosis. Lay summary: The regimen of coblopasvir and sofosbuvir is a safe and effective treatment for Chinese patients with genotype 1, 2, 3 and 6 HCV infection, including those with compensated cirrhosis. Therefore, this regimen would be a novel choice of treatment for this patient population. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the efficacy of antepartum administration of three doses of hepatitis B immunoglobulin (HBIG) in interrupting mother‐to‐child transmission (MTCT) of hepatitis B virus (HBV). In this trial, a total of 728 HBeAg‐positive pregnant women with chronic HBV infection who had an HBV DNA level higher than 6log10 copies/mL were enrolled. They were divided into three groups based on individual preference. Subjects in group A and group B received 200 IU (unit) HBIG and 400 IU (unit) HBIG intramuscularly once a month at the third, second and first month before delivery, respectively. Subjects in the control group (C) received no special treatment. All the infants received passive‐active immunoprophylaxis. The HBsAg‐positive rate of all infants at 7‐12 months of age was 5.1% (37/728). Specifically, the HBsAg‐positive rate of infants was comparable in all three groups (5.3% vs 5.1% vs 5%, P = 0.988). No significant difference was found in anti‐HBs levels between the infants aged 7‐12 months in the three groups (P = 0.469). HBV DNA levels of the umbilical cord blood in the HBV‐infected group were higher than those in the uninfected group (5.2 vs 3.4log10 copies/mL, P < 0.001), and these with family history of HBV infection were also higher (45.9% vs 28.5%, P = 0.034). To conclude, administration of passive‐active immunoprophylaxis to infants contributed to effective prevention of the MTCT of HBV; extra antepartum administration of HBIG during pregnancy could not decrease the rate of MTCT or increase the anti‐HBs levels of infants born to HBsAg‐positive mothers with HBV DNA higher than 6log10 copies/mL. [ABSTRACT FROM AUTHOR]

Wilson disease (WD) is a rare autosomal recessive genetic disorder that is associated with various mutations in the ATP7B gene. Although ATP7B variants are frequently identified, the exact mutation patterns remain unknown because of the absence of pedigree studies, and the functional consequences of individual ATP7B variants remain to be clarified. In this study, we recruited 65 clinically diagnosed WD patients from 60 unrelated families. Pedigree analysis showed that besides several ATP7B homozygous variants (8/65, 12.3%), compound heterozygous variants (43/65, 66.2%) were present in the majority of WD patients. There were 20% of the patients had one (12/65, 18.5%) or multiple (1/65, 1.5%) variants in only a single allele, characterized by a high ratio of splicing or frameshift variants. Nine ATP7B variants were cloned into the pAG426GPD yeast expression vector to evaluate their functional consequences, and the results suggested different degrees of functional disruption from mild or uncertain to severe, consistent with the corresponding phenotypes. Our study revealed the complex ATP7B mutation patterns in WD patients and the applicability of a yeast model system to the evaluation of the functional consequences of ATP7B variants, which is essential for WD cases that are difficult to interpret. [ABSTRACT FROM AUTHOR]

Accumulated evidences indicate that single nucleotide polymorphisms (SNP) are associated with risk of hepatocellular carcinoma (HCC). Activating transcription factor 6 (ATF6) is an important modulator of the unfolded protein response (UPR), which is regarded to be involved in carcinogenesis. So we speculate that SNPs in ATF6 may be associated with susceptibility to HCC. We carried out a two-stage association study in three independent case-control groups in a total of 1,082 chronic hepatitis B (CHB) patients and 816 hepatitis B virus (HBV) related HCC patients in Han Chinese. Four SNPs which can represent all potential functional SNPs with MAF > 0.1 recorded in HapMap database in ATF6 gene were genotyped using TaqMan methods. Functional analyses were conducted to verify the biological significances of the associated SNP. We identified a missense SNP (rs2070150) was significantly associated with susceptibility to HCC ( p = 0.008, 0.001 and 0.007 in Beijing_302, Beijing_You'an and Guangxi samples, respectively). This SNP was further validated in four independent groups of major HBV outcomes, indicating it may associate exclusively to HCC. ATF6 mRNA expression was significantly decreased as the disease progressed ( p <0.001). Functional analyses show that the protective allele of rs2070150 could significantly increase the expression levels of ATF6 mRNA, as well as ATF6 regulated genes such as GRP78, XBP1 and CHOP. These findings indicate that a common missense SNP in ATF6 may contribute to susceptibility of HCC functionally. [ABSTRACT FROM AUTHOR]

A review of the article "Vitamin D in Liver Diseases: From Mechanisms to Clinical Trials" by Yuan-Ping Han, Ming Kong, and Sujun Zheng, which appeared in the "Journal of Gastroenterology and Hepatology" on November 3, 2012, is presented.

Background: Wilson's disease (WD) is an autosomal recessive genetic disease caused by mutations in ATP7B and characterized by copper metabolism disorders. Methods: Direct sequencing of the ATP7B gene is the most sensitive and widely used confirmatory testing method. Fourteen probands with WD and 12 family members participated in this study. The ATP7B gene was analyzed by direct sequencing. Results: Twenty‐nine different variants (27 substitutions, 1 duplication, 1 deletion) were found. Of the 23 reported variants, nine nondisease variants, 11 disease variants, one silent variant, and two variants with uncertain functions were identified. The six novel variants included c.1875T>A, c.2306T>C, c.3028A>G, c.3243G>A, c.3437_3438 delTG, and c.3903+5G>A. Conclusion: These findings will assist in the diagnosis of WD. The novel variants have enriched the WD database. [ABSTRACT FROM AUTHOR]

Background & Aims: Our previous study found that rs4845384 in ADAR1 gene to be associated with HBeAg seroconversion. However, the effect of rs4845384 on HBsAg seroclearance is unknown. To assess the relationship between rs4845384 and HBsAg seroclearance., Methods: Two independent case-control studies were conducted to test whether rs4845384 in ADAR1 was associated with HBsAg clearance. Reporter gene assays and quantitative PCR experiments were also carried out to verify the functional significances of this polymorphism., Results and Conclusions: The rs4845384 polymorphism was associated with HBsAg seroclearance both spontaneously (P = 0.028, OR = 1.36, 95% CI = 1.03-1.78) and interferon induced (P = 0.013, OR = 1.83, 95% CI = 1.13-2.96), in a total of 725 subjects. Luciferase assays showed that pGL3-rs4845384G constructs had higher expression level than pGL3-rs4845384A constructs, especially in HepG2. 2.15 cell line. Quantitative real-time RT-PCR showed that chronic hepatitis B (CHB) patients had lower ADAR1 mRNA level than healthy individuals. The AA carriers of rs4845384 had lower ADAR1 mRNA expression than non-AA carriers. The non-response susceptible allele rs4845384A was functional for regulation of ADAR1 expression, so as to influence HBsAg seroclearance of CHB patients., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)