Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the ...potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts’ personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
Summary
Background
The accuracy of Enhanced Liver Fibrosis (ELF; ADVIA Centaur, Siemens Healthcare Diagnostics, Tarrytown, NY, USA) in assessing liver fibrosis in chronic hepatitis B (CHB) is to be ...determined.
Aim
To derive and validate a combined ELF‐liver stiffness measurement (LSM) algorithm to predict advanced fibrosis in CHB patients.
Methods
Using the data of a previously reported cohort of 238 CHB patients, an ALT‐based LSM algorithm for liver fibrosis was used as a training cohort to evaluate the performance of ELF against liver histology. The best combined ELF‐LSM algorithm was then validated in new cohort of 85 CHB patients not previously reported.
Results
In the training cohort, LSM has better performance of diagnosing advanced (≥F3) fibrosis (area under the receiver operating characteristics curve AUROC 0.83, 95% confidence interval CI 0.76–0.91 than ELF (AUROC 0.69, 95% CI 0.63–0.75). The optimal cut‐off values of ELF were 8.4 to exclude advanced fibrosis, and 10.8 to confirm advanced fibrosis. In the training cohort, an ELF ≤ 8.4 had a sensitivity of 95% to exclude advanced fibrosis; an ELF > 10.8 had a specificity of 92% to confirm advanced fibrosis. In the combined algorithm, low ELF or low LSM could be used to exclude advanced fibrosis as both of them had high sensitivity (≥90%). To confirm advanced fibrosis, agreement between high ELF and high LSM could improve the negative predictive value specificity (from 65% and 74% to 80%).
Conclusions
An Enhanced Liver Fibrosis ‐ liver stiffness measurement algorithm could improve the accuracy of prediction of either ELF or LSM alone. Liver biopsy could be correctly avoided in approximately 60% of patients.
Aliment Pharmacol Ther 2011; 33: 1104–1112
Summary
Background The role of anti‐viral therapy in prevention of hepatocellular carcinoma (HCC) recurrence is to be defined.
Aim To investigate the role ...of anti‐viral therapy in prevention of tumour recurrence after curative treatment of hepatitis B virus (HBV)‐related HCC.
Methods A systematic electronic search on keywords including HCC and different anti‐viral therapies was performed through eight electronic databases, including Medline, EMBASE and Cochrane Databases. The primary outcome was HCC recurrence after curative treatment of HBV‐related HCC. The secondary outcomes were mortality related to HCC, mortality related to liver failure and the overall mortality.
Results Nine cohort studies were included with a total number of 551 patients: 204 patients with anti‐viral treatment group and 347 patients without anti‐viral treatment (control group). There was significant difference in the incidence of HCC recurrence in favour of the anti‐viral treatment group (55% vs. 58%; odds risk (OR) = 0.59, 95% CI 0.35–0.97, P = 0.04). The risk of HCC was reduced by 41% in the anti‐viral treatment group. There were also significant differences in favour of anti‐viral treatment group in terms of liver‐related mortality (0% vs. 8%; OR = 0.13, 95% CI 0.02–0.69, P = 0.02) and overall mortality (38% vs. 42%; OR = 0.27, 95% CI 0.14–0.50, P < 0.001).
Conclusions Anti‐viral therapy has potential beneficial effects after the curative treatment of HBV‐related hepatocellular carcinoma in terms of tumour recurrence, liver‐related mortality and overall survival. Anti‐viral therapy should be considered after curative treatment of hepatocellular carcinoma.
The clinical relevance of immune landscape intratumoural heterogeneity (immune-ITH) and its role in tumour evolution remain largely unexplored. Here, we uncover significant spatial and phenotypic ...immune-ITH from multiple tumour sectors and decipher its relationship with tumour evolution and disease progression in hepatocellular carcinomas (HCC). Immune-ITH is associated with tumour transcriptomic-ITH, mutational burden and distinct immune microenvironments. Tumours with low immune-ITH experience higher immunoselective pressure and escape via loss of heterozygosity in human leukocyte antigens and immunoediting. Instead, the tumours with high immune-ITH evolve to a more immunosuppressive/exhausted microenvironment. This gradient of immune pressure along with immune-ITH represents a hallmark of tumour evolution, which is closely linked to the transcriptome-immune networks contributing to disease progression and immune inactivation. Remarkably, high immune-ITH and its transcriptomic signature are predictive for worse clinical outcome in HCC patients. This in-depth investigation of ITH provides evidence on tumour-immune co-evolution along HCC progression.
Fatty liver disease is commonly associated with obesity, insulin resistance and diabetes. Severe fatty liver is sometimes accompanied by steatohepatitis and may lead to the development of ...hepatocellular carcinoma. At present, there is no effective treatment for non-alcoholic fatty liver disease (NAFLD); thus, recent investigations have focused on developing effective therapeutics to treat this condition. This study aimed to evaluate the effects of kefir on the hepatic lipid metabolism of ob/ob mice, which are commonly used to model fatty liver disease.
In this study, we used leptin receptor-deficient ob/ob mice as an animal disease model of NAFLD. Six-week-old ob/ob mice were orally administered the dairy product kefir (140 mg kg(-1) of body weight (BW) per day) for 4 weeks. The data demonstrated that kefir improved fatty liver syndrome on BW, energy expenditure and basal metabolic rate by inhibiting serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities (P<0.05) and by decreasing the triglyceride (TG) and total cholesterol (TC) contents of the liver (P<0.05). Oral kefir administration also significantly reduced the macrovesicular fat quantity in liver tissue. In addition, kefir markedly decreased the expression of the genes sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) (P<0.05) but not the expression of peroxisome proliferator-activated receptor α (PPARα) or hepatic carnitine palmitoyltransferase-1α (CPT1α) in the livers of ob/ob mice.
On the basis of these results, we conclude that kefir improves NAFLD on BW, energy expenditure and basal metabolic rate by inhibiting the lipogenesis pathway and that kefir may have the potential for clinical application to the prevention or treatment of NAFLD.
Both endoscopic obturation and transjugular intrahepatic portosystemic shunts (TIPSs) have proven to be effective in preventing rebleeding from gastric varices. This study compared the efficacy and ...complications of these modalities.
Cirrhotic patients with acute bleeding from gastric varices were considered for inclusion. After initial control, eligible patients were randomly allocated to two groups: TIPS (n = 35) and obturation using cyanoacrylate (n = 37). In the cyanoacrylate group, treatment was repeated regularly until gastric varices were obliterated. Patients of both groups received regular follow-up. The end points were gastric variceal rebleeding or death.
Stent shunt insertion was successful in all TIPS patients, and mean portal pressure gradient decreased from 21.4 +/- 7.5 mm Hg to 7.5 +/- 3.5 mm Hg ( P < 0.001). Variceal obliteration was achieved in 19 patients in the cyanoacrylate group (51 %) compared with seven TIPS patients (20 %) ( P < 0.02). After a median follow up of 33 months, upper gastrointestinal bleeding occurred in 15 TIPS patients (43 %) and 22 cyanoacrylate patients (59 %) ( P = 0.12). Rebleeding from gastric varices was encountered in four TIPS patients (11 %) and 14 cyanoacrylate patients (38 %) ( P = 0.014; odds ratio 3.6, 95 %CI 1.2 - 11.1). Blood transfusion requirements were lower in the TIPS group than in the cyanoacrylate group ( P < 0.01). Survival and frequency of complications were similar in both groups.
TIPS proved more effective than glue injection in preventing rebleeding from gastric varices, with similar survival and frequency of complications.
Significance We used massively parallel sequencing to study the size profiles of plasma DNA samples at single-base resolution and in a genome-wide manner. We used chromosome arm-level z -score ...analysis (CAZA) to identify tumor-derived plasma DNA for studying their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These findings have shed light on fundamental biological characteristics of plasma DNA and related diagnostic applications for cancer.
The analysis of tumor-derived circulating cell-free DNA opens up new possibilities for performing liquid biopsies for the assessment of solid tumors. Although its clinical potential has been increasingly recognized, many aspects of the biological characteristics of tumor-derived cell-free DNA remain unclear. With respect to the size profile of such plasma DNA molecules, a number of studies reported the finding of increased integrity of tumor-derived plasma DNA, whereas others found evidence to suggest that plasma DNA molecules released by tumors might be shorter. Here, we performed a detailed analysis of the size profiles of plasma DNA in 90 patients with hepatocellular carcinoma, 67 with chronic hepatitis B, 36 with hepatitis B-associated cirrhosis, and 32 healthy controls. We used massively parallel sequencing to achieve plasma DNA size measurement at single-base resolution and in a genome-wide manner. Tumor-derived plasma DNA molecules were further identified with the use of chromosome arm-level z -score analysis (CAZA), which facilitated the studying of their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of plasma mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These results have improved our understanding of the size profile of tumor-derived circulating cell-free DNA and might further enhance our ability to use plasma DNA as a molecular diagnostic tool.
The strong coupling between antiferromagnetism and ferroelectricity at room temperature found in BiFeO3 generates high expectations for the design and development of technological devices with novel ...functionalities. However, the multi-domain nature of the material tends to nullify the properties of interest and complicates the thorough understanding of the mechanisms that are responsible for those properties. Here we report the realization of a BiFeO3 material in thin film form with single-domain behaviour in both its magnetism and ferroelectricity: the entire film shows its antiferromagnetic axis aligned along the crystallographic b axis and its ferroelectric polarization along the c axis. With this we are able to reveal that the canted ferromagnetic moment due to the Dzyaloshinskii-Moriya interaction is parallel to the a axis. Furthermore, by fabricating a Co/BiFeO3 heterostructure, we demonstrate that the ferromagnetic moment of the Co film does couple directly to the canted moment of BiFeO3.
Klebsiella pneumoniae-caused liver abscess (KLA) is an emerging infectious disease. However, factors other than K1-specific loci that contribute to the pathogenesis of this disease have not been ...identified. pLVPK is a 219,385-bp plasmid of K. pneumoniae CG43, an invasive K2 strain associated with KLA. We aimed in this study to evaluate the involvement of pLVPK in K. pneumoniae virulence and its clinical significance in abscess formation. A pLVPK-cured CG43 was isolated and its virulence was examined in a mouse model. The prevalence of pLVPK-derived loci terW, iutA, rmpA, silS, and repA was investigated in 207 clinical isolates by screening with specific primers. Loss of pLVPK abolished the ability of K. pneumoniae to disseminate into extraintestinal sites and, consequently, attenuated abscess formation in mice. Primary K. pneumoniae abscess isolates (n = 94) were more likely to be terW ⁺-iutA ⁺-rmpA ⁺-silS ⁺ than those related to non-abscess infections (n = 113) (62% vs. 27%; p < 0.0001). Logistic regression analysis indicated that the presence of the terW-rmpA-iutA-silS loci was a significant risk factor (odds ratio, 4.12; 95% confidence interval, 2.02-8.4; p < 0.0001) for abscess formation. pLVPK is a determinant for K. pneumoniae virulence and infection with strains carrying the pLVPK-derived terW-rmpA-iutA-silS loci may predispose patients to abscess formation.
Lead sulfide quantum dots (PbS QDs) show great potential for efficient, low cost photovoltaic applications. Currently, device efficiencies are limited by the high density of trap states caused by ...lattice imperfections on the QD surface. Introducing a thin shell of a wide bandgap semiconductor to the QD surface is a promising method to passivate these trap states. Here we demonstrate solar cells made from PbS–CdS core–shell QDs, yielding a 147 mV increase in V OC compared to core only PbS QDs. We explore the physical reason for this enhancement and demonstrate that it is indeed caused by improved passivation of the PbS surface by the CdS shell, leading to a lower electron trap density.
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