Uncertainty-weighted Multi-tasking for T1ρ and T2 Mapping in the Liver with Self-supervised Learning.

Multi-parametric mapping of MRI relaxations in liver has the potential of revealing pathological information of the liver. A self-supervised learning based multi-parametric mapping method is proposed to map T1ρ and T2 simultaneously, by utilising the relaxation constraint in the learning process. Data noise of different mapping tasks is utilised to make the model uncertainty-aware, which adaptively weight different mapping tasks during learning. The method was examined on a dataset of 51 patients with non-alcoholic fatter liver disease. Results showed that the proposed method can produce comparable parametric maps to the traditional multi-contrast pixel wise fitting method, with a reduced number of images and less computation time. The uncertainty weighting also improves the model performance. It has the potential of accelerating MRI quantitative imaging.

Risk factors for sessile serrated lesions among Chinese patients undergoing colonoscopy.

BACKGROUND AND AIM: Serrated polyps have been recognized as a premalignant lesion accounting for a significant proportion of colorectal cancer. Limited data are available regarding the risk factors for colorectal sessile serrated lesions (SSLs). We aimed to investigate clinical risk factors of SSLs and compared them with colorectal adenomas in a study population of Chinese individuals. METHODS: A retrospective case-control study was performed in an academic tertiary-referral center in Hong Kong. Subjects with SSLs and adenomas were identified from the hospital pathology database from January 2010 to December 2020, and additional clinical data were retrieved from the electronic patient record system. We compared clinical features and risk factors of SSL patients with those without these lesions. RESULTS: A total of 2295 subjects were included in the study, including 459 subjects with SSLs, 918 subjects with adenomas, and 918 subjects with normal colonoscopy. By multivariable logistic regression, compared with normal subjects, patients with SSLs only were significantly more likely to have dyslipidemia (adjusted OR: 1.431, 95% CI 1.008-2.030) and diabetes mellitus (adjusted OR: 2.119, 95% CI 1.439-3.122). CONCLUSIONS: Dyslipidemia and diabetes were independent risk factors for SSLs. Our findings suggest these metabolic factors may be important for the risk of SSLs. The findings may improve our understanding of SSLs and shed light on patient selection for screening and risk stratification.

The utility of non-invasive tests to assess advanced fibrosis in Asian subjects with chronic hepatitis B and concomitant hepatic steatosis.

BACKGROUND: Chronic hepatitis B (CHB) is endemic to Asia and is a leading cause of liver-related morbidity. The prevalence of concomitant CHB and hepatic steatosis (HS) is increasing in Asia. Non-invasive tests (NITs) including FIB-4, NFS and APRI assess fibrosis in populations with a single aetiology, but not in subjects with concomitant CHB and HS. AIM: To explore the accuracy of NITs in predicting advanced fibrosis in patients with concomitant CHB and HS. METHODOLOGY: This multicentre study of CHB patients who underwent liver biopsy explored clinical characteristics of these subjects, stratified by presence of HS. Fibrosis scores from NITs were compared against histological fibrosis stage in CHB subjects with and without HS. RESULTS: 2262 subjects were enrolled, 74.5% were males, and the mean age was 39.5 years ±11.8 SD. 984 (44.4%) had HS, 824 (36.4%) had advanced fibrosis. In the CHB group, the AUROC for advanced fibrosis were 0.65 (95% CI 0.62-0.69) for FIB-4 and 0.63 (95% CI 0.60-0.66) for APRI. The specificities were 0.94 for FIB-4 greater than 3.25 and 0.81 for APRI greater than 1.5. In the CHBHS group, the AUROC for advanced fibrosis were 0.67 (95% CI 0.63-0.71) for FIB-4, 0.60 (95% CI 0.56-0.64) for APRI and 0.65 (95% CI 0.61-0.69) for NFS. The specificities were 0.95 for FIB-4 greater than 3.25, 0.88 for APRI greater than 1.5 and 0.99 for NFS greater than 0.675. CONCLUSION: The performance of NITs to exclude advanced fibrosis did not differ greatly regardless of HS. FIB-4 and NFS have the best negative predictive values of 0.80 and 0.78, respectively, to exclude advanced fibrosis in CHBHS subjects.

Detecting Early-Stage Liver Fibrosis Using Macromolecular Proton Fraction Mapping Based on Spin-Lock MRI: Preliminary Observations.

BACKGROUND: Liver fibrosis is characterized by macromolecule depositions. Recently, a novel technology termed macromolecular proton fraction quantification based on spin-lock magnetic resonance imaging (MPF-SL) is reported to measure macromolecule levels. HYPOTHESIS: MPF-SL can detect early-stage liver fibrosis by measuring macromolecule levels in the liver. STUDY TYPE: Retrospective. SUBJECTS: Fifty-five participants, including 22 with no fibrosis (F0) and 33 with early-stage fibrosis (F1-2), were recruited. FIELD STRENGTH/SEQUENCE: 3 T; two-dimensional (2D) MPF-SL turbo spin-echo sequence, 2D spin-lock T1rho turbo spin-echo sequence, and multi-slice 2D gradient echo sequence. ASSESSMENT: Macromolecular proton fraction (MPF), T1rho, liver iron concentration (LIC), and fat fraction (FF) biomarkers were quantified within regions of interest. STATISTICAL TESTS: Group comparison of the biomarkers using Mann-Whitney U tests; correlation between the biomarkers assessed using Spearman's rank correlation coefficient and linear regression with goodness-of-fit; fibrosis stage differentiation using receiver operating characteristic curve (ROC) analysis. P-value < 0.05 was considered statistically significant. RESULTS: Average T1rho was 41.76 ± 2.94 msec for F0 and 41.15 ± 3.73 msec for F1-2 (P = 0.60). T1rho showed nonsignificant correlation with either liver fibrosis (ρ = -0.07; P = 0.61) or FF (ρ = -0.14; P = 0.35) but indicated a negative correlation with LIC (ρ = -0.66). MPF was 4.73 ± 0.45% and 5.65 ± 0.81% for F0 and F1-2 participants, respectively. MPF showed a positive correlation with liver fibrosis (ρ = 0.59), and no significant correlations with LIC (ρ = 0.02; P = 0.89) or FF (ρ = 0.05; P = 0.72). The area under the ROC curve was 0.85 (95% confidence interval [CI] 0.75-0.95) and 0.55 (95% CI 0.39-0.71; P = 0.55) for MPF and T1rho to discriminate between F0 and F1-2 fibrosis, respectively. DATA CONCLUSION: MPF-SL has the potential to diagnose early-stage liver fibrosis and does not appear to be confounded by either LIC or FF. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Liver-related and extrahepatic events in patients with non-alcoholic fatty liver disease: a retrospective competing risks analysis.

BACKGROUND & AIM: Non-alcoholic fatty liver disease (NAFLD), and especially fibrotic non-alcoholic steatohepatitis, is associated with high risks of liver-related events (LRE) and extrahepatic events (EHE). We evaluated the competitive risk occurrence of LRE and EHE in a large cohort of biopsy-proven NAFLD stratified according to baseline severity of fibrosis. METHODS: Two thousand one hundred thirty-five patients with biopsy-proven NAFLD were enrolled. Observed cumulative incidence functions (CIFs) were used to evaluate the risk of LRE and EHE; cause-specific Cox model and predicted CIFs were fitted to identify predictors of LRE and EHE. A replication cohort of NAFLD patients with liver fibrosis severity estimated by liver stiffness measurement by transient elastography was also enrolled. RESULTS: Observed CIFs indicated that the 60-month probabilities of LRE and EHE were 0.2% and 3% in F0-F1, 2% and 3.8% in F2 and 9.7% and 6.4% in F3-F4 patients, respectively. The cause-specific Cox model indicated that in F0-F1 and F2 patients, age > 50 years (HR 2.7) was the only predictor of LRE, while age > 50 years (HR 2.96), previous cardiovascular events (CVE, HR 2.07), and previous extra-hepatic cancer (HR 2.36) were independent risk factors for EHE. In F3-F4 patients, age > 55 years (HR 1.73), obesity (HR 1.52), PLT < 150 000/mmc (HR 3.66) and log(GGT) (HR 1.77) were associated with LRE, while age > 55 years (HR 1.74) and previous CVE (HR 2.51) were independent predictors of EHE. Predicted CIFs for HE and EHE in F0-F1, F2 and F3-F4 patients stratified the risk of events. The results were externally replicated. CONCLUSION: The likelihood of EHE in NAFLD patients is relevant and increases according to the severity of liver fibrosis, while the risk of LRE is negligible in F0-F1, low but clinically relevant in F2 and high in F3-F4 patients.

Association of genetic variations with NAFLD in lean individuals.

BACKGROUND & AIMS: How adiposity influences the effect of genetic variants on non-alcoholic fatty liver disease (NAFLD) in the Asian population remains unclear. We aimed to study the association between genetic risk variants and susceptibility/severity of NAFLD in the lean, overweight and obese individuals. METHODS: Nine hundred and four community subjects underwent proton-magnetic resonance spectroscopy and transient elastography examination. Lean (<23 kg/m2 ), overweight (23-24.9 kg/m2 ) and obesity (≥25 kg/m2 ) were defined according to the body mass index cut-offs for Asians. NAFLD was defined as intrahepatic triglycerides ≥5%. PNPLA3, TM6SF2, MBOAT7 and 9 other gene polymorphisms were analysed by rhAMPTM SNP assays. RESULTS: Five hundred and twenty-nine (58.5%), 162 (17.9%) and 213 (23.6%) subjects were lean, overweight and obese, respectively. The prevalence of NAFLD was 12.4%, 41.4% and 59.1% in the three groups (P < .001). Amongst those with NAFLD, lean subjects (30.3%) were more likely to carry the PNPLA3 rs738409 GG genotype than overweight (17.9%) and obese subjects (17.4%) (P = .003). Compared with the CC genotype, the GG genotype was associated with the greatest increase in the risk of NAFLD in lean subjects (odds ratio [OR] 6.04), compared with overweight (OR 3.43, 95% CI [1.06, 11.14]) and obese subjects (OR 2.51, 95% CI [0.93, 6.78]). Additionally, the TM6SF2 rs58542926 TT genotype was associated with reduced serum triglycerides only in lean subjects. A gene-BMI effect was not observed for the other gene polymorphisms. CONCLUSIONS: The PNPLA3 rs738409 gene polymorphism has a greater effect on liver fat in Asian lean individuals than in overweight or obese ones.

The global NAFLD policy review and preparedness index: Are countries ready to address this silent public health challenge?

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent, yet largely underappreciated liver condition which is closely associated with obesity and metabolic disease. Despite affecting an estimated 1 in 4 adults globally, NAFLD is largely absent on national and global health agendas. METHODS: We collected data from 102 countries, accounting for 86% of the world population, on NAFLD policies, guidelines, civil society engagement, clinical management, and epidemiologic data. A preparedness index was developed by coding questions into 6 domains (policies, guidelines, civil awareness, epidemiology and data, NAFLD detection, and NAFLD care management) and categorising the responses as high, medium, and low; a multiple correspondence analysis was then applied. RESULTS: The highest scoring countries were India (42.7) and the United Kingdom (40.0), with 32 countries (31%) scoring zero out of 100. For 5 of the domains a minority of countries were categorised as high-level while the majority were categorised as low-level. No country had a national or sub-national strategy for NAFLD and <2% of the different strategies for related conditions included any mention of NAFLD. National NAFLD clinical guidelines were present in only 32 countries. CONCLUSIONS: Although NAFLD is a pressing public health problem, no country was found to be well prepared to address it. There is a pressing need for strategies to address NAFLD at national and global levels. LAY SUMMARY: Around a third of the countries scored a zero on the NAFLD policy preparedness index, with no country scoring over 50/100. Although NAFLD is a pressing public health problem, a comprehensive public health response is lacking in all 102 countries. Policies and strategies to address NAFLD at the national and global levels are urgently needed.

Secular trend of treatment uptake in patients with chronic hepatitis B: A territory-wide study of 135 395 patients from 2000 to 2017.

BACKGROUND AND AIMS: The uptake of antiviral treatment for patients with chronic hepatitis B (CHB) has been suboptimal. We aimed to determine the secular trend of treatment uptake in the territory-wide CHB cohort in Hong Kong from 2000 to 2017 and the factors for no treatment despite fulfilling treatment criteria. METHODS: Chronic hepatitis B patients under public clinics and hospitals were identified through electronic medical records. The treatment indications were defined according to the Asian-Pacific guidelines published at the time of patients' first appearance in four periods: 2000-2004, 2005-2009, 2010-2013, and 2014-2017. RESULTS: There were 135 395 CHB patients were included; 1493/12472 (12.0%), 7416/43426 (17.1%), 10 129/46559 (21.8%), 8051/32 938 (24.4%) patients fulfilled treatment criteria in the four periods, respectively. The treatment uptake rate increased with time: 35.1%, 43.4%, 60.2%, and 68.6% respectively. High fibrosis indices (APRI, FIB-4, and Forns indices) appeared to be the main factors for treatment indication in non-cirrhotic patients, with over 90% fulfilling treatment criteria due to high fibrosis indices alone. Of those fulfilling treatment criteria by high fibrosis indices, less than 60% of patients (25.2%, 36.1%, 46.0%, and 58.9%, respectively) had antiviral treatment initiated. Normal platelet count (odds ratio 0.42, P < 0.001) was the independent factor associated with not initiating antiviral treatment in patients fulfilling treatment criteria. CONCLUSIONS: Treatment uptake rates have been increasing over time. Normal platelet count, which reflects less advanced liver disease, precludes patients from receiving antiviral treatment even if treatment indication is fulfilled. Hence, the importance to identify non-cirrhotic patients with significant liver fibrosis should be emphasized.

Unhealthy lifestyle habits and physical inactivity among Asian patients with non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Lifestyle modification is the cornerstone for the management of non-alcoholic fatty liver disease (NAFLD). We aim to understand lifestyle habits of NAFLD patients, compare across Asian regions and identify area of deficiency. METHODS: In the multi-centre controlled attenuation parameter (CAP)-Asia study, we collected clinical data and lifestyle habit data of NAFLD patients from Singapore, mainland China, Hong Kong, Taiwan and Malaysia. Physical activity was assessed using the International Physical Activity Questionnaire. RESULTS: A total of 555 patients were included in the final analysis (mean age 54.5 ± 11.2 years, 54.1% men and median liver stiffness 6.7 kPa). More patients from mainland China (27.4%) and Taipei (25.0%) were smokers. Modest drinking was more common in Taiwan (25.0%) and Hong Kong (18.2%); only 1.3% had binge drinking. Majority of patients drank coffee (64.0%) and tea (80.2%), with varying amounts and durations in different regions. Soft drinks consumption was most common in Singapore (62.2%) and Malaysia (57.7%). Only 29.7% of patients met the Physical Activity Guidelines Recommendations, with no major differences across regions. Patients with liver stiffness <10 kPa were more likely to report any vigorous activity, and sitting time was an independent factor associated with high CAP. Tea and coffee consumption were independently associated with high CAP and liver stiffness, respectively. CONCLUSIONS: Despite some heterogeneity, unhealthy lifestyle and physical inactivity are common across Asian regions. Patients with liver stiffness <10 kPa were more likely to report any vigorous activity. Healthcare providers may use the comparative data to identify areas of deficiency.

Modelling NAFLD disease burden in four Asian regions-2019-2030.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) account for an increasing proportion of liver disease in the Asia-Pacific region. Many areas in the region are experiencing epidemics of metabolic syndrome among rapidly ageing populations. AIMS: To estimate using modelling the growth in NAFLD populations, including cases with significant fibrosis that are most likely to experience advanced liver disease and related mortality. METHODS: A disease progression model was used to summarise and project fibrosis progression among the NAFLD populations of Hong Kong, Singapore, South Korea and Taiwan. For each area, changes in the adult prevalence of obesity was used to extrapolate long-term trends in NAFLD incidence. RESULTS: In the areas studied, prevalent NAFLD cases were projected to increase 6%-20% during 2019-2030, while prevalent NASH cases increase 20%-35%. Incident cases of hepatocellular carcinoma are projected to increase by 65%-85%, while incident decompensated cirrhosis cases increase 65%-100% by 2030. Likewise, NAFLD-related mortality is projected to increase between 65% and 100% from 2019 to 2030. NAFLD disease burden is expected to increase alongside rising trends in metabolic syndrome and obesity among populations in the region. This leads to more cases of advanced liver disease and associated mortality. CONCLUSIONS: Preventing the growth of diabetic and obese populations will be a key factor in reducing ongoing increases in NAFLD-related disease burden in the Asia-Pacific region.

The safety of stopping nucleos(t)ide analogue treatment in patients with HBeAg-negative chronic hepatitis B.

BACKGROUND: The rates of hepatitis B surface antigen (HBsAg) seroclearance after stopping nucleos(t)ide analogues (NA) in European (19% in 2 years) and Asian (13% in 6 years) patients with chronic hepatitis B (CHB) vary dramatically. We evaluated the incidence of hepatitis flare and HBsAg seroclearance in hepatitis B e antigen (HBeAg)-negative Chinese CHB patients who had stopped NA. METHODS: This was a territory-wide retrospective study in Hong Kong. We identified HBeAg-negative CHB patients from January 2000 to December 2017 who had stopped NA treatment for more than 3 months. Hepatitis flare was defined as ALT >2×ULN. RESULTS: The 1076 patients were predominantly middle-aged men (mean age 52 years, male 74.8%) when starting NA; they stopped NA after 82 ± 35 months of treatment. At 44.3 ± 24.6 months after stopping NA, 147 (13.6%) patients had hepatitis flare, which led to resumption of NA; whereas 77 (7.2%) patients had flare but did not resume NA. Decompensation occurred in 7/914 (0.8%) patients. A total of 695 (64.6%) patients remained on NA treatment at the last visit. Eleven patients had achieved HBsAg seroclearance (6 of them had hepatitis flare and 1 of these 6 patients achieved HBsAg seroclearance after NA was restarted). Hepatic events developed in 75/695 (10.8%) patients who had NA resumed vs 43/381 (11.3%) patients who did not resume NA (P = .677). CONCLUSIONS: Hepatitis flare and retreatment were common in HBeAg-negative CHB patients who stopped NA treatment; whereas HBsAg seroclearance rarely occurred. Stopping NA to achieve functional cure should not be recommended at this moment.

Development and validation of a model for hepatitis B e antigen seroconversion in entecavir-treated patients with chronic hepatitis B.

Achieving hepatitis B e antigen (HBeAg) seroconversion is a satisfactory endpoint during antiviral treatment for chronic hepatitis B (CHB). This study aimed to develop and validate a novel scoring system to predict HBeAg seroconversion during entecavir (ETV) treatment. A total of 526 patients with HBeAg-positive CHB treated with ETV for at least 1 year were randomly assigned to the training and validation cohorts. Baseline parameters including hepatitis B virus DNA, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and alanine aminotransferase level were quantified. Patients who achieved HBeAg seroconversion were compared with those without HBeAg seroconversion. A prediction model was established to predict HBeAg seroconversion during ETV treatment. After a median follow up of 2.67 years, 93 (36.0%) and 87 (32.5%) patients in the training and validation cohorts developed HBeAg seroconversion. A prediction score composed of age, HBsAg and HBcAb quantification was derived. Areas under receiver operating characteristic curve at 5 years of this prediction score were 0.70 and 0.72 in the training and validation cohorts. By using the dual cutoff values of 0.28 and 0.58, the model was endowed with high sensitivity and specificity to exclude or identify patients developing HBeAg seroconversion (90.3% sensitivity and 90.2% specificity in the training cohort as well as 92.8% sensitivity and 84.4% specificity in the validation cohort, respectively). A novel prediction score that uses baseline clinical variables was developed and validated. The score accurately estimates the probabilities of developing HBeAg seroconversion at 5-years ETV therapy in patients with CHB.

Nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by excess accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)); in up to 40% of individuals, there are additional findings of portal and lobular inflammation and hepatocyte injury (which characterize nonalcoholic steatohepatitis (NASH)). A subset of patients will develop progressive fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma and cardiovascular complications are life-threatening co-morbidities of both NAFL and NASH. NAFLD is closely associated with insulin resistance; obesity and metabolic syndrome are common underlying factors. As a consequence, the prevalence of NAFLD is estimated to be 10-40% in adults worldwide, and it is the most common liver disease in children and adolescents in developed countries. Mechanistic insights into fat accumulation, subsequent hepatocyte injury, the role of the immune system and fibrosis as well as the role of the gut microbiota are unfolding. Furthermore, genetic and epigenetic factors might explain the considerable interindividual variation in disease phenotype, severity and progression. To date, no effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery. However, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation. Diagnosis of NAFLD can be established by imaging, but detection of the lesions of NASH still depend on the gold-standard but invasive liver biopsy. Several non-invasive strategies are being evaluated to replace or complement biopsies, especially for follow-up monitoring.

Non-alcoholic fatty liver disease: spectral patterns observed from an in vivo phosphorus magnetic resonance spectroscopy study.

BACKGROUND & AIMS: Liver biopsy is the gold standard for diagnosing non-alcoholic fatty liver disease (NAFLD) but with practical constraints. Phosphorus magnetic resonance spectroscopy ((31)P-MRS) allows in vivo assessment of hepatocellular metabolism and has shown potential for biochemical differentiation in diffuse liver disease. Our aims were to describe spectroscopic signatures in biopsy-proven NAFLD and to determine diagnostic performance of (31)P-MRS for non-alcoholic steatohepatitis (NASH). METHODS: (31)P-MRS was performed in 151 subjects, comprised of healthy controls (n=19) and NAFLD patients with non-NASH (n=37) and NASH (n=95). Signal intensity ratios for phosphomonoesters (PME) including phosphoethanolamine (PE), phosphodiesters (PDE) including glycerophosphocholine (GPC), total nucleotide triphosphate (NTP) including α-NTP, and inorganic phosphate (Pi), expressed relative to total phosphate (TP) or [PME+PDE] and converted to percentage, were obtained. RESULTS: Compared to controls, both NAFLD groups had increased PDE/TP (p<0.001) and decreased Pi/TP (p=0.011). Non-NASH patients showed decreased PE/[PME+PDE] (p=0.048), increased GPC/[PME+PDE] (p<0.001), and normal NTP/TP and α-NTP/TP. Whereas, NASH patients had normal PE/[PME+PDE] and GPC/[PME+PDE], but decreased NTP/TP (p=0.004) and α-NTP/TP (p<0.001). The latter was significantly different between non-NASH and NASH (p=0.047) and selected as discriminating parameter, with area under the receiver-operating characteristics curve of 0.71 (95% confidence interval, 0.62-0.79). An α-NTP/TP cutoff of 16.36% gave 91% sensitivity and cutoff of 10.57% gave 91% specificity for NASH. CONCLUSIONS: (31)P-MRS shows distinct biochemical changes in different NAFLD states, and has fair diagnostic accuracy for NASH.

Serum hepatitis B surface antigen kinetics in severe reactivation of hepatitis B e antigen negative chronic hepatitis B patients receiving nucleoside/nucleotide analogues.

BACKGROUND: Kinetics of serum hepatitis B surface antigen (HBsAg) level in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients presented with severe reactivation and received oral antiviral therapy is unknown. We aimed to investigate the kinetics of HBsAg level among these patients. METHODS: HBeAg-negative patients on antiviral therapy with follow-up for 2 years were studied. Those presented with severe reactivation (alanine aminotransferase [ALT] ≥5 times of normal) were compared to those with mild hepatitis. Serum HBsAg level was measured by Elecsys HBsAg II Quant assay (Roche) at baseline and 6-monthly. RESULTS: A total of 192 (74 severe reactivation) patients were studied. Eighty-one (42%), 74 (39%) and 37 (19%) patients were on lamivudine, entecavir and telbivudine, respectively. Forty-four (23%) patients had early HBsAg decline, that is, ≥0.5 log10 reduction, at month 6. Patients with severe reactivation had higher serum baseline ALT (1,415 ±897 versus 73 ±39 IU/l), HBV DNA (6.4 ±1.6 versus 5.2 ±1.2 log10 IU/ml) and HBsAg (3.3 ±1.0 versus 2.9 ±0.6 log10 IU/ml), as well as an earlier HBsAg decline (50% versus 6%; all P<0.001) than those without. The HBsAg change of patients with severe reactivation was higher at months 0-6 (-0.58 ±-1.26 versus -0.01 ±-0.26 log10 IU/ml; P<0.001) but then became comparable from months 6-24 (-0.19 ±-0.60 versus -0.13 ±-0.19 log10 IU/ml; P=0.85), compared to those presented with mild hepatitis. CONCLUSIONS: Patients who presented with severe reactivation of HBeAg-negative hepatitis were more likely to develop early HBsAg decline during antiviral therapy. It may indicate a transient strong immune clearance with rapid initial reduction in serum HBsAg, which cannot be sustained due to a faster clearance of serum HBsAg.

Polymorphisms near IL28B and serologic response to peginterferon in HBeAg-positive patients with chronic hepatitis B.

BACKGROUND & AIMS: A limited number of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B respond to treatment with peginterferon alfa (PEG-IFN). We investigated whether IL28B genotypes are associated with response. METHODS: We studied 205 HBeAg-positive patients who were treated with PEG-IFN (some were also treated with lamivudine) at 11 European and Asian hospitals; genotype analysis was performed for IL28B rs12980275 and rs12979860. Response was defined as HBeAg loss with the appearance of antibodies to hepatitis B e antigen (anti-HBe) at the end of PEG-IFN therapy (HBeAg seroconversion), along with HBeAg seroconversion and hepatitis B surface antigen clearance during long-term follow-up. RESULTS: The patients were infected with hepatitis B virus (HBV) genotypes A (13%), B (20%), C (47%), and D (13%). The proportions of IL28B genotypes were 77%, 19%, and 5% for AA/AG/GG at rs12980275 and also for CC/CT/TT at rs12979860, respectively. IL28B genotype was significantly associated with HBeAg seroconversion at the end of treatment (P < .001); the adjusted odds ratio for seroconversion was 3.16 (95% confidence interval [CI], 1.26-8.52; P = .013) for AA versus AG/GG at rs12980275 after adjustment for HBV genotype, age, levels of HBV DNA and alanine aminotransferase, and combination therapy. IL28B genotype was independently associated with an increased probability of HBeAg seroconversion during long-term follow-up (adjusted hazard ratio [HR], 2.14; 95% CI, 1.14-4.31; P = .018 for AA vs AG/GG by Cox regression analysis). Similar results were obtained for rs12979860. IL28B genotype was also associated with hepatitis B surface antigen clearance (HR, 3.47 for AA vs AG/GG; 95% CI, 1.04-13.48; P = .042). CONCLUSIONS: Polymorphisms near IL28B are independently associated with serologic response to PEG-IFN in patients with HBeAg-positive chronic hepatitis B.

Prediction of off-treatment response to lamivudine by serum hepatitis B surface antigen quantification in hepatitis B e antigen-negative patients.

BACKGROUND: The timing of antiviral therapy cessation in hepatitis B e antigen (HBeAg)-negative patients is controversial. Here, we aimed to investigate the role of HBV DNA and hepatitis B surface antigen (HBsAg) monitoring to predict off-treatment sustained response. METHODS: A total of 53 HBeAg-negative chronic hepatitis B patients who received lamivudine for 34 ±23 (range 12-76) months and had lamivudine stopped for 47 ±35 months were studied. Primary outcome was sustained response, defined as HBV DNA≤200 IU/ml, at 12 months post-treatment (SR-12). RESULTS: A total of 9 (17%) patients achieved SR-12. HBV DNA at baseline, month 6 and end of treatment had no association with SR-12. HBsAg levels tended to decrease more significantly during treatment among SR-12 responders. At the end of treatment, both HBsAg ≤2 log IU/ml and reduction by >1 log from baseline had sensitivity, specificity, positive and negative predictive values for SR-12 of 78%, 96%, 78% and 96%, respectively. All 5 patients with HBsAg≤2 log IU/ml and reduction >1 log at the end of treatment achieved SR-12 and all 40 patients with HBsAg>2 log IU/ml and reduction ≤1 log did not have SR-12. The cumulative probability of sustained response and HBsAg clearance at 5 years among patients with HBsAg≤2 log IU/ml were 88% and 72%, respectively, that among patients with HBsAg reduction >1 log were 74% and 61%, respectively. CONCLUSIONS: Monitoring of HBsAg level can guide the timing of stopping lamivudine in HBeAg-negative chronic hepatitis B.

Factors associated with unreliable liver stiffness measurement and its failure with transient elastography in the Chinese population.

BACKGROUND AND AIM: Liver stiffness measurement (LSM) with transient elastography is a non-invasive and reliable test for liver fibrosis. However a small proportion of patients may have unreliable LSM or LSM failure. The aim of the present study was to investigate the factors associated with unreliable LSM or LSM failure in Chinese patients. METHODS: We prospectively recruited liver patients for LSM. Unreliable LSM was defined as < 10 valid shots, an interquartile range (IQR)/LSM > 30%, or a success rate < 60%. LSM failure was defined as zero valid shots. RESULTS: Among 3205 patients with LSM, 371 (11.6%) and 88 (2.7%) had unreliable LSM and LSM failure, respectively. The rates started to increase when body mass index (BMI) ≥ 28.0 kg/m(2) . Comparing patients with BMI ≥ 28.0-29.9 kg/m(2) versus those with BMI ≥ 30.0 kg/m², the rates of unreliable LSM (16.4% vs 18.9%; P = 0.62) and LSM failure (11.8% vs 17.8%; P = 0.16) were similar. BMI ≥ 28.0 kg/m² was the most important factor associated with unreliable LSM (odds ratio [OR] = 2.9, 95% confidence interval [CI] = 2.1-3.9, P < 0.0001) and LSM failure (OR = 10.1, 95% CI = 6.4-14.2, P < 0.0001). Central obesity, defined as waist circumference > 80 cm in women and > 90 cm in men, was another independent risk factor of unreliable LSM (OR = 1.3, 95% CI = 1.0-1.6, P = 0.04) and LSM failure (OR = 5.8, 95% CI = 2.9-11.5, P < 0.0001). CONCLUSION: BMI ≥ 28.0 kg/m² and central obesity were the independent risk factors of unreliable LSM and LSM failure in Chinese, and these rates were significantly higher in patients with extreme BMI.