Point-of-Care Noninvasive Prediction of Liver-Related Events in Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Individual risk prediction of liver-related events (LRE) is needed for clinical assessment of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) patients. We aimed to provide point-of-care validated liver stiffness measurement (LSM)-based risk prediction models for the development of LRE in patients with NAFLD, focusing on selecting patients for clinical trials at risk of clinical events. METHODS: Two large multicenter cohorts were evaluated, 2638 NAFLD patients covering all LSM values as the derivation cohort and 679 more advanced patients as the validation cohort. We used Cox regression to develop and validate risk prediction models based on LSM alone, and the ANTICIPATE and ANTICIPATE-NASH models for clinically significant portal hypertension. The main outcome of the study was the rate of LRE in the first 3 years after initial assessment. RESULTS: The 3 predictive models had similar performance in the derivation cohort with a very high discriminative value (c-statistic, 0.87-0.91). In the validation cohort, the LSM-LRE alone model had a significant inferior discrimination (c-statistic, 0.75) compared with the other 2 models, whereas the ANTICIPATE-NASH-LRE model (0.81) was significantly better than the ANTICIPATE-LRE model (0.79). In addition, the ANTICIPATE-NASH-LRE model presented very good calibration in the validation cohort (integrated calibration index, 0.016), and was better than the ANTICIPATE-LRE model. CONCLUSIONS: The ANTICIPATE-LRE models, and especially the ANTICIPATE-NASH-LRE model, could be valuable validated clinical tools to individually assess the risk of LRE at 3 years in patients with NAFLD/NASH.

Clinical Outcomes and Quantitative HBV Surface Antigen Levels in Diverse Chronic Hepatitis B Patients in Canada: A Retrospective Real-World Study of CHB in Canada (REVEAL-CANADA).

BACKGROUND: Hepatitis B surface antigen (HBsAg) loss is associated with improved clinical outcomes for individuals with chronic hepatitis B (CHB); however, the effects of varying HBsAg levels on clinical outcomes in diverse cohorts are understudied. METHODS: In this cross-sectional, multicentre, retrospective study, the data on adult subjects enrolled in the Canadian HBV Network with CHB seen from 1 January 2012 to 30 January 2021 with the treatment and virologic data within 1 year of HBsAg testing were analyzed. Patients were tested for HBsAg using qualitative (for HBsAg-negative samples) and/or commercial quantitative assays. Fibrosis or hepatic necroinflammation was determined by the liver stiffness measurement (LSM). The baseline data were summarized using descriptive statistics and compared by using univariable/multivariable analyses. RESULTS: This study included 844 CHB patients, with a median age of 49.6 years (IQR 40.1-60.5), and 37% were female. In total, 751 patients (78.6%) had known ethnicity data, and 76.7% self-reported as Asian, 11.4% as Black, 6.8% as White, and 4.8% as other. Among the 844 patients, 237 (28.0%) were HBsAg (-) (1000 IU/mL. Overall, 80% (682) had known HBeAg status at the last follow-up, and the majority (87.0%) were HBeAg-negative. In addition, 54% (461/844) had prior antiviral therapy, 19.7% of which (16.3, 23.7, n = 91) were HBsAg (-). The treated patients had a lower risk of cirrhosis (16.46, 95% CI 1.89-143.39, p = 0.01) or HCC (8.23, 95% CI 1.01-67.39, p = 0.05) than the untreated patients. A lower proportion of the HBsAg-loss group had cirrhosis (5.7% vs. 10.9%, p = 0.021) and HCC (0.9% vs. 6.2%, p = 0.001). CONCLUSION: In this retrospective, ethnically diverse cohort study, CHB patients who received antiviral therapy and/or had HBsAg loss were less likely to develop cirrhosis and HCC, confirming the results of the studies in less diverse cohorts. No association was found between the qHBsAg level and fibrosis determined with LSM. Individuals who achieved HBsAg loss had low-level qHBsAg within 1 year of seroclearance.

Ribavirin Does Not Enhance Hepatitis B Virus Nucleotide Antiviral Activity: A Pilot Study.

PURPOSE: There is a need for effective and affordable treatments that achieve hepatitis B virus (HBV) functional cure and prevent long-term complications. The use of immune-modulators combined with HBV antivirals is a promising therapeutic strategy to achieve these goals. Based on ribavirin (RBV) monotherapy data, we hypothesized that RBV could improve virological responses when used in combination with tenofovir.  Methods: In this randomized, open label, controlled pilot trial, we evaluated RBV (n=4) dosed for the initial 24 weeks of treatment versus no RBV (n=4) in tenofovir recipients dosed over 48 weeks.  Results: Although well tolerated and safe in combination with tenofovir, RBV demonstrated no beneficial effects on virologic, biochemical or immunological markers of chronic HBV infection over 48 weeks of serial evaluation.  Conclusions: Our data does not suggest a HBV-specific immunomodulatory effect or an impact of RBV on HBV virological and antigen suppression.

Nationwide retrospective study of hepatitis B virological response and liver stiffness improvement in 465 patients on nucleos(t)ide analogue.

BACKGROUND: Hepatitis B virus (HBV) nucleos(t)ide analog (NA) therapy reduces liver disease but requires prolonged therapy to achieve hepatitis B surface antigen (HBsAg) loss. There is limited North American real-world data using non-invasive tools for fibrosis assessment and few have compared 1st generation NA or lamivudine (LAM) to tenofovir disoproxil fumarate (TDF). AIM: To assess impact of NA on virological response and fibrosis regression using liver stiffness measurement (LSM) (i.e., FibroScan®). METHODS: Retrospective, observational cohort study from the Canadian HBV Network. Data collected included demographics, NA, HBV DNA, alanine aminotransferase (ALT), and LSM. Patients were HBV monoinfected patients, treatment naïve, and received 1 NA with minimum 1 year follow-up. RESULTS: In 465 (median 49 years, 37% female, 35% hepatitis B e antigen+ at baseline, 84% Asian, 6% White, and 9% Black). Percentage of 64 (n = 299) received TDF and 166 were LAM-treated with similar median duration of 3.9 and 3.7 years, respectively. The mean baseline LSM was 11.2 kPa (TDF) vs 8.3 kPa (LAM) (P = 0.003). At 5-year follow-up, the mean LSM was 7.0 kPa in TDF vs 6.7 kPa in LAM (P = 0.83). There was a significant difference in fibrosis regression between groups (i.e., mean -4.2 kPa change in TDF and -1.6 kPa in LAM, P < 0.05). The last available data on treatment showed that all had normal ALT, but more TDF patients were virologically suppressed (< 10 IU/mL) (n = 170/190, 89%) vs LAM-treated (n = 35/58, 60%) (P < 0.05). None cleared HBsAg. CONCLUSION: In this real-world North American study, approximately 5 years of NA achieves liver fibrosis regression rarely leads to HBsAg loss.

Molecular epidemiology and clinical characteristics of hepatitis D virus infection in Canada.

Background & Aims: HDV affects 4.5-13% of chronic hepatitis B (CHB) patients globally, yet the prevalence of HDV infection in Canada is unknown. To investigate the prevalence, genotype, demographics, and clinical characteristics of HDV in Canada, we conducted a retrospective analysis of (1) HDV antibody and RNA positivity among referred specimens, and (2) a cross-sectional subset study of 135 HDV seropositive +/-RNA (HDV+) patients compared with 5,132 HBV mono-infected patients in the Canadian HBV Network. Methods: Anti-HDV IgG-positive specimens collected between 2012 and 2019 were RNA tested and the genotype determined. Patients enrolled in the Canadian HBV Network were >18 years of age and HBsAg-positive. Clinical data collected included risk factors, demographics, comorbidities, treatment, fibrosis assessment, and hepatic complications. Results: Of the referred patients, 338/7,080 (4.8%, 95% CI 4.3-5.3) were HDV seropositive, with 219/338 RNA-positive (64.8%, 95% CI 59.6-69.7). The HDV+ cohort were more likely to be born in Canada, to be White or Black/African/Caribbean than Asian, and reporting high-risk behaviours, compared with HBV mono-infected patients. Cirrhosis, complications of end-stage liver disease, and liver transplantation were significantly more frequent in the HDV+ cohort. HDV viraemia was significantly associated with elevated liver transaminases and cirrhosis. Five HDV genotypes were observed among referred patients but no association between genotype and clinical outcome was detected within the HDV+ cohort. Conclusions: Nearly 5% of the Canadian HBV referral population is HDV seropositive. HDV infection is highly associated with risk behaviours and both domestic and foreign-born patients with CHB. HDV was significantly associated with progressive liver disease highlighting the need for increased screening and surveillance of HDV in Canada. Lay summary: Evidence of HDV infection was observed in approximately 5% of Canadians who were infected with HBV referred to medical specialists. HDV-positive patients were more likely to be male, born in Canada, or White or Black/African/Caribbean compared to Asian, and to have reported high-risk activities such as injection or intranasal drug use or high-risk sexual contact compared with patients infected with only HBV. Patients infected with HDV were also more likely to suffer severe liver disease, including liver cancer, compared with HBV mono-infected patients.

Anxiety in cirrhosis: a prospective study on prevalence and development of a practical screening nomogram.

OBJECTIVES: The prevalence and effects of anxiety on health-related quality of life and clinical outcomes in cirrhosis are not well understood. This is increasingly relevant during COVID-19. Our aim was to use the Mini-International Neuropsychiatric Interview (MINI) to determine the prevalence of anxiety, its association with clinical outcomes in cirrhosis and to develop a rapid cirrhosis-specific anxiety screening nomogram. METHODS: Adults with a diagnosis of cirrhosis were prospectively recruited as outpatients at three tertiary care hospitals across Alberta and followed for up to 6 months to determine the association with unplanned hospitalization/death. The Hospital Anxiety and Depression scale (HADS) was used as a screening tool as it is free of influence from somatic symptoms. Anxiety was diagnosed using the MINI. RESULTS: Of 304 patients, 17% of patients had anxiety by the MINI and 32% by the HADS. Anxious patients had lower health-related quality of life as assessed by the chronic liver disease questionnaire (P < 0.001) and EuroQol Visual Analogue Scale (P < 0.001), and also had higher levels of frailty using the Clinical Frailty score (P = 0.004). Multivariable analysis revealed smoking and three HADS subcomponents as independent predictors of anxiety. These were used to develop a rapid screening nomogram. CONCLUSION: A formal diagnosis of anxiety was made in approximately one in five patients with cirrhosis, and it was associated with worse HrQoL and frailty. The use of a 4-question nonsomatic symptom-based nomogram requires validation but is promising as a rapid screen for anxiety in cirrhosis.

Learning from a rare phenomenon - spontaneous clearance of chronic hepatitis C virus post-liver transplant: A case report.

BACKGROUND: Hepatitis C virus (HCV) can lead to chronic liver damage resulting in cirrhosis and hepatocellular carcinoma. Spontaneous clearance of HCV has been documented after an acute infection in 20%-45% of individuals. However, spontaneously resolved chronic hepatitis C following liver transplant (LT) is rare and has been documented only in a few case reports. The phenomenon of spontaneous clearance of chronic hepatitis C occurs together with other meaningful events, which are typically associated with significant changes in the host immunity. CASE SUMMARY: We report three cases of spontaneous resolution of chronic hepatitis C following liver transplantation. These patients either failed or had no HCV treatment prior to transplant, but had spontaneous resolution of HCV post-LT as documented by undetectable polymerase chain reaction (PCR). Diagnosis of HCV was based on viremia through PCR or liver biopsy. All three patients currently undergo surveillance and have no recurrence of HCV. CONCLUSION: Examining each patient's clinical course, we learned about many viral, host and cellular-factors that may have enhanced the host's immunity leading to spontaneous clearance of HCV. Though HCV treatment has excellent cure rates, understanding this mechanism may provide clinicians with insights regarding timing and duration of treatment.

Impact of statin treatment on non-invasive tests based predictions of fibrosis in a referral pathway for NAFLD.

OBJECTIVE: In non-alcoholic fatty liver disease (NAFLD), fibrosis determines the risk of liver complications. Non-invasive tests (NITs) such as FIB-4, NAFLD Fibrosis Score (NFS) and Hepamet, have been proposed as a tool to triage NAFLD patients in primary care (PC). These NITs include AST±ALT in their calculations. Many patients with NAFLD take statins, which can affect AST/ALT, but it is unknown if statin affects NITs fibrosis prediction. METHODS: We included 856 patients referred through a standardised pathway from PC with a final diagnosis of NAFLD. 832 had reliable vibration controlled transient elastography (VCTE) measurements. We assessed the effects of statins on the association between NITs and VCTE at different fibrosis thresholds. RESULTS: 129 out of 832 patients were taking a statin and 138 additional patients had indication for a statin. For any given FIB-4 value, patients on a statin had higher probabilities of high VCTE than patients not on a statin. Adjusting for body mass index, diabetes and age almost completely abrogated these differences, suggesting that these were related to patient's profile rather to a specific effect of statins. Negative predictive values (NPVs) of FIB-4 <1.3 for VCTE >8, 10, 12 and 16 were, respectively, 89, 94, 96% and 100% in patients on a statin and 92, 95, 98% and 99% in patients not on a statin. Statins had similar impact on Hepamet predictions but did not modify NFS predictions. CONCLUSION: In patients with NAFLD referred from PC, those on statins had higher chances of a high VCTE for a given FIB-4 value, but this had a negligible impact on the NPV of the commonly used FIB-4 threshold (<1.3).

Post-liver transplantation chronic kidney disease is associated with increased cardiovascular disease risk and poor survival.

Chronic kidney disease (CKD) is common following liver transplantation (LT). We aimed to investigate the frequency, risk factors, and impact of CKD on cardiovascular disease (CVD), graft, and patient survival. We analyzed 752 patients who received LT at the University of Alberta. Development of CKD was defined as eGFR <60 ml/min for greater than 3 months, intrinsic renal disease or presence of end-stage renal disease requiring renal replacement therapy. 240 patients were female (32%), and mean age at LT was 53 ± 11 years. CKD was diagnosed in 448 (60%) patients. On multivariable analysis, age (OR 1.3; P = 0.01), female sex (OR 3.3; P < 0.001), baseline eGFR (OR 0.83; P < 0.001), MELD (OR 1.03; P = 0.01), de novo metabolic syndrome (OR 2.3; P = 0.001), and acute kidney injury (OR 3.5; P < 0.001) were associated with CKD. A higher tacrolimus concentration to dose ratio was protective for CKD (OR 0.69; P < 0.001). CKD was associated with post-transplant CVD (26% vs. 16% P < 0.001), reduced graft (HR 1.4; P = 0.02), and patient survival (HR 1.3; P = 0.03). CKD is a frequent complication following LT and is associated with an increased risk of CVD and reduced graft and patient survival.

Noninvasive Diagnosis of Portal Hypertension in Patients With Compensated Advanced Chronic Liver Disease.

INTRODUCTION: We aimed to explore the prevalence of portal hypertension in the most common etiologies of patients with compensated advanced chronic liver disease (cACLD) and develop classification rules, based on liver stiffness measurement (LSM), that could be readily used to diagnose or exclude clinically significant portal hypertension (CSPH) in clinical practice. METHODS: This is an international cohort study including patients with paired LSM/hepatic venous pressure gradient (HVPG), LSM ≥10 kPa, and no previous decompensation. Portal hypertension was defined by an HVPG >5 mm Hg. A positive predictive value ≥90% was considered to validate LSM cutoffs for CSPH (HVPG ≥10 mm Hg), whereas a negative predictive value ≥90% ruled out CSPH. RESULTS: A total of 836 patients with hepatitis C (n = 358), nonalcoholic steatohepatitis (NASH, n = 248), alcohol use (n = 203), and hepatitis B (n = 27) were evaluated. Portal hypertension prevalence was >90% in all cACLD etiologies, except for patients with NASH (60.9%), being even lower in obese patients with NASH (53.3%); these lower prevalences of portal hypertension in patients with NASH were maintained across different strata of LSM values. LSM ≥25 kPa was the best cutoff to rule in CSPH in alcoholic liver disease, chronic hepatitis B, chronic hepatitis C, and nonobese patients with NASH, whereas in obese NASH patients, the positive predictive value was only 62.8%. A new model for patients with NASH (ANTICIPATE-NASH model) to predict CSPH considering body mass index, LSM, and platelet count was developed, and a nomogram was constructed. LSM ≤15 kPa plus platelets ≥150 × 10/L ruled out CSPH in most etiologies. DISCUSSION: Patients with cACLD of NASH etiology, especially obese patients with NASH, present lower prevalences of portal hypertension compared with other cACLD etiologies. LSM ≥25 kPa is sufficient to rule in CSPH in most etiologies, including nonobese patients with NASH, but not in obese patients with NASH.

Reduced immune responses to hepatitis B primary vaccination in obese individuals with nonalcoholic fatty liver disease (NAFLD).

Obesity and cirrhosis are associated with poor hepatitis B virus (HBV) vaccine responses, but vaccine efficacy has not been assessed in nonalcoholic fatty liver disease (NAFLD). Sixty-eight HBV-naïve adults with NAFLD were enrolled through the Canadian HBV network and completed three-dose HBV or HBV/HAV vaccine (Engerix-B®, or Twinrix®, GlaxoSmithKline). Anti-HBs titers were measured at 1-3 months post third dose. In 31/68 subjects enrolled at the coordinating-site, T-cell proliferation and follicular T-helper cells (pTFH) were assessed using PBMC. Immune response was also studied in NAFLD mice. NAFLD patients were stratified as low-risk-obesity, BMI < 35 (N = 40) vs. medium-high-risk obesity, BMI > 35 (N = 28). Anti-HBs titers were lower in medium/high-risk obesity, 385 IU/L ± 79 vs. low-risk obesity class, 642 IU/L ± 68.2, p = 0.02. High-risk obesity cases, N = 14 showed lower vaccine-specific-CD3+ CD4+ T-cell response compared to low-risk obesity patients, N = 17, p = 0.02. Low vaccine responders showed dysfunctional pTFH. NAFLD mice showed lower anti-HBs levels and T-cell response vs. controls. In conclusion, we report here that obese individuals with NAFLD exhibit decreased HBV vaccine-specific immune responses.

Impact of specialized multidisciplinary care on cirrhosis outcomes and acute care utilization.

Background: Multidisciplinary care has the potential to improve outcomes among patients with cirrhosis, yet its impact on this population remains unclear, with existing studies demonstrating discrepant results. Using data from the multidisciplinary outpatient Cirrhosis Care Clinic (CCC) at the University of Alberta Hospital, we aimed to evaluate acute care utilization and survival outcomes of patients followed by the CCC compared with those receiving standard care (SC). Methods: We performed a retrospective chart review of 212 patients with cirrhosis admitted to University of Alberta Hospital between 2014 and 2015. CCC patients (n = 36) were followed through the CCC before index admission. SC patients (n = 176) were managed outside of the CCC. Readmission time in hospital was collected until 1 year, death, or liver transplant. Results: CCC patients had more advanced liver disease (higher prevalence of ascites, encephalopathy, and varices). Despite this, acute care utilization was significantly lower among CCC patients (adjusted length of stay lower by 3 days, p = 0.03, and adjusted survival days spent in hospital lower by 9%, p = 0.02). CCC patients also had improved 1-year transplant-free survival, with an adjusted 1-year relative risk reduction of 53% (p = 0.03). Total mean cost of care was lower in the CCC group by $2,280 per patient-month of life. Discussion: For patients admitted with cirrhosis, specialized post-discharge multidisciplinary outpatient care is associated with decreased acute care utilization, improved 1-year transplant-free survival probability, and the potential for cost savings to the system.

Selective Internal Radiation Therapy for Hepatocellular Carcinoma Across the Barcelona Clinic Liver Cancer Stages.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common lethal cancer, and there is a need for effective therapies. Selective internal radiation therapy (SIRT) has been increasingly used, but is not supported by guidelines due to a lack of solid evidence. AIMS: Determine the efficacy and safety of SIRT in HCC across the Barcelona Clinic Liver Cancer (BCLC) stages A, B, and C. METHODS: Consecutive patients that received SIRT between 2006 and 2016 at two centers in Canada were evaluated. RESULTS: We analyzed 132 patients, 12 (9%), 62 (47%), and 58 (44%) belonged to BCLC stages A, B, and C; mean age was 61.2 (SD ± 9.2), and 89% were male. Median survival was 12.4 months (95% CI 9.6-16.6), and it was different across the stages: 59.7 (95% CI NA), 12.8 (95% CI 10.2-17.5), and 9.3 months (95% CI 5.9-11.8) in BCLC A, B, and C, respectively (p = 0.009). Independent factors associated with survival were previous HCC treatment (HR 2.01, 95% CI 1.23-3.27, p = 0.005), bi-lobar disease (HR 2.25, 95% CI 1.30-3.89, p = 0.003), ascites (HR 1.77, 95% CI 0.99-3.13, p = 0.05), neutrophil-to-lymphocyte ratio (HR 1.11, 95% CI 1.02-1.20, p = 0.01), Albumin-Bilirubin (ALBI) grade-3 (HR 2.69, 95% CI 1.22-5.92, p = 0.01), tumor thrombus (HR 2.95, 95% CI 1.65-5.24, p < 0.001), and disease control rate (HR 0.62, 95% CI 0.39-0.96, p = 0.03). Forty-four (33%) patients developed severe adverse events, and ALBI-3 was associated with higher risk of these events. CONCLUSIONS: SIRT has the potential to be used across the BCLC stages in cases with preserved liver function. When using it as a rescue treatment, one should consider variables reflecting liver function, HCC extension, and systemic inflammation, which are associated with mortality.

Assisting Atomic Dispersion of Fe in N-Doped Carbon by Aerosil for High-Efficiency Oxygen Reduction.

Utilizing Zn as a "fencing" agent has enabled the pyrolytic synthesis of atomically dispersed metal-nitrogen-carbon (AD-MNC) materials for broad electrocatalysis such as fuel cells, metal-air batteries, and water electrolyzers. Yet the Zn residue troubles the precise identification of the responsible sites in active service. Herein we developed a simple aerosil-assisted method for preparing AD-MNC materials to cautiously avoid the introduction of Zn. The combined analysis of extended X-ray absorption fine structure (EXAFS) and aberration-corrected high-resolution transition electron microscopy verified the atomic dispersion of Fe species in the as-made Fe-NC sample with a well-defined structure of Fe-N4. Besides, the EXAFS studies indicated the formation of oxygenated Fe-N4 moieties (O-Fe-N4) after the removal of aerosil nanoparticles. Therefore, the immobilization of Fe atoms in the carbon substrate was attributed to the heavily doping N and rich oxygen dangling species at the aerosil surface. Electrochemical measurements revealed that the as-made Fe-NC material furnished with O-Fe-N4 moieties exhibited excellent oxygen reduction reaction (ORR) performance, characterized by individually indicating ∼22 mV higher half-wave potentials, with respect to commercial Pt/C catalyst. Density functional theory (DFT) computations suggested that the dangling oxygen ligand on the Fe-N4 moiety could significantly boost the cleavage of OOH* and the reductive release of *OH intermediates, leading to the enhancement of overall ORR performance.

Safety and immunogenicity of the therapeutic vaccine TG1050 in chronic hepatitis B patients: a phase 1b placebo-controlled trial.

Treatment of chronic hepatitis B (CHB) typically requires life-long administration of drugs. Cohort and pre-clinical studies have established the link between a functional T-cell-mounted immunity and resolution of infection. TG1050 is an adenovirus 5-based vaccine that expresses HBV polymerase and domains of core and surface antigen and has shown immunogenicity and antiviral effects in mice. We performed a phase 1 clinical trial to assess safety and explore immunogenicity and early efficacy of TG1050 in CHB patients. This randomized, double blind, placebo-controlled study included two sequential phases: one single dose cohort (SD, n = 12) and one multiple (3) doses cohort (MD, n = 36). Patients, virally suppressed under nucleoside(d)tide analog NUC therapy, were randomized 1:1:1 across 3 dose levels (DL) and assigned to receive 109, 1010, 1011 virus particles (vp) of TG1050 and then randomized within each DL to placebo (3:1 and 9:3 vaccines/placebo in each DL, respectively, for the SD and MD cohorts). Cellular (ELISPOT) and antibody responses (anti-Adenovirus), as well as evolution of circulating HBsAg and HBcrAg, were monitored. All doses were well tolerated in both cohorts, without severe adverse event. TG1050 was capable to induce IFN-γ producing T-cells targeting 1 to 3 encoded antigens, in particular at the 1010vp dose. Overall, minor decreases of HBsAg were observed while a number of vaccinees reached unquantifiable HBcrAg by end of the study. In CHB patients under NUC, TG1050 exhibited a good safety profile and was capable to induce HBV-specific cellular immune response. These data support further clinical evaluation, especially in combination studies.

Impact of Implementing a "FIB-4 First" Strategy on a Pathway for Patients With NAFLD Referred From Primary Care.

Detection of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is essential for stratifying patients according to the risk of liver-related morbidity. Noninvasive methods such as vibration-controlled transient elastography (VCTE) and Fibrosis-4 index (FIB-4) have been recommended to identify patients for further assessment. The aim of this study was to assess the potential impact of implementing a "FIB-4 First" strategy to triage patients entering a NAFLD assessment pathway. The pathway for patients with suspected NAFLD was piloted at a tertiary liver center. Referral criteria were 16-65 years old, elevated alanine aminotransferase and/or steatosis on imaging, and absence of a previous liver diagnosis. A registered nurse risk-stratified all patients based on VCTE and FIB-4 was calculated. Potential alternative diagnoses were excluded with bloodwork. A total of 565 patients underwent risk stratification with VCTE with a 97% success rate. Ten percent had VCTE of at least 8 kPa; 560 patients had FIB-4 available for analysis and 87% had values less than 1.3. Of those with a FIB-4 of at least 1.3, 69% had a VCTE less than 8 kPa. Further modeling showed that the presence of diabetes, age, and body mass index had only a moderate impact on the association between FIB-4 and elastography values if using a FIB-4 threshold of 1.3. Conclusion: A FIB-4 threshold of 1.3 was acceptable for excluding the presence of advanced fibrosis (assessed by VCTE). A staged risk-stratification model using FIB-4 and VCTE could save up to 87% of further assessments. This model could improve accessibility by moving the initial fibrosis evaluation to the medical home and helping to prioritize patients for further specialized care.

Epidemiologic and clinical features of chronic hepatitis B virus infection in 8 Canadian provinces: a descriptive study by the Canadian HBV Network.

BACKGROUND: Published Canadian epidemiologic data on hepatitis B virus (HBV) infection include single-centre studies or are focused on Indigenous populations. We performed a study to characterize the demographic and clinical features, liver disease status and treatment of people with chronic hepatitis B in Canada. METHODS: In this descriptive, opportunistic, cross-sectional study, available data for people known to be monoinfected with HBV were collected by the Canadian HBV Network from existing clinical databases, with support from the National Microbiology Laboratory, Public Health Agency of Canada. Data were collected in all provinces with the exception of New Brunswick and Newfoundland and Labrador. We analyzed the data using parametric and nonparametric statistical methods, with a significance level of p < 0.05. RESULTS: In the 9380 unique patient records reviewed, the median age was 48 years, and 5193 patients (55.4%) were male. Ethnicity information was available for 7858 patients, of whom 5803 (73.8%) were Asian, 916 (11.6%) were black and 914 (11.6%) were white. Most of those tested (5556/6796 [81.8%]) were negative for HBV e-antigen, and most of those with fibrosis data (3481/4260 [81.7%]) had minimal liver fibrosis, with more advanced fibrosis noted in older people (> 40 yr). Of the 980 patients with genotype data, 521 (53.2%) had genotype B or C infection. Most of the 9241 patients with known confirmed treatment status received tenofovir disoproxil fumarate (1655 [17.9%]), lamivudine (1434 [15.5%]) or entecavir (548 [5.9%]). INTERPRETATION: Based on available data, Canadian patients with chronic hepatitis B are predominantly Asian and negative for HBV e-antigen, and have genotype B or C infection. Interprovincial variations were noted in antiviral treatment regimen. This multicentre nationwide study provides data regarding patients with chronic hepatitis B and may inform future studies on the epidemiologic features of HBV infection in Canada.

Caries prevalence and experience in individuals with osteogenesis imperfecta: A cross-sectional multicenter study.

OBJECTIVE: Dentinogenesis Imperfecta (DI) forms a group of dental abnormalities frequently found associated with Osteogenesis Imperfecta (OI), a hereditary disease characterized by bone fragility. The objectives of this study were to quantify the dental caries prevalence and experience among different OI-types in the sample population and quantify how much these values change for the subset with DI. METHODS: To determine which clinical characteristics were associated with increased Caries Prevalence and Experience (CPE) in patients with OI, the adjusted DFT scores were used to account for frequent hypodontia, impacted teeth and retained teeth in OI population. For each variable measured, frequency distributions, means, proportions and standard deviations were generated. Groups means were analyzed by the unpaired t-test or ANOVA as appropriate. For multivariate analysis, subjects with caries experience of zero were compared with those with caries experience greater than zero using logistic regression. RESULTS: The stepwise regression analysis while controlling for all other variables demonstrated the presence of DI (OR 2.43; CI 1.37-4.32; P = 0.002) as the significant independent predictor of CPE in the final model. CONCLUSION: This study found no evidence that CPE of OI subjects differs between the types of OI. The presence of DI when controlled for other factors was found to be the significant predictor of CPE.

Are Predictive Energy Expenditure Equations Accurate in Cirrhosis?

Malnutrition is associated with significant morbidity and mortality in cirrhosis. An accurate nutrition prescription is an essential component of care, often estimated using time-efficient predictive equations. Our aim was to compare resting energy expenditure (REE) estimated using predictive equations (predicted REE, pREE) versus REE measured using gold-standard, indirect calorimetry (IC) (measured REE, mREE). We included full-text English language studies in adults with cirrhosis comparing pREE versus mREE. The mean differences across studies were pooled with RevMan 5.3 software. A total of 17 studies (1883 patients) were analyzed. The pooled cohort was comprised of 65% men with a mean age of 53 ± 7 years. Only 45% of predictive equations estimated energy requirements to within 90⁻110% of mREE using IC. Eighty-three percent of predictive equations underestimated and 28% overestimated energy needs by ±10%. When pooled, the mean difference between the mREE and pREE was lowest for the Harris⁻Benedict equation, with an underestimation of 54 (95% CI: 30⁻137) kcal/d. The pooled analysis was associated with significant heterogeneity (I2 = 94%). In conclusion, predictive equations calculating REE have limited accuracy in patients with cirrhosis, most commonly underestimating energy requirements and are associated with wide variations in individual comparative data.

Impact of Sofosbuvir-Based Regimens for the Treatment of Hepatitis C After Liver Transplant on Renal Function: Results of a Canadian National Retrospective Study.

OBJECTIVES: We assessed the impact of sofosbuvir-based regimens on renal function in liver transplant recipients with recurrent hepatitis C virus and the role of renal function on the efficacy and safety of these regimens. MATERIALS AND METHODS: In an expanded pan-Canadian cohort, 180 liver transplant recipients were treated with sofosbuvir-based regimens for hepatitis C virus recurrence from January 2014 to May 2015. Mean age was 58 ± 6.85 years, and 50% had F3/4 fibrosis. Patients were stratified into 4 groups based on baseline estimated glomerular filtration rate (calculated by the Modification of Diet in Renal Disease formula): < 30, 30 to 45, 46 to 60, and > 60 mL/min/173 m2. The primary outcome was posttreatment changes in renal function from baseline. Secondary outcomes included sustained virologic response at 12 weeks posttreatment and anemia-related and serious adverse events. RESULTS: Posttreatment renal function was improved in most patients (58%). Renal function declined in 22% of patients, which was more marked in those with estimated glomerular filtration rate < 30 mL/min/173 m2, advanced cirrhosis (P = .05), and aggressive hepatitis C virus/fibrosing cholestatic hepatitis (P < .05). High rates (80%-88%) of sustained virologic response at 12 weeks posttreatment were seen across all renal function strata. Cirrhotic patients with glomerular filtration rates < 30 mL/min/173 m2 had sustained virologic response rates at 12 weeks posttreatment comparable to the overall patient group. Rates of anemia-related adverse events and transfusion requirements increased across decreasing estimated glomerular filtration rate groups, with notably more occurrences with ribavirin-based regimens. CONCLUSIONS: Sofosbuvir-based regimens improved overall renal function in liver transplant recipients, with sustained virologic response, suggesting an association of subclinical hepatitis C virus-related renal disease. Sustained virologic response rates at 12 weeks posttreatment (80%-88%) were comparable regardless of baseline renal function but lower in cirrhosis.