Machine learning in primary biliary cholangitis: A novel approach for risk stratification.

Background & Aims: Machine learning (ML) provides new approaches for prognostication through the identification of novel subgroups of patients. We explored whether ML could support disease sub-phenotyping and risk stratification in primary biliary cholangitis (PBC).

Methods: ML was applied to an international dataset of PBC patients.

Vaccination at the forefront of the fight against hepatitis B and C.

Vaccination is a key intervention for the elimination of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections to fulfil the WHO’s 2030 global elimination goal. Innovations in 2021 promise to curb HBV transmission by reducing mother-to-child transmission and enhancing vaccine immunogenicity in at-risk adult groups. Additionally, an HCV vaccination trial was conducted, and there were also advances in our understanding of the immunology underpinning the lack of protection against HCV reinfection.

The impact of the first, second and third waves of covid-19 on hepatitis B and C testing in Ontario, Canada.

The COVID-19 pandemic interrupted routine healthcare services. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are often asymptomatic, and therefore, screening and on/post-treatment monitoring are required. Our aim was to determine the effect of the first, second and third waves of the pandemic on HBV and HCV testing in Ontario, Canada.

Off-Therapy Response After Nucleos(t)ide Analogue Withdrawal in Patients With Chronic Hepatitis B: An International, Multicenter, Multiethnic Cohort (RETRACT-B Study).

Background & Aims: Functional cure, defined based on hepatitis B surface antigen (HBsAg) loss, is rare during nucleos(t)ide analogue (NA) therapy and guidelines on finite NA therapy have not been well established. We aim to analyze off-therapy outcomes after NA cessation in a large, international, multicenter, multiethnic cohort of patients with chronic hepatitis B (CHB).

Methods: This cohort study included patients with virally suppressed CHB who were hepatitis B e antigen (HBeAg)-negative and stopped NA therapy.

Long-term outcomes of laparoscopic liver resection for hepatocellular carcinoma: A propensity score matched analysis of a high-volume North American center.

Background: Laparoscopic liver resections for malignancy are increasing worldwide, and yet data from North America are lacking. We aimed to assess the long-term outcomes of patients undergoing laparoscopic liver resection and open liver resection as a treatment for hepatocellular carcinoma.

Methods: Patients undergoing liver resection for hepatocellular carcinoma between January 2008 and December 2019 were retrospectively studied.

Preferences of Persons With or at Risk for Hepatitis C for Long-Acting Treatments.

Background: Whereas safe, curative treatments for hepatitis C virus (HCV) have been available since 2015, there are still 58 million infected persons worldwide, and global elimination may require new paradigms. We sought to understand the acceptability of approaches to long-acting HCV treatment.

Methods: A cross-sectional, 43-question survey was administered to 1457 individuals with or at risk of HCV at 28 sites in 9 countries to assess comparative interest in a variety of long-acting strategies in comparison with oral pills.

Determinants of Ligand Specificity and Functional Plasticity in Type I Interferon Signaling.

The Type I Interferon family of cytokines all act through the same cell surface receptor and induce phosphorylation of the same subset of response regulators of the STAT family. Despite their shared receptor, different Type I Interferons have different functions during immune response to infection. In particular, they differ in the potency of their induced anti-viral and anti-proliferative responses in target cells.

Recognition of Long-COVID-19 Patients in a Canadian Tertiary Hospital Setting: A Retrospective Analysis of Their Clinical and Laboratory Characteristics.

A proportion of patients with COVID-19 have symptoms past the acute disease phase, which may affect quality of life. It is important for clinicians to be aware of this "long-COVID-19" syndrome to better diagnose, treat, and prevent it. We reviewed clinical and laboratory characteristics of a COVID-19 cohort in a Toronto, Ontario tertiary care center.

Clinical Utility of Magnetic Resonance Imaging Biomarkers for Identifying Nonalcoholic Steatohepatitis Patients at High Risk of Progression: A Multicenter Pooled Data and Meta-Analysis.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide. NAFLD is associated with excess risk of all-cause mortality, and its progression to nonalcoholic steatohepatitis (NASH) and fibrosis accounts for a growing proportion of cirrhosis and hepatocellular cancer and thus is a leading cause of liver transplant worldwide. Noninvasive precise methods to identify patients with NASH and NASH with significant disease activity and fibrosis are crucial when the disease is still modifiable.

Controversies in Treating Chronic Hepatitis B Virus Infection: Discordant Serologic Results.

Despite effective vaccines and approved therapeutic agents, hepatitis B virus (HBV) remains a prevalent global health problem. Current guidelines rely on a combination of serologic, virological, and biochemical markers to identify the phase in the natural history of chronic HBV infection. Discordant serologic results can occur, which may lead to misclassification.

Impact of COVID-19 on Prescribing Trends of Direct-Acting Antivirals for the Treatment of Hepatitis C in Ontario, Canada.

Introduction: Direct-acting antivirals (DAAs) are curative treatments for hepatitis C. However, initiation of these treatments requires adequate healthcare access. Coronavirus 2019 (COVID-19) resulted in restrictions to healthcare services in March 2020.

Hepatitis C virus infection in First Nations populations in Ontario from 2006 to 2014: a population-based retrospective cohort analysis.

Background: Hepatitis C virus (HCV) infection causes substantial morbidity and mortality in Canada and is of concern among First Nations communities. In partnership with the Ontario First Nations HIV/AIDS Education Circle, we described trends in HCV testing and epidemiologic features among Status First Nations people in Ontario.

Methods: In this retrospective study, we used health administrative databases for 2006-2014 in Ontario with 3 cohorts of Status First Nations people: those tested for HCV for the first time, those who tested positive for HCV antibodies or RNA, and those with no HCV laboratory or testing records.

Health care costs associated with hepatitis C virus infection in First Nations populations in Ontario: a retrospective matched cohort study.

Background: Colonization and marginalization have affected the risk for and experience of hepatitis C virus (HCV) infection for First Nations people in Canada. In partnership with the Ontario First Nations HIV/AIDS Education Circle, we estimated the publicly borne health care costs associated with HCV infection among Status First Nations people in Ontario.

Methods: In this retrospective matched cohort study, we used linked health administrative databases to identify Status First Nations people in Ontario who tested positive for HCV antibodies or RNA between 2004 and 2014, and Status First Nations people who had no HCV testing records or only a negative test result (control group, matched 2:1 to case participants).

Metabolic dysfunction-associated fatty liver disease increases risk of adverse outcomes in patients with chronic hepatitis B.

Background & Aims: A recent consensus document has defined metabolic dysfunction-associated fatty liver disease (MAFLD) as hepatic steatosis together with overweight, diabetes, and/or a combination of other metabolic risk factors. The clinical relevance of this novel diagnosis is unknown among patients with chronic hepatitis B (CHB). We studied the association between MAFLD (with or without steatohepatitis) and adverse clinical outcomes in patients with CHB.

Effects of on-treatment ALT flares on serum HBsAg and HBV RNA in patients with chronic HBV infection.

As pegylated interferon alpha (PEG-IFN-α) is increasingly used in combination regimens of novel drugs, we aimed to characterize ALT flares and their relationship with serum HBsAg and HBV RNA kinetics in a large combined cohort of chronic hepatitis B (CHB) patients on PEG-IFN-α-based therapy. In this post hoc analysis of four international randomized trials, 269/130/124/128 patients on PEG-IFN-α monotherapy, PEG-IFN-α plus nucleos(t)ide analogue (NA) de novo combination, PEG-IFN-α add-on to NA or NA monotherapy were included, respectively. A flare was defined as an episode of ALT ≥5 × ULN.

High Sustained Virologic Response Rates of Glecaprevir/Pibrentasvir in Patients With Dosing Interruption or Suboptimal Adherence.

Introduction: Pangenotypic, all-oral direct-acting antivirals, such as glecaprevir/pibrentasvir (G/P), are recommended for treatment of hepatitis C virus (HCV) infection. Concerns exist about the impact on efficacy in patients with suboptimal adherence, particularly with shorter treatment durations. These post hoc analyses evaluated adherence (based on pill count) in patients prescribed 8- or 12-week G/P, the impact of nonadherence on sustained virologic response at post-treatment week 12 (SVR12), factors associated with nonadherence, and efficacy in patients interrupting G/P treatment.

Mean HBsAg decline at week 24 of PEG-IFN-based treatment predicts subsequent rate of HBsAg clearance - suggesting a valuable endpoint for early development HBV trials.

Earlier identification of potentially efficacious treatments in early development trials requires on-treatment response markers. We hypothesized that mean week 12 or 24 HBsAg decline could be a useful marker for subsequent off-treatment sustained HBsAg clearance at the treatment arm level in HBV trials. We used individual patient data from the studies HBV 9901 (peginterferon [PEG-IFN] versus PEG-IFN+lamivudine for HBeAg-positive CHB), PARC (PEG-IFN±ribavirin for HBeAg-negative CHB) and published data from 0149 (PEG-IFN±tenofovir for HBeAg-positive and HBeAg-negative CHB) and LIRA-B (PEG-IFN for HBeAg-positive CHB) to define the relationship between mean week HBsAg decline and HBsAg loss at 6 months post-treatment.

Hepatitis B e antigen loss in adults and children with chronic hepatitis B living in North America: A prospective cohort study.

Hepatitis B e antigen (HBeAg) is a soluble viral protein in plasma of patients with hepatitis B virus infection. HBeAg loss is an important first stage of viral antigen clearance. We determined the rate and predictors of HBeAg loss in a North American cohort with chronic hepatitis B viral infection (CHB).

The Inflammatory Cytokine Profile Associated With Liver Damage Is Broader and Stronger in Patients With Chronic Hepatitis B Compared to Patients With Acute Hepatitis B.

Liver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to different types of liver damage across patients at different stages of disease. We measured 25 inflammatory markers in patients with acute hepatitis B and chronic hepatitis B with hepatitis B e antigen seroconversion and chronic patients stopping nucleoside analogue therapy.