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Background: Pegylated interferon (Peg-IFN) is recommended as first-line therapy for chronic hepatitis B (CHB) but has significant side effects and is rarely used compared to oral nucleos(t)ide analogues (NA). There are limited recent clinical efficacy or economic analysis data comparing approved CHB therapy in North America., Methods: This retrospective study examined clinical outcomes, off-treatment durability, and cost-effectiveness of Peg-IFN versus NA for CHB. Demographic (age, sex, ethnicity), clinical data (i.e., liver tests, hepatitis B virus DNA, serology, transient elastography) and documented side effects were collected by retrospective chart review of patients followed in the University of Calgary Liver Unit who received Peg-IFN therapy from January 2007 to December 2020. The cost-effectiveness of Peg-IFN versus NA therapy was modelled over a 10-year time horizon., Results: Sixty-eight CHB patients were treated with Peg-IFN (median age 45.65, 74% male, 84% Asian); 50/68 (74%) completed 48 weeks of treatment with a median follow-up of 6.54 years (interquartile range 5.07). At the last known follow-up, 23/68 (34%) have not required NA treatment and one had HBsAg loss; 27 have been started on NA. Predictors of obtaining a sustained virological response included being hepatitis B e antigen-negative at treatment end and a quantitative hepatitis B surface antigen <1000 IU/mL. Economic modelling showed that finite Peg-IFN was not cost-effective versus NA at a 10-year time horizon., Conclusions: PEG-IFN remains a potential treatment for CHB although there is a significant intolerance/failure rate. Using PEG-IFN based on patient preference is reasonable and optimal patient selection may improve treatment cost-effectiveness., (© Canadian Association for the Study of the Liver, 2023.)

Background: Individuals infected with hepatitis B (HBV), hepatitis C (HCV), and human immunodeficiency (HIV) viruses can experience compensated advanced chronic liver disease (cACLD) leading to esophageal varices (EV). In patients at low risk of esophageal varices needing treatment (EVNT), non-invasive criteria based on liver stiffness measurement (LSM) with platelets, or fibrosis biomarkers, may avoid unnecessary screening esophagogastroduodenoscopies (EGD). These approaches have not been compared among people infected with HIV, HBV, and HCV patients., Methods: Patients with a diagnosis of cACLD (LSM ≥10 kPa) and EGD availability were included from two cohorts. Baveno VI and expanded Baveno VI criteria (based on LSM and platelets), fibrosis biomarkers Fibrosis-4 Index (FIB-4), AST-to-Platelets Ratio Index (APRI), AST-to-ALT ratio (AAR), and RESIST criteria (based on platelets and albumin) were applied to determine the proportion of spared EGD and of missed EVNT., Results: Three hundred fifty three patients (30.6% with HIV, 25.3% monoinfected with HBV, and 44.1% with HCV) were included. The prevalence of EVNT was 8.2%. Both Baveno VI and expanded Baveno VI criteria performed well in patients with virus-related cACLD, by sparing 26.1% and 51.6% EGD, respectively, while missing <2% EVNT. The proportion of spared EGD were 48.2%, 58%, and 24.3% by FIB-4 (<2.78), APRI (<1.1), and AAR (<0.75), respectively, while missing <3% EVNT. RESIST criteria spared 47.8% EGD while missing 1.9% EVNT., Conclusions: Non-invasive criteria based on LSM can spare unnecessary EGD in virus-related cACLD. Simple fibrosis biomarkers can ameliorate resource utilization for EVNT screening in low resource settings., (© Canadian Association for the Study of the Liver, 2023.)

BACKGROUND: Identifying strategies for stopping nucleos(t)ide analogues (NUC) in patients with chronic hepatitis B (CHB) is a major goal in CHB management. Our study describes our tertiary-centre experience stopping nucleos(t)ide analogues (NUC) in CHB. METHODS: We conducted a retrospective cohort study of all individuals with CHB seen at the Calgary Liver Unit between January 2009 and May 2020 who stopped NUC. We collected baseline demographics and HBV lab parameters before and after stopping NUC with results stratified by off-treatment durability. Clinical flare was defined as alanine aminotransferase (ALT) over twice the upper limit of normal and virological flare as HBV DNA >2000 IU/mL. RESULTS: Forty-seven (3.5%) of the 1337 individuals with CHB stopped NUC therapy. During follow-up, six patients (12.8%) restarted NUCs because of a flare. All flares occurred within six months of discontinuation. Median time to restart treatment was 90 days (Q1 65, Q3 133). Upon restarting, all showed suppression of HBV DNA and ALT normalization. Factors associated with restarting NUC therapy included hepatitis B e antigen (HBeAg) positive status at first appointment and longer NUC consolidation therapy. Age, sex, ethnicity, liver stiffness measurement, choice of NUC, and quantitative hepatitis B surface antigen (qHBsAg) level at stopping were not associated with sustained response off-treatment. Six patients had functional cure with HBsAg loss. CONCLUSIONS: Stopping long-term NUC is feasible in HBeAg negative CHB. Hepatic flares can occur despite low levels of qHBsAg. Finite NUC therapy can be considered in eligible patients who are adherent to close monitoring and follow-up, particularly in the first six months after stopping NUC therapy., (Copyright © 2022 Canadian Association for the Study of the Liver.)

BACKGROUND: Herpes simplex virus (HSV) is a rare cause of acute viral hepatitis but has high mortality rates and primarily affects immunocompromised hosts. We report a case of HSV hepatitis in a 20-year-old female kidney transplant recipient who had 1000-fold elevations in transaminases on post-transplant day 14, and the strategies employed for diagnoses and treatment. METHODS: Routine laboratory, serological, and molecular viral testing was completed, and she underwent a bone marrow biopsy given initial suspicion of hemophagocytic lymphohistiocytosis (HLH). HSV serologic results and high transaminases triggered a liver biopsy. RESULTS: The patient presented with elevated transaminases (ALT 1731 U/L and AST 1400) and ferritin (1431 μg/L). Transaminases and ferritin peaked with an ALT of 6609 U/L, AST of 6525 U/L, and ferritin >50000 μg/L. Bone marrow biopsy revealed no definitive HLH. HSV-DNA PCR of blood was positive, and she was empirically started on intravenous acyclovir 10 mg/kg 3 times per day. Liver biopsy confirmed the histological diagnosis of HSV hepatitis. CONCLUSIONS: Given the high mortality rates associated with HSV hepatitis, it is crucial to determine pre-transplant HSV status, initiate appropriate antiviral prophylaxis, and to have a low threshold for investigating for HSV hepatitis and initiating treatment in patients with a suspected diagnosis., (Copyright © 2022 Canadian Association for the Study of the Liver.)

Coronavirus disease 2019 (COVID-19) has challenged how care is delivered to patients with chronic liver disease (CLD). In an attempt to update Canadian health care practitioners taking care of individuals with CLD, the Canadian Association for the Study of the Liver (CASL) hosted a webinar on May 7, 2020, with more than 120 participants. The resultant article is a partnership between members of CASL's executive and education committees to provide best practice management principles on liver disease during COVID-19 to the broader hepatology community., Competing Interests: Dr Brahmania reports personal fees from Roche, Eisai, and Abbvie; grants and personal fees from Merck; and grants from Allergan. Dr Congly reports grants from Gilead Sciences, Boehringer Ingelheim, Genfit, Allergan, and Sequana Medical and personal fees from Intercept Pharmaceuticals and Eisai. Dr Coffin reports grants for the Canadian HBV Network from Janssen; grants from Glaxo Smith Kline and Gilead Sciences; and personal fees from Springbank Pharmaceuticals and Altimmune. Dr Jayakumar and Dr Burak have no disclosures to report. Dr Feld reports receiving grants and consulting fees from AbbVie, Arbutus Biopharma, Enanta Pharmaceuticals, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, and Roche., (Copyright © 2020 Canadian Association for the Study of the Liver.)

Background: The greatest risk of chronic hepatitis B (CHB) is from mother-to-child transmission. Approximately 20% of individuals in sub-Saharan Africa are hepatitis B virus (HBV) surface antigen-positive (HBsAg+), but the prevalence of occult hepatitis B (OHB) is unknown. Aim: This study investigated CHB and OHB prevalence and viral variants in a cohort of pregnant women in Gondor, Ethiopia., Methods: Patients were prospectively recruited from the University of Gondar Hospital ( N = 200; median age 27 [inter-quartile range] 8.3y) from March through June 2016. Data were collected using an investigator-administered questionnaire. Plasma was tested for HBsAg and HBV core antibody (anti-HBc), and HBV genotype and presence of HBV variants (ie, vaccine escape mutants [VEMs]) were determined by polymerase chain reaction, Sanger sequencing, and phylogenetic analysis., Results: Of women tested, 1% (2/200) were HBsAg+; 26.8% (47/182) of HBsAg-negative patients were anti-HBc+, of whom 37/47 (78.7%) had detectable HBV DNA. The overall rate of OHB was 20.3%. Both HBsAg+ cases were HBV genotype D, and 36/37 (97.3%) of OHB individuals were genotype D. None carried VEM, but both HBsAg+ cases and 32/37 (86.5%) of the OHB cases showed lamivudine-resistant mutations., Conclusions: Twenty-seven percent of pregnant women in this cohort showed evidence of CHB or prior HBV exposure (ie, HBsAg+ or anti-HBc+) and clinically relevant HBV variants. Data from this single-centre study suggests high HBV prevalence, reinforcing the World Health Organization's recommendation for universal prenatal HBV screening and infant vaccination., Competing Interests: None declared., (Copyright © 2020 Canadian Association for the Study of the Liver.)

Background: Approximately 60% of incident hepatitis C virus (HCV) infections are due to intravenous drug use; therefore, understanding the socio-demographics of people who inject drugs (PWID) is necessary to achieve HCV elimination., Methods: In this prospective cohort study of PWID, we determined patients' baseline HCV antibody, hepatitis B virus (HBV), and HIV serological status. HCV antibody- negative (anti-HCV-negative) cases were followed for seroconversion (median 17 mo with q3m testing) as part of a larger study to develop a vaccine for HCV. An interviewer-administered baseline questionnaire completed with all patients evaluated socio-demographic and clinical characteristics., Results: We tested 257 PWID (median age 40 [range 49-31]y, 81% men, 63% Caucasian, 28% Indigenous). Of these, 28% were positive for HCV antibodies (anti-HCV-positive) (median age 42 [range 49-36]y, 74% men, 69% Caucasian, 29% Indigenous). Compared with anti-HCV-negative PWID, anti-HCV-positive PWID reported injecting more morphine and hydromorphone, using more hydromorphone via non-injection routes, and were more likely to be enrolled in methadone programs. More than 60% reported previous HCV testing, but recent testing (<2 y) was more frequent in the anti-HCV-negative group ( p = 0.03). All were HBV negative, but more than 50% of the anti-HCV-positive group had anti-HBs titres more than 10 IU/L compared with 35% of the anti-HCV-negative group ( p = 0.01), and 3 of 257 were HIV positive (1 co-infected with HCV-HIV)., Conclusions: In this prospective study, differences in age, timing of HCV testing and risk behaviours were found between anti-HCV-positive and anti-HCV-negative groups., Competing Interests: Dr Coffin has received investigator- initiated research grant support from Gilead Sciences and GSK and served on an advisory board for SpringBank Pharmaceuticals and Altimmune in the past 24 months. Dr Macphail reports grants from Collaborative Research and Innovation Opportunity through Alberta Innovates Health Solutions during the conduct of the study; grants, personal fees, and non-financial support from Gilead Sciences; grants, personal fees, and non-financial support from Merck Canada; personal fees and non-financial support from AbbVie Canada; grants from Coverdale Clinics–Bioscript Solutions, outside the submitted work., (Copyright © 2020 Canadian Association for the Study of the Liver.)

Background: xpert guidelines recommend hepatocellular carcinoma (HCC) surveillance among patients with high-risk chronic hepatitis B (CHB); however, physician screening practices are often variable., Methods: An online survey of HCC screening practice was distributed to members of the Canadian Association for the Study of the Liver. Data were analyzed using appropriate statistical tests with p < .05 significance., Results: Of 71 respondents, 86% ( n = 61) were gastroenterologists or hepatologists, and 72% ( n = 51) reported having been in clinical practice for more than 5 years. A significant number of survey respondents performed HCC screening without consideration of concomitant non-alcoholic fatty liver disease (50.7%); non-Asian, non-African ethnicity (46.4%); and family history of HCC (28.6%). Most (67.6%) performed screening with ultrasound (US) at the time of specialty clinic visits, 28.2% had an automatic recall system, and only 2.8% referred back to primary care physicians to organize screening. More than half (54.9%) included alpha-fetoprotein in screening. Obstacles to screening included lack of an automatic recall system (42.9%), patient non-compliance (30.0%), and limited US/MRI access (17.1%)., Conclusions: HCC screening practices with hepatitis B patients vary widely among Canadian specialists, especially in unique populations with limited data to inform screening recommendations. Implementation of an automatic recall system could potentially increase HCC surveillance., Competing Interests: Dr Coffin reports grants from Gilead Sciences, grants from GSK, and personal fees and other from Springbank, outside the submitted work., (Copyright © 2019 Canadian Association for the Study of the Liver.)

Competing Interests: Dr Coffin reports investigator- initiated research grant and research materials from GSK, Gilead Sciences, and Arbutus Biopharma; educational grants from Merck, Gilead Sciences, and Janssen Inc.; advisory board roles with Gilead Sciences, Springbank Pharmaceuticals, and GSK; Clinical Trial Guidance and Publication Committee role with Springbank Pharmaceuticals; and local-site principal investigator participation in clinical trials with Gilead Sciences, Springbank Pharmaceuticals, Janssen Inc., and Transgene. Dr Fung reports speaking and teaching fees from Gilead, Merck, and Abbvie and advisory board and consulting roles with Gilead, Merck, Abbvie, and Lupin. Dr Tam reports clinical investigator role with AbbVie, Allergan, BMS, Boehringer Ingelheim, Genfit, Gilead, Intercept, Janssen, Merck, Novartis, Roche, and Shire; advisory board role with AbbVie, BMS, Boehringer Ingelheim, Gilead, Intercept, Janssen, Lupin, Merck, PendoPharm, and Roche; and speaker honoraria from AbbVie, BMS, Gilead, Intercept, Merck, PenoPharm, and Roche.

Hepatitis B virus (HBV) infection is an important public health problem in Canada. In keeping with evolving evidence and understanding of HBV pathogenesis, the Canadian Association for the Study of Liver Disease periodically publishes HBV management guidelines. The goals of the 2018 guidelines are to (1) highlight the public health impact of HBV infection in Canada and the need to improve diagnosis and linkage to care, (2) recommend current best-practice guidelines for treatment of HBV, (3) summarize the key HBV laboratory diagnostic tests, and (4) review evidence on HBV management in special patient populations and include more detail on management of HBV in pediatric populations. An overview of novel HBV tests and therapies for HBV in development is provided to highlight the recent advances in HBV clinical research. The aim and scope of these guidelines are to serve as an up-to-date, comprehensive resource for Canadian health care providers in the management of HBV infection., Competing Interests: Scott Fung reports speaking and teaching fees from Gilead, Merck, and Abbvie and advisory board and consulting roles with Gilead, Merck, Abbvie and Lupin. Carla Coffin reports investigator initiated research grant/research materials from GSK, Gilead Sciences, Arbutus Biopharma, and Bristol-Myers Squibb; educational grants from Merck, Gilead Sciences, and Janssen Inc.; advisory board roles with Merck, Gilead Sciences, and GSK; CTPC committee role with Springbank Pharmaceuticals; and local site PI participation in Clinical Trials with Gilead Sciences, Springbank Pharmaceuticals, and Transgene. Curtis Cooper reports Speaker fees from Gilead Sciences, Merck, and ABBVIE; advisor role with Gilead Sciences, Merck, and ABBVIE; and research/program support from Gilead Sciences, Merck, and ABBVIE. Karen Doucette reports clinical trials with Gilead, Merck, AbbVie, BMS, and Pfizer; speaker honorarium from Merck and Gilead; and educational grants from Merck, Gilead, BMS, and Astellas. Claire Fournier reports local site PI/sub-investigator participation in clinical trials for Transgene, Beckmann, Gilead, Bristol-Myers Squibb Canada, and Immune carta. Erin Kelly reports speaking fees from Lupin, Intercept, and Gilead and advisory board role with Intercept. Hin Hin Ko reports speaker fees from Merck, Intercept, Lupin, Allergan, and Procter and Gamble; advisory board role with Intercept and Lupin; and subinvestigator for studies role with Gilead, Merck, and Intercept. Mang Ma reports clinical investigator role with AbbVie, Gilead, Transgene, Sillagen, and BTG International and advisory board role with AbbVie, Gilead, and Merck. Alnoor Ramji reports clinical investigator role with Abbvie, Allergan, BMS, Gilead, Janssen, Intercept, Norvartis, and Merck; consultant role with Abbvie, Gilead, Intercept, and Lupin; speaker fees from Abbvie, Intercept, Gilead, and Merck; grants from Abbvie, Gilead, Intercept, and Merck. Edward Tam reports clinical investigator role with AbbVie, Allergan, BMS, Boehringer Ingelheim, Genfit, Gilead, Intercept, Janssen, Merck, Novartis, Roche, and Shire; advisory board role with AbbVie, BMS, Boehringer Ingelheim, Gilead, Intercept, Janssen, Lupin, Merck, PendoPharm, and Roche; and speaker honoraria from AbbVie, BMS, Gilead, Intercept, Merck, PenoPharm, and Roche. Jean Pierre Villeneuve reports clinical investigator role with Transgene, and Immune carta., (Copyright © 2018 Canadian Association for the Study of the Liver.)