Publications by authors named "Eric Yoshida"

297 Publications

Anti-SLA and AMA-positive celiac disease: A report of two cases and evaluation of autoimmune liver serology.

Hepatol Forum 2020 May 21;1(2):68-71. Epub 2020 May 21.

Division of Gastroenterology, University of British Columbia, Vancouver, Canada.

Antibodies to soluble liver antigen (anti-SLA) and anti-mitochondrial autoantibodies (AMA) are two specific serological markers of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). They are rarely detected in the sera of patients with non-liver autoimmune disorders. The biochemical, serological, and histological findings of two celiac disease (CD) patients who were seropositive for anti-SLA and/or AMA were evaluated. The data of two female patients who were 28 and 34 years old at the time of CD diagnosis were analyzed. The first patient presented with elevated liver function tests (LFTs) and immunoglobulin (Ig) G values. She was seropositive for both anti-SLA and AMA. A liver biopsy suggested features of AIH but no bile duct injury was noted. In addition to a gluten-free diet (GFD), immunosuppressive therapy was administered to normalize the LFTs. The second patient presented with elevated LFTs, a high IgG level, and a positive anti-SLA finding. A GFD was initiated, which resulted in an excellent clinical and biochemical response. Seropositivity for AMA in the first patient and anti-SLA in the second patient remained unchanged during follow-up but neither patient developed primary biliary cholangitis or AIH. Despite the high specificity of anti-SLA and AMA, these autoantibodies can be detected in CD without having any clinical relevance.
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http://dx.doi.org/10.14744/hf.2020.2020.0005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349346PMC
May 2020

Outcomes of liver transplant recipients with high MELD scores: an experience from a Canadian centre.

Can J Surg 2022 Jul-Aug;65(4):E425-E439. Epub 2022 Jul 5.

From the Department of Surgery, Division of General Surgery, University of British Columbia, Vancouver, B.C. (Bleszynski, Punnen, Desai Chartier-Plante, Segedi, Scudamore, Chung, Buczkowski, Kim); the Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, B.C. (Hussaini); and the Department of Medicine, Division of Gastroenterology, University of British Columbia Vancouver, B.C. (Marquez, Yoshida, Jayakumar)

Background: The frequency with which patients with high Model for End-Stage Liver Disease (MELD) scores undergo liver transplantation has been increasing. Canadian literature regarding the outcomes of liver transplantation in recipients with high MELD scores is limited. The primary objective of this study was to assess patient and graft survival among recipients with high (> 35) and low (≤ 35) MELD scores. Secondary objectives were to potentially identify independent predictors of graft failure and patient mortality.

Methods: We conducted a retrospective chart review of patients undergoing liver transplantation at a single Canadian centre from 2012 to 2017.

Results: A total of 332 patients were included in the study: 280 patients had a MELD score of 35 or lower, and 52 had a MELD score above 35. Patients with high MELD scores had higher rates of pretransplant acute kidney injury and dialysis ( < 0.001), admission to the intensive care unit (ICU) or intubation ( < 0.001), intraoperative blood product transfusions ( < 0.001) and post-transplantation acute kidney injury and dialysis ( < 0.001), as well as longer ICU ( < 0.001) and hospital stays ( = 0.002). One- and 3-year patient survival in recipients with MELD scores of 35 or lower was 93.1% and 84.9% versus 85.0% and 80.0% in recipients with MELD scores above 35 ( = 0.37). One- and 3-year graft survival in recipients with MELD scores of 35 or lower was 91.7% and 90.9% versus 77.2% and 72.8% in recipients with MELD scores above 35 ( < 0.001). Prior liver transplant was an independent predictor of patient mortality, and no independent predictors of graft failure were identified. When MELD was replaced with D-MELD (donor age × recipient MELD), it predicted graft failure but not patient survival.

Conclusion: No difference in patient mortality was found between MELD groups. Graft survival was significantly lower in recipients with MELD scores above 35. D-MELD may potentially be used as an adjunct in determining risk of graft failure in recipients with high MELD scores.
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http://dx.doi.org/10.1503/cjs.025520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337864PMC
July 2022

hepatitis B surface antigen (HBsAg)-positive, core antibody (anti-HBc)-negative, hepatitis B virus infection post-liver transplant from an anti-HBc, HBsAg-negative donor.

Hepatol Forum 2021 Sep 15;2(3):117-119. Epub 2021 Sep 15.

Department of Medicine, University of British Columbia, Vancouver BC, Canada.

Liver transplant donors and recipients are routinely screened for hepatitis B virus (HBV) infection by measuring the levels of hepatitis B surface antigen (HBsAg) and hepatitis B core (anti-HBc) antibodies. Organs are accepted from donors who are HB-negative, and increased monitoring is required for organs from donors considered at increased risk. Transplant recipients are vaccinated if there is no sign of previous infection or immunity and monitored for reactivation in case of previous HBV infection. In cases where both the donor and the recipient are HBV-negative, no antiviral prophylaxis is used post transplant. This report describes a case of an HBV-immunized, anti-HBc-negative patient who underwent an orthotopic liver transplant from an anti-HBc-negative donor. The patient did not receive post-transplant antiviral prophylaxis due to mutual anti-HBc-seronegative status. However, the recipient developed HBV infection with isolated HBsAg and persistently negative anti-HBc. Mutations in the core/pre-core regions of the HBV gene were not implicated for unique serology in this case. Immunosuppression post liver transplant is the likely etiology for isolated HBsAg seroconversion despite significantly elevated HBV DNA. Our experience suggests that HBV DNA screening of liver transplant donors and recipients, in addition to HBV DNA monitoring of recipients, may reduce the risk of transplant-associated HBV.
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http://dx.doi.org/10.14744/hf.2021.2021.0019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138942PMC
September 2021

Liver biochemical flare with immune checkpoint therapy in metastatic Merkel cell carcinoma: A liver biopsy is always necessary.

Hepatol Forum 2022 Jan 28;3(1):27-29. Epub 2021 Dec 28.

Department of Gastroenterology, University of British Columbia, Vancouver, Canada.

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine carcinoma of the skin. Treatment for locoregional MCC includes local excision with regional lymphadenectomy, followed by adjuvant radiotherapy. Immune checkpoint inhibitors (ICI) have emerged as a breakthrough treatment of metastatic MCC. Nevertheless, T-cell immune response is triggered against self-antigens resulting in immune-mediated toxicities, including ICI-mediated hepatotoxicity. We report a case of recurrent metastatic MCC treated with avelumab, a PD-L1 inhibitor, with subsequent significant liver biochemical flare. The initial clinical diagnosis was ICI-mediated hepatotoxicity. Workup to rule out competing causes of liver injury came back negative. Hence, avelumab was discontinued, and the patient was initiated on steroid therapy with stepwise escalation. Owing to clinical and laboratory deterioration, it was then decided to perform a percutaneous liver biopsy to document steroid-refractory ICI-mediated hepatotoxicity and/or rule out other causes of potential liver injury. The liver biopsy showed MCC tumor cells almost entirely infiltrating the hepatic parenchyma, confirmed by immunohistochemistry. At that point, steroid therapy was discontinued, and the patient was transitioned into palliative care. In conclusion, patients with apparent ICI-related hepatotoxicity should always be considered for a liver biopsy to exclude massive infiltrative malignancy as the true cause of liver dysfunction.
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http://dx.doi.org/10.14744/hf.2021.2021.0036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138913PMC
January 2022

A Narrative Review of the Efficacy and Design of Safety Labels on Tobacco Products to Promote the Use of Safety Labels on Alcohol Products in Canada.

Cureus 2022 May 24;14(5):e25306. Epub 2022 May 24.

Division of Gastroenterology, Faculty of Medicine, University of British Columbia, Vancouver, CAN.

Alcohol is consumed by approximately three-quarters of Canadians. Alcohol causes acquired liver disease, increases the risk of cancer, has detrimental effects on mental health, and leads to adverse pregnancy outcomes. Alcohol-related morbidity and mortality are high, and urgent public health measures are warranted to prevent and control these. Tobacco safety labels have been shown in numerous studies to reduce tobacco consumption. Much can be learned from the design of tobacco safety labels in creating promising alcohol safety labels that can possibly help reduce alcohol consumption. The aim of this paper is to review the efficacy of tobacco safety labels in reducing tobacco consumption and the design of tobacco safety labels and to propose a promising design for alcohol safety labels based on our findings. English peer-reviewed papers published in western countries since 2000 were searched on PubMed and Google Scholar. Keywords and synonyms were used to search pertinent papers, which were subsequently screened by title and abstract and fully reviewed if relevant. Findings from studies comparing designs of safety labels on alcohol and tobacco products are similar. Graphics, higher emotion content, and greater size are associated with greater attention, awareness, negative emotions, intention to quit, and reduction in consumption. Mixed results are found for testimonials containing safety labels on tobacco products. It is unclear whether testimonials on alcohol safety labels reduce alcohol consumption or not. Safety labels with specific information, such as tobacco-related costs and alcohol-related cancer risks, are more effective in reducing tobacco consumption. In conclusion, preliminary alcohol safety labels show promise. Large safety labels with graphics and high emotional content appear to be most effective and may reduce alcohol consumption.
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http://dx.doi.org/10.7759/cureus.25306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226242PMC
May 2022

Nanolattice-Forming Hybrid Collagens in Protective Shark Egg Cases.

Biomacromolecules 2022 07 24;23(7):2878-2890. Epub 2022 Jun 24.

Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California 93106, United States.

Nanoscopic structural control with long-range ordering remains a profound challenge in nanomaterial fabrication. The nanoarchitectured egg cases of elasmobranchs rely on a hierarchically ordered latticework for their protective function─serving as an exemplary system for nanoscale self-assembly. Although the proteinaceous precursors are known to undergo intermediate liquid crystalline phase transitions before being structurally arrested in the final nanolattice architecture, their sequences have so far remained unknown. By leveraging RNA-seq and proteomic techniques, we identified a cohort of nanolattice-forming proteins comprising a collagenous midblock flanked by domains typically associated with innate immunity and network-forming collagens. Structurally homologous proteins were found in the genomes of other egg-case-producing cartilaginous fishes, suggesting a conserved molecular self-assembly strategy. The identity and stabilizing role of cross-links were subsequently elucidated using mass spectrometry and small-angle X-ray scattering. Our findings provide a new design approach for protein-based liquid crystalline elastomers and the self-assembly of nanolattices.
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http://dx.doi.org/10.1021/acs.biomac.2c00341DOI Listing
July 2022

Epidemiology of portal vein thrombosis in liver cirrhosis: A systematic review and meta-analysis.

Eur J Intern Med 2022 Jun 7. Epub 2022 Jun 7.

Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang 110840, PR China; Postgraduate College, Shenyang Pharmaceutical University, Shenyang 110016, PR China; Postgraduate College, China Medical University, Shenyang 110122, PR China. Electronic address:

Background: Portal vein thrombosis (PVT) may be associated with negative outcomes in patients with liver cirrhosis. However, the prevalence and incidence of PVT in liver cirrhosis are heterogeneous among studies and have not been sufficiently determined yet.

Methods: The PubMed, EMBASE, and Cochrane Library databases were searched. Eligible studies would explore the prevalence and/or incidence of PVT in liver cirrhosis without hepatocellular carcinoma or abdominal surgery. Pooled proportion with 95% confidence interval (CI) was calculated using a random-effect model. Factors associated with the presence/occurrence of PVT were also extracted.

Results: Among the 8549 papers initially identified, 74 were included. Fifty-four studies explored the prevalence of PVT in liver cirrhosis with a pooled prevalence of 13.92% (95%CI=11.18-16.91%). Based on cross-sectional data, Child-Pugh class B/C, higher D-dimer, ascites, and use of non-selective beta-blockers (NSBBs) were associated with the presence of PVT in liver cirrhosis. Twenty-three studies explored the incidence of PVT in liver cirrhosis with a pooled incidence of 10.42% (95%CI=8.16-12.92%). Based on cohort data, Child-Pugh class B/C, higher model of end-stage liver disease score, higher D-dimer, lower platelets count, decreased portal flow velocity, ascites, use of NSBBs, and moderate or high-risk esophageal varices could predict the occurrence of PVT in liver cirrhosis.

Conclusion: Approximately one seventh of cirrhotic patients have PVT, and one tenth will develop PVT. Progression of liver cirrhosis and portal hypertension seems to be in parallel with the risk of PVT. Prospective studies with detailed information about classification and extension of PVT in liver cirrhosis are needed.
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http://dx.doi.org/10.1016/j.ejim.2022.05.032DOI Listing
June 2022

Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome.

Hepatology 2022 May 14. Epub 2022 May 14.

Department of Pathophysiology, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Background And Aims: A few case reports of autoimmune hepatitis-like liver injury have been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We evaluated clinical features, treatment response and outcomes of liver injury following SARS-CoV-2 vaccination in a large case series.

Approach And Results: We collected data from cases in 18 countries. The type of liver injury was assessed with the R-value. The study population was categorized according to features of immune-mediated hepatitis (positive autoantibodies and elevated immunoglobulin G levels) and corticosteroid therapy for the liver injury. We identified 87 patients (63%, female), median age 48 (range: 18-79) years at presentation. Liver injury was diagnosed a median 15 (range: 3-65) days after vaccination. Fifty-one cases (59%) were attributed to the Pfizer-BioNTech (BNT162b2) vaccine, 20 (23%) cases to the Oxford-AstraZeneca (ChAdOX1 nCoV-19) vaccine and 16 (18%) cases to the Moderna (mRNA-1273) vaccine. The liver injury was predominantly hepatocellular (84%) and 57% of patients showed features of immune-mediated hepatitis. Corticosteroids were given to 46 (53%) patients, more often for grade 3-4 liver injury than for grade 1-2 liver injury (88.9% vs. 43.5%, p = 0.001) and more often for patients with than without immune-mediated hepatitis (71.1% vs. 38.2%, p = 0.003). All patients showed resolution of liver injury except for one man (1.1%) who developed liver failure and underwent liver transplantation. Steroid therapy was withdrawn during the observation period in 12 (26%) patients after complete biochemical resolution. None had a relapse during follow-up.

Conclusions: SARS-CoV-2 vaccination can be associated with liver injury. Corticosteroid therapy may be beneficial in those with immune-mediated features or severe hepatitis. Outcome was generally favorable, but vaccine-associated liver injury led to fulminant liver failure in one patient.
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http://dx.doi.org/10.1002/hep.32572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348326PMC
May 2022

N-acetylcysteine for non-acetaminophen induced acute liver failure: A review.

Saudi J Gastroenterol 2022 Mar-Apr;28(2):85-91

Division of Gastroenterology, University of British Columbia, Vancouver General Hospital, Vancouver, BC, Canada.

The use of N-acetylcysteine (NAC) for non-acetaminophen-induced acute liver failure (NAI-ALF) has been increasing despite controversy in its efficacy. National guidelines are in disagreement for NAC use as standard of care; however, many healthcare centers continue to adopt the use of NAC outside of acetaminophen poisoning. While NAC may have multiple mechanisms of action in treatment of ALF, this has not translated to clinical benefit. Murine models have reported antioxidant and anti-inflammatory properties, as well as improvement in liver-specific microcirculation. Multiple case studies and series have reported positive outcomes of NAC treatment for ALF of various etiologies. While prospective studies suggested the benefit of NAC treatment, these studies have methodological and statistical shortcomings that affect the validity of the results. In this review, we aimed to summarize the existing literature on the efficacy of NAC for NAI-ALF including mechanism of action, case studies and series demonstrating outcomes, and prospective studies that have led to its current widespread use, along with the reported rate of adverse events.
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http://dx.doi.org/10.4103/sjg.sjg_406_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007071PMC
April 2022

Epidemiology and Risk Factors of Portal Venous System Thrombosis in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

Front Med (Lausanne) 2021 17;8:744505. Epub 2022 Jan 17.

Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang, China.

Background: Patients with inflammatory bowel disease (IBD) may be at risk of developing portal venous system thrombosis (PVST) with worse outcomes. This study aims to explore the prevalence, incidence, and risk factors of PVST among patients with IBD.

Methods: PubMed, Embase, and Cochrane Library databases were searched. All the eligible studies were divided according to the history of colorectal surgery. Only the prevalence of PVST in patients with IBD was pooled if the history of colorectal surgery was unclear. The incidence of PVST in patients with IBD after colorectal surgery was pooled if the history of colorectal surgery was clear. Prevalence, incidence, and risk factors of PVST were pooled by only a random-effects model. Subgroup analyses were performed in patients undergoing imaging examinations. Odds ratios (ORs) with 95% CIs were calculated.

Results: A total of 36 studies with 143,659 patients with IBD were included. Among the studies where the history of colorectal surgery was unclear, the prevalence of PVST was 0.99, 1.45, and 0.40% in ulcerative colitis (UC), Crohn's disease (CD), and unclassified IBD, respectively. Among the studies where all the patients underwent colorectal surgery, the incidence of PVST was 6.95, 2.55, and 3.95% in UC, CD, and unclassified IBD after colorectal surgery, respectively. Both the prevalence and incidence of PVST became higher in patients with IBD undergoing imaging examinations. Preoperative corticosteroids therapy (OR = 3.112, 95% CI: 1.017-9.525; = 0.047) and urgent surgery (OR = 1.799, 95% CI: 1.079-2.998; = 0.024) are significant risk factors of PVST in patients with IBD after colorectal surgery. The mortality of patients with IBD with PVST after colorectal surgery was 4.31% (34/789).

Conclusion: PVST is not rare, but potentially lethal in patients with IBD after colorectal surgery. More severe IBD, indicated by preoperative corticosteroids and urgent surgery, is associated with a higher risk of PVST after colorectal surgery. Therefore, screening for PVST by imaging examinations and antithrombotic prophylaxis in high-risk patients should be actively considered.

Systematic Review Registration: Registered on PROSPERO, Identifier: CRD42020159579.
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http://dx.doi.org/10.3389/fmed.2021.744505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801813PMC
January 2022

Patient-specific genetic factors predict treatment failure in sofosbuvir-treated patients with chronic hepatitis C.

Liver Int 2022 04 21;42(4):796-808. Epub 2022 Feb 21.

BC Children's Hospital Research Institute, Vancouver, Canada.

Background & Aims: According to pivotal clinical trials, cure rates for sofosbuvir-based antiviral therapy exceed 96%. Treatment failure is usually assumed to be because of virological resistance-associated substitutions or clinical risk factors, yet the role of patient-specific genetic factors has not been well explored. We determined if patient-specific genetic factors help predict patients likely to fail sofosbuvir treatment in real-world treatment situations.

Methods: We recruited sofosbuvir-treated patients with chronic hepatitis C from five Canadian treatment sites, and performed a case-control pharmacogenomics study assessing both previously published and novel genetic polymorphisms. Specifically studied were variants predicted to impair CES1-dependent production of sofosbuvir's active metabolite, interferon-λ signalling variants expected to impact a patient's immune response to the virus and an HLA variant associated with increased spontaneous and treatment-induced viral clearance.

Results: Three hundred and fifty-nine sofosbuvir-treated patients were available for analyses after exclusions, with 34 (9.5%) failing treatment. We identified CES1 variants as novel predictors for treatment failure in European patients (rs115629050 or rs4513095; odds ratio (OR): 5.43; 95% confidence interval (CI): 1.64-18.01; P = .0057), replicated associations with IFNL4 variants predicted to increase interferon-λ signalling (eg rs12979860; OR: 2.25; 95% CI: 1.25-4.06; P = .0071) and discovered a novel association with a coding variant predicted to enhance the activity of IFNL4's receptor (rs2834167 in IL10RB; OR: 1.81; 95% CI: 1.01-3.24; P = .047).

Conclusions: Ultimately, this work demonstrates that patient-specific genetic factors could be used as a tool to identify patients at higher risk of treatment failure and allow for these patients to receive effective therapy sooner.
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http://dx.doi.org/10.1111/liv.15175DOI Listing
April 2022

Effect of oral simethicone on the quality of colonoscopy: A systematic review and meta-analysis of randomized controlled trials.

J Dig Dis 2022 Mar 14;23(3):134-148. Epub 2022 Mar 14.

Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, China.

Objective: In this systematic review and meta-analysis, we aimed to investigate the effect of oral simethicone (SIM), an antifoaming agent, on the quality of colonoscopy in terms of bowel preparation quality, adenoma or polyp detection rate (ADR/PDR) and cecal intubation rate (CIR).

Methods: All randomized controlled trials (RCTs) on the use of SIM during bowel preparation for colonoscopy published up to 17 March 2021 were identified from the PubMed, EMBASE and Cochrane Library databases. Bowel preparation quality, ADR/PDR/CIR, cecal intubation time (CIT), withdrawal time (WT), patients' tolerability, acceptability and volume of foam and bubbles were compared between the SIM and non-SIM groups.

Results: Thirty-eight RCTs with 10 505 patients were included. Oral SIM significantly increased the rate of total Boston bowel preparation scale (BBPS) score ≥6 (risk ratio [RR]  1.13, P < 0.0001), acceptability (RR  1.15, P = 0.01) and the rate of no or minimal foam and bubbles (RR  1.28, P < 0.00001) and decreased abdominal distension (RR  0.64, P < 0.0001). However, it had no significant impact on overall ADR, overall PDR, CIR, CIT or WT. The rate of total BBPS score ≥6 remained significantly higher in the SIM group when a single-dose laxative regimen or a SIM dosage of ≥320 mg was employed; and ADR, PDR and CIR were significantly increased in the SIM group among colonoscopy clinicians who achieved an ADR <31%, PDR <45% and CIR <96%, respectively.

Conclusions: Oral SIM can improve bowel preparation quality, especially in patients receiving a SIM dosage of ≥320 mg or a single-dose laxative regimen. SIM may be preferred by junior colonoscopy physicians/trainees with a lower ADR/PDR or CIR.
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http://dx.doi.org/10.1111/1751-2980.13084DOI Listing
March 2022

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.

Liver Int 2022 03 13;42(3):607-614. Epub 2021 Dec 13.

Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.

Background: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH).

Patients And Methods: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression.

Results: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients.

Conclusion: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.
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http://dx.doi.org/10.1111/liv.15121DOI Listing
March 2022

End stage liver disease etiology & transplantation referral outcomes of major ethnic groups in British Columbia, Canada: A cohort study.

Medicine (Baltimore) 2021 Oct;100(42):e27436

Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract: Liver disease etiology and transplantation outcomes may vary by ethnicity. We aimed to determine if disparities exist in our province.We reviewed the provincial database for liver transplant referrals. We stratified cohorts by ethnicity and analyzed disease etiology and outcomes.Four thousand nine hundred sixteen referrals included 220 South Asians, 413 Asians, 235 First Nations (Indigenous), and 2725 Caucasians. Predominant etiologies by ethnicity included alcohol (27.4%) and primary sclerosing cholangitis (PSC) (8.8%) in South Asians, hepatitis B (45.5%) and malignancy (13.9%) in Asians, primary biliary cholangitis (PBC) (33.2%) and autoimmune hepatitis (AIH) (10.8%) in First Nations, and hepatitis C (35.9%) in Caucasians. First Nations had lowest rate of transplantation (30.6%, P = .01) and highest rate of waitlist death (10.6%, P = .03). Median time from referral to transplantation (268 days) did not differ between ethnicities (P = .47). Likelihood of transplantation increased with lower body mass index (BMI) (hazard ratio [HR] 0.99, P = .03), higher model for end stage liver disease (MELD) (HR 1.02, P < .01), or fulminant liver failure (HR 9.47, P < .01). Median time from referral to ineligibility status was 170 days, and shorter time was associated with increased MELD (HR 1.01, P < .01), increased age (HR 1.01, P < .01), fulminant liver failure (HR 2.56, P < .01) or South Asian ethnicity (HR 2.54, P < .01). Competing risks analysis revealed no differences in time to transplant (P = .66) or time to ineligibility (P = .91) but confirmed increased waitlist death for First Nations (P = .04).We have noted emerging trends such as alcohol related liver disease and PSC in South Asians. First Nations have increased autoimmune liver disease, lower transplantation rates and higher waitlist deaths. These data have significance for designing ethnicity specific interventions.
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http://dx.doi.org/10.1097/MD.0000000000027436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8542110PMC
October 2021

Evolution of Nonmalignant Portal Vein Thrombosis in Liver Cirrhosis: A Pictorial Review.

Clin Transl Gastroenterol 2021 10 1;12(10):e00409. Epub 2021 Oct 1.

Liver Cirrhosis Study Group, Department of Gastroenterology, The General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, China.

Portal vein thrombosis (PVT) is a common complication in liver cirrhosis, especially in advanced cirrhosis. It may be related to a higher risk of liver-related events and liver function deterioration. Imaging examinations can not only provide an accurate diagnosis of PVT, such as the extent of thrombus involvement and the degree of lumen occupied, but also identify the nature of thrombus (i.e., benign/malignant and acute/chronic). Evolution of PVT, mainly including development, recanalization, progression, stability, and recurrence, could also be assessed based on the imaging examinations. This article briefly reviews the pathophysiology, diagnosis, classification, and evolution of PVT with an emphasis on their computed tomography imaging features.
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http://dx.doi.org/10.14309/ctg.0000000000000409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483868PMC
October 2021

Novel variant in glycophorin c gene protects against ribavirin-induced anemia during chronic hepatitis C treatment.

Biomed Pharmacother 2021 Nov 22;143:112195. Epub 2021 Sep 22.

Department of Medical Genetics, University of British Columbia, Vancouver, Canada; BC Children's Hospital Research Institute, Vancouver, Canada; Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, Canada; Pharmaceutical Outcomes Program, British Columbia Children's Hospital, Vancouver, Canada. Electronic address:

Background: The current use of ribavirin in difficult-to-cure chronic hepatitis C patients (HCV) and patients with severe respiratory infections is constrained by the issue of ribavirin-induced hemolytic anemia that affects 30% of treated patients, requiring dosage modification or discontinuation. Though some genetic variants have been identified predicting this adverse effect, known clinical and genetic factors do not entirely explain the risk of ribavirin-induced anemia.

Methods: We assessed the associations of previously identified variants in inosine triphosphatase (ITPA), solute carrier 28A2 (SLC28A2) and vitamin D receptor (VDR) genes with ribavirin-induced anemia defined as hemoglobin decline of ≥30 g/L on treatment, followed by a staged discovery (n = 114), replication (n = 74), and combined (n = 188) genome-wide association study to uncover potential new predictive variants.

Results: We identified a novel association in the gene coding glycophorin C (rs6741425; OR:0.12, 95%CI:0.04-0.34, P = 2.94 × 10) that predicts protection against ribavirin-induced anemia. We also replicated the associations of ITPA and VDR genetic variants with the development of ribavirin-induced anemia (rs1127354; OR:0.13, 95%CI:0.04-0.41, P = 8.66 ×10; and rs1544410; OR:1.65, 95%CI:1.01-2.70, P = 0.0437).

Conclusions: GYPC variation affecting erythrocyte membrane strength is important in predicting risk for developing ribavirin-induced anemia. ITPA and VDR genetic variants are also important predictors of this adverse reaction.
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http://dx.doi.org/10.1016/j.biopha.2021.112195DOI Listing
November 2021

Women in the 2019 hepatitis C cascade of care: findings from the British Columbia Hepatitis Testers cohort study.

BMC Womens Health 2021 09 13;21(1):330. Epub 2021 Sep 13.

British Columbia Centre for Disease Control, Vancouver, BC, Canada.

Background: Women living with hepatitis C virus (HCV) are rarely addressed in research and may be overrepresented within key populations requiring additional support to access HCV care and treatment. We constructed the HCV care cascade among people diagnosed with HCV in British Columbia, Canada, as of 2019 to compare progress in care and treatment and to assess sex/gender gaps in HCV treatment access.

Methods: The BC Hepatitis Testers Cohort includes 1.7 million people who tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 2000 to 2019. Test results were linked to medical visits, hospitalizations, cancers, prescription drugs, and mortality data. Six HCV care cascade stages were identified: (1) antibody diagnosed; (2) RNA tested; (3) RNA positive; (4) genotyped; (5) initiated treatment; and (6) achieved sustained virologic response (SVR). HCV care cascade results were assessed for women, and an 'inverse' cascade was created to assess gaps, including not being RNA tested, genotyped, or treatment initiated, stratified by sex.

Results: In 2019, 52,638 people with known sex were anti-HCV positive in BC; 37% (19,522) were women. Confirmatory RNA tests were received by 86% (16,797/19,522) of anti-HCV positive women and 83% (27,353/33,116) of men. Among people who had been genotyped, 68% (6756/10,008) of women and 67% (12,640/18,828) of men initiated treatment, with 94% (5023/5364) of women and 92% (9147/9897) of men achieving SVR. Among the 3252 women and 6188 men not yet treated, higher proportions of women compared to men were born after 1975 (30% vs. 21%), had a mental health diagnosis (42% vs. 34%) and had used injection drugs (50% vs. 45%). Among 1619 women and 2780 men who had used injection drugs and were not yet treated, higher proportions of women than men used stimulants (64% vs. 57%), and opiates (67% vs. 60%).

Conclusions: Women and men appear to be equally engaged into the HCV care cascade; however, women with concurrent social and health conditions are being left behind. Treatment access may be improved with approaches that meet the needs of younger women, those with mental health diagnoses, and women who use drugs.
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http://dx.doi.org/10.1186/s12905-021-01470-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436483PMC
September 2021

Successful Liver Transplantation in a Patient With Acute COVID-19 Infection and Acute Liver Failure: A Case Report.

Transplant Direct 2021 Oct 26;7(10):e747. Epub 2021 Aug 26.

Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Al Minufiyah, Egypt.

Current liver transplantation societies recommend recipients with active coronavirus disease 2019 (COVID-19) be deferred from transplantation for at least 2 wks, have symptom resolution and at least 1 negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test. This approach does not address patients who require urgent transplantation and will otherwise die from liver failure. We report a successful orthotopic liver transplant (OLT) in a patient with active COVID-19 infection. This is only the second to be reported worldwide and the first in Canada.
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http://dx.doi.org/10.1097/TXD.0000000000001210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405130PMC
October 2021

Drug-Induced Liver Injury From Enobosarm (Ostarine), a Selective Androgen Receptor Modulator.

ACG Case Rep J 2021 Jan 7;8(1):e00518. Epub 2021 Jan 7.

Division of Gastroenterology, The University of British Columbia, Vancouver, British Columbia, Canada.

Anabolic steroids are well-known to cause liver injury, which may manifest with jaundice and elevated liver enzymes. Selective androgen receptor modulators (SARMs) have been developed to enhance muscle bulk without the side effects associated with exogenous androgen steroids. We report a case of significant cholestatic liver injury associated with a SARM, ostarine (enobosarm), similar to that associated with anabolic steroids. Liver injury from SARMs has not been reported frequently, and we speculate that this may be seen more often as the consumption of SARMs increases in the athletic market.
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http://dx.doi.org/10.14309/crj.0000000000000518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8337042PMC
January 2021

The Cedar Project: exploring the role of colonial harms and childhood maltreatment on HIV and hepatitis C infection in a cohort study involving young Indigenous people who use drugs in two Canadian cities.

BMJ Open 2021 07 8;11(7):e042545. Epub 2021 Jul 8.

Faculty of Medicine, School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada.

Objectives: This study examined associations between childhood maltreatment, colonial harms and sex/drug-related risks for HIV and hepatitis C virus (HCV) infection among young Indigenous people who use drugs.

Design: The Cedar Project is a cohort involving young Indigenous people who use drugs in British Columbia (BC), Canada. Indigenous collaborators, collectively known as the Cedar Project Partnership, govern the entire research process.

Setting: Vancouver is a large city on the traditional territory of the Coast Salish peoples. Prince George is a mid-sized city, on the traditional territory of Lheidli T'enneh First Nation.

Participants: 420 participants completed the Childhood Trauma Questionnaire and returned for follow-up from 2003 to 2016.

Primary/secondary Outcome Measures: Primary outcomes were HIV and HCV infection over the study period. Secondary outcomes included sex and substance use-related risks.

Results: Prevalence of childhood maltreatment was 92.6% experienced any maltreatment; 73.4% experienced emotional abuse; 62.6% experienced physical abuse; 60.3% experienced sexual abuse; 69.5% experienced emotional neglect and 79.1% experienced physical neglect. We observed significant associations between childhood maltreatment and apprehensions into residential schools and foster care. All maltreatment types were associated with higher odds of sex/substance use-related risks; sexual abuse was associated with higher odds of HCV infection (adjusted OR: 1.67; 95% CI 1.05 to 2.66; p=0.031).

Conclusions: Findings reflect high prevalence of childhood maltreatment and their associations with HIV/HCV risk and HCV infection. Public health prevention and treatment initiatives must be trauma informed and culturally safe to support healing, health, and well-being.
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http://dx.doi.org/10.1136/bmjopen-2020-042545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268907PMC
July 2021

Prevalence and Clinical and Endoscopic Characteristics of Cervical Inlet Patch (Heterotopic Gastric Mucosa): A Systematic Review and Meta-Analysis.

J Clin Gastroenterol 2022 03;56(3):e250-e262

Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang.

Background: Cervical inlet patch (CIP), also called gastric inlet patch, is a heterotopic columnar mucosal island located in the cervical esophagus, which has been under-recognized by clinicians.

Aim: We conducted a systemic review and meta-analysis to explore the prevalence and clinical and endoscopic characteristics of CIP.

Materials And Methods: Studies were searched through the PubMed, EMBASE, and Cochrane Library databases. The prevalence of CIP with 95% confidence interval (CI) was pooled by using a random-effect model. The association of CIP with demographics, clinical presentations, and endoscopic features was evaluated by odds ratios (ORs).

Results: Fifty-three studies including 932,777 patients were eligible. The pooled prevalence of CIP was 3.32% (95% CI=2.86%-3.82%). According to the endoscopic mode, the pooled prevalence of CIP was higher in studies using narrow-band imaging than in those using white light and esophageal capsule endoscopy (9.34% vs. 2.88% and 0.65%). The pooled prevalence of CIP was higher in studies where the endoscopists paid specific attention to the detection of this lesion (5.30% vs. 0.75%). CIP was significantly associated with male (OR=1.24, 95% CI=1.09-1.42, P=0.001), gastroesophageal reflux disease (OR=1.32, 95% CI=1.04-1.68, P=0.03), reflux symptoms (OR=1.44, 95% CI=1.14-1.83, P=0.002), dysphagia (OR=1.88, 95% CI=1.28-2.77, P=0.001), throat discomfort (OR=4.58, 95% CI=1.00-21.02, P=0.05), globus (OR=2.95, 95% CI=1.52-5.73, P=0.001), hoarseness (OR=4.32, 95% CI=1.91-9.78, P=0.0004), cough (OR=3.48, 95% CI=1.13-10.72, P=0.03), Barrett's esophagus (OR=2.01, 95% CI=1.37-2.94, P=0.0003), and esophagitis (OR=1.62, 95% CI=1.27-2.07, P=0.0001).

Conclusion: CIP appears to be common by using narrow-band imaging, especially if the endoscopists would like to pay attention to the detection of this lesion. CIP is clearly associated with acid-related symptoms and Barrett's esophagus.
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http://dx.doi.org/10.1097/MCG.0000000000001516DOI Listing
March 2022

Isolated Liver Rejection After Lung and Combined Kidney-Liver Transplantation: A Case Report.

Transplant Proc 2021 May 6;53(4):1333-1336. Epub 2021 Mar 6.

Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada.

Liver allografts are unique in solid organ transplantation as they are less susceptible to both acute and chronic rejection. Operational tolerance, defined as prolonged graft survival in the absence of immunosuppression, is also achieved more frequently with liver allografts. It is unknown if the presence of multiple allografts in the same individual, levels of immunosuppression, or the presence of cystic fibrosis (CF) impacts the livers ability to ward off rejection or achieve operational tolerance. We describe an unsensitized, ABO-compatible patient with CF who underwent double lung transplantation and several years later a combined liver-kidney transplant. He developed isolated late acute T-cell mediated rejection of his liver allograft despite a high level of immunosuppression (IS) required for his lung and kidney allografts. To our knowledge, this is the first case of isolated liver rejection in a patient with 3 separate organ allografts, or in a patient with CF, to be reported in the literature. This isolated liver rejection is out of keeping with typically accepted ideas about orthotopic liver tolerance.
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http://dx.doi.org/10.1016/j.transproceed.2021.02.004DOI Listing
May 2021

Elevated risk of colorectal, liver, and pancreatic cancers among HCV, HBV and/or HIV (co)infected individuals in a population based cohort in Canada.

Ther Adv Med Oncol 2021 11;13:1758835921992987. Epub 2021 Feb 11.

BC Centre for Disease Control, Vancouver, Canada.

Introduction: Studies of the impact of hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV mono and co-infections on the risk of cancer, particularly extra-hepatic cancer, have been limited and inconsistent in their findings.

Methods: In the British Columbia Hepatitis Testers Cohort, we assessed the risk of colorectal, liver, and pancreatic cancers in association with HCV, HBV and HIV infection status. Using Fine and Gray adjusted proportional subdistribution hazards models, we assessed the impact of infection status on each cancer, accounting for competing mortality risk. Cancer occurrence was ascertained from the BC Cancer Registry.

Results: Among 658,697 individuals tested for the occurrence of all three infections, 1407 colorectal, 1294 liver, and 489 pancreatic cancers were identified. Compared to uninfected individuals, the risk of colorectal cancer was significantly elevated among those with HCV (Hazard ration [HR] 2.99; 95% confidence interval [CI] 2.55-3.51), HBV (HR 2.47; 95% CI 1.85-3.28), and HIV mono-infection (HR 2.30; 95% CI 1.47-3.59), and HCV/HIV co-infection. The risk of liver cancer was significantly elevated among HCV and HBV mono-infected and all co-infected individuals. The risk of pancreatic cancer was significantly elevated among individuals with HCV (HR 2.79; 95% CI 2.01-3.70) and HIV mono-infection (HR 2.82; 95% CI 1.39-5.71), and HCV/HBV co-infection.

Discussion/conclusion: Compared to uninfected individuals, the risk of colorectal, pancreatic and liver cancers was elevated among those with HCV, HBV and/or HIV infection. These findings highlight the need for targeted cancer prevention and diligent clinical monitoring for hepatic and extrahepatic cancers in infected populations.
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http://dx.doi.org/10.1177/1758835921992987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887683PMC
February 2021

Occult Hepatitis B Reactivation after Liver Transplant: The Role of a Novel Mutation in the Surface Antigen.

J Clin Transl Hepatol 2021 Feb 7;9(1):136-138. Epub 2020 Dec 7.

Department of Medicine, University of British Columbia, Vancouver, BC, Canada.

Occult hepatitis B infection is characterized by loss of hepatitis B surface antigen (HBsAg) and persistence of low levels of hepatitis B virus (HBV) replication that may or may not be detectable in plasma/serum. We present a case of HBV reactivation in a male patient who underwent orthotopic liver transplant for hepatocellular carcinoma secondary to active hepatitis C (HCV) infection. Pre-transplant, he was HBsAg-negative and hepatitis B core antibody-positive, with an undetectable HBV viral load that was incidentally found to be positive at a very low HBV viral load on the day of transplant. Post-transplant, his HBsAg remained undetectable, with an undetectable HBV viral load, until eradication of his HCV infection with direct acting antiviral agents. After eradication of HCV, there was reactivation of HBV, with a high viral load and emergence of serum HBsAg. A deep sequencing genetic analysis of his HBV both pre- and post-transplant revealed the presence of a mutation in the "a" determinant of the HBV surface antigen. The role of HBV genotype 'a' determinant mutation in HBV reactivation post-transplant is unknown and needs further examination. Our experience suggests a possible role for antiviral prophylaxis in these patients or monitoring of HBV viral loads post-transplant.
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http://dx.doi.org/10.14218/JCTH.2020.00090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868691PMC
February 2021

Incidental alpha-1-antitrypsin deficiency found in post-transplant liver allografts: Report of two cases.

Hepatol Forum 2021 Jan 8;2(1):31-33. Epub 2021 Jan 8.

Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC, Canada.

Alpha-1 antitrypsin deficiency is an autosomal recessive disease most commonly caused by misfolding of the Alpha-1-antitrypsin protein, which prevents its release from hepatocytes into the systemic circulation. This results in increased lifetime risk of liver and lung disease. Due to its variable penetrance, presentation and natural history, patients with alpha-1 antitrypsin deficiency are often underdiagnosed. In this report, we present two cases of alpha-1 antitrypsin deficiency in deceased-donor liver transplant allografts diagnosed post-transplant. There is currently no known adverse outcome directly linked to alpha-1 antitrypsin deficiency in the immediate post-transplant follow-up period. Thus, these allografts should not be excluded from transplantation.
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http://dx.doi.org/10.14744/hf.2020.2020.0013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138925PMC
January 2021

Prenatal hepatitis C screening, diagnoses, and follow-up testing in British Columbia, 2008-2019.

PLoS One 2020 31;15(12):e0244575. Epub 2020 Dec 31.

British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.

Objective: Current guidelines in British Columbia recommend prenatal screening for hepatitis C antibodies (anti-HCV) if risk factors are present. We aimed to estimate frequency of prenatal anti-HCV testing, new diagnoses, repeated and follow-up testing among BC women.

Methods: BC Centre for Disease Control Public Health Laboratory data estimated the number of BC women (assigned female at birth or unknown sex) aged 13-49 who received routine prenatal serological screening (HIV, hepatitis B, syphilis and rubella) from 2008-2019. Anti-HCV tests ordered the same day as routine prenatal screens were considered prenatal anti-HCV tests. Assessment of follow-up was based on HCV RNA and/or genotype testing within one year of new prenatal anti-HCV diagnoses.

Results: In 2019, 55,202 routine prenatal screens were carried out for 50,392 BC women. Prenatal anti-HCV tests increased significantly, from 19.6% (9,704/49,515) in 2008 to 54.6% (27,516/50,392) in 2019 (p<0.001). New prenatal anti-HCV diagnoses (HCV positive diagnoses at first test or seroconversions) declined from 14.3% in 2008 to 10.1% in 2019. The proportion of women with new prenatal anti-HCV diagnoses that were a result of a first HCV test declined from 0.3% (29/9,701) in 2008 to 0.03% (8/27,500) in 2019. For women known to be anti-HCV positive at the time of prenatal screening, the proportion who had a prenatal anti-HCV test increased from 35.6% in 2008 to 50.8% in 2019.

Conclusion: Prenatal anti-HCV testing increased substantially over the study period. However, new HCV diagnoses remained relatively stable, suggesting that a considerable proportion of BC women with low or no risk are being screened as part of prenatal care. The vast majority of women with new HCV diagnoses receive appropriate follow-up HCV RNA and genotype testing, which may indicate interest in HCV treatment. These findings contribute to the discussion around potential for prenatal anti-HCV screening in an effort to eliminate HCV.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244575PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775094PMC
March 2021

Review of Clinically Relevant Drug Interactions with Next Generation Hepatitis C Direct-acting Antiviral Agents.

J Clin Transl Hepatol 2020 Sep 30;8(3):322-335. Epub 2020 Jul 30.

Pharmaceutical Sciences, Vancouver General Hospital, Vancouver, BC, Canada.

In this review, we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C, specifically sofosbuvir/velpatasvir (Epclusa), sofosbuvir/velpatasvir/voxilaprevir (Vosevi), glecaprevir/pibrentasvir (Maviret), and elbasvir/grazoprevir (Zepatier). We searched MEDLINE (1948-January 2020), Embase (1964-January 2020), Google, and GoogleScholar using the terms pharmacokinetics, drug interaction, drug metabolism, sofosbuvir, velpatasvir, Epclusa, voxilaprevir, Vosevi, glecaprevir, pibrentasvir, Maviret, elbasvir, grazoprevir, and Zepatier, from inception to January 13, 2020. The search was limited to randomized controlled trials, studies, prospective and retrospective human studies, drug monographs, abstracts, and conference proceedings. All relevant published literature on pharmacokinetic and pharmacodynamic interactions involving DAAs were reviewed and the data extracted. Numerous clinically relevant drug-drug interactions (DDIs) were identified with the newer generation DAAs and commonly prescribed drugs. NS3/4A protease inhibitors are more likely to be involved in DDIs, followed by NS5A inhibitors and NS5B polymerase inhibitor. The majority of clinically relevant DDIs are predictable, according to known pharmacokinetic, pharmacodynamics, and physicochemical properties of DAAs; however, in select cases, unpredictable DDIs do occur. As expected, many drug interactions exist between newer generation DAAs and commonly prescribed medications. While the majority of clinically relevant interactions are predictable, many require therapeutic dose adjustment or careful selection of non-interacting drugs. In select cases, severe and unpredictable drug interactions can occur. Clinicians should consult hepatitis C virus pharmacotherapy experts and tertiary drug interaction resources when initiating DAA therapy in patients taking other medications.
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http://dx.doi.org/10.14218/JCTH.2020.00034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562806PMC
September 2020

Biomarkers for hepatocellular cancer.

World J Hepatol 2020 Sep;12(9):558-573

Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver V5Z 1M9, Canada.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. If diagnosed early, curative treatment options such as surgical resection, loco-regional therapies, and liver transplantation are available to patients, increasing their chances of survival and improving their quality of life. Unfortunately, most patients are diagnosed with late stage HCC where only palliative treatment is available. Therefore, biomarkers which could detect HCC early with a high degree of sensitivity and specificity, may play a crucial role in the diagnosis and management of the disease. This review will aim to provide an overview of the different biomarkers of HCC comprising those used in the diagnosis of HCC in at risk populations, as well as others with potential for prognosis, risk predisposition and prediction of response to therapeutic intervention.
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http://dx.doi.org/10.4254/wjh.v12.i9.558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522562PMC
September 2020

Real-World Effectiveness of Obeticholic Acid in Patients with Primary Biliary Cholangitis.

Hepatol Commun 2020 Sep 6;4(9):1332-1345. Epub 2020 Jul 6.

Toronto Centre for Liver Disease Toronto General Hospital University Health Network Toronto ON Canada.

Patients with primary biliary cholangitis (PBC) with incomplete response to ursodeoxycholic acid are at risk of disease progression and need additional therapy. Obeticholic acid (OCA) was approved in Canada in May 2017, but its effectiveness in a real-world setting has not been described. We sought to describe our experience with OCA in a Canadian cohort. OCA-naive patients treated at two Canadian centers were included. Clinical and biochemical data were collected at OCA initiation and during follow-up. Primary outcomes were changes in serum alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (TB) over the duration of therapy. Secondary outcomes were changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), immunoglobulin M (IgM), platelets, and albumin; and achievement of the primary endpoint of the original phase 3 study that led to OCA approval (A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis [POISE]), dose reductions, discontinuations, and tolerability. Repeated-measures models were used to assess changes in biochemistry over time. Sixty-four patients were included; 4 carried a diagnosis of overlap with autoimmune hepatitis. Mean age was 54.6 years, median ALP was 250 U/L, TB was 13 µmol/L, platelet count was 225 × 10/L, and 24% had liver stiffness measurements ≥16.9 kPa. There was a significant reduction in mean ALP of 55 U/L ( < 0.001), GGT of 138 U/L ( < 0.001), ALT of 11.9 U/L ( < 0.001), AST of 5.7 U/L ( < 0.05), and IgM of 0.70 g/L ( < 0.001) over 12 months; TB remained stable ( = 0.98). Forty-four patients met POISE-inclusion criteria, 39% (n = 17) of whom had 12-month biochemical measurements. In this subset, 18% (n = 3/17) met the 12-month POISE primary endpoint, but considering follow-up to 19 months, 43% achieved this target (n = 9/21). Pruritus was the most commonly reported complaint. : Use of OCA was associated with improvement in biochemical surrogates of outcome in PBC in a real-world setting.
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http://dx.doi.org/10.1002/hep4.1518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471421PMC
September 2020

Terlipressin May Decrease In-Hospital Mortality of Cirrhotic Patients with Acute Gastrointestinal Bleeding and Renal Dysfunction: A Retrospective Multicenter Observational Study.

Adv Ther 2020 10 28;37(10):4396-4413. Epub 2020 Aug 28.

Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly Called General Hospital of Shenyang Military Area), Shenyang, China.

Background: Acute gastrointestinal bleeding (GIB) rapidly reduces effective blood volume, thereby precipitating acute kidney injury (AKI). Terlipressin, which can induce splanchnic vasoconstriction and increase renal perfusion, has been recommended for acute GIB and hepatorenal syndrome in liver cirrhosis. Thus, we hypothesized that terlipressin might be beneficial for cirrhotic patients with acute GIB and renal impairment.

Methods: In this Chinese multi-center study, 1644 cirrhotic patients with acute GIB were retrospectively enrolled. AKI was defined according to the International Club of Ascites (ICA) criteria. Renal dysfunction was defined as serum creatinine (sCr) > 133 μmol/L at admission and/or any time point during hospitalization. Incidence of renal impairment and in-hospital mortality were the primary end-points.

Results: The incidence of any stage ICA-AKI, ICA-AKI stages 1B, 2, and 3, and renal dysfunction in cirrhotic patients with acute GIB was 7.1%, 1.8%, and 5.0%, respectively. The in-hospital mortality was significantly increased by renal dysfunction (14.5% vs. 2.2%, P < 0.001) and ICA-AKI stages 1B, 2, and 3 (11.1% vs. 2.8%, P = 0.011), but not any stage ICA-AKI (5.7% vs. 2.7%, P = 0.083). The in-hospital mortality was significantly decreased by terlipressin in patients with renal dysfunction (3.6% vs. 20.0%, P = 0.044), but not in those with any stage ICA-AKI (4.5% vs. 6.0%, P = 0.799) or ICA-AKI stages 1B, 2, and 3 (0.0% vs. 14.3%, P = 0.326).

Conclusion: Renal dysfunction increased the in-hospital mortality of cirrhotic patients with acute GIB. Terlipressin might decrease the in-hospital mortality of cirrhotic patients with acute GIB and renal dysfunction.

Trial Registration: NCT03846180 ( https://clinicaltrials.gov ).
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http://dx.doi.org/10.1007/s12325-020-01466-zDOI Listing
October 2020
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