Acquired Fanconi Syndrome from Tenofovir Treatment in a Patient with Hepatitis B.

Fanconi syndrome is a rare disease of generalized proximal tubule dysfunction which can be acquired secondary to certain medications, including tenofovir, a commonly used hepatitis B treatment. Signs and symptoms of ensuing renal wasting can be severe but vague, leading to potentially avoidable invasive investigations and delays in diagnosis. We present a case of a 62-year-old female with chronic hepatitis B on tenofovir treatment who was found to have subacute weakness, anorexia, and weight loss. She underwent extensive investigations including computed tomography (CT) imaging, bronchoscopy, upper and lower endoscopy, and psychiatric evaluation. Finally, persistent electrolyte derangements led to urine studies, which demonstrated acquired Fanconi syndrome secondary to tenofovir. After discontinuing tenofovir disoproxil fumarate and starting tenofovir alafenamide, her symptoms resolved and her renal function recovered. This case illustrates the importance of maintaining clinical suspicion for tenofovir-induced Fanconi syndrome, given the common use of tenofovir as first-line hepatitis B treatment and the availability of less nephrotoxic alternatives.

Survey of the Impact of COVID-19 on Chronic Liver Disease Patient Care Experiences and Outcomes.

Background: The COVID-19 pandemic has a secondary impact on the health of patients with chronic liver disease (CLD). Our objective was to study this impact on care provision, telemedicine, and health behaviours in CLD patients. Methods: CLD patients of an urban gastroenterology clinic who attended a telemedicine appointment between March 17, 2020 and September 17, 2020, completed an online survey on care delays, health behaviours, and experience with telemedicine. Chart review was conducted in 400 randomly selected patients: 200 charts from during the pandemic were compared to 200 charts the previous year. Data were extracted for clinicodemographic variables, laboratory investigations, and clinical outcomes. Results: Of 399 patients invited to participate, 135 (34%) completed the online survey. Fifty (39%) patients reported 83 care delays due to the COVID-19 pandemic, with the majority (71%) of delays persisting beyond 2 months. Ninety-five (75%) patients were satisfied with telemedicine appointments. There was a longer delay between lab work and appointments in patients seen during the pandemic compared to 2019 (P = 0.01). Compared to the year prior, during the COVID pandemic, there was a similar number of cases of cirrhosis decompensation (n = 26, 13% versus n = 22, 11%) and hospitalization (n = 12, 6% versus n = 5, 3%). Conclusion: The COVID-19 pandemic has led to care delays for CLD outpatients, with most delays on the scale of months. These patient-reported experiences and clinical observations can direct optimization of CLD care as effects from the pandemic evolve.

An online mind-body program improves mental health and quality of life in primary biliary cholangitis: A randomized controlled trial.

BACKGROUND AND AIMS: People with primary biliary cholangitis (PBC) experience high rates of mental distress and fatigue despite standard of care therapy. We aimed to assess the impact of an online mind-body intervention on these symptoms. METHODS: This 12-week RCT used sequential mixed-methods evaluation. Alongside standard of care, participants with primary biliary cholangitis were randomized to receive weekly countdown emails, or the intervention consisting of (i) a weekly 20-30 minute-mind-body follow-along video, (ii) weekly 5-10-minute psychology-based "managing chronic disease skills videos," and (iii) 10-minute telephone check-ins. The primary outcome was a change in the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes evaluated changes in fatigue, perceived stress, resilience, and health-related quality of life. ANCOVA determined between-group differences. RESULTS: Of the 87 randomized patients (control group: n = 44, intervention group: n = 43), the between-group HADS total score improved by 20.0% (95% CI 4.7, 35.2, p = 0.011). Significant improvements were seen in depression (25.8%), perceived stress (15.2%), and 2 primary biliary cholangitis-40 domains [emotional symptoms (16.3%) and social symptoms (11.8%)] with a mean satisfaction of 82/100. This corresponded with end-of-study qualitative findings. Although no improvements were observed in fatigue in the main analysis, a significant benefit was observed in the subgroup of intervention participants (20/36;56%) who completed the mind-body video routine at least 3 times per week. CONCLUSION: This intervention improved measures of mental wellness and quality of life with high satisfaction and reasonable adherence. Future studies could explore strategies to optimize adherence and target fatigue.

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.

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.

Ethnicity, disease severity, and survival in Canadian patients with primary biliary cholangitis.

BACKGROUND AND AIMS: We investigated associations between ethnicity, survival, and disease severity in a diverse Canadian cohort of patients with primary biliary cholangitis (PBC). APPROACH AND RESULTS: Patients with PBC were included from the Canadian Network for Autoimmune Liver Disease. Ethnicity was defined using a modified list adopted from Statistics Canada, and ethnicities with small samples were grouped. Clinical events were defined as liver decompensation, HCC, liver transplantation, or death. Clinical event-free and liver transplantation-free survival were analyzed using Cox regression. Trajectories of serum liver function tests were assessed over time using mixed-effects regression. Health-related quality of life was assessed using the Short Form 36, the PBC-40 questionnaire, and the 5-D Itch scale and analyzed using mixed-effects regression. The cohort included 1538 patients with PBC from six sites and was comprised of 82% White, 4.7% Indigenous, 5.5% East Asian, 2.6% South Asian, and 5.1% miscellaneous ethnicities. Indigenous patients were the only ethnic group with impaired liver transplant-free and event-free survival compared to White patients (HR, 3.66; 95% CI, 2.23-6.01; HR, 3.09; 95% CI, 1.94-4.92). Indigenous patients were more likely to have a clinical event before diagnosis (10%) than all other ethnic groups despite similar age at diagnosis. Indigenous patients presented with higher alkaline phosphatase, total bilirubin, and GLOBE scores than White patients; and these relative elevations persisted during follow-up. CONCLUSIONS: Indigenous Canadians with PBC present with advanced disease and have worse long-term outcomes compared to White patients.

Hepatic steatosis as measured by the computed attenuation parameter predicts fibrosis in long-term methotrexate use.

INTRODUCTION: To determine predictors of hepatic steatosis by the computed attenuation parameter (CAP) and fibrosis via transient elastography (TE) in persons on methotrexate (MTX) therapy with rheumatologic and dermatologic diseases. METHODS: A single-centred retrospective cohort study was performed. Patients on >6 months of MTX for a rheumatologic or dermatologic disease who had undergone TE from January 2015 to September 2019 were included. Multivariate analysis was performed to determine predictors of steatosis and fibrosis. RESULTS: A total of 172 patients on methotrexate were included. Psoriasis was the most frequent diagnosis (n = 55), followed by rheumatoid arthritis (n = 45) and psoriatic arthritis (n = 34). Steatosis (CAP ≥245 dB/m) was present in 69.8% of patients. Multivariate regression analysis revealed that diabetes mellitus (OR 10.47, 95% CI 1.42-75.35), hypertension (OR 5.15, 95% CI 1.75-15.38), and BMI ≥30 kg/m2 (OR 16.47, 95% CI 5.56-45.56) were predictors of steatosis (CAP ≥245 dB/m). Predictors of moderate to severe fibrosis (Metavir ≥F2 = TE ≥8.0 kPa) by multivariate regression analysis included moderate to severe steatosis (CAP ≥270 dB/m) (OR 8.36, 95% CI 1.88-37.14), diabetes mellitus (OR 2.85, 95% CI 1.09-7.48), hypertension (OR 5.4, 95% CI 2.23-13.00), dyslipidemia (OR 3.71, 95% CI 1.50-9.18), and moderate alcohol use (OR 3.06, 95% CI 1.2-7.49). CONCLUSIONS: In patients on MTX for rheumatologic and dermatologic diseases, hepatic steatosis as measured by CAP was common and moderate to severe steatosis predicted moderate to severe fibrosis.

Internet-Based Patient Education Prior to Colonoscopy: Prospective, Observational Study of a Single Center's Implementation, with Objective Assessment of Bowel Preparation Quality and Patient Satisfaction.

BACKGROUND: Nonpharmacologic factors, including patient education, affect bowel preparation for colonoscopy. Optimal cleansing increases quality and reduces repeat procedures. This study prospectively analyzes use of an individualized online patient education module in place of traditional patient education. AIMS: To determine the effectiveness of online education for patients, measured by the proportion achieving sufficient bowel preparation. Secondary measures include assessment of patient satisfaction. METHODS: Prospective, single-center, observational study. Adults aged 19 years and over, with an e-mail account, scheduled for nonurgent colonoscopy, with English proficiency (or someone who could translate for them) were recruited. Demographics and objective bowel preparation quality were collected. Patient satisfaction was assessed via survey to assess clarity and usefulness of the module. RESULTS: Nine hundred consecutive patients completed the study. 84.6% of patients achieved adequate bowel preparation as measured by Boston bowel preparation score ≥ 6 and 90.1% scored adequately using Ottawa bowel preparation score ≤7. 94.2% and 92.1% of patients rated the web-education module as 'very useful' and 'very clear', respectively (≥8/10 on respective scales). CONCLUSIONS: Our analysis suggests that internet-based patient education prior to colonoscopy is a viable option and achieves adequate bowel preparation. Preparation quality is comparable to previously published trials. Included patients found the process clear and useful. Pragmatic benefits of a web-based protocol such as time and cost savings were not formally assessed but may contribute to greater satisfaction for endoscopists and patients.

Aiming for a shorter time to diagnosis: pediatric eosinophilic esophagitis in British Columbia.

Longer time to diagnosis for patients with eosinophilic esophagitis can lead to adverse patient outcomes, but the length of diagnostic delay has not been quantified for patients with eosinophilic esophagitis in Canada. Our study defines the time to diagnosis (TTD) for pediatric patients with eosinophilic esophagitis in British Columbia and identifies factors that predict increased time to diagnosis. The median TTD was 21 months (1.75 years; IQR = 7, 45) with a median age at EoE diagnosis of 105 months (8.75 years; IQR = 44, 156). Caucasians experienced significantly longer TTD compared to other ethnicities (24 months (IQR = 7, 52) and 12 months (IQR = 4.5, 23) respectively, p = 0.008). Caucasian ethnicity (p = 0.037) and older age at the time of diagnosis (p = 0.006) predicted increased TTD. Our model explained 7.9% (Adjusted R2 = 0.079) of the total variance for our cohort.

Validation of the St. Paul's Endoscopy Comfort Scale (SPECS) for Colonoscopy.

AIMS: Patient comfort during colonoscopy is an important measure of quality, which can improve patient satisfaction and compliance with future procedures. Our aim was to develop and validate a pain assessment tool based on objective behavioural cues tailored to outpatients undergoing colonoscopy: St. Paul's endoscopy comfort score (SPECS). METHODS: A single-centre, prospective study was conducted in consecutive adults undergoing planned outpatient colonoscopy. Patient comfort was independently assessed by the physician, nurse and a research assistant (observer) using the SPECS and the Gloucester scale (GS). In addition, the nurse-assessed patient comfort score (NAPCOMS), nonverbal pain Assessment tool (NPAT) and Richmond agitation sedation scale (RASS) were completed by the observer. Data on subject demographics, sedation dose and duration of the procedure were collected. Following the procedure, patients completed a patient satisfaction questionnaire, including a visual analogue scale (VAS) to measure their overall perceived pain during the procedure. RESULTS: The study enrolled 350 subjects. The SPECS showed excellent inter-rater reliability among all three raters with an intra-class coefficient (ICC) of 0.81 (95% CI, 0.78-0.84), while the GS showed good reliability with an ICC of 0.77 (95% CI, 0.73-0.80). The SPECS demonstrated moderate agreement with the patient-reported VAS ratings. CONCLUSIONS: The St. Paul's endoscopy comfort score was successfully validated, demonstrating excellent inter-rater reliability.

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.

Hepatocellular carcinoma screening practices among patients with chronic hepatitis B by Canadian gastroenterologists and hepatologists: An online survey.

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.

Rate of Corticosteroid-Induced Mood Changes in Patients with Inflammatory Bowel Disease: A Prospective Study.

BACKGROUND: Corticosteroid is an effective therapeutic option for inflammatory bowel disease flares, but its adverse effects may compromise treatment adherence and reduce patients' quality of life. There is lack of data on the incidence of corticosteroid-induced mood changes in this patient population, which may be underappreciated by healthcare providers in clinical practice and interfere with optimal care. This study aimed to determine the rate of mood changes in this patient population. METHODS: In this prospective observational study, adult outpatients treated with prednisone for inflammatory bowel disease flares were considered for inclusion. Participants completed validated questionnaires (Beck Depression Inventory-II and Activation Subscale of Internal State Scale version two) before starting prednisone, after two weeks of prednisone, and at the end of prednisone taper to assess for mood changes. Harvey-Bradshaw Index and Simple Clinical Colitis Activity Index were used to monitor clinical disease activity. RESULTS: Fifty-three subjects were included in the analyses. The rate of mood change after two weeks of prednisone was 49.1%, primarily driven by increase in mood towards (hypo)mania. Younger age was an independent risk factor. Mood state returned to pretreatment level at the end of treatment. There was no correlation between clinical disease activity change and mood change. CONCLUSIONS: Oral prednisone for inflammatory bowel disease flare is associated with high rate of mood change. As prednisone is a critical part of induction therapy, ways to minimize this adverse event must be studied. For now, healthcare providers should inform patients and monitor closely for this adverse event.

Management of Hepatitis B Virus Infection: 2018 Guidelines from the Canadian Association for the Study of Liver Disease and Association of Medical Microbiology and Infectious Disease Canada.

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.

Utility of Transient Elastography in Estimating Hepatic Iron Concentration in Comparison to Magnetic Resonance Imaging in Patients Who are Transfusion-Dependent: A Canadian Center Experience.

Transfusion-dependent hereditary anemias such as ß-thalassemia (ß-thal), predispose patients to iron overload and its numerous clinical sequelae. Accurate assessment of overall iron status and prompt initiation of chelation therapy to prevent irreversible end-organ damage can be achieved using magnetic resonance imaging (MRI) to measure liver iron concentration (LIC) as a surrogate marker of total body iron; however, its access may be associated with long wait times and delay in treatment. We report an observational cohort study at a single tertiary care center assessing the theoretical role of transient elastography (TE), which measures liver stiffness, in estimating LIC compared to other established diagnostic measures. While regression analyses confirm a moderate correlation between LIC per R2 MRI and serum ferritin level (pooled estimate of correlation = 0.55), there was no significant correlation between TE reading and LIC based on R2 MRI (pooled estimate of correlation = -0.06), and only a weak correlation was observed with serum ferritin level (pooled estimate of correlation = 0.45). These results suggest TE may not be sensitive enough to detect subtle changes in the hepatic parenchymal stiffness associated with liver iron deposition.

Diagnosis and management of eosinophilic esophagitis in children.

QUESTION: After a few years of difficulty swallowing solids and feeling like food was getting stuck, a 13-year-old boy in my practice with peanut allergy and asthma was recently diagnosed with eosinophilic esophagitis (EoE). What is EoE and how is it diagnosed and managed? ANSWER: Eosinophilic esophagitis is an immune-mediated disease resulting in inflammation of the esophagus. It is increasing in prevalence and incidence in countries like Canada, and frequently occurs in children with other allergic conditions. Unexplained feeding difficulties, vomiting, and solid-food dysphagia, especially in boys with atopy, supports the possibility of having EoE. A formal diagnosis is obtained by reviewing esophageal biopsies obtained through upper endoscopy performed while the patient is taking a proton pump inhibitor. Once EoE has been established, management should involve working collaboratively with gastroenterology and allergy specialists. Medical or dietary treatments are acceptable therapeutic approaches.