Hepatitis B Virus Reactivation with Immunosuppression: A Hidden Threat?

Hepatitis B virus (HBV) reactivation in the setting of immunosuppressive therapy is an increasingly recognized and preventable cause of elevated liver enzymes and clinical hepatitis in treated patients. However, not all immunosuppressive therapies confer the same risk. The purpose of this article was to review the literature on risks of HBV reactivation associated with immunosuppressive agents and propose a management algorithm. We searched Google Scholar, PubMed, and MEDLINE for studies related to hepatitis B reactivation and various immunosuppressive agents. The risk of HBV reactivation was found to differ by agent and depending on whether a patient had chronic HBV (HBsAg+) or past HBV (HBsAg-, anti-HBc+). The highest risk of reactivation (>10%) was associated with anti-CD20 agents and hematopoietic stem cell transplants. Multiple societies recommend HBV-specific anti-viral prophylaxis for patients with positive HBsAg prior to the initiation of immunosuppressive therapy, while the guidance for HBsAg- patients is more variable. Clinicians should check HBV status prior to beginning an immune-suppressive therapy. Patients with positive HBsAg should be initiated on antiviral prophylaxis in the majority of cases, whereas HBsAg- individuals should be evaluated on a case-by-case basis. Further research is required to determine the optimum duration of therapy.

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.

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

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

Implementation of a Whole Food Plant Based Diet in a Food as Prevention Program in a Resource Constrained Environment.

Background: The efficacy of a Whole Food Plant-based (WFPB) diet has been shown in randomized controlled trials in diabetes, cardiovascular disease and obesity. However, it's effectiveness in routine clinical settings is less well documented. This study describes the implementation and outcomes of a "Food as Prevention" program run by a single clinician. Methods: Participants were referred to a "Food as Prevention" program run by a single gastroenterologist at an academic teaching center. The program included 5 physician-led discussion and small group educational sessions. Data collected included demographics, weight and biochemical measurements before and after completion of the program. Statistical analysis included paired t-test and Pearson correlation coefficients were used to assess differences before and after WFPB implementation. Results: A total of 17 participants (age 59 years; 59% female) with an average weight of 90.0 kg attended a median of 3 group sessions. Majority of patients had hyperlipidemia (71%) followed by hypertension (47%) and coronary artery disease (35%), fatty liver disease (35%) and diabetes mellitus (29%). Adoption of a WFPB diet led to significant decreases in weight (4.3 kg; p < 0.01), total cholesterol (0.72 mmol/L; p = 0.046), and triglycerides (0.53 mmol/L; p = 0.005) with an increase in high-density lipoprotein (HDL) (0.10 mmol/L; p = 0.01).Conclusions Implementation of the WFPB diet in this novel pilot program led to weight loss and improvement in biochemical markers of disease. Future studies are needed to implement this model on a larger scale.

Effectiveness and Renal Safety of Tenofovir Alafenamide Fumarate among Chronic Hepatitis B Patients: Real-World Study.

Tenofovir alafenamide fumarate (TAF) has high plasma stability resulting in fewer renal adverse events compared to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. We aimed to study the effectiveness and renal safety of TAF in a real-world setting, in patients with or without compromised kidney function. CHB patients (Nucleos(t)ide Analogue [NA]-naïve or experienced) who received TAF >1 year from 11 academic institutions as part of the Canadian Hepatitis B Network (CanHepB) were included. Kidney function was measured by estimated glomerular filtration rate (eGFR) as per Cockcroft-Gault. Patients were followed for up to 160 weeks. Of 176 patients receiving TAF, 143 switched from NA (88% TDF), and 33(19%) were NA naïve. Majority of NA-naïve patients (75%) achieved undetectable HBV DNA after one year of TAF treatment. Majority of patients with eGFR <60 mL/min who had renal deterioration during TDF (76%) reversed to eGFR increase after one year of TAF (p=0.009). Among patients with stage 2 chronic kidney disease (CKD) (eGFR 60-89), the estimated eGFR decline during TDF was halted after switching to TAF (p=0.09). NA-experienced patients with abnormal ALT before TAF showed a significant decline after switching to TAF: -0.005 [-0.006 - -0.004] log10 ULN U/L/month, p<0.001). In CHB patients, TAF was safe, well-tolerated and effective in this real-world cohort. Switching to TAF led to improved kidney function, particularly in those with stage 2 CKD, which suggests that the indication for TAF in the guidelines could be extended to patients with an eGFR higher than 60 mL/min.

The Z-Profile Study: a multicenter, retrospective cohort study to assess the real-world use and effectiveness of elbasvir/grazoprevir in Canadian adult patients with chronic hepatitis C.

Background: Canada was the first country to approve elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic HCV infection for genotypes 1 and 4 with or without ribavirin and genotype 3 with sofosbuvir, with no recommendation for baseline resistance testing. The aim of this study was to describe the effectiveness of EBR/GZR and the profile of patients selected for treatment in a Canadian real-world setting. Methods: This multicenter retrospective study of HCV-infected patients treated with EBR/GZR took place among selected Canadian health care providers, with no exclusion criteria. Primary outcome measures included parameters associated with patient profile and sustained virologic response at 12 weeks (SVR12) and 24 weeks after treatment. Results: A total of 408 patients were included; 244 had available SVR12 information (per-protocol population [PP]). Genotype distribution included 1a (54.7%), 1b (17.2%), 3 (11.8%), 4 (10.0%), and other (6.4%). The majority (88.7%) of participants were treated for 12 weeks without ribavirin. Fifty-nine (14.5%) participants, predominantly with genotype 1a (49/59) infection, were tested for baseline resistance-associated substitutions (bRAS). SVR12 was achieved by 95.9% of the PP. In an exploratory analysis assessing potential predictors of SVR12, participants who had undergone bRAS testing (OR 0.14, 95% CI 0.03-0.64) and participants who had undergone liver transplant (OR 0.05, 95% CI 0.00-0.68) had significantly lower odds of achieving SVR12. Conclusions: This study supports the real-world effectiveness of EBR/GZR-including a broad range of genotypes and diverse fibrosis stages-in the absence of bRAS testing and in special populations.

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.

The Benefit of Fentanyl in Effective Sedation and Quality of Upper Endoscopy: A Double-Blinded Randomized Trial of Fentanyl Added to Midazolam Versus Midazolam Alone for Sedation.

AIMS: Our goals were to compare the effect of adding fentanyl to midazolam in a double-blinded, randomized, placebo-controlled trial and determine if fentanyl enhances sedation, increases adverse events or effects time of the procedure or discharge. METHODS: Patients 18 to 65 years scheduled for outpatient upper endoscopy were eligible for the study. Patients were randomized to receive either 100 mcg/2 mL of Fentanyl or 2 mL of placebo IV with a double-blinded protocol. All patients received 2 mg of intravenous midazolam initially. Additional midazolam could be given to achieve adequate sedation. RESULTS: There were 68 patients randomized to the Fentanyl group and 69 patients to the placebo group. The mean dose of midazolam was 4.0 mg for the Fentanyl group and 5.2 mg for placebo group (P=0.003). Both endoscopist and nurse independently rated sedation to be better in the fentanyl group (P=0001). The patient did not perceive any difference in sedation (P=0.4). Procedure time was significantly shorter in the Fentanyl group (8.5 versus 11.1 minutes, P=0.001), with no difference in the discharge time. There was significantly less retching observed in patients in the fentanyl group (P<0.001). There were no major complications. CONCLUSIONS: Endoscopists and nurses found adding fentanyl significantly improved sedation, led to a shorter procedure time, and allowed for less midazolam to be used per case. It did not affect the patient experience of sedation and was safe. Fentanyl use for routine outpatient upper endoscopy should be considered as a safe option to improve procedural sedation.NCT:01514695 (www.clinicaltrials.gov)Accepted as an abstract for the Canadian Digestive Diseases Week meeting in February 2014.

Should albumin be used in all patients with spontaneous bacterial peritonitis?

Patients with cirrhosis who develop spontaneous bacterial peritonitis (SBP) have been reported to experience a high incidence of renal impairment and mortality. Renal dysfunction is possibly related to altered systemic hemodynamics that leads to decreased effective arterial blood volume. Albumin, a plasma volume expander, has been investigated to determine whether it plays a role in patients with SBP. The current literature suggests that albumin can reduce renal impairment and mortality in high-risk SBP patients, defined as patients with a serum bilirubin level of greater than 68.4 µmol/L, a blood urea nitrogen level of greater than 10.7 mmol/L or a serum creatinine level greater than 88.4 µmol/L. The rationale for albumin and other volume expanders in SBP is discussed, accompanied by a review of the current literature.

Emergency interventions for hyperkalaemia

It brings information about the hyperkalaemia, its incidence, consequences and treatment by using emergency interventions.

Selective serotonin reuptake inhibitors and risk of upper GI bleeding: confusion or confounding?

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) represent a relatively new class of antidepressants. Several studies have reported bleeding disorders associated with the use of SSRIs, which are considered the result of a decrease in platelet serotonin leading to a defect in platelet aggregation. To what extent the use of SSRIs increases the risk of gastrointestinal bleeding is unclear. METHODS: A comprehensive literature search for studies addressing SSRI use and upper gastrointestinal tract bleeding (UGIB) was conducted using Medline, EMBASE, and Cochrane databases with a recursive manual reference search up to May 2005. Any observational and interventional studies were systematically reviewed, and critical appraisal was conducted on available studies. RESULTS: Published clinical evidence on the relationship between SSRI use and gastrointestinal bleeding is limited to observational studies without any clinical trials. Three cohort studies and one case-control study met inclusion criteria. These studies combined different affinity SSRIs in the class and had differing control groups with conflicting conclusions. Both a cohort study and a case-control study investigating the concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin found that combined use with an SSRI increased the risk of UGIB. CONCLUSIONS: Only a few epidemiology studies have investigated the association between SSRIs and UGIB. They provide weak evidence to support the hypothesis of a link between SSRIs and UGIB at a population level. Available evidence shows that concurrent use of NSAIDs or aspirin with SSRIs greatly increases the risk of UGIB. The preventive strategy should be considered in those SSRI users at high risk, especially the elderly or those with a history of UGIB and taking nonselective NSAIDs or aspirin.

Subaortic stenosis: at risk substrates and treatment strategies.

Subaortic stenosis can be a complex disease of multiple anatomic etiologies. At the core is either an elongated and narrow outflow tract as compared to normal or a fully muscle-rimmed VSD used as an intraventricular routing pathway. An array of treatment modalities is needed for an effective management strategy.