Unique portal venous phase imaging discordance between CEUS and MRI: a valuable predictor of intrahepatic cholangiocarcinoma?

PURPOSE: We have long noted unique portal venous phase (PVP) imaging discordance of focal liver masses between CEUS, showing rapid marked washout, and MRI, showing progressive or sustained enhancement. We postulate association of this unique discordance with intrahepatic cholangiocarcinoma (ICC) and causal relationship to different contrast agent behavior. We investigate this unique discordance, propose its clinical significance for ICC diagnosis, and confirm further histologic associations. METHODS: Cases were collected within our CEUS department and from pathology records over a ten-year interval. This retrospective review includes 99 patients, 73 with confirmed ICC and 26 other diagnoses, showing unique PVP discordance. The CEUS and MRI enhancement characteristics were compared for all patients. RESULTS: Unique discordance is identified in 67/73 (92%) ICC and difference between the PVP appearance on MRI and CEUS is statistically significant (p <  0.0001). Arterial phase enhancement did not show statistically significant difference between CEUS and MRI, p >  0.05. Other diagnoses showing unique discordance include especially lymphoma (n = 7), sclerosed hemangioma (n = 6), HCC (n = 4), metastases (n = 2), and other rare entities. CONCLUSION: ICC shows this discrepant intermodality enhancement pattern in a statistically significant number of cases and should be considered along with other LR-M features in at-risk patients. Discordance is also rarely seen in a number of other liver lesions.

Clinical consensus statement: Establishing the roles of locoregional and systemic therapies for the treatment of intermediate-stage hepatocellular carcinoma in Canada.

BACKGROUND: Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context. METHODS: A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement. RESULTS & CONCLUSION: The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings.

Nodules Identified on Surveillance Ultrasound for HCC: CEUS or MRI as the Initial Test?

OBJECTIVES: Following positive surveillance ultrasound (US), magnetic resonance imaging (MRI) is recommended for further characterization. We propose contrast-enhanced ultrasound (CEUS) shows equivalent efficacy. METHODS: This prospective institutional review board approved study recruited 195 consecutive at-risk patients with a positive surveillance US. All had CEUS and MRI. Biopsy (n = 44) and follow-up are gold standard. MRI and CEUS results are classified according to liver imaging reporting and data system (LI-RADS) and patient outcome. RESULTS: As an US-based modality, CEUS is superior in confirming findings from surveillance US, correlation in 189/195 (97%) on CEUS compared to 153/195 (79%) on MRI. Within these negative MRI examinations, there are 2 hepatocellular carcinoma (HCC) and 1 cholangiocarcinoma (iCCA) diagnosed on CEUS and proven by biopsy. From 195 patients, there are 71 malignant diagnoses from all sources, including 58 LR-5 (45 on MRI and 54 on CEUS) and 13 others, including HCC outside of LR-5 category, and LR-M with biopsy proven iCCA (3 on MRI and 6 on CEUS). CEUS and MRI show concordant results in the majority of patients (146/195, 75%), including 57/146 malignant and 89/146 benign diagnoses. There are 41/57 concordant LR-5 and 6/57 concordant LR-M. When CEUS and MRI are discordant, CEUS upgraded 20 (10 biopsy-proven) from MRI LR-3/4 to CEUS LR-5 or LR-M by showing washout (WO) that MRI failed to show. Additionally, CEUS characterized time and intensity of WO and diagnosed 13/20 LR-5 by showing late and weak WO and 7 LR-M by showing fast and marked WO. CEUS is 81% sensitive and 92% specific in diagnosing malignancy. MRI is 64% sensitive and 93% specific. CONCLUSIONS: CEUS performance is at least equivalent if not superior to MRI for initial evaluation of lesions from surveillance US.

The effectiveness of a multifaceted, group-facilitated audit and feedback intervention to increase tranexamic acid use during total joint arthroplasty.

PURPOSE: Intraoperative tranexamic acid (TXA) is used to reduce blood loss and the need for transfusions following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Despite evidence in literature and local practice protocols supporting TXA as a part of standard of care for joint arthroplasty, TXA administration is underutilized. We aimed to use group-facilitated audit and feedback as the foundation of a knowledge translation strategy to increase TXA use for THA and TKA procedures. METHODS: Anesthesiologists consented to receive two data reports summarizing their individual rates of TXA use and postoperative blood transfusions compared with site peers. Variables collected included patient demographics, TXA usage, and the frequency and volume of red blood cell transfusions administered in the 72-hr postoperative period. The facilitated feedback session discussed report findings and focused on factors contributing to local practice patterns and opportunities for change. RESULTS: Tranexamic acid use increased for THA procedures at the intervention site from 66.6 to 74.4% (absolute change, 7.9%; 95% confidence interval [CI], 2.4 to 13.3). Likewise, TXA use for TKA procedures increased from 62.4 to 82.3% (absolute change, 19.9%; 95% CI 15.0 to 25.0). CONCLUSIONS: Physicians and their teams were able to review their practice data on TXA utilization, reflect on differences compared with evidence-based guidelines, discuss findings with peers, and identify opportunities for improvement. The intervention increased the use of TXA for both TKA and THA and shifted the dosage to better align with evidence-based practice guidelines.

RéSUMé: OBJECTIF : L'acide tranexamique (ATX) peropératoire est utilisé pour réduire les pertes sanguines et les besoins transfusionnels après les arthroplasties totales de la hanche (ATH) et du genou (ATG). Malgré les données probantes et les protocoles de pratique locaux appuyant l'utilisation d'ATX dans le cadre de la norme de soins en cas d'arthroplastie, l'administration de cet agent est sous-utilisée. Notre objectif était d'utiliser l'audit et la rétroaction facilités par le groupe comme base d'une stratégie d'application des connaissances afin d'accroître l'utilisation de l'ATX lors des ATH et ATG. MéTHODE: Les anesthésiologistes ont consenti à recevoir deux rapports de données résumant leurs taux individuels d'utilisation d'ATX et de transfusions sanguines postopératoires par rapport à leurs pairs au sein du même établissement. Les variables recueillies comprenaient les données démographiques des patients, l'utilisation d'ATX et la fréquence et le volume des transfusions d'érythrocytes administrées au cours d'une période postopératoire de 72 heures. La séance de rétroaction facilitée a porté sur les conclusions du rapport et s'est concentrée sur les facteurs contribuant aux habitudes de pratique locales et aux possibilités de changement. RéSULTATS: L'utilisation d'acide tranexamique a augmenté pour les procédures d'ATH au site d'intervention, passant de 66,6 % à 74,4 % (variation absolue, 7,9 %; intervalle de confiance [IC] à 95 %, 2,4 à 13,3). De même, l'utilisation d'ATX pour les procédures d'ATG est passée de 62,4 % à 82,3 % (variation absolue, 19,9 %; IC 95 %, 15,0 à 25,0). CONCLUSION: Les médecins et leurs équipes ont pu passer en revue leurs données de pratique sur l'utilisation d'ATX, réfléchir aux différences par rapport aux lignes directrices fondées sur des données probantes, discuter des résultats avec leurs pairs et identifier les possibilités d'amélioration. L'intervention a augmenté l'utilisation d'ATX pour l'ATG et l'ATH et a modifié la posologie pour mieux s'aligner sur les lignes directrices de pratique fondées sur des données probantes.

Anxiety in cirrhosis: a prospective study on prevalence and development of a practical screening nomogram.

OBJECTIVES: The prevalence and effects of anxiety on health-related quality of life and clinical outcomes in cirrhosis are not well understood. This is increasingly relevant during COVID-19. Our aim was to use the Mini-International Neuropsychiatric Interview (MINI) to determine the prevalence of anxiety, its association with clinical outcomes in cirrhosis and to develop a rapid cirrhosis-specific anxiety screening nomogram. METHODS: Adults with a diagnosis of cirrhosis were prospectively recruited as outpatients at three tertiary care hospitals across Alberta and followed for up to 6 months to determine the association with unplanned hospitalization/death. The Hospital Anxiety and Depression scale (HADS) was used as a screening tool as it is free of influence from somatic symptoms. Anxiety was diagnosed using the MINI. RESULTS: Of 304 patients, 17% of patients had anxiety by the MINI and 32% by the HADS. Anxious patients had lower health-related quality of life as assessed by the chronic liver disease questionnaire (P < 0.001) and EuroQol Visual Analogue Scale (P < 0.001), and also had higher levels of frailty using the Clinical Frailty score (P = 0.004). Multivariable analysis revealed smoking and three HADS subcomponents as independent predictors of anxiety. These were used to develop a rapid screening nomogram. CONCLUSION: A formal diagnosis of anxiety was made in approximately one in five patients with cirrhosis, and it was associated with worse HrQoL and frailty. The use of a 4-question nonsomatic symptom-based nomogram requires validation but is promising as a rapid screen for anxiety in cirrhosis.

Do Low-Risk Patients With Dyspepsia Need a Gastroscopy? Use of Gastroscopy for Otherwise Healthy Patients With Dyspepsia.

BACKGROUND: Choosing Wisely Canada (CWC) recommends not to perform gastroscopy for dyspepsia in otherwise healthy adults less than 55 years of age (2014). The aim of this study was to evaluate the use of gastroscopy in a young, healthy population with uncomplicated dyspepsia. METHODS: A retrospective review of gastroscopies completed during 3-month periods in 2015, 2016, and 2017 identified all patients undergoing gastroscopy for the primary indication of dyspepsia. Low-risk patients for dyspepsia were defined as adults, aged 18 to 54 years without alarm symptoms, comorbidities and/or abnormal imaging findings or laboratory values. Gastroscopy and pathology reports were reviewed to identify clinically actionable findings. Clinical outcomes were followed to December 31, 2018 including gastroenterology referrals, emergency room visitation and hospitalization. RESULTS: Among 1358 patients having a gastroscopy for dyspepsia, 480 (35%) were low-risk patients. Sixteen patients 3.3% (16/480) had a clinically actionable result found on gastroscopy or biopsy. No malignant lesions were detected. Low-risk patients were followed up for an average of 2.75 years, 8% (39/480) visited the emergency department (ED), 1% (3/480) of patients were admitted to hospital and 12% (59/480) of patients were re-referred for a dyspepsia-related concern. INTERPRETATION: A high rate of low yield, high cost, invasive endoscopic investigations were performed in this population of otherwise healthy patients under age 55 years. These data suggest limited uptake of current recommendations against the routine use of gastroscopy to investigate dyspepsia.

Trends and Projections in National United States Health Care Spending for Gastrointestinal Malignancies (1996-2030).

BACKGROUND & AIMS: The management of gastrointestinal (GI) cancers is associated with high health care spending. We estimated trends in United States (US) health care spending for patients with GI cancers between 1996 and 2016 and developed projections to 2030. METHODS: We used economic data, adjusted for inflation, developed by the Institute for Health Metrics and Evaluations for the Disease Expenditure Project. Corresponding US age-adjusted prevalence of GI cancers was estimated from the Global Burden of Diseases Study. Prevalence-adjusted temporal trends in the US health care spending in patients with GI cancers, stratified by cancer site, age, and setting of care, were estimated using joinpoint regression, expressed as annual percentage change (APC) with 95% confidence intervals (CIs). Autoregressive integrated moving average models were used to project spending to 2030. RESULTS: In 2016, total spending for GI cancers was primarily attributable to colorectal ($10.50 billion; 95% CI, $9.35-$11.70 billion) and pancreatic cancer ($2.55 billion; 95% CI, $2.23-$2.82 billion), and primarily for inpatient care (64.5%). Despite increased total spending, more recent per-patient spending for pancreatic (APC 2008-2016, -1.4%; 95% CI, -2.2% to -0.7%), gallbladder/biliary tract (APC 2010-2016, -4.3%; 95% CI, -4.8% to -3.8%), and gastric cancer (APC 2011-2016, -4.4%; 95% CI, -5.8% to -2.9%) decreased. Increasing price and intensity of care provision was the largest driver of higher expenditures. By 2030, it is projected more than $21 billion annually will be spent on GI cancer management. CONCLUSIONS: Total spending for GI cancers in the US is substantial and projected to increase. Expenditures are primarily driven by inpatient care for colorectal cancer, although per-capita spending trends differ by GI cancer type.

Impact of the COVID-19 Pandemic on Hospitalizations for Alcoholic Hepatitis or Cirrhosis in Alberta, Canada.

BACKGROUND & AIMS: Coronavirus disease 2019 (COVID-19) pandemic lockdown and restrictions had significant disruption to patient care. We aimed to evaluate the impact of COVID-19 restrictions on hospitalizations of patients with alcoholic and nonalcoholic cirrhosis as well as alcoholic hepatitis (AH) in Alberta, Canada. METHODS: We used validated International Classification of Diseases (ICD-9 and ICD-10) coding algorithms to identify liver-related hospitalizations for nonalcoholic cirrhosis, alcoholic cirrhosis, and AH in the province of Alberta between March 2018 and September 2020. We used the provincial inpatient discharge and laboratory databases to identify our cohorts. We used elevated alanine aminotransferase or aspartate aminotransferase, elevated international normalized ratio, or bilirubin to identify AH patients. We compared COVID-19 restrictions (April-September 2020) with prior study periods. Joinpoint regression was used to evaluate the temporal trends among the 3 cohorts. RESULTS: We identified 2916 hospitalizations for nonalcoholic cirrhosis, 2318 hospitalizations for alcoholic cirrhosis, and 1408 AH hospitalizations during our study time. The in-hospital mortality rate was stable in relation to the pandemic for alcoholic cirrhosis and AH. However, nonalcoholic cirrhosis patients had lower in-hospital mortality rate after March 2020 (8.5% vs 11.5%; P = .033). There was a significant increase in average monthly admissions in the AH cohort (22.1/10,000 admissions during the pandemic vs 11.6/10,000 admissions before March 2020; P < .001). CONCLUSIONS: Before and during COVID-19 monthly admission rates were stable for nonalcoholic and alcoholic cirrhosis; however, there was a significant increase in AH admissions. Because alcohol sales surged during the pandemic, future impact on alcoholic liver disease could be detrimental.

A new proposal for secondary surveillance following potentially curative therapy of HCC: alternating MRI and CEUS.

PURPOSE: A high recurrence rate following ablative therapy of hepatocellular carcinoma (HCC) necessitates routine follow-up imaging (secondary surveillance) to facilitate early re-treatment. We evaluate our unique secondary surveillance algorithm (with use of alternating MRI and CEUS) by assessment of the relative diagnostic accuracy of MRI and CEUS in detection of residual/recurrent tumor. Potential benefits of alternating surveillance are compared to the use of MRI alone. MATERIALS AND METHODS: This prospective observational IRB approved study included 231 patients with 354 treated tumors between January 2017 and June 2020. Treated lesions underwent secondary surveillance for a minimum of 7 months and up to 3 years, median follow-up 14 months. Secondary surveillance involved MRI performed at 1 month after treatment, followed by CEUS and MRI at alternate 3-month intervals (i.e., CEUS at month 4, MRI at month 7, etc.), for a total of 2 years. An equivocal finding on one imaging modality triggered expeditious evaluation with the alternate modality. Arterial phase hyperenhancement and washout comprise the classic features of recurrent tumor on both modalities. RESULTS: A total of 746 MRI and 712 CEUS examinations were performed, and a total of 184 tumor recurrences detected, MRI (n = 82) and CEUS (n = 102) (p = 0.19). There was no difference in the sensitivity (71.0-85.0% and 80.9-92.0%), specificity (97.4-99.2% and 98.5-99.9%), and area under the ROC curve (0.85-0.92 and 0.91-0.96) between MRI and CEUS, respectively. 23 of 82 recurrent tumors identified on MRI were equivocal and confirmed with expedited CEUS. 9 equivocal cases on MRI were disproved by expedited CEUS. On CEUS, 1 of the 102 recurrent tumors was equivocal and confirmed on MRI, and 2 equivocal CEUS cases were disproved by MRI. CONCLUSION: MRI and CEUS performed similarly in our secondary surveillance algorithm for HCC in their ability to detect tumor recurrence, and showed no significant difference in their relative diagnostic test accuracy measures. Of greater interest, equivocal results on MRI (typically due to difficulty in distinguishing tumor recurrence from post-treatment change/shunting) were either confirmed or disproven by CEUS in all cases. Secondary surveillance of treated HCC with alternating MRI and CEUS shows equivalent performance of each modality. CEUS resolves equivocal MRI and optimally demonstrates APHE and washout in tumor recurrence.

Frailty is associated with increased risk of cirrhosis disease progression and death.

BACKGROUND AND AIMS: The Liver Frailty Index (LFI) is a well-studied tool that evaluates frailty in patients with cirrhosis. Consisting of grip strength, chair stands, and balance testing, the LFI has been associated with increased mortality in patients awaiting liver transplant. We aimed to extend our understanding of frailty in cirrhosis by exploring the relationship between the LFI and the risk of (1) cirrhosis progression, (2) mortality, and (3) unplanned hospitalizations, in both compensated and decompensated disease. APPROACH AND RESULTS: Adult patients with cirrhosis from four centers in North America and one in India were included. Frailty was measured at baseline using the LFI and categorized as robust (LFI < 3.2), prefrail (LFI 3.2-4.5), and frail (LFI > 4.5). Progression of cirrhosis was defined by an increase in clinical stage, ranging from 1 to 5, from baseline using the D'Amico classification. Factors associated with progression, mortality, and hospitalizations were evaluated using multivariate regression models, with transplant as a competing risk. In total, 822 patients with cirrhosis were included. Average Model for End-Stage Liver Disease (MELD) score was 15.5 ± 6.0. In patients with compensated cirrhosis, being frail versus robust was associated with increased risk of progression to the next cirrhosis stage or to death (HR, 2.45; 95% CI, 1.14-5.29) and with an increased risk of unplanned hospitalizations (2.32; 95% CI, 1.13-4.79), after adjusting for age, sex, and MELD score. Similar HRs were observed in patients with decompensated cirrhosis. CONCLUSIONS: Frailty was an independent predictor of cirrhosis progression or death and unplanned hospitalization across patients with compensated and decompensated cirrhosis. Future studies are needed to evaluate the possibility of slowing cirrhosis disease progression by reversing or preventing frailty.

Real-world tertiary referral centre experience stopping nucleos(t)ide analogue therapy in patients with chronic hepatitis B.

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

The Impact of Comorbidities on Calgary Hospital Utilization in Patients With Chronic Obstructive Pulmonary Disease and Heart Failure.

Background Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are chronic conditions with high acute care utilization. Disease-specific order sets were developed for patients with COPD or HF in Calgary to reduce total days in hospital for this population of patients. However, many patients have comorbidities which may contribute to hospital utilization; thus, disease-specific order sets may not be an optimal solution to reduce overall acute care utilization. Methods Inpatient data on Calgary hospitalizations for COPD or HF between April 1, 2017 - March 31, 2019 and associated diagnoses were identified. Outcomes included total days in hospital and length of stay for COPD and HF patients stratified by number of comorbidities. Results Total days in hospital increased with the number of comorbidities for both conditions. During the study period, 131 patients with COPD and no comorbidities had a median length of stay of three days (IQR: 3) compared to 3,911 COPD patients with one to five comorbidities with a median length of stay of seven days (IQR: 9). There were 47 patients with HF and no comorbidities with a median length of stay of four days (IQR: 5) compared to 6,273 HF patients with one to five comorbidities with a median length of stay of nine days (IQR: 12). Common comorbidities included hypertension, type 2 diabetes, and acute renal failure. COPD and HF are frequently comorbid.  Conclusions Total days in hospital for patients with COPD or HF is positively correlated with the number of comorbidities. COPD or HF patients with between one to five comorbidities (compared to those with no comorbidities, and those with more than five comorbidities) represent the majority of total days in hospital, and the majority of patients. This highlights the importance of focusing on patients with comorbidities in efforts to reduce hospital utilization, and suggests that concurrent management of commonly occurring comorbidities for HF and COPD patients may be necessary to achieve this goal.

COVID-19 outbreak among physicians at a Canadian curling bonspiel: a descriptive observational study.

BACKGROUND: Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to occur among individuals who congregate in large groups, especially during indoor activities. Our objective was to provide a detailed clinical description of an outbreak of coronavirus disease 2019 (COVID-19) that occurred after a sporting and social event during the early days of the pandemic. METHODS: We conducted a descriptive study of a curling bonspiel in Edmonton held on Mar. 11-14, 2020. We used standardized interviews between Apr. 17 and May 5, 2020, to collect demographic data, travel history, symptoms (type, onset and duration), self-reported testing results for SARS-CoV-2 ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR), and clinical outcomes. We also obtained results of convalescent SARS-CoV-2 immunoglobulin G serology. RESULTS: All 73 curlers (55 active health care workers) who participated in the bonspiel were interviewed for the study. Convalescent SARS-CoV-2 immunoglobulin G serology was completed in 62 (85%) participants. Of the 73 participants (55 [75%] male, median age 51 [range 26-79] yr, 58 [79%] physicians), 40 curlers (55%) tested positive for SARS-CoV-2 RNA by RT-PCR; an additional 16 participants developed symptoms but had negative swabs or were not tested (14 were probable cases), for a 74% attack rate (confirmed or probable cases). Anosmia with ageusia or dysgeusia occurred in 39 of 54 (72%) confirmed or probable cases. The clinical course was mild in most participants (1 emergency visit, no hospital admissions). Transmission likely occurred from multiple individuals with minor nonspecific symptoms during the event, possibly during shared meals. INTERPRETATION: The 74% attack rate (confirmed or probable cases) highlights the infectivity of SARS-CoV-2 during sporting and social events. This reinforces the need for public health measures (masking, physical distancing and limiting the size of social gatherings) during future waves of COVID-19 in Canada.

WGO Guidance for the Care of Patients With COVID-19 and Liver Disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the least deadly but most infectious coronavirus strain transmitted from wild animals. It may affect many organ systems. Aim of the current guideline is to delineate the effects of SARS-CoV-2 on the liver. Asymptomatic aminotransferase elevations are common in coronavirus disease 2019 (COVID-19) disease. Its pathogenesis may be multifactorial. It may involve primary liver injury and indirect effects such as "bystander hepatitis," myositis, toxic liver injury, hypoxia, and preexisting liver disease. Higher aminotransferase elevations, lower albumin, and platelets have been reported in severe compared with mild COVID-19. Despite the dominance of respiratory disease, acute on chronic liver disease/acute hepatic decompensation have been reported in patients with COVID-19 and preexisting liver disease, in particular cirrhosis. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a higher risk of respiratory disease progression than those without MAFLD. Alcohol-associated liver disease may be severely affected by COVID-19-such patients frequently have comorbidities including metabolic syndrome and smoking-induced chronic lung disease. World Gastroenterology Organization (WGO) recommends that interventional procedures such as endoscopy and endoscopic retrograde cholangiopancreatography should be performed in emergency cases or when they are considered strictly necessary such as high risk varices or cholangitis. Hepatocellular cancer surveillance may be postponed by 2 to 3 months. A short delay in treatment initiation and non-surgical approaches should be considered. Liver transplantation should be restricted to patients with high MELD scores, acute liver failure and hepatocellular cancer within Milan criteria. Donors and recipients should be tested for SARS-CoV-2 and if found positive donors should be excluded and liver transplantation postponed until recovery from infection.

Real-world clinical and virological outcomes in a retrospective multiethnic cohort study of 341 untreated and tenofovir disoproxil fumarate-treated chronic hepatitis B pregnant patients in North America.

BACKGROUND: There are limited long-term data on outcomes of chronic hepatitis B (CHB) in untreated and tenofovir disoproxil fumarate (TDF)-treated women during pregnancy. AIMS: To assess clinical outcomes in a multiethnic cohort of patients during pregnancy and post-partum in a low HBV endemic region. METHODS: Retrospective real-world study of women with CHB (treated or untreated with TDF) from 2011 to 2019; data including ALT, HBV DNA, HBeAg and liver stiffness measurement were collected during pregnancy and post-partum. RESULTS: In 341 women (446 pregnancies) followed for a median of 33 months (IQR: 26.7-39.5) post-partum, 19% (65/341) received TDF (11 initiated pre-pregnancy, 53 for mother-to-child transmission (MTCT) prevention). During follow-up, 72/341 had subsequent pregnancy, including 18/53 on TDF for MTCT risk, of whom 7/18 were re-treated. In all TDF-treated women, HBV DNA declined but rebounded after TDF withdrawal (median baseline, near birth and early follow-up levels were 7.2, 3.0 and 5.5 log IU/mL respectively [P < 0.01]). In HBeAg+ patients (65/341) ALT flares were more common (P = 0.03), especially for those who stopped TDF post-partum, requiring re-treatment in 21% (11/53). In comparison, 54% (116/215) of untreated women had a post-partum ALT flare; one with fulminant hepatitis underwent transplant 13 months post-partum. HBsAg clearance occurred in 2.6% (9/341, 3/9 HBeAg+, 2/9 TDF treated) at median 30 months (IQR: 23-40) and 37% (24/65) of HBeAg+ patients had HBeAg loss at median 17 months (IQR: 12-26) post-partum. CONCLUSIONS: Post-partum ALT flares were common, especially after TDF withdrawal. Overall, 37% achieved HBeAg clearance and 2.9% had HBsAg loss during long-term follow-up.

Impact of Hepatitis B Virus Genetic Variation, Integration, and Lymphotropism in Antiviral Treatment and Oncogenesis.

Chronic Hepatitis B Virus (HBV) infection poses a significant global health burden. Although, effective treatment and vaccinations against HBV are available, challenges still exist, particularly in the development of curative therapies. The dynamic nature and unique features of HBV such as viral variants, integration of HBV DNA into host chromosomes, and extrahepatic reservoirs are considerations towards understanding the virus biology and developing improved anti-HBV treatments. In this review, we highlight the importance of these viral characteristics in the context of treatment and oncogenesis. Viral genotype and genetic variants can serve as important predictive factors for therapeutic response and outcomes in addition to oncogenic risk. HBV integration, particularly in coding genes, is implicated in the development of hepatocellular carcinoma. Furthermore, we will discuss emerging research that has identified various HBV nucleic acids and infection markers within extrahepatic sites (lymphoid cells). Intriguingly, the presence of hepatocellular carcinoma (HCC)-associated HBV variants and viral integration within the lymphoid cells may contribute towards the development of extrahepatic malignancies. Improved understanding of these HBV characteristics will enhance the development of a cure for chronic HBV infection.

Risk stratification of patients with nonalcoholic fatty liver disease using a case identification pathway in primary care: a cross-sectional study.

BACKGROUND: Identification of patients with nonalcoholic fatty liver disease (NAFLD) with advanced liver fibrosis in primary care remains an unmet need. Our primary objective was to implement a pathway driven by shear wave elastography (SWE) to facilitate risk stratification of patients with NAFLD within primary care and evaluate whether SWE assessment can reduce referrals of patients with NAFLD at low risk for fibrosis to hepatology. METHODS: A multidisciplinary NAFLD clinical care pathway was codeveloped by hepatologists, radiologists and primary care physicians in Calgary to provide access to SWE-based screening of patients with NAFLD risk factors in primary care. The study outcome measures were estimated NAFLD-related referrals to the hepatology service in Calgary after implementation of the NAFLD pathway and characteristics of patients with NAFLD at risk for advanced fibrosis. The NAFLD pathway was implemented in January 2018 and was made available to all primary care physicians in the Calgary Health Zone. Patients with NAFLD who had liver stiffness (SWE value ≥ 8.0 kPa) or an inconclusive assessment were referred to hepatology. A serum liver fibrosis score was also measured with the fibrosis-4 (FIB-4) index, and performance of an FIB-4 index score of 1.30 or greater to risk stratify patients with NAFLD was evaluated. Demographic, clinical and laboratory characteristics of study groups were compared. RESULTS: Between March and October 2018, 2084 patients with suspected NAFLD were evaluated. Nonalcoholic fatty liver disease was confirmed by ultrasonography in 1958 (94.1%). A majority of the cohort had elevated liver enzyme values (1028 [52.5%]) and obesity (body mass index ≥ 30) (1063/1764 [60.3%]). Most patients with NAFLD (1791 [91.5%]) had an SWE value less than 8.0 kPa and were not referred to hepatology. Sixty-seven patients (3.4%) had an SWE value of 8.0 kPa or more, and 100 (5.1%) had an inconclusive SWE; these patients were referred to hepatology. Using an FIB-4 index score cut-off of 1.30 would have led to hepatology referral of 396/1251 patients (31.6%). INTERPRETATION: Implementation of a primary care-accessible SWE pathway for patients with NAFLD facilitated fibrosis risk stratification and greatly reduced hepatology referrals. Using the FIB-4 index score alone would led to higher rates of referral of patients with NAFLD.