The cirrhosis care Alberta (CCAB) protocol: implementing an evidence-based best practice order set for the management of liver cirrhosis - a hybrid type I effectiveness-implementation trial.

BACKGROUND: Liver cirrhosis is a leading cause of morbidity, premature mortality and acute care utilization in patients with digestive disease. In the province of Alberta, hospital readmission rates for patients with cirrhosis are estimated at 44% at 90 days. For hospitalized patients, multiple care gaps exist, the most notable stemming from i) the lack of a structured approach to best practice care for cirrhosis complications, ii) the lack of a structured approach to broader health needs and iii) suboptimal preparation for transition of care into the community. Cirrhosis Care Alberta (CCAB) is a 4-year multi-component pragmatic trial which aims to address these gaps. The proposed intervention is initiated at the time of hospitalization through implementation of a clinical information system embedded electronic order set for delivering evidence-based best practices under real-world conditions. The overarching objective of the CCAB trial is to demonstrate effectiveness and implementation feasibility for use of the order set in routine patient care within eight hospital sites in Alberta. METHODS: A mixed methods hybrid type I effectiveness-implementation design will be used to evaluate the effectiveness of the order set intervention. The primary outcome is a reduction in 90-day cumulative length of stay. Implementation outcomes such as reach, adoption, fidelity and maintenance will also be evaluated alongside other patient and service outcomes such as readmission rates, quality of care and cost-effectiveness. This theory-based trial will be guided by Normalization Process Theory, Consolidated Framework on Implementation Research (CFIR) and the Reach-Effectiveness-Adoption-Implementation-Maintenance (RE-AIM) Framework. DISCUSSION: The CCAB project is unique in its breadth, both in the comprehensiveness of the multi-component order set and also for the breadth of its roll-out. Lessons learned will ultimately inform the feasibility and effectiveness of this approach in "real-world" conditions as well as adoption and adaptation of these best practices within the rest of Alberta, other provinces in Canada, and beyond. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04149223, November 4, 2019.

Choosing Wisely Canada-Top Five List in Hepatology: Official Position Statement of the Canadian Association for the Study of the Liver (CASL) and Choosing Wisely Canada (CWC).

INTRODUCTION AND AIM: The prevalence and incidence of chronic liver disease is increasing resulting, in substantial direct and indirect medical costs. Overuse of investigations, treatments and procedures contribute to rising health care costs and can expose patients to unnecessary harm and delay in receiving care. The Choosing Wisely Canada (CWC) campaign has encouraged professional societies to develop statements that are directly actionable by their members in an effort to promote higher-value health care that will lead to downstream effect on how other practitioners make decisions. MATERIAL AND METHODS: The Canadian Association for the Study of the Liver (CASL) established its Choosing Wisely top five list of recommendations using the framework put forward by CWC. CASL convened a task force that developed a list of draft recommendations and shared this with CASL membership electronically with eventual ranking of the top five recommendations by consensus at Canadian Digestives Disease Week (CDDW) 2017. Following revisions, the CASL Executive Committee endorsed the final list, which was disseminated online by CWC (July 2017). RESULTS: The top five recommendations physicians and patients should question include: 1) Don't order serum ammonia to diagnose or manage hepatic encephalopathy (HE). 2) Don't routinely transfuse fresh frozen plasma, vitamin K, or platelets to reverse abnormal tests of coagulation in patients with cirrhosis prior to abdominal paracentesis, endoscopic variceal band ligation, or any other minor invasive procedures. 3) Don't order HFE genotyping based on serum ferritin values alone to diagnose hereditary hemochromatosis. 4) Don't perform computed tomography (CT) or magnetic resonance imaging (MRI) routinely to monitor benign focal liver lesions. 5) Don't repeat hepatitis C viral load testing in an individual who has established chronic infection, outside of anti-viral treatment. CONCLUSION: The Choosing Wisely recommendations will foster patient-physician discussions, reduce unnecessary treatment and testing, avert adverse effects from testing and treatment along with reducing medical expenditure in hepatology.

Autoantibodies and liver disease: uses and abuses.

Confirming whether a patient has autoimmune liver disease is challenging, given its varied presentation and complex definitions. In the continued absence of pathognomonic serum markers, diagnosis requires evaluation of laboratory investigations and, frequently, a liver biopsy - all of which need to be interpreted in the correct clinical context, with an emphasis on exclusion of viral infections, drug toxicity and metabolic disease. However, clear diagnosis is important for appropriate and timely therapy. Autoantibodies remain important tools for clinicians, and were the first proposed serological markers to aid in differentiating viral from chronic autoimmune hepatitis. Their presence is occasionally considered to be synonymous with autoimmune liver disease - a misinterpretation of their clinical significance. The present article summarizes the serum autoantibodies currently investigated in clinical and research practice, along with a description of their value in adult chronic liver diseases, with an emphasis on their appropriate use in the diagnosis and management of patients with autoimmune liver disease.

Hepatitis C eradication and improvement of cryoglobulinemia-associated rash and membranoproliferative glomerulonephritis with interferon and ribavirin after kidney transplantation.

Postrenal transplant hepatitis C is increasing in frequency due to the high prevalence of hepatitis C among patients with renal failure. Despite this, there is still no standard hepatitis C treatment available for renal transplanted recipients. Combination antiviral hepatitis C therapy, the standard of care in the nontransplant population, is generally avoided because of documented renal graft rejection secondary to interferon treatment. A case of a male patient with postrenal transplant hepatitis C, which was associated with cryoglobulinemia and glomerulonephritis of the graft, is presented. He was treated with standard interferon with ribavirin. Sustained viral clearance was achieved despite ongoing evidence of cryoglobulinemia. Renal function, which had been deteriorating before treatment, improved as evidenced by the stabilization of serum creatinine and marked improvement of proteinuria. In conclusion, in selected patients, combination antiviral therapy may still be a viable option postrenal transplant.

The effect of methoxsalen on nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism in vivo.

Nicotine is metabolized to the inactive metabolite cotinine by cytochrome P450 2A6. NNK, or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, is a potent procarcinogen shown to be activated to a reactive mutagenic metabolite by the enzyme CYP2A6. We studied the effect of inhibiting CYP2A6 on smoking behavior and metabolism of the procarcinogen NNK. In study 1, abstinent smokers (n=7) received methoxsalen (a potent CYP2A6 inhibitor), 30-50 mg orally, one-half hour before three subcutaneous nicotine injections (31 microg/kg) were given at hourly intervals. Methoxsalen increased mean plasma nicotine by 47% (p<.01) and mean nicotine area under the curve (AUC) by 63% (p<.0001); and decreased nicotine clearance by 39% (p<.0001), relative to placebo. In study 2, smokers (n=11) were told to maintain their same number of cigarettes smoked while receiving methoxsalen, 10 mg orally three times daily for 3 days. On day 3 of methoxsalen treatment, a 29% increase in plasma nicotine/expired-air CO (an index of smoke exposure) (p=0.03) was observed. Urinary levels of trans 3'-hydroxycotinine (metabolized by CYP2A6 from cotinine) also were decreased (p<.0001), and significantly more NNK was metabolized to the inactive NNAL-glucuronide (1.04+/-0.54 pmol/mg on day 1 to 1.37+/-0.74 pmol/mg on day 4, p<.01) relative to placebo. Thus, treatment with the CYP2A6 inhibitor methoxsalen in vivo increases the routing of NNK to the inactive NNAL-glucuronide and decreases smoking. CYP2A6 inhibition may have potential as an exposure reduction or cessation strategy in tobacco dependence.