Eliminating hepatitis C in a rural Appalachian county: protocol for the Kentucky Viral Hepatitis Treatment Study (KeY Treat), a phase IV, single-arm, open-label trial of sofosbuvir/velpatasvir for the treatment of hepatitis C

ObjectivesThe overall goal of the Kentucky Viral Hepatitis Treatment Study (KeY Treat) is to eliminate hepatitis C transmission from a county in Appalachian Kentucky by removing the barriers to accessing hepatitis C virus (HCV) treatment.Methods/analysisKeY Treat is a phase IV, open-label, single-arm clinical trial of sofosbuvir/velpatasvir (SOF/VEL) for the treatment of viraemic HCV infections. Those eligible for KeY Treat are at least 18 years of age, viraemic and are residents of the target county. Pregnant women are not eligible. Rapid HCV RNA screening is used to determine eligibility, and those with a quantifiable viral load (VL) consenting to participate initiate SOF/VEL on the same day. All pharmacologic treatment and related medical care is provided free of charge using a non-specialist provider model. Follow-up visits occur at 2, 6 and 12 weeks during treatment to assess medication adherence (measured via VL and self-report), side effects and engagement in risk behaviours. Post-treatment visits occur at 12 weeks (sustained virologic response (SVR12) visit), 6 months and 12 months post-treatment completion to assess re-infection. A control county has also been identified, and prevalence and incidence of chronic HCV infections will be compared with the target community longitudinally. The primary outcome to assess elimination is SVR12. However, several outcomes will be measured to assess the effectiveness of removing the barriers to HCV treatment, including treatment entry, completion and re-infection. Analyses will be conducted via a generalised linear model framework that can incorporate flexible covariate adjustment and multiple outcome types with a compatible link function. Mathematical modelling will be completed assessing the impact and cost-effectiveness of the intervention.Ethics and disseminationKeY Treat has been approved by the Institutional Review Board at the University of Kentucky. Results from KeY Treat will be presented at conferences and published in peer-reviewed journals.Trial registration numberNCT03949764.

SUN-508 Dissociation of Clinical Course of Coexisting Autoimmune Hepatitis and Graves Disease

Title: Dissociation of Clinical Course of Coexisting Autoimmune Hepatitis and Graves Disease Introduction: The association between Graves’ disease and coexisting autoimmune hepatitis is well known. Treatment of autoimmune hepatitis with glucocorticoids can concurrently lower thyroid hormone levels. Additionally, recurrence of hyperthyroidism has been shown to be associated with recurrence of autoimmune hepatitis. We present a case of a patient with autoimmune hepatitis and Graves’ thyrotoxicosis, which initially improved with prednisone therapy, but thyrotoxicosis recurred during the prednisone taper while hepatitis stayed in remission. Clinical Case: A 47-year old female initially presented with fatigue, nausea, and jaundice. Liver enzymes showed elevated AST (1634 U/L) and ALT (1956 U/L) with total bilirubin 15.1 mg/dL. Liver biopsy was consistent with autoimmune hepatitis. Treatment was initiated with ursodiol 300 mg TID and liver enzymes improved to ALT 579 IU/L and AST 544 IU/L with total bilirubin 1.9 mg/dL. Nine months later, she presented with worsening upper and lower extremity weakness, slurred speech, abdominal pain, and nausea and vomiting. AST and ALT were again elevated to >1,000 U/L. TFTs were checked due to symptoms of palpitations and heat intolerance. TSH was 0.024 uIU/mL with elevated free T4 of 3.74 ng/dL and TSI of 435%. She was treated with prednisone, cholestyramine, and propranolol and discharged with a one-month prednisone taper starting at 60 mg daily. LFTs and TFTs normalized after one month. Cholestyramine was discontinued and prednisone was tapered to 5 mg daily. Seven months later, she had symptoms of palpitations and heat intolerance. TFTs were consistent with hyperthyroidism (TSH 0.049 uIU/mL, free T4 3.96 ng/dL). LFTs remained in normal range. Since thionamides have relative contraindications in patients with liver disease, prednisone was increased from 5 mg to 20 mg daily and cholestyramine was resumed to treat hyperthyroidism. After five months, TSH remained suppressed to 0.019 uIU/mL however free T4 improved to 1.74 ng/dL. The patient was referred for total thyroidectomy. Conclusion: This case illustrates an example of the rarely reported occurrence of thyrotoxicosis recrudescence despite initial improvement with treatment of underlying autoimmune hepatitis. Recognition of recurrence of hyperthyroidism independent of recurrence of autoimmune hepatitis indicates the need for early definitive therapy for hyperthyroidism.

Challenges in early identification of causes and treatment of cholestasis in patients with hyperthyroidism: a case report and literature review

Early identification of the causes of cholestasis is important for appropriate management of patients with hyperthyroidism. We report a patient who had hyperthyroidism and severe cholestasis after methimazole (MMI) treatment. The patient was diagnosed as having MMI-induced cholestatic hepatitis. Treatment with MMI was stopped at admission to hospital. However, his serum total bilirubin (TBil) level rose from 410.5 µmol/L to 519.9 µmol/L and prothrombin time activity (PTA) dropped from 81.0% to 52.2% in 10 days. To prevent further deterioration of his liver function, plasma exchange was performed three times, and dexamethasone (10 mg, intravenously) was used each time. His PTA rose to 101% and his TBil continued to increase to 669.8 µmol/L after plasma exchange. He was subsequently diagnosed as having thyrotoxicosis-induced cholestasis and treated with radioactive iodine (380 MBq) 2 weeks after admission. His hyperthyroidism was significantly relieved, but the TBil level further increased to 776.8 µmol/L. Three weeks after admission, oral prednisone (30 mg/day) was used in this patient. Subsequently, his TBil levels gradually decreased and his liver function almost normalized within 3 months. We discuss the literature on cholestasis in the context of hyperthyroidism.

Pathogenetic aspects of dogs’ infectious hepatitis treatment

The article presents the mechanisms of development and dynamics of changes in the treatment of dogs’ infectious hepatitis. According to reports from doctors of veterinary medicine in clinics of small animals of Zhytomyr, the following infectious diseases are dominated in dogs: parvovirus enteritis, viral hepatitis, parainfluenic dogs, leptospirosis, carnivorous plague, trichophytosis and food toxicoinfection. One of the most common diseases in clinical practice was infectious hepatitis, which became the object of our research. The study of various aspects of the liver function pathology in diseases of viral etiology is especially relevant because of the exclusive compensatory potentials of this organ, their clinical manifestation is often found in the stage of severe morphofunctional violations, often not subject to reverse development. The purpose of our work was to study the influence Adenovirus саnіnе – a pathogen of dogs’ infectious hepatitis, on the functional state of the liver, to find out the effectiveness of the drug hepato-lik in the complex intensive care of sick dogs. The subject of the study were patients with infectious dogs’ hepatitis. The main diagnostic criterion was the use of express texts, which confirmed the previous diagnosis – infectious dogs’ hepatitis. For the study of the effectiveness of the used treatment of infectious hepatitis, an experimental animal was developed on the organism of the dogs – from 10 patients and control – out of 10 healthy. The applied treatment for infectious dogs’ hepatitis was comprehensive, and included silence, calmness and diet therapy. In order to restore the functional status of the dogs’ liver with hepatitis, the treatment regimen included 5% glucose solution with 5% solution of ascorbic acid in a dose, 40% solution of glutargin and 2% solution of riboxin for 5–10 days. Assigned vitamin preparation hepavicle and used symptomatic therapy. For the normalization of the function and regeneration of the liver after the action of adenovirus, as well as to reduce the negative effects of drugs having hepatotoxic action used hepato-lik. In order to assess the efficacy of the treatment, animals were examined clinically and blood samples were taken for the conduct of studies on the 10th and 30th day of treatment. The scheme of treatment for infectious dogs’ hepatitis using hepatoprotector hepatolique has been used to improve the functional state of the liver, which was manifested in the restoration of the white-oxidative, pigmentary, anti-toxic function, improvement of detoxification function, the suppression of liver inflammation, and also contributed to the preservation and restoration of the structure of hepatocytes, normalization of ammonia levels in the dog's organism, accelerated the regeneration of the liver cells, and had little positive effect on erythrocytopoies and on the general condition of the orgnism in general.