Research Article Details
| Article ID: | A12023 |
| PMID: | 30639779 |
| Source: | Clin Gastroenterol Hepatol |
| Title: | Validation of Chronic Liver Disease Questionnaire for Nonalcoholic Steatohepatitis in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis. |
| Abstract: | BACKGROUND & AIMS: The chronic liver disease questionnaire for nonalcoholic steatohepatitis (CLDQ-NASH) was developed in a systematic manner for assessment of patient-reported outcomes. This instrument collects data on 36 items grouped into 6 domains: abdominal symptoms, activity/energy, emotional health, fatigue, systemic symptoms, and worry. We aimed to validate the CLDQ-NASH in a large group of patients with NASH. METHODS: We collected data from patients with biopsy-proven NASH enrolled in 2 international phase 3 trials of selonsertib (NCT03053050 and NCT03053063). Our final analysis comprised 1667 patients who completed the CLDQ-NASH (age, 58 ± 9 y; 40% male; 52% with cirrhosis; and 69% with type 2 diabetes). The CLDQ-NASH was administered before treatment initiation. A standard patient-reported outcome instrument validation pipeline with internal consistency and validity assessment was applied. RESULTS: The domains of CLDQ-NASH showed good to excellent internal consistency: the Cronbach's α values were 0.80 to 0.94 and item-to-own-domain correlations were greater than 0.50 for 33 of 36 items. All items correlated to the greatest extent with their own domains (discriminant validity). Known-group validity tests indicated that the instrument consistently discriminated between patients with NASH based on the presence of cirrhosis (vs bridging fibrosis; all but 1 P value < .02), obesity (all but 1 P value < .001), psychiatric comorbidities (all P values < .0001), fatigue (all P values < .001), and type 2 diabetes (all but 1 P value < .01). Of the CLDQ-NASH domains, the highest correlated domains with the Short Form-36 were as follows: physical functioning for activity (rho = 0.70), mental health for emotional (rho = 0.72), vitality for fatigue (rho = 0.75), and body pain for systemic (rho = 0.72) (all P values < .0001). In contrast, the domains of abdominal and worry, which are disease-specific, did not correlate with the domains in the Short Form-36 (all rho ≤ 0.50). CONCLUSIONS: We validated the CLDQ-NASH by an analysis of data from 1667 patients with biopsy-proven NASH enrolled in phase 3 trials, observing excellent psychometric characteristics of the instrument. |
| DOI: | 10.1016/j.cgh.2019.01.001 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D326 | Selonsertib | Chemical drug | DB14916 | MAP3K5 inhibitor; ASK1 inhibitor | Anti-oxidative stress; Anticancer agent | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |