Dataset Information

Fatigue and Pruritus in Patients with Advanced Fibrosis Due to Nonalcoholic Steatohepatitis: The Impact on Patient-Reported Outcomes.

ABSTRACT: Fatigue and pruritus are common in patients with chronic liver diseases of all etiologies, but clinical awareness is mostly restricted to those with cholestatic liver diseases. We assessed the impact of fatigue and pruritus on patient-reported outcomes (PROs) of patients with advanced nonalcoholic steatohepatitis (NASH). Specifically, PROs (Short Form-36, Chronic Liver Disease Questionnaire-NASH, Euro-Qol 5 Dimension, and Work Productivity and Activity Impairment instruments) were assessed at baseline in patients with histologically confirmed bridging fibrosis (F3) or compensated cirrhosis (F4) due to NASH enrolled in STELLAR 3 and 4. Presence of fatigue and pruritus were indicated by a score of 4 or less on the respective items of the Chronic Liver Disease Questionnaire-NASH (scale range, 1-7). Among the included 1,669 patients with advanced NASH (mean age = 58 ± 9 years, 48% F3, 42% with psychiatric comorbidities), 33% and 27% had fatigue and pruritus, respectively. Patients with NASH with fatigue were younger, more likely to be female, cirrhotic, and diabetic, and had higher body mass index and more comorbidities (all P < 0.05). All PRO scores of patients with fatigue were significantly impaired (mean up to -31% of a PRO range size in comparison to patients without fatigue). In multivariate analysis, predictors of fatigue included diabetes, history of depression or nervous system comorbidities, and lower serum albumin (P < 0.05). Patients with pruritus had demographic characteristics similar to those with fatigue, but a higher prevalence of dermatologic comorbidities. All PROs were impaired (by up to -19% of a range size, all P < 0.01) in patients with NASH with pruritus. Female gender, lower serum albumin, and a history of depression, nervous system, and dermatologic comorbidities were associated with increased risk of pruritus (P < 0.05). Conclusion: Clinically significant fatigue and pruritus are common in patients with advanced NASH, and these symptoms negatively affect PROs.

SUBMITTER: Younossi ZM

PROVIDER: S-EPMC7603531 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Fatigue and Pruritus in Patients with Advanced Fibrosis Due to Nonalcoholic Steatohepatitis: The Impact on Patient-Reported Outcomes.

Younossi Zobair M ZM Wong Vincent Wai-Sun VW Anstee Quentin M QM Romero-Gomez Manuel M Trauner Michael H MH Harrison Stephen A SA Lawitz Eric J EJ Okanoue Takeshi T Camargo Marianne M Kersey Kathryn K Myers Robert P RP Goodman Zachary Z Stepanova Maria M

Hepatology communications 20200828 11

Fatigue and pruritus are common in patients with chronic liver diseases of all etiologies, but clinical awareness is mostly restricted to those with cholestatic liver diseases. We assessed the impact of fatigue and pruritus on patient-reported outcomes (PROs) of patients with advanced nonalcoholic steatohepatitis (NASH). Specifically, PROs (Short Form-36, Chronic Liver Disease Questionnaire-NASH, Euro-Qol 5 Dimension, and Work Productivity and Activity Impairment instruments) were assessed at ba ...[more]

PMID: 33163834

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Project description:Patient-reported outcomes (PROs) are important endpoints for clinical trials. The impact of investigational drugs on PROs of patients with advanced nonalcoholic steatohepatitis (NASH) was investigated. Patients with NASH with bridging fibrosis or compensated cirrhosis were enrolled in a phase 2, randomized, placebo-controlled study of selonsertib, firsocostat, or cilofexor, alone or in two-drug combinations (NCT03449446). PROs included Short Form 36 (SF-36), Chronic Liver Disease Questionnaire (CLDQ)-NASH, EuroQol Five Dimension (EQ-5D), Work Productivity and Impairment (WPAI), and 5-D Itch before and during treatment. A total of 392 patients with NASH (mean ± SD, 60 ± 9 years old; 35% men; 89% white; 72% diabetes; and 56% compensated cirrhosis) were included. Baseline Physical Functioning (PF) and Bodily Pain of SF-36 and Fatigue and Worry of CLDQ-NASH were significantly lower in patients with cirrhosis (total CLDQ-NASH score mean ± SD, 4.91 ± 1.06 with cirrhosis vs. 5.16 ± 1.14 without cirrhosis; P < 0.05). Lower baseline PRO scores were independently associated with age, female sex, greater body mass index, diabetes, clinically overt fatigue, and comorbidities (all P < 0.05). After 48 weeks of treatment, patients with ≥1-stage fibrosis improvement without worsening of NASH experienced improvement in EQ-5D and five out of six CLDQ-NASH domains (P < 0.05). Patients with ≥2-point decrease in their nonalcoholic fatty liver disease activity score (NAS) also had improvements in PF and Role Physical scores and all domains of CLDQ-NASH (P < 0.05). Progression to cirrhosis was associated with a decrease in PF scores of SF-36 (P ≤ 0.05). Fibrosis regression was independently associated with greater improvements in PF and EQ-5D scores, while NAS improvement was associated with improvement in fatigue and pruritus (all P < 0.05). Conclusion: Patients with advanced NASH experienced improvement in their PROs after fibrosis regression or improvement in disease activity.

Project description:BACKGROUND AND OBJECTIVES:Among patients on hemodialysis, pruritus has been associated with poorer mental and physical quality of life, sleep quality, depression, and mortality. We evaluated patients with nondialysis CKD to describe the prevalence of pruritus, identify associated factors, and investigate associations with patient-reported outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Using cross-sectional data from patient questionnaires in the CKD Outcomes and Practice Patterns Study (CKDopps), we asked patients with CKD stages 3-5 (nondialysis) from the United States, Brazil, and France to identify how much they were bothered by pruritus. Response options ranged from "not at all" to "extremely." Log-Poisson regression, yielding prevalence ratios, was used to evaluate associations of moderate-to-extreme pruritus with patient characteristics, CKD stage, self-reported depression symptoms, and restless sleep. Mixed linear regression was used to examine associations between pruritus and physical and mental component summary scores, with lower scores indicating poorer quality of life. RESULTS:Of the 5658 CKDopps patients enrolled in the United States, Brazil, and France, 3780 (67%) answered the pruritus question. The prevalence of moderate-to-extreme pruritus was 24%, and more likely in older patients, women, and those with stage 5 CKD, lung disease, diabetes, and physician-diagnosed depression. In adjusted models, patients with moderate pruritus had physical and mental component summary scores 3.5 (95% confidence interval [95% CI], -4.6 to -2.3) and 2.3 (95% CI, -3.2 to -1.5) points lower, respectively, than patients without pruritus, and they also had a higher adjusted prevalence of patient-reported depression (prevalence ratio, 1.83; 95% CI, 1.58 to 2.11) and restless sleep (prevalence ratio, 1.69; 95% CI, 1.49 to 1.91) compared with patients without pruritus. These patient-reported outcomes were progressively worse with increasing severity of pruritus. CONCLUSIONS:Our findings demonstrate high prevalence of pruritus in nondialysis CKD, as well as strong associations of pruritus with poor health-related quality of life, self-reported depression symptoms, and self-reported poor sleep.

Project description:ImportanceNonalcoholic steatohepatitis (NASH) is projected to be the leading cause of liver transplantation by 2020. Advanced fibrosis (stage F3-F4) on liver biopsy independently predicts all-cause and liver-related mortality in NASH. There are no known efficacious treatments for advanced fibrosis related to NASH. Thiazolidinedione therapy has been extensively evaluated in NASH, and new randomized clinical trials (RCTs) of its efficacy have been completed.ObjectiveTo synthesize the evidence about the association of thiazolidinedione therapy with advanced liver fibrosis in NASH.Data sourcesMEDLINE, Ovid MEDLINE In-Process, Cochrane Library, EMBASE, clinicaltrials.gov, PubMed, and Scopus databases (without language restrictions), as well as other registries and scientific meeting presentations, from database inception through August 15, 2016.Study selectionRandomized clinical trials evaluating the effect of thiazolidinedione therapy on histologic features of the liver in biopsy-proven NASH.Data extraction and synthesisTwo investigators extracted study data independently and in duplicate and rated the risk of bias using the Cochrane Risk of Bias Tool.Main outcomes and measuresThe primary outcome was a dichotomous improvement in advanced fibrosis on liver biopsy, defined as an improvement in fibrosis stage from F3-F4 to F0-F2. Secondary outcomes were at least a 1-point improvement in fibrosis of any stage and NASH resolution. This meta-analysis also evaluated adverse effects of thiazolidinedione therapy, including weight gain, lower limb edema, congestive heart failure, bone fractures, cancer, and anemia. With the use of random-effects models, dichotomous variables are presented as odds ratios (ORs) with 95% CIs, and continuous variables are presented as weighted mean differences with 95% CIs.ResultsThis study analyzed 8 RCTs (5 evaluating pioglitazone use and 3 evaluating rosiglitazone maleate use) enrolling 516 patients with biopsy-proven NASH for a duration of 6 to 24 months. Among all studies combined, thiazolidinedione therapy was associated with improved advanced fibrosis (OR, 3.15; 95% CI, 1.25-7.93; P = .01; I2 = 0%), fibrosis of any stage (OR, 1.66; 95% CI, 1.12-2.47; P = .01; I2 = 0%), and NASH resolution (OR, 3.22; 95% CI, 2.17-4.79; P < .001; I2 = 0%). Analyses restricted to RCTs enrolling patients without diabetes yielded similar results for improvement in advanced fibrosis (OR, 2.95; 95% CI, 1.04-10.90; P = .02; I2 = 0%), improvement in fibrosis of any stage (OR, 1.76; 95% CI, 1.02-3.03; P = .02; I2 = 0%), and NASH resolution (OR, 3.40; 95% CI, 1.95-5.93; P < .001; I2 = 0%). All effects were accounted for by pioglitazone use. Weight gain and lower limb edema occurred more frequently with thiazolidinedione therapy (initial body weight +2.70%; 95% CI, 1.96%-4.34%; P = .001). The small sample size of included RCTs prevented evaluation of more serious adverse effects of thiazolidinedione therapy.Conclusions and relevancePioglitazone use improves advanced fibrosis in NASH, even in patients without diabetes. Whether this finding translates to improvement in risk for clinical outcomes requires further study.

Project description:Rationale & objectiveChronic kidney disease (CKD)-associated pruritus, generalized itching related to CKD, affects many aspects of hemodialysis patients' lives. However, information regarding the relationship between pruritus and several key outcomes in hemodialysis patients remains limited.Study designProspective cohort.Setting & participants23,264 hemodialysis patients from 21 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4 to 6 (2009-2018).ExposurePruritus severity, based on self-reported degree to which patients were bothered by itchy skin (5-category ordinal scale from "not at all" to "extremely").OutcomesClinical, dialysis-related, and patient-reported outcomes.Analytical approachCox regression for time-to-event outcomes and modified Poisson regression for binary outcomes, adjusted for potential confounders.ResultsThe proportion of patients at least moderately bothered by pruritus was 37%, and 7% were extremely bothered. Compared with the reference group ("not at all"), the adjusted mortality HR for patients extremely bothered by pruritus was 1.24 (95% CI, 1.08-1.41). Rates of cardiovascular and infection-related deaths and hospitalizations were also higher for patients extremely versus not at all bothered by pruritus (HR range, 1.17-1.44). Patients extremely bothered by pruritus were also more likely to withdraw from dialysis and miss hemodialysis sessions and were less likely to be employed. Strong monotonic associations were observed between pruritus severity and longer recovery time from a hemodialysis session, lower physical and mental quality of life, increased depressive symptoms, and poorer sleep quality.LimitationsResidual confounding, recall bias, nonresponse bias.ConclusionsOur findings demonstrate how diverse and far-reaching poor outcomes are for patients who experience CKD-associated pruritus, specifically those with more severe pruritus. There is need for change in practice patterns internationally to effectively identify and treat patients with pruritus to reduce symptom burden and improve quality of life and possibly even survival.

Project description:UnlabelledThe characteristics of nonalcoholic fatty liver disease (NAFLD) in elderly patients are unknown. Therefore, we aimed to examine the differences between elderly and nonelderly patients with NAFLD and to identify determinants of nonalcoholic steatohepatitis (NASH) and advanced fibrosis (bridging fibrosis or cirrhosis) in elderly patients. This is a cross-sectional analysis of adult participants who were prospectively enrolled in the NASH Clinical Research Network studies. Participants were included based on availability of the centrally reviewed liver histology data within 1 year of enrollment, resulting in 61 elderly (age ≥65 years) and 735 nonelderly (18-64 years) participants. The main outcomes were the presence of NASH and advanced fibrosis. Compared to nonelderly patients with NAFLD, elderly patients had a higher prevalence of NASH (56% versus 72%, P = 0.02), and advanced fibrosis (25% versus 44%, P = 0.002). Compared to nonelderly patients with NASH, elderly patients with NASH had higher rates of advanced fibrosis (35% versus 52%, P = 0.03), as well as other features of severe liver disease including the presence of ballooning degeneration, acidophil bodies, megamitochondria, and Mallory-Denk bodies (P ≤ 0.05 for each). In multiple logistic regression analyses, independent determinants of NASH in elderly patients included higher aspartate aminotransferase (AST) (odds ratio [OR] = 1.12, P = 0.007) and lower platelets (OR = 0.98, P = 0.02); and independent determinants of advanced fibrosis included higher AST (OR = 1.08, P = 0.007), lower alanine aminotransferase value (OR = 0.91, P = 0.002), and an increased odds of having low high-density lipoprotein (OR = 8.35, P = 0.02).ConclusionElderly patients are more likely to have NASH and advanced fibrosis than nonelderly patients with NAFLD. Liver biopsy may be considered in elderly patients and treatment should be initiated in those with NASH and advanced fibrosis.

Dataset Information

Fatigue and Pruritus in Patients with Advanced Fibrosis Due to Nonalcoholic Steatohepatitis: The Impact on Patient-Reported Outcomes.

Publications

Fatigue and Pruritus in Patients with Advanced Fibrosis Due to Nonalcoholic Steatohepatitis: The Impact on Patient-Reported Outcomes.

Similar Datasets

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