Pickle Juice Intervention for Cirrhotic Cramps Reduction: The PICCLES Randomized Controlled Trial.

INTRODUCTION: Muscle cramps are common among persons with cirrhosis and associated with poor health-related quality of life. Treatment options are limited. We sought to determine whether pickle juice can improve muscle cramp severity. METHODS: We enrolled 82 patients with cirrhosis and a history of >4 muscle cramps in the previous month from December 2020 to December 2021. Patients were randomized 1:1 to sips of pickle juice vs tap water at cramp onset. Our primary outcome assessed at 28 days was the change in cramp severity measured by the visual analog scale for cramps (VAS-cramps, scaled 0-10). Cramps were assessed 10 times over 28 days using interactive text messages. Secondary outcomes included the proportion of days with VAS-cramps <5, change in sleep quality, and global health-related quality of life measured using the EQ-5D. RESULTS: Overall, 74 patients completed the trial, aged 56.6 ± 11.5 years, 54% male, 41% with ascites, 38% with encephalopathy, and model for end-stage liver disease-sodium score 11.2 ± 4.9. Many patients were receiving other cramp therapies at baseline. The baseline VAS for cramps was 4.2 ± 3.4, the EQ-5D was 0.80 ± 0.10, and 43% rated sleep as poor. At trial completion, the respective values for the pickle juice and control arms were -2.25 ± 3.61 points on the VAS for cramps, compared with control tap water (-0.36 ± 2.87), P = 0.03; a proportion of cramp-days with VAS-cramps <5 were 46% vs 35% (P = 0.2); and the change in sleep quality was not different (P = 0.1). The end-of-trial EQ-5D was 0.78 ± 0.10 vs 0.80 ± 0.10 (P = 0.3). No differences in weight change were observed for those with and without ascites. DISCUSSION: In a randomized trial, sips of pickle brine consumed at cramp onset improve cramp severity without adverse events.

Identifying Patients With Hepatic Encephalopathy Using Administrative Data in the ICD-10 Era.

Hepatic encephalopathy (HE) is a common complication of cirrhosis resulting in relapsing-remitting mental status changes ranging from deficits in executive function to coma. Incident HE is associated with an abrupt increase in mortality1 and frequent hospitalization.2 To further the understanding of the burden and impact of HE at the population level, valid algorithms are required to identify patients in administrative data. An International Classification of Diseases (ICD)-9 code is specific for HE (572.2), offering a 0.92 positive predictive value (PPV) and 0.36 negative predictive value (NPV).3 When applied in an algorithm to patients with ICD-9 codes for cirrhosis (eg, 571.5), Kanwal et al4 found a PPV and NPV of 0.86 and 0.87. Unfortunately, the switch to ICD-10 in 2015 rendered algorithms validated using ICD-9 invalid. Kaplan et al5 previously showed that lactulose and rifaximin use correlated with grade of HE for Child classification. Herein, we validate a diagnostic coding algorithm for HE using ICD-10 and medication records.

Incidence and Bedside Predictors of the First Episode of Overt Hepatic Encephalopathy in Patients With Cirrhosis.

INTRODUCTION: Hepatic encephalopathy (HE) is associated with marked increases in morbidity and mortality for patients with cirrhosis. We aimed to determine the risk of and predictors for HE in contemporary patients. METHODS: We prospectively enrolled 294 subjects with Child A-B (70% Child A) cirrhosis and portal hypertension without previous HE from July 2016 to August 2018. The primary outcome was the development of overt HE (grade >2). We assessed the predictive power of model for end-stage liver disease-sodium (MELD-Na) score, the Inhibitory Control Test, the Sickness Impact Profile score, and the Bilirubin-Albumin-Beta-Blocker-Statin score. We also derived a novel predictive model incorporating MELD-Na score, impact of cirrhosis on daily activity (Likert 1-9), frailty (chair-stands per 30 seconds), and health-related quality of life (Short-Form 8, 0-100). RESULTS: The cohort's median age was 60 years, 56% were men, and the median MELD-Na score was 9. During a follow-up of 548 ± 281 days, 62 (21%) had incident overt HE with 1-year probability of 14% ± 2%, 10% ± 2%, and 25% ± 5% for Child A and B. The best model for predicting the risk of overt HE included MELD-Na, Short-Form 8, impact on activity rating, and chair-stands within 30 seconds. This model-MELDNa-Actvity-Chairstands-Quality of Life Hepatic Encephalopathy Score-offered an area under the receiver operating curve (AUROC) for HE development at 12 months of 0.82 compared with 0.55, 0.61, 0.70, and 0.72 for the Inhibitory Control Test, Sickness Impact Profile, Bilirubin-Albumin-Beta-Blocker-Statin, and MELD-Na, respectively. The AUROC for HE-related hospitalization was 0.92. DISCUSSION: This study provides the incidence of HE in a well-characterized cohort of contemporary patients. Bedside measures such as activity, quality of life, and physical function accurately stratified the patient's risk for overt HE.

Comprehensive Health-State Utilities in Contemporary Patients With Cirrhosis.

Cost-effectiveness analysis depends on generalizable health-state utilities. Unfortunately, the available utilities for cirrhosis are dated, may not reflect contemporary patients, and do not capture the impact of cirrhosis symptoms. We aimed to determine health-state utilities for cirrhosis, using both the standard gamble (SG) and visual analog scale (VAS). We prospectively enrolled 305 patients. Disease severity (Child-Pugh [Child] class, Model for End-Stage Liver Disease with sodium [MELD-Na] scores), symptom burden (sleep quality, cramps, falls, pruritus), and disability (activities of daily living) were assessed. Multivariable models were constructed to determine independent clinical associations with utility values. The mean age was 57 ± 13 years, 54% were men, 30% had nonalcoholic steatohepatitis, 26% had alcohol-related cirrhosis, 49% were Child class A, and the median MELD-Na score was 12 (interquartile range [IQR], 8-18). VAS displayed a normal distribution with a wider range than SG. The Child-specific SG-derived utilities had a median value of 0.85 (IQR, 0.68-0.98) for Child A, 0.78 (IQR, 0.58-0.93) for Child B, and 0.78 (IQR, 0.58-0.93) for Child C. VAS-derived utilities had a median value of 0.70 (IQR, 0.60-0.85) for Child A, 0.61 (IQR, 0.50-0.75) for Child B, and 0.55 (IQR, 0.40-0.70) for Child C. VAS and SG were weakly correlated (Spearman's rank correlation coefficient, 0.12; 95% confidence interval, 0.006-0.23). In multivariable models, disability, muscle cramps, and MELD-Na were significantly associated with SG utilities. More clinical covariates were significantly associated with the VAS utilities, including poor sleep, MELD-Na, disability, falls, cramps, and ascites. Conclusion: We provide health-state utilities for contemporary patients with cirrhosis as well as estimates of the independent impact of specific symptoms on each patient's reported utility.

Medically tailored meals for the management of symptomatic ascites: the SALTYFOOD pilot randomized clinical trial.

BACKGROUND: Ascites is a costly, morbid complication of cirrhosis. Although a low-sodium diet is central to the clinical management of ascites, its efficacy is limited by poor adherence. We aimed to determine the feasibility and impact of low-sodium medically tailored meals (MTM) intervention. METHODS: We enrolled 40 persons with cirrhosis and ascites at the time of a paracentesis in a 12-week, 1:1 randomized trial of standard of care (SOC) (low-sodium diet educational handout) or MTM with <2,000 mg of sodium, >2,100 kcal, and >80 g of protein including a nocturnal protein supplement. We determined the proportion of eligible candidates recruited and adherence to MTM. The primary outcome was the number of paracenteses performed during weeks 0-12. We also collected ascites-specific quality-of-life (ASI-7) scores. RESULTS: The median age of the enrolled subjects was 54 (IQR, 47-63) years, 46% were female, with median MELD-Na 18 (IQR, 11-23) and albumin 2.7 (IQR, 2.5-3.3) g/dL. At baseline, subjects reported a median of two (IQR, 1-3) paracenteses in the prior 4 weeks. Adherence to the meal schedule was excellent save for when hospitalizations occurred. After 12 weeks, patients in the MTM arm required fewer paracenteses per week than those in the SOC group [median (IQR): 0.34 (0.14-0.54) vs 0.45 (0.25-0.64)]. During the trial, four (20%) SOC patients died, whereas two (10%) died and one (5%) was transplanted in the MTM arm. Ascites-specific quality of life improved to a greater degree in the MTM arm compared to the SOC arm, by 25% (IQR, -11% to 61%) vs 13% (IQR, -28% to 54%). CONCLUSION: A trial of MTM for persons with ascites is feasible and potentially effective. Both arms experienced benefits, highlighting the role for improved education and closer monitoring in this challenging condition.

Do Nutritional Interventions Improve the Outcomes of Patients with Cirrhosis and Ascites: A Systematic Review of Randomized Trials.

PURPOSE OF REVIEW: Ascites is a common, morbid complication of cirrhosis. Nutritional interventions such as sodium-restriction and high-protein diet are considered standard of care. However, their evidence base is limited. We performed a systematic review of randomized trials of nutritional interventions for ascites. RECENT FINDINGS: Increasing consumption of calories and protein alone was ineffective. Studies reached contradictory conclusions regarding sodium restriction in patients taking combination diuretics. Intravenous amino acid infusion alone did not improve outcomes, peripheral parenteral nutrition did not improve outcomes except alone but reduced mortality in conjunction with branched-chain amino acid evening snack. SUMMARY: Patients may benefit from sodium restriction and a protein-rich evening snack. Future trials should prioritize standardizing nutritional targets and tailoring interventions to the specific needs of patients including the socioeconomic factors impacting adherence.

Bedside Measures of Frailty and Cognitive Function Correlate with Sarcopenia in Patients with Cirrhosis.

BACKGROUND: Frailty and sarcopenia are associated with mortality and poor outcomes among patients with cirrhosis. Frailty is multifactorial but due in part to sarcopenia and cognitive dysfunction. Data are limited regarding the correlation of bedside frailty and cognitive function measures with sarcopenia. AIMS: To evaluate the correlations between frailty measures and muscle indices from computed tomography (CT). METHODS: We prospectively enrolled 106 patients with clinically compensated cirrhosis (and no prior hepatic encephalopathy). All patients underwent CT scan and cognitive testing (via inhibitory control test, ICT), and were subject to hand grip, 30-s chair stands, mid-arm muscle area (MAMA), and a four-question algorithm based on the Sickness Impact Profile (SIP) predictive of minimal HE. We evaluated Spearman correlations between all measures as well as the sensitivity and specificity of each measure for falls. RESULTS: In total, 106 (35.3%) patients (55 men) had CT scans to measure skeletal muscle area and quality. Hand grip correlated strongly with skeletal muscle area (correlation coefficient 0.64, p < 0.001) and mildly with ICT performance (0.34, p = 0.002). However, for women, the strongest correlation with hand grip was ICT performance (0.60, p < 0.001). Chair stand performance correlated best with SIP (correlation coefficient - 0.35, p < 0.001). MAMA was not correlated with CT-based muscle indices among women but was for men. Poor chair stand performance (< 10/30-s) had a sensitivity/specificity for falls of 73%/54%; low muscle radiation attenuation (density) was 40%/80% sensitive/specific. CONCLUSION: Bedside measures of physical function, muscle bulk, and cognitive performance are correlated with CT-based muscle measures. Bedside measures of frailty may provide an advantage over sarcopenia for outcome assessment that should be confirmed prospectively.

Design and rationale of a randomized-controlled trial of home-delivered meals for the management of symptomatic ascites: the SALTYFOOD trial.

Background: When patients with cirrhosis develop ascites, it is associated with sharply increased mortality and healthcare utilization with decreased quality of life. Dietary salt restriction is first-line therapy for ascites but it is limited by poor adherence. Methods: We will recruit 40 patients with cirrhosis and ascites who have received a recent paracentesis or hospitalization for a 1:1 randomized trial of standard care (education on salt restriction) versus home-delivered meals. Our primary outcome is the number of paracenteses needed over 12 weeks. Secondary outcomes include hospital-bed days, health-related quality of life (HRQOL, Ascites Symptom Inventory-7 and Visual Analogue Scale) and performance on batteries of physical function including hand grip (kg) and walk speed (m/s). All subjects follow up through a series of calls where any paracenteses, hospital readmissions, weight changes and diuretic dosage changes are recorded. In a final Week 12 visit, knowledge of dietary sodium intake, quality of life and frailty are reassessed, and satisfaction with the meal-delivery program is evaluated. Paired comparison testing will be conducted between the two arms. Discussion: A nutritionally standardized meal-delivery program for patients with cirrhosis and ascites post discharge has a variety of potential patient-based benefits, including the effective management of ascites, reduction of healthcare utilization and improvement of HRQOL. We have three core hypotheses. First, patients will report interest in and satisfaction with a home-delivered meals program. Second, subjects on a salt-restricted (2 g sodium) meal-delivery program will have fewer therapeutic paracenteses and all-cause readmissions than subjects receiving standard of care. Third, subjects on a salt-restricted (2 g sodium) meal-delivery program will report increased HRQOL compared to subjects receiving standard of care.

Contemporary Epidemiology of Cirrhosis.

PURPOSE OF REVIEW: We sought to review the contemporary epidemiology of cirrhosis, focusing on the relative burden of the most common chronic liver diseases. RECENT FINDINGS: The key findings in the review highlight the increasing prevalence and impact of alcohol-related liver disease, particularly among young people, and the epidemic of nonalcoholic fatty liver commensurate with rising rates of obesity. We also contrast recent advances in the care of persons with hepatitis C with the lamentable rise in new infections associated with intravenous drug use. Finally, we highlight the impact of both conventional complications of cirrhosis (namely hepatic encephalopathy) but also the host of patient-reported outcomes adversely impacted by the symptoms of cirrhosis. Cirrhosis is associated with an expanding footprint in contemporary public health. In order to improve global outcomes, we must not only focus on the identifying and treating persons with viral hepatitis but also preventing the rise of alcohol-related liver disease and nonalcoholic fatty liver disease while attending to the urgent patient-centered needs posed by the symptoms of cirrhosis.

Erratum: Design and rationale of a randomized-controlled trial of home-delivered meals for the management of symptomatic ascites: the SALTYFOOD trial.

[This corrects the article DOI: 10.1093/gastro/goz005.].

Frailty, Psychoactive Medications, and Cognitive Dysfunction Are Associated With Poor Patient-Reported Outcomes in Cirrhosis.

Cirrhosis is associated with disabling symptoms and diminished health-related quality of life (HRQOL). However, for patients with compensated disease, data are limited regarding associations with poor patient-reported outcomes (PROs). We prospectively enrolled 300 patients with cirrhosis and portal hypertension without a history of hepatic encephalopathy (HE) and reviewed medical and pharmacy records. We characterized determinants of PROs using the 8-item Short-Form Health Survey (SF-8) scale (0-100) and sleep quality using the Pittsburgh Sleep Quality Index (PSQI; poor sleep >5). Disability and frailty measures were assessed using activities of daily living (ADLs), falls, hand-grip, and chair-stands. Cognitive function was measured using weighted-lures from the Inhibitory Control Test (ICT). The median age of our cohort was 60 (interquartile range [IQR], 52-66) years, 56.3% were male, and 70% Child class A. All patients had portal hypertension, 76% had varices, and 41% had a history of ascites (predominantly well controlled). The median Model for End-Stage Liver Disease with Sodium (MELD-Na) score was 9 (IQR, 7-13). The overall median SF-8 was 70 (IQR, 54-86). Multivariate analysis showed that after adjusting for age, sex, education, and MELD-Na, performance on chair-stands (9.28 HRQOL points [95% confidence interval {CI}, 4.76-13.8] per 10-stands), ADL dependence (-6.06 [-10.8 to -1.36]), opiate use (-5.01 [-7.84 to -2.19]), benzodiazepine use (-3.50 [-6.58 to -0.42]), and ICT performance (-0.10 [-0.20 to 0.001] per weighted-lure) were significantly associated with HRQOL. Among patients completing the ICT, poor HRQOL (score <50) was significantly associated with chair-stands (odds ratio [OR] per 10-stands, 0.24; 95% CI [0.11-0.56]) and weighted lures (OR per weighted-lure, 1.01 [1.00-1.03]). Poor sleep quality was associated with opiate use (OR, 2.85 [1.11-7.29]) and lures (OR per-lure, 1.03 [1.00-1.05]). Conclusion: Disability, chair-stand performance, cognitive dysfunction, as well as psychoactive medication use are significantly associated with PROs in patients with clinically stable cirrhosis.