The influence of prehabilitation in patients with liver cirrhosis before liver transplantation: a randomized clinical trial.

BACKGROUND: The high prevalence of liver cirrhosis in Slovakia leads to a great need for transplant treatment. The outcome of liver transplantation is influenced by several factors. AIM: The main objective of this study is to test the effectiveness of prehabilitation compared to standard of care. DESIGN: Prospective, double-arm, randomized, open-registry study. SETTING: Patient in F. D. Roosevelt Teaching Hospital, Slovakia, Banská Bystrica. POPULATION: The participants consisted of patients with liver cirrhosis (55 men, 25 women). METHODS: The patients were randomized to the active prehabilitation group (N.=39) or the standard of care group (SOC) (N.=41). SOC represents the standard of care for patients prior to liver transplantation, consisting of a formal oral interview lasting 30 minutes. In addition to SOC, each patient with decompensated liver cirrhosis also underwent a prehabilitation intervention that included rehabilitation and nutrition support. Patients completed the exercises under the supervision of a physician during hospitalisation. RESULTS: After one month, the liver frailty index improved in the prehabilitation group (P=0.05). No improvement in MELD (Model of End Stage Liver Disease) was found in the group that underwent the prehabilitation program (P=0.28), and no improvement was found in the Child-Pugh score after one month (P=0.13). In the prehabilitation groups compared with the SOC group, differences were not found in the MELD score (P=0.11). Better clinical outcomes according to the Child-Pugh score was found for the prehabilitation group compared with the SOC group (P=0.02). According to LFI, there was no difference between the groups (P=0.26). Very low adherence was found after three months. Only three patients in the SOC group and six patients in the prehabilitation group came to the check-up. Due to low adherence after 3 months in patients with liver cirrhosis, it is not possible to make an adequate comparison between groups after three months. CONCLUSIONS: Despite the great effort to maintain adherence, it was not possible to draw a conclusion about the effectiveness of prehabilitation in patients before liver transplantation compared to standard of care because the main problem in Slovak patients with liver cirrhosis is low adherence. More studies are needed to identify the barriers that lead to low adherence in patients with liver cirrhosis. CLINICAL REHABILITATION IMPACT: A promising result was found due to improvement of the Liver Frailty Index and the Child-Pugh Score after one month in the prehabilitation group.

Liver injury associated with the use of selective androgen receptor modulators and post-cycle therapy: Two case reports and literature review.

BACKGROUND: Muscle growth promoters are being developed for the treatment of disease-induced loss of muscle mass. Ligandrol and ostarine are selective androgen receptor modulators (SARMs) with a non-steroidal structure and a presumably more favorable side effect profile. In recent years, these substances with or without "post-cycle therapy" (PCT) are often misused by amateur athletes aiming to promote muscle growth. At the same time, reports on their toxic effects on organ systems are emerging. CASE SUMMARY: We report two cases of liver injury in young men who used ligandrol and/or ostarine for a few weeks followed by the use of substances for PCT. Acute liver injury occurred in both cases after stopping SARMs while on PCT. The clinical picture was dominated by jaundice and fatigue. The biochemical pattern showed a mixed type of injury with normal alkaline phosphatase and high concentrations of bilirubin and serum bile acids. Histological evidence showed predominantly cholestatic injury with canalicular bile plugs, ductopenia, and mild hepatocellular damage without significant fibrosis. The patients recovered from the condition after 3 mo. The off target effects of SARMs were likely idiosyncratic, but our report highlights the yet unrecognized effects of other toxic substances used for PCT, supra-therapeutic doses, and the complete absence of monitoring for adverse effects. CONCLUSION: Among muscle-building amateur athletes, SARMs (ligandrol or ostarine) and/or substances in PCT may cause cholestatic liver injury with prolonged recovery.

Frailty in Nonalcoholic Fatty Liver Cirrhosis: A Comparison with Alcoholic Cirrhosis, Risk Patterns, and Impact on Prognosis.

Background: Physical frailty increases susceptibility to stressors and predicts adverse outcomes of cirrhosis. Data on disease course in different etiologies are scarce, so we aimed to compare the prevalence and risk factors of frailty and its impact on prognosis in nonalcoholic fatty liver (NAFLD) and alcoholic (ALD) cirrhosis. Patients and Methods. Cirrhosis registry RH7 operates since 2014 and includes hospitalized patients with decompensated cirrhosis, pre-LT evaluation, or curable hepatocellular carcinoma (HCC). From the RH7, we identified 280 ALD and 105 NAFLD patients with at least 6 months of follow-up. Results: Patients with NAFLD compared with ALD were older and had a higher proportion of females, higher body mass index (BMI) and mid-arm circumference (MAC), lower MELD score, CRP, and lower proportion of refractory ascites. The liver frailty index did not differ, and the prevalence of HCC was higher (17.1 vs. 6.8%, p=0.002). Age, sex, serum albumin, and C-reactive protein (CRP) were independent predictors of frailty. In NAFLD, frailty was also associated with BMI and MAC and in ALD, with the MELD score. The Cox model adjusted for age, sex, MELD, CRP, HCC, and LFI showed that NAFLD patients had higher all-cause mortality (HR = 1.88 95% CI 1.32-2.67, p < 0.001) and were more sensitive to the increase in LFI (HR = 1.51, 95% CI 1.05-2.2). Conclusion: Patients with NAFLD cirrhosis had a comparable prevalence of frailty compared to ALD. Although prognostic indices showed less advanced disease, NAFLD patients were more sensitive to frailty, which reflected their higher overall disease burden and led to higher all-cause mortality.

Applicability and prognostic value of frailty assessment tools among hospitalized patients with advanced chronic liver disease.

AIM: To assess and compare the feasibility and prognostic value of various frailty assessment tools among decompensated cirrhosis inpatients. METHODS: Our prospective observational registry included consecutive patients admitted for cirrhosis between June 2017 and July 2018. Exclusion criteria were intensive-care unit admission, hepatocellular carcinoma outside of the Milan criteria, and other malignancies. Frailty at baseline was assessed with the Liver Frailty Index (LFI), Clinical Frailty Scale (CFS), Fried Frailty Score (FFS), and Short Physical Performance Battery test (SPPB). The follow-up lasted for at least 180 days. RESULTS: The study enrolled 168 patients (35.1% women, median age 57.9 years). The most frequent primary etiology was alcohol-related liver disease (78.6%). The Median Model for End-Stage Liver Disease (MELD) was 16. The 80th percentile of frailty scores was LFI>5.4, CFS>4, FFS>3, and SPPB<5, and it identified patients with higher mortality. LFI and CFS had the highest numerical prognostic value for in-hospital, and 90- and 180-day mortality. In a bivariate analysis of the risk of death or liver transplantation, the combination of MELD and LFI had the highest concordance (0.771±0.04). In a multivariate model, MELD score (HR 1.17, 95% CI 1.12-1.22), overt encephalopathy (2.39, 1.27-4.48), infection at baseline (2.32, 1.23-4.34), and numerical LFI (1.41, 1.02-1.95) were independent predictors of overall mortality. CONCLUSION: Frailty assessment using the evaluated tools is feasible among hospitalized cirrhotic patients, identifying those with worse prognosis. CFS had the highest applicability and accuracy for the initial assessment and LFI for the initial and follow-up assessments.

Adherence to Oral Nutritional Supplements After Being Discharged from the Hospital is Low but Improves Outcome in Patients with Advanced Chronic Liver Disease.

PURPOSE: Patients with advanced chronic liver disease (ACLD) often have a poor nutritional status. In the management, current guidelines recommend dietary counseling and oral nutritional supplements (ONS). Nutritional goals and adherence to ONS are difficult to achieve while studies addressing adherence are scarce. We aimed to evaluate adherence to ONS, the associated factors, and its impact on outcome among ALCD patients who are discharged from the hospital. PATIENTS AND METHODS: We identified consecutive hospitalized patients with ACLD from the cirrhosis registry and ONS prescription at discharge. Baseline demographics, anthropometrics, hand-grip strength (HGS), nutritional, and laboratory parameters were recorded. Adherence was assessed at 30, 90, and 180 days, but not in patients who did not survive or in those who underwent liver transplantation (LT) before the time-point. RESULTS: From the registry containing 1004 patients, we included 450 cases, the median age was 56.3 (IQR 47-62), 60% were males, 63.8% had alcoholic etiology, and the median model for end-stage liver disease score (MELD) was 16 (11-21). During follow-up, 13.6%, 23.6%, and 31.1% of patients have died within 30, 90, and 180 days, respectively, and 21 underwent LT. Adherence to ONS in surviving patients was observed in 46%, 26.1%, and 16.9% within 30, 90, and 180 days, respectively. Baseline refractory ascites (HR=0.43, 0.24-0.76), HGS (HR=1.03, 1.01-1.06), and mid-arm circumference (HR=0.93, 0.88-0.99) were independently associated with 30-day adherence. Among patients who survived beyond 30 days, adherents for >30 days had improved synthetic liver function, HGS, a higher probability of LT (HR=1.7, 1.03-2.8) and lower risk of death (HR=0.65, 0.45-0.89), particularly those with MELD>16 (OR=0.55, 0.36-0.85) and low HGS (OR=0.61, 0.39-0.93). CONCLUSION: In ACLD patients after discharge, adherence to ONS steeply declined and was associated with baseline refractory ascites and low muscle strength. Adherence to ONS also improved liver function, muscle strength, and survival.