Iliana Mani

Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators have been reported to improve lung function and reduce CF exacerbations. We aimed to investigate the efficacy of CFTR-modulators in CF-associated liver disease (CFLD) during long-term treatment. Longitudinal data were collected from genetically confirmed adult CF patients receiving CFTR-modulators. CFLD was diagnosed using conventional criteria combined with liver stiffness measurement (LSM). A total of 57 patients [56.1% male; median age at baseline (T0), 26 years (interquartile range [IQR], 23–35)] were included. Patients received lumacaftor/ivacaftor and/or elexacaftor/tezacaftor/ivacaftor for a median of 43 months (range, 15–123) until last assessment (T2). The prevalence of CFLD decreased from 15 (26.3%) at T0 to 8 (14.0%) at T2 (p = 0.016), and no new cases of CFLD were observed. Median LSM decreased from 6.2 (IQR 4.9–8.0) to 5.0 kPa (IQR 4.1–6.2) in the overall cohort (p < 0.001) and from 10.2 (IQR 6.8–13) to 6.2 kPa (IQR 5.0–12.4) in the CFLD subgroup (p = 0.025). Mild, transient fluctuations in liver enzymes occurred in 26.3% of patients. In conclusion, adults with CF receiving long-term CFTR modulators, showed improvement of liver disease assessed by ultrasonography and transient elastography. At the last assessment, half of the patients no longer met the criteria for CFLD.

Background: Physical frailty (PF) is a syndrome of decreased physical function and reserves, preventing patients from coping with stressful events. PF screening tools in patients with liver cirrhosis (LC) can help evaluate the risk of complications and death. The aim of this study was to assess the performance of five screening tools in detecting PF and their ability to predict 18-month mortality in LC. Methods: The Short Physical Performance Battery (SPPB), Fried frailty phenotype (FFP), Clinical Frailty Scale (CFS) and 6-Minute Walk Test (6MWT) were compared with the Liver Frailty Index (LFI) as the method of reference. Patients with an LFI ≥ 4.5, SPPB ≤ 8, FFP ≥ 3, CFS ≥ 6 points, and those walking p < 0.001 for each). Kaplan–Meier survival curves at 18 months showed higher mortality in frail patients compared to non-frail patients by any method (log rank p < 0.05). In the multivariate models, PF defined by any method emerged as an independent prognostic factor of 18-month mortality after adjustment for age, gender, and MELD-score. Conclusions: Patients characterized as frail by five screening tools were not identical. However, PF defined by either method was proven to be an independent poor prognostic factor for long-term mortality after adjustment for covariates.

The current guidelines suggest routine screening for non-alcoholic fatty liver disease (NAFLD) in patients with polycystic ovary syndrome (PCOS). Hepatokines seem to be promising surrogate endpoints for the diagnosis and severity of NAFLD. PCOS has its onset in adolescence and its metabolic sequalae begin during the same period. There are scarce data on the hepatokine profile of adolescent PCOS patients. This case–control study examined the serum profile of the hepatokines sex hormone-binding globulin (SHBG), selenoprotein P, fibroblast growth factor 21 (FGF21), and fetuin A in a sample of adolescent PCOS patients, and their association to metabolic and hormonal parameters. The selenoprotein P and SHBG serum concentrations were significantly decreased in PCOS patients vs. the controls (median (IQR), 2.47 (0.40) vs. 2.66 (0.36) μg/mL, p = 0.025; mean ± SD, 41.71 ± 19.41 vs. 54.94 ± 22.12 nmol/L, p = 0.011, respectively), whereas selenoprotein P was significantly and positively associated with testosterone (r = 0.325, p = 0.007) and the free androgen index (r = 0.361, p = 0.002). The SHBG demonstrated multiple significant negative correlations with adverse metabolic parameters. Among the PCOS patients, the FGF21 concentrations were significantly higher in those with NAFLD, whereas a 1 pg/mL increase in the FGF21 concentration increased the odds of NAFLD diagnosis by liver ultrasound by 1%, suggesting FGF21 as a potential biomarker for hepatic disease in females with PCOS in adolescence. Fetuin A was the least differentiated hepatokine between the PCOS patients and controls with the least associations with metabolic and hormonal parameters.

Background/Aims: Myosteatosis implies impaired muscle quality. The aim of the study was to investigate the association of myosteatosis with other muscle abnormalities and its role in the prognosis of liver cirrhosis (LC). Method: Skeletal muscle index (SMI) and myosteatosis were measured by computed tomography. Myosteatosis was defined as muscle radiodensity and evaluated according to dry body mass index (BMI). Median values and interquartile range were used for continuous and count (percentage) for categorical variables. Results: A total of 197 consecutive patients were included (age 61 (IQR 52–68); 67% male; MELD score 11 (interquartile range 7.5–16)). Myosteatosis was identified in 73.6% and sarcopenia in 44.6% of patients. Myosteatosis was positively associated with age (p = 0.024) and Child–Pugh (p = 0.017) and inversely associated with SMI (p = 0.026). Patients with myosteatosis exhibited lower 360-day survival (log-rank p = 0.001) compared to those without it. MELD (p < 0.001) and myosteatosis (p = 0.048) emerged as negative prognostic factors of survival in multivariate model. Individuals combining low muscle strength and impaired muscle quality and quantity displayed more advanced LC, impaired muscle performance, lower BMI (p < 0.001 each) and a three times higher mortality rate compared to those with low muscle quality alone. Conclusions: The presence of myosteatosis was associated with advanced age, low skeletal mass and more severe LC. Myosteatosis was associated with poor prognosis and may represent a prodromal phase of muscle degeneration before the development of sarcopenia.

The aim of this case–control study was to assess the burden of non-alcoholic fatty liver disease (NAFLD) in adolescents with polycystic ovary syndrome (PCOS) and its associations with insulin resistance, hyperandrogenism, and other metabolic characteristics of the syndrome. A total of 87 Caucasian adolescent girls (47 with PCOS and 40 controls), aged 12.3–20.4 years, underwent blood sampling for glucose metabolism, hormonal and lipid profile, gynecological and liver ultrasound, and liver elastography. Indices of insulin resistance, liver steatosis, and liver fibrosis were calculated. NAFLD diagnosed by ultrasound was more prevalent in adolescents with PCOS than controls (22.7% vs. 6.1%, p = 0.046), and was also verified by liver steatosis indices. The latter was not apparent for hepatic fibrosis, as assessed by Fibroscan^® and calculated indices. The homeostatic model assessment for insulin resistance (HOMA-IR) was found to predict NAFLD diagnosis by the liver fat score (LFS) index (β = 0.709, p = 0.002). Adolescents with PCOS and high free androgen index (FAI) presented worse NAFLD than those adolescents with PCOS and lower FAI. In addition, adolescents with PCOS and concurrent NAFLD had worse insulin sensitivity indices (HOMA-IR, QUICKI, and glucose to insulin ratio) than adolescents with PCOS alone. Adolescent insulin resistance could be considered a confounder of the association between PCOS and NAFLD.

Background Spontaneous bacterial peritonitis (SBP) is associated with a high mortality. The aim was to investigate whether bacterial deoxyribonucleic acid (bactDNA) could offer an accurate identification of pathogens and to explore its prognostic role during and early after an SBP episode. Methods Consecutive patients with SBP (SBP-group) and patients with decompensated cirrhosis without SBP/bacterascites (control-group) were enrolled. Standard culture methodology was used to isolate and identify pathogens from blood and ascitic fluid (AF). The SeptiFast test was used to identify bactDNA directly from AF. Results Fifty-five patients, median age 60 (interquartile range [IQR] 53-74), model-for-end-stage liver disease (MELD) score 18 (IQR 13-29), with SBP were prospectively included. AF cultures were positive in 52.7% (17.2% drug-resistant bacteria) and bactDNA in 29.1% (58.2% combined sensitivity). BactDNA results were 84.6% concordant with AF cultures. Three patients had positive bactDNA in the culture-negative SBP-group. BactDNA was negative in all 36 of the control group (100% specificity). In multivariate analysis for 7-day survival, factors adversely affecting outcome were MELD (P=0.049) and C-reactive protein (P=0.012). After patients who died during the first week post-admission were excluded, patients with positive bactDNA had a poor prognosis compared to those with a negative test (log-rank P=0.005). Variables independently associated with 30-day mortality were neutrophil-to-lymphocyte ratio (P=0.011) and positive bactDNA (P=0.020). Conclusions No evidence was found for the usefulness of bactDNA to improve bacterial identification during an SBP episode. However, bactDNA was a predictor of 30-day mortality in the subset of patients who recovered from the infection episode.

COVID-19 pandemic has resulted in a growing number of beds in common hospital wards and intensive care units being occupied by COVID-19 patients and the majority of medical and nursing staff being dedicated to their care. The present review summarizes the impact of COVID-19 on patients with underlying chronic liver diseases (CLD). Deferrals of all non-urgent activities in healthcare facilities, including a decrease in liver-clinic visits for patients with CLD, inadequate hepatocellular carcinoma (HCC) surveillance, and postponement of liver transplant activities are the most important consequences. Delays in viral hepatitis elimination programs were also reported, leading to future development of advanced CLD and HCC. Patients with chronic hepatitis B (CHB) and C without cirrhosis are not at risk for a more severe COVID-19 infection course. However, CHB status must be known in patients who are going to receive immunosuppression for preventing disease flare. In addition, checking for drug-drug interactions and potential hepatotoxicity reactions from agents administered to treat both SARS-CoV-2 and CLD arc required. Patients with nonalcoholic fatty liver disease appeared to be at a high risk for severe COVID-19, even after adjustment for comorbidities. Patients with cirrhosis may develop decompensation, acute-on-chronic liver failure, or severe COVID-19. The mortality rate is worse in patients with high model for end-stage liver disease score, regardless of the etiology of cirrhosis.