Fat mass: a novel digital biomarker for remote monitoring that may indicate risk for malnutrition and new complications in decompensated cirrhosis.

BACKGROUND: Cirrhosis is associated with sarcopaenia and fat wasting, which drive decompensation and mortality. Currently, nutritional status, through body composition assessment, is not routinely monitored in outpatients. Given the deleterious outcomes associated with poor nutrition in decompensated cirrhosis, there is a need for remotely monitoring this to optimise community care. METHODS: A retrospective analysis was conducted on patients monitored remotely with digital sensors post hospital discharge, to assess outcomes and indicators of new cirrhosis complications. 15 patients had daily fat mass measurements as part of monitoring over a median 10 weeks, using a Withing's bioimpedance scale. The Clinical Frailty Score (CFS) was used to assess frailty and several liver disease severity scores were assessed. RESULTS: 73.3% (11/15) patients were male with a median age of 63 (52-68). There was a trend towards more severe liver disease based on CLIF-Consortium Acute Decompensation (CLIF-C AD) scores in frail patients vs. those not frail (53 vs 46, p = 0.072). When the cohort was split into patients who gained fat mass over 8 weeks vs. those that lost fat mass, the baseline CLIF-C AD scores and WBC were significantly higher in those that lost fat (58 vs 48, p = 0.048 and 11.2 × 109 vs 4.7 × 109, p = 0.031). CONCLUSIONS: This proof-of-principle study shows feasibility for remote monitoring of fat mass and nutritional reserve in decompensated cirrhosis. Our results suggest fat mass is associated with greater severity of acute decompensation and may serve as an indicator of systemic inflammatory response. Further prospective studies are required to validate this digital biomarker.

Reduced sCD36 following weight loss corresponds to improved insulin sensitivity, dyslipidemia and liver fat in obese children.

BACKGROUND/OBJECTIVES: Childhood obesity is a major health problem with serious long-term metabolic consequences. CD36 is important for the development of obesity-related complications among adults. We aimed to investigate circulating sCD36 during weight loss in childhood obesity and its associations with insulin resistance, dyslipidemia, hepatic fat accumulation and low-grade inflammation. SUBJECTS/METHODS: The impact of a 10-week weight loss camp for obese children (N=113) on plasma sCD36 and further after a 12-month follow-up (N=68) was investigated. Clinical and biochemical data were collected, and sCD36 was measured by an in-house assay. Liver fat was estimated by ultrasonography and insulin resistance by the homeostasis model assessment (HOMA-IR). RESULTS: Along with marked weight loss, sCD36 was reduced by 21% (P=0.0013) following lifestyle intervention, and individual sCD36 reductions were significantly associated with the corresponding decreases in HOMA-IR, triglycerides and total cholesterol. The largest sCD36 decrease occurred among children who reduced HOMA-IR and liver fat. After 12 months of follow-up, sCD36 was increased (P=0.014) and the metabolic improvements were largely lost. CONCLUSIONS: Weight-loss-induced sCD36 reduction, coincident with improved insulin resistance, circulating lipids and hepatic fat accumulation, proposes that sCD36 may be an early marker of long-term health risk associated with obesity-related complications.

Single-centre experience of the macrophage activation marker soluble (s)CD163 - associations with disease activity and treatment response in patients with autoimmune hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is characterised by liver inflammation with reversibility upon anti-inflammatory treatment. Soluble (s)CD163, a specific macrophage activation marker, is associated with inflammation in other liver diseases, but never investigated in AIH. AIM: To investigate sCD163 in patients with acute AIH and in complete and incomplete responders to standard anti-inflammatory pharmacotherapy, and during follow-up in treatment naive patients. METHODS: In a cross-sectional design, we studied 121 AIH patients (female/male 89/32, median age 49 years); of these, we prospectively studied 10 treatment naïve AIH patients during prednisolone treatment and tapering. Twenty patients had variant syndromes of AIH and primary biliary cholangitis or primary sclerosing cholangitis. sCD163 was compared with markers of disease activity, severity and treatment response. RESULTS: In the patients with acute AIH (n = 21), sCD163 was sixfold increased compared with the normalised levels in patients (n = 32) with complete response to standard treatment [9.5 (3.3-28.8) vs. 1.6 (0.8-3.2) mg/L, P < 0.01)], while the patients (n = 27) with incomplete response had higher sCD163 [2.2 (1.3-7.9), P < 0.05] than the complete responders. sCD163 was positively associated with ALAT, IgG and bilirubin (rho: 0.45-0.59, P < 0.001, all), and negatively to external coagulation factors (rho:-0.34, P < 0.001). In the treatment naïve patients, sCD163 fell during high-dose prednisolone treatment and tapering. Immunohistochemical staining confirmed increased CD163 expression in liver biopsies from patients with acute AIH. CONCLUSIONS: sCD163 was markedly elevated in AIH in the acute phase, normalised by successful treatment in complete responders, but remained higher in the incompletely responding cases. Our results demonstrate macrophage activation in AIH paralleling disease activity, severity and treatment response, suggesting a role for macrophage activation in AIH.

Fibrosis is not just fibrosis - basement membrane modelling and collagen metabolism differs between hepatitis B- and C-induced injury.

BACKGROUND: While morphological patterns differ, the molecular phenotype of liver fibrosis is considered a stereotypical response to chronic liver injury. However, with different cellular triggers and networks regulating fibrosis, the molecular responses of the injured liver may not be identical. AIM: To investigate whether differences in extracellular matrix (ECM) composition of the liver during fibrogenesis in two seemingly similar types of viral hepatitis could be reflected by differences in ECM turnover. METHODS: Utilising a cross-sectional design, we measured specific ECM protein fragments in plasma from 197 chronic hepatitis B (CHB) patients and 403 chronic hepatitis C (CHC) patients matched for inflammation grade and fibrosis stage. Markers of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3, P4NP7S). RESULTS: P4NP7S, C3M, C4M and C6M were significantly elevated in CHB compared to CHC. In contrast, Pro-C3 was significantly elevated in CHC compared to CHB. Pro-C3, C3M and C4M were increased in parallel with inflammation and fibrosis in both cohorts. C6M and P4NP7S were associated with inflammation and fibrosis only in CHC. Basement membrane collagen fragments P4NP7S and C4M were significantly higher in matched activity and fibrosis cohorts within CHB vs CHC. CONCLUSION: The main parameters to determine extracellular matrix biomarker levels are inflammation, fibrosis, and type of viral insult. Compared to CHC, CHB appears to induce a higher basement membrane turnover. This suggests that there are aetiology-dependent molecular signatures in liver fibrosis that could have pathogenic and diagnostic implications.

[A randomized single blind study of the efficacy of pregabalin in the treatment of opioid withdrawal syndrome]. / Randomizirovannoe kontroliruemoe issledovanie effektivnosti pregabalina v terapii sindroma otmeny opiatov.

AIM: To study the efficacy and safety of pregabalin (lyrica) in the complex treatment of opioid withdrawal syndrome (OWS). STUDY DESIGN: single-blind randomized symptom-triggered protocol with an active control. Thirty-four patients were randomly assigned to two groups. The first group (n=19) received up to 600 mg a day of pregabalin for six days along with symptomatic therapy (basic and symptom-triggered). The second group (n=15) received up to 600 micrograms of clonidine a day as the main treatment along with the same basic and symptomatic regimen. Opiate withdrawal severity, craving, sleep disturbance, anxiety and depression, as well as general clinical impressions and side-effects were assessed daily using internationally validated quantitative psychometric instruments. RESULTS: In the pregabalin group, 15 out of 19 (79%) patients completed treatment compared to 7 out of 15 (47%) patients in the clonidine group (p=0.05; Fisher exact test). There were no statistically significant differences between groups on any assessments of the severity of OWS (reduction of the severity of opiate withdrawal), perhaps because of the small sample size. In the pregabalin group, there were lower indicators of the severity of craving for opiates (p=0.05), anxiety (p=0.05) and depression (p<0.05), while patient-rated self-assessment of their general health condition was significantly better compared to the second group (p<0.05). There were no significant differences in the frequency of adverse events between the groups, though the better tolerability of treatment was noted in the pregabalin group. CONCLUSION: Treatment regimen of OWS with pregabalin is effective and safe and patients tolerate it better that leads to a higher detoxification completion rate (retention).

The macrophage activation marker sCD163 is associated with changes in NAFLD and metabolic profile during lifestyle intervention in obese children.

BACKGROUND: Obesity is associated with metabolic derangement and non-alcoholic fatty liver disease (NAFLD). Macrophages are involved in liver inflammation and fibrosis, and soluble (s)CD163 is a macrophage activation marker. OBJECTIVES: To associate sCD163 with parameters of paediatric obesity and NAFLD, as well as changes in these parameters during lifestyle intervention. METHODS: We studied 117 obese children during a 10-week lifestyle intervention; 71 completed the 12-month follow-up. We recorded clinical and biochemical data, and performed liver ultrasonography. RESULTS: Baseline sCD163 was higher in children with elevated alanine transaminase (ALT) (2.3 ± 0.7 vs. 2.0 ± 0.6 mg L(-1), P = 0.03), steatosis (2.3 ± 0.7 vs. 2.0 ± 0.6 mg L(-1), P = 0.01) and high paediatric NAFLD fibrosis index (2.3 ± 0.7 vs. 1.9 ± 0.6 mg L(-1) , P = 0.03). Baseline sCD163 was independently associated with ALT, cholesterol and high-sensitivity C-reactive protein (hs-CRP). The change in sCD163 during lifestyle intervention was associated with changes in ALT, homeostatic model assessment of insulin resistance (HOMA-IR), hs-CRP and cholesterol, and inversely associated with the change in high-density lipoprotein cholesterol. CONCLUSION: sCD163 was associated with markers of liver injury and metabolic parameters in obese children, and changes in these parameters during lifestyle intervention. This may suggest that activated macrophages play a role in NAFLD and sCD163 may serve as a marker of liver disease severity and treatment effect.