A novel smartphone scleral-image based tool for assessing jaundice in decompensated cirrhosis patients

BACKGROUND AND AIM: Serum bilirubin is an established marker of liver disease. Reliable tools for non-invasive assessment of jaundice in cirrhosis patients, at risk of clinical decompensation, are highly desirable. While smartphone-based imaging has been described in neonatal jaundice, it has not been investigated in advanced cirrhosis patients. METHODS: We included 46 hospitalized patients with acute cirrhosis decompensation and jaundice. Scleral images using an Android smartphone were taken to derive "Scleral Color Values (SCV)," which were matched with same day serum bilirubin measurements. In 29 patients, repeat SCV and bilirubin measurements were performed over time. We analyzed the relationship of SCV and its dynamics with serum bilirubin, clinical scores, and patient outcomes. RESULTS: Of 46 patients, 26 (57%) had alcoholic hepatitis as the decompensation precipitant. Seven patients died during admission; a further 12 following hospital discharge. SCV had an excellent linear correlation with serum bilirubin (rho = 0.90, P < 0.001); changes in SCV and serum bilirubin across different time points, were also closely associated (rho = 0.77, P < 0.001). SCV correlated significantly with CLIF Consortium Acute Decompensation score (rho = 0.38, P < 0.001) and grade of Acute-on-Chronic Liver Failure (rho = 0.42, P = 0.039). SCV was higher in patients who died, however, not significantly (86.1 [IQR 83.0-89.7] vs 82.3 [IQR 78.5-83.3], P = 0.22). The associations of SCV with clinical parameters mirrored those of serum bilirubin. CONCLUSION: Smartphone-based assessment of jaundice shows excellent concordance with serum bilirubin and is associated with clinical parameters in acute cirrhosis decompensation. This approach offers promise for remote assessment of cirrhosis patients at-risk of decompensation, post hospital discharge

Biomarkers of extracellular matrix formation are associated with acute-on-chronic liver failure

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is characterised by organ failure(s), high short-term mortality, and, pathophysiologically, deranged inflammatory responses. The extracellular matrix (ECM) is critically involved in regulating the inflammatory response. This study aimed to determine alterations in biomarkers of ECM turnover in ACLF and their association with inflammation, organ failures, and mortality. METHODS: We studied 283 patients with cirrhosis admitted for acute decompensation (AD) with or without ACLF, 64 patients with stable cirrhosis, and 30 healthy controls. A validation cohort (25 ACLF, 9 healthy controls) was included. Plasma PRO-C3, PRO-C4, PRO-C5, PRO-C6, and PRO-C8 (i.e. collagen type III–VI and VIII formation) and C4M and C6M (i.e. collagen type IV and VI degradation) were measured. Immunohistochemistry of PRO-C6 was performed on liver biopsies (AD [n = 7], ACLF [n = 5]). A competing-risk regression analysis was performed to explore the prognostic value of biomarkers of ECM turnover with 28- and 90-day mortality. RESULTS: PRO-C3 and PRO-C6 were increased in ACLF compared to AD (p = 0.089 and p <0.001, respectively), whereas collagen degradation markers C4M and C6M were similar. Both PRO-C3 and PRO-C6 were strongly associated with liver function and inflammatory markers. Only PRO-C6 was associated with extrahepatic organ failures and 28- and 90-day mortality (hazard ratio [HR; on log-scale] 6.168, 95% CI 2.366–16.080, p <0.001, and 3.495, 95% CI 1.509–8.093, p = 0.003, respectively). These findings were consistent in the validation cohort. High PRO-C6 expression was observed in liver biopsies of patients with ACLF. CONCLUSIONS: This study shows, for the first time, evidence of severe net interstitial collagen deposition in ACLF and makes the novel observation of the association between PRO-C6 and (extrahepatic) organ failures and mortality. Further studies are needed to define the pathogenic significance of these observations. LAY SUMMARY: This study describes a disrupted turnover of collagen type III and VI in Acute-on-chronic liver failure (ACLF). Plasma biomarkers of these collagens (PRO-C3 and PRO-C6) are associated with the severity of liver dysfunction and inflammation. PRO-C6, also known as the hormone endotrophin, has also been found to be associated with multi-organ failure and prognosis in acute decompensation and ACLF