Background Intestinal failure associated liver disease (IFALD) is a life-threatening complication of irreversible intestinal failure (IF). With the advent of modern management of IF, clinical manifestations of IFALD (jaundice) are not always evident, but progression of fibrosis resulting in cirrhosis can continue.1 The recognition of IFALD is important as children with progressive IFALD if identified early can have timely interventions (medical/surgical) to halt or reverse the progression of liver disease.

The conventional method of assessment of severity of liver disease is based on invasive measurements like liver biopsy (LBx) for diagnosis of fibrosis. The ideal investigation would be less invasive, can be repeated and reproducible. Indirect assessment of hepatic fibrosis with aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), AST-to-platelet ratio index (APRI) and Fib-4 score has been evaluated for other chronic liver diseases e.g.-viral hepatitis. We hypothesized that the non-invasive markers for hepatic fibrosis could be used for assessing the severity of IFALD, thus avoiding the need for LBx.

Aim To evaluate the accuracy of non-invasive tests (APRI, AAR, Fib-4) compared with LBx findings in grading severity of IFALD.

Materials and Methods Retrospective audit of 180 patients <18 years with IFALD2 and at least 1 adequate LBx from January 1993-June 2020. Fibrosis stage was assessed using the Ishak score (IS) scored as 0–6 and divided into 2 subgroups according to the histopathologic staging of hepatic fibrosis: mild (IS 1&2) vs. moderate-severe fibrosis (IS-3–6). Categorical variables were described as proportions and quantitative variables were expressed as median with interquartile range. Chi-Square test was used to compare categorical variables and Independent t-test/Mann-Whitney Test was used to find out the association between stage of fibrosis and parameters. The cut off values for APRI, AAR & Fib-4 score were established with liver biopsy as gold standard. The receiver operating curve (ROC) was used for establishing the cut off values. The level of significance was set at p<0.05.

Results Demographics are as in table-1. Age, platelet counts, bilirubin, AST, ALT, APRI and AAR were significantly different between the two groups however, multivariate analysis showed that none of the factors independently predicted the presence of moderate-severe fibrosis. As an assessment tool the APRI score seemed to be the most predictive with the area under the ROC of APRI-0.70, AAR-0.63 and Fib-4–0.58. We identified a cut-off value for APRI of 0.72 as the point with the best sensitivity (80%) and specificity (50%) to predict moderate-severe fibrosis.

The limitations of the study is that it is retrospective, management of IFALD and composition of parenteral nutrition has changed over the last 3 decades and the absence of direct markers and radiological assessment of liver fibrosis for comparison.

Conclusion Non-invasive markers can identify moderate-severe fibrosis in patients with IFALD. Amongst the various non-invasive tests available, APRI was the most predictive score in assessing the severity. It is possible that the sequential assessment of non-invasive markers may help clinicians to assess progression of liver fibrosis and therefore optimise timely medical/surgical non-transplant management and referral to transplant centre.

References

1. Khalaf RT, Sokol RJ. New insights into intestinal failure-associated liver disease in children. Hepatology 2020;71(4):1486–98.

2. Lacaille F, Gupte G, Colomb V, D’Antiga L, Hartman C, Hojsak I, Kolacek S, Puntis J, Shamir R; ESPGHAN Working Group of Intestinal Failure and Intestinal Transplantation. Intestinal failure-associated liver disease: a position paper of the ESPGHAN Working Group of Intestinal Failure and Intestinal Transplantation. J Pediatr Gastroenterol Nutr 2015 Feb;60(2):272–83.