ABSTRACT
Introduction: Liver biopsy is the gold standard for diagnosing and staging non-alcoholic fatty liver disease (NAFLD), but liver biopsy has its limitations. Non-invasive tests (NITs) eliminate many of the drawbacks of liver biopsy. We did a retrospective observational study to validate the NAFLD Fibrosis Score (NFS score) and Fibrosis Score 4 (FIB-4 index) against the gold standard liver biopsy in a cohort of South Indian patients with NAFLD. Aims: The aim of this study was to validate the diagnostic accuracy of non-invasive fibrosis scoring systems (FIB-4 index and NFS), compared to that of liver histology, to predict AF in a cohort of south Indian patients with NAFLD. Material and methods: A retrospective observational analytical study of patients who had a liver biopsy with a diagnosis of NAFLD and had all the data for aetiology assessment and NIT calculation within 4 weeks of biopsy were included in the study. On liver biopsy, NAFLD was scored as per NIH's NASH committee grading system. NFS and FIB-4 index were calculated, and scores more than 0.676 and 2.67, respectively, were taken as the cut-off to predict advanced fibrosis (AF). The sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve for NFS score and FIB-4 score to diagnose AF were calculated. Results: A total of 147 patients were included in the study. Of these, 56 (38.1%) patients had AF (Stage 3, 4). Patients with AF were more likely to be older and have diabetes mellitus (DM). Patients with AF had lower platelet count, higher aspartate aminotransferase (AST), lower albumin, and higher AST/alanine aminotransferase ratio. An NFS of >0.676 had a sensitivity of 68% and specificity of 100%, and an FIB-4 index of >2.67 had a sensitivity of 67% and specificity of 95.6 % in diagnosing AF in our study. Conclusion: The non-invasive scoring systems NFS and FIB-4 index can be used as a bedside tool for diagnosing liver fibrosis in NAFLD allowing liver biopsy to be used in a more targeted manner for patients diagnosed with AF on NITs.
ABSTRACT
Liver transplantation (LT) is the standard of care for end-stage liver failure and hepatocellular carcinoma. Over the years, immunosuppression regimens have improved, resulting in enhanced graft and patient survival. At present, the side effects of immunosuppressive agents are a significant threat to post-LT quality of life and long-term outcome. The role of personalized immunosuppression is to reach a delicate balance between optimal immunosuppression and minimal side effects. Today, immunosuppression in LT is more of an art than a science. There are no validated markers for overimmunosuppression and underimmunosuppression, only a few drugs have therapeutic drug monitoring and immunosuppression regimens vary from center to center. The immunosuppressive agents are broadly classified into biological agents and pharmacological agents. Most regimens use multiple agents with different modes of action to reduce the dosage and minimize the toxicities. The calcineurin inhibitor (CNI)-related toxicities are reduced by antibody induction or using mTOR inhibitor/antimetabolites as CNI sparing or CNI minimization strategies. Post-liver transplant immunosuppression has an intensive phase in the first three months when alloreactivity is high, followed by a maintenance phase when immunosuppression minimization protocols are implemented. Over time some patients achieve "tolerance," defined as the successful stopping of immunosuppression with good graft function and no indication of rejection. Cell-based therapy using immune cells with tolerogenic potential is the future and may permit complete withdrawal of immunosuppressive agents.
