Clinical factors associated with pathological changes in the liver graft in the long-term post-transplant period

V. E. Syutkin; S. E. Voskanyan; S. V. Lishchuk; E. A. Dubova; V. S. Rudakov; A. S. Lukianchikova; E. A. Ionova; A. N. Bashkov; E. I. Matkevich

doi:10.20340/vmi-rvz.2026.1.TX.1

Clinical factors associated with pathological changes in the liver graft in the long-term post-transplant period

V. E. Syutkin, S. E. Voskanyan, S. V. Lishchuk, E. A. Dubova, V. S. Rudakov, A. S. Lukianchikova, E. A. Ionova, A. N. Bashkov, E. I. Matkevich

https://doi.org/10.20340/vmi-rvz.2026.1.TX.1

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Abstract

Background. Abandonment of protocol liver biopsies in most transplant centers allows clinically significant graft pathology — fibrosis, steatosis, chronic hepatitis, ductopenia — to remain undetected for prolonged periods, even in the absence of graft dysfunction or laboratory abnormalities, resulting in unexpected late graft failure.
Objective. To assess the prevalence of bile duct loss, graft steatosis, active hepatitis, and liver fibrosis, and to identify independent clinical and laboratory factors associated with these pathological changes in the long-term posttransplant period.
Materials and Methods. Histological findings from 168 adequate liver biopsy specimens obtained from 178 adult liver transplant recipients were retrospectively analyzed. All biopsies were performed no earlier than 12 months post-transplantation (median follow-up 57.8 [26.3; 94.9] months). Liver function test values were normalized to sex-specific upper limits of normal. Overt graft dysfunction was defined as elevation of ALT, AST, or alkaline phosphatase above 1.5× ULN. Fibrosis was assessed using METAVIR and the liver allograft fibrosis (LAF) scale, evaluating portal, sinusoidal, and centrilobular components separately. Statistical methods included Mann–Whitney U test, chi-square test, Spearman rank correlation, and multivariate logistic regression.
Results. Graft steatosis (>5% of hepatocytes) was detected in 29.2% of cases, steatohepatitis in 14.9%, active hepatitis (METAVIR A2–A3) in 10.1%, advanced fibrosis (METAVIR F3–F4) in 14.9%, and ductopenia in 16.1%. On multivariate analysis, steatosis and steatohepatitis were independently associated with elevated BMI, eGFR <45 ml/min/1.73 m², and fatty liver disease as the original indication for transplantation; steatohepatitis was additionally associated with post-transplant diabetes. Advanced portal fibrosis (LAFp) was independently associated with overt graft dysfunction, time elapsed since transplantation, and low eGFR; sinusoidal fibrosis with low eGFR alone; centrilobular fibrosis with younger donor age and cyclosporine use. Ductopenia was independently associated with autoimmune liver disease as the transplant indication and with biliary strictures.
Conclusion. Late graft disease encompasses at least two distinct pathological patterns — chronic hepatitis and graft steatotic liver disease — differing in risk factors, progression kinetics, and laboratory markers. Reduced eGFR emerges as an unexpectedly robust independent predictor of multiple histological injury patterns in adult recipients. These findings provide a rationale for reintroducing protocol biopsy in the long-term post-transplant follow-up.

Keywords

liver transplantation [D016031], graft dysfunction [D006084], fatty liver [D005234], steatohepatitis [D005234], liver fibrosis [D008103], bile ducts [D001650], biopsy [D001706], glomerular filtration rate [D051437]

About the Authors

V. E. Syutkin

Federal Medical Biophysical Center of Federal Medical Biological Agency
Russian Federation

Vladimir E. Syutkin, Dr. Sci. (Med.), Professor, Department of Surgery with courses in oncologic surgery, endoscopy, surgical pathology, clinical transplantation, and organ donation; Leading Researcher, Liver Transplantation Department, N.V. Sklifosovsky Research Institute of Emergency Care, Moscow Health Department