BOSTON — In the staging of liver fibrosis in the post-liver transplant setting, readings from noninvasive tests commonly have major discrepancies when compared with liver biopsy results, particularly in cases of severe steatosis, according to the results of a new study.
Our findings support liver biopsy as “the gold standard for confirmation of allograft fibrosis that is predicted by transient elastography and assessment of its underlying cause,” said first study author Nazire Albayrak, MD, of the Department of Pathology and Laboratory Medicine, University of California, San Francisco.
Liver fibrosis is known to be the main driver of chronic liver disease as well as a key factor influencing post-liver transplant morbidity and mortality.
While a liver biopsy is indeed considered the gold standard for diagnosing liver fibrosis, such biopsies have important drawbacks, including the involvement of invasive surgery, discomfort, the potential for complications, and the consumption of time.
To help assist in the assessment of fibrosis, noninvasive tests, including serum biomarker indices and hepatic imaging techniques, have gained interest and have been validated in the detection and monitoring of chronic liver disease.
Although these tests have been adopted for clinical use post-liver transplant, research is lacking on their reliability in this setting, the study authors noted here at the United States and Canadian Academy of Pathology 2025 Annual Meeting.
To compare the results of such tests with confirmed assessments on liver biopsy, Albayrak and colleagues evaluated results on the two most widely used noninvasive tests: FibroScan, which uses ultrasound to assess liver stiffness, and Fibrosis-4 (FIB-4), an index that calculates liver fibrosis with a score based on age, platelet count, and levels of aspartate aminotransferase and alanine aminotransferase.
They identified 108 liver transplant recipients who had received a liver biopsy between 2015 and 2024 and who had testing with FibroScan within 6 months of transplant and lab values within 1 month.
Liver biopsies with < 7 portal tracts and/or < 1 cm in total core length were excluded.
The median age of the study participants was 63 years, 54% were male, and the median graft age was 5.4 years. More than half had type 2 diabetes (60.1%) and/or obesity (58%).
The most common posttransplant major liver biopsy diagnoses included recurrent and new steatotic liver disease (45.4% and 26.8%, respectively), recurrent hepatitis C (8.3%), and organ rejection (7.4%).
All of the patients with recurrent steatotic liver disease had diabetes, while 82.7% of patients with new steatotic liver disease had diabetes and/or obesity.
The patients had a median fibrosis stage of 1, as determined by trichrome stain. A median stiffness of 8.2 kPa and a FIB-4 of 2.032 were both predictors of stage 2 fibrosis.
Importantly, for patients with no fibrosis, FibroScan and FIB-4 each overestimated the degree of fibrosis (P < .0001); FIB-4 also predicted more fibrosis than liver biopsy in stage 1 of disease (P < .0001).
Overall, major discrepancies occurred in 25% of cases, and most were associated with severe stenosis, observed on 62.5% of biopsies and imaging.
Specific over-assessments included 24% (21/88) of stage F0-2 cases that were wrongfully described as stage F3-4 on FibroScan.
Conversely, 30% (6/20) of stage F3-4 cases on liver biopsy were undercalled as stage F0-2 on FibroScan.
On FIB-4 scoring, 29.6% (26/88) that were stage F0-2 were called stage F3-4, while 45% (9/20) of patients that were stage F3-4 were undercalled as stage F0-2.
Specific examples of cases involving discrepancies included:
- A liver biopsy from a recipient showing a liver stiffness measurement of 14 kPa (stage F4, indicative of cirrhosis) was assessed as having no fibrosis according to trichrome stain and as having nodularity (nodules) with regenerative changes on reticulin stain.
- A trichrome-stained section from a recipient with a liver stiffness measurement of 7.4 kPa (stage F1, indicative of mild scarring) showed nodular architecture surrounded by fibrous bands, consistent with a much more serious assessment of cirrhosis.
- A trichrome-stained wedge liver biopsy from a recipient with a liver stiffness measurement of 3.6 kPa (stage F0, no scarring) suggested bridging with nodularity to support advanced fibrosis.
The high rate of discrepancies observed in the study could have been related to the fact that a higher proportion of patients had obesity, and as many as 40% had moderate to severe steatosis, Albayrak cautioned.
“Also, one of the overcalls was due to amyloid infiltration,” she said.
The bottom-line result remains, however, that “major discrepancies in fibrosis assessment occurred in more than 50% of cases,” in the study, she concluded.
Further commenting on the issue, Nigar Anjuman Khurram, MD, of the UPMC Presbyterian Hospital in Pittsburgh, added that various other factors are known to elevate estimations of fibrosis potentially falsely on FibroScan.
“Physiological factors such as hepatic inflammation, cholestasis, and vascular congestion may [also] alter liver stiffness readings, compromising accuracy,” she told Medscape Medical News.
“Additionally, technical considerations, including probe positioning, patient cooperation, and operator proficiency, can introduce measurement variability,” she said.
Khurram presented separate research at the meeting showing that yet another factor — ferritin — may also not be as reliably predictive of liver fibrosis as expected.
“Ferritin estimation alone, in the absence of liver biopsy, remains a key parameter in guiding hemochromatosis management,” she said. However, “in our study, we observed that despite normal serum ferritin levels, some patients exhibited fibrosis progression to advanced stages, as confirmed by histological examination.”
These findings indicate that ferritin levels, “while useful clinically to guide therapy, cannot be used to replace liver biopsy as a gold standard,” said Khurram.
Albayrak and Khurram had no disclosures to report.