NASH—A Global Problem in Need of Better Diagnostic Tests and Treatments

Liver biopsy is the only diagnostic procedure that can reliably assess the presence of nonalcoholic steatohepatitis (NASH) and early fibrosis, but efforts are being made to develop noninvasive testing for a disease that is becoming an increasing clinical and economic burden, researchers reported in Gut.

“Today, the lack of awareness of nonalcoholic fatty liver disease (NAFLD) by the clinical community has contributed to a lack of NASH-specific drugs and reliable biomarkers,” noted the authors of the report.¹

NAFLD includes nonalcoholic fatty liver (NAFL, or simple steatosis) and NASH. NASH is characterized by steatosis, hepatocyte damage, lobular inflammation, and fibrosis with a centrilobular (zone 3) pattern of injury in adults. In younger children, portal predominance of the characteristic lesions or mixed forms is more frequent than the zone 3 pattern. NAFLD affects 10%-24% of the worldwide population and is the most common cause of chronic liver disease.²

The lack of a predictable correlation between abnormal standard liver tests and the severity of histologic lesions has contributed to the under-recognition of NASH, according to the researchers.

Noninvasive tests (NITs) have emerged for evaluating liver fibrosis in patients with NAFLD, including elastography devices and blood tests. However, a diagnosis of NASH is still based on liver biopsy, an invasive procedure that is not appropriate for the large number of patients with NAFLD.

Other fibrosis tests, including fibrosis-4 (FIB-4) index, fibrotest/fibrosure, enhanced liver fibrosis test, and liver stiffness measurement by vibration-controlled transient elastography, are now used in clinical practice. A combination of NITs has improved the noninvasive diagnosis of advanced fibrosis, allowing for a better transition between primary care or diabetologists and liver specialists. Other NITs, such as the multiparametric NIS4 test, have not yet achieved acceptable accuracy and validation for the noninvasive diagnosis of NASH.

Pathologic diagnosis will soon be supported by artificial intelligence, and advances in microscopy techniques may improve liver biopsy assessment, according to the authors. Obeticholic acid may become an approved treatment based on favorable results of an interim analysis of a phase 3 trial.

“Given the rapidly growing global burden of NAFLD/NASH, efforts to discover accurate, noninvasive diagnostic and prognostic biomarkers, to develop effective treatments for individuals with advanced NASH, and to implement preventive methods must continue,” stated the researchers.

Disclosures: Some of the authors reported affiliations with pharmaceutical companies. Please see the original reference for a full list of disclosures.

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References

1. Geier A, Tiniakos D, Denk H, Trauner M. From the origin of NASH to the future of metabolic fatty liver disease. Gut. Published online February 25, 2021. doi: 10.1136/gutjnl-2020-323202

2. Younossi ZM. Non-alcoholic fatty liver disease—a global public health perspective. J Hepatol. 2019;70(3):531-544.