Lysosomal acid lipase deficiency (LAL-D) could be a cause for cryptogenic liver disease, according to a retrospective multicenter study conducted by researchers from Brazil.

“Despite being a rare disease, LAL-D investigation should be considered for individuals with chronic liver disease of unknown etiology,” the researchers wrote in an abstract published in Annals of Hepatology.

The researchers have proposed a new algorithm for the diagnosis of patients with presumed chronic cryptogenic hepatitis that includes metabolic dysfunction-associated fatty liver disease (MAFLD) and LAL-D investigation.

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By implementing the new algorithm with the study cohort, the researchers established a diagnosis for 34.9% of patients, reducing the number of undiagnosed patients by 18.3%.

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The reanalysis of clinical, laboratory, and histological data of a Brazilian cohort diagnosed with presumed chronic cryptogenic hepatitis revealed that one-third of patients had MAFLD.

Sixty (21.3%) patients were diagnosed with nonalcoholic fatty liver disease, 9 (3.2%) with alpha-1 antitrypsin deficiency, 7 (2.7%) with alcoholic liver disease, 5 (1.78%) with autoimmune hepatitis, 5 (1.78%) with hemochromatosis, 4 (1.4%) with biliary-related hepatitis, 4 (1.4%) with viral hepatitis, 4 (1.4%) with Budd Chiari, 3 (1%) with LAL-D, 3 (1%) with glycogenosis, 2 (0.7%) with drug-induced liver injury, and 1 (0.35%) with Wilson disease.

Most (n=175, 53.6%) patients remained with the diagnosis of with cryptogenic hepatitis.

Almost half (47.5%) of the patients underwent liver transplantation and were later diagnosed with nonalcoholic steatohepatitis after histopathological examination of the explanted liver.

The initial study cohort included 326 patients (mean age, 60 years, 42.9% male) with presumed chronic cryptogenic hepatitis. However, 45 patients were excluded from the analysis due to incomplete etiological investigation.

The researchers used the Czaja’s algorithm to reanalyze the data.


Lopes GCG, Rocha ACC, Mateus JN, et al. P-38 cryptogenic chronic hepatitis: looking for an etiological diagnosis. Ann Hepatol. 2023;28:100940. doi:10.1016/j.aohep.2023.100940