# Cryptogenic chronic hepatitis: looking for an ideal diagnostic algorithm

## TL;DR

This study explores better ways to diagnose cryptogenic chronic hepatitis by identifying new causes and proposing an improved diagnostic algorithm.

## Contribution

The study introduces a new diagnostic algorithm that incorporates MAFLD and LAL-D, improving diagnostic accuracy for cryptogenic liver disease.

## Key findings

- One-third of patients with cryptogenic liver disease were diagnosed with MAFLD.
- LAL-D was found in 1% of patients with chronic liver disease of unknown etiology.
- The new algorithm reduced undiagnosed cases by 11.4%.

## Abstract

Cryptogenic chronic hepatitis is a growing cause of liver transplants, affecting 5%–15% of patients with chronic liver diseases. This study aimed to identify underlying causes of cryptogenic liver disease in a Brazilian cohort and propose a new diagnostic algorithm, including investigation for metabolic-dysfunction-associated fatty liver disease (MAFLD) and lysosomal acid lipase deficiency (LAL-D).

A retrospective analysis was conducted on 326 patients with presumed cryptogenic hepatitis.

Using Czaja’s algorithm, non-alcoholic fatty liver disease was diagnosed in 21.3% of patients, while alpha-1 antitrypsin deficiency, alcoholic liver disease, autoimmune hepatitis, hemochromatosis, biliary-related hepatitis, viral hepatitis, Budd–Chiari syndrome, glycogenosis, drug-induced liver injury, and Wilson’s disease were diagnosed in smaller proportions (< 3.5% each). LAL-D was found in 1% of patients, and 53.6% of patients remained with cryptogenic hepatitis. The etiology of the liver disease in a subset of patients undergoing liver transplantation was updated post hoc based on explant histology, and non-alcoholic steatohepatitis was found in 52.5% of patients. By incorporating the concept of MAFLD, the new algorithm could diagnose 49.1% of patients, reducing the number of individuals without an etiological diagnosis by 11.4%.

One-third of patients with initially presumed cryptogenic liver disease were diagnosed with MAFLD. LAL-D should be considered in patients with chronic liver disease of unknown etiology. The updated diagnostic algorithm proposed in this study could improve diagnostic accuracy and aid in the management of patients with cryptogenic hepatitis.