Cryptogenic hepatitis

Cryptogenic autoimmune hepatitis; unclear hepatitis; hepatitis of unknown cause;

Cryptogenic hepatitis is a form of liver inflammation of unknown origin (Herold 2025) that cannot be explained by conventional clinical, histological and laboratory tests (Czaja 2011).

Chronic hepatitis is classified according to Desmet's score into:

• Grade 1 so-called minimal hepatitis:
  • low portal inflammatory infiltration
  • no border zone hepatitis
  • no or at most minimal acinar destruction of the parenchymal cells
• Grade 2 so-called mild or low-grade hepatitis:
  • Minor focal border zone hepatitis
  • low or moderate portal inflammatory infiltrates
  • no group necrosis
  • individual parenchymal single cell necroses (Piper 2013)
• Grade 3 so-called moderate or moderately severe hepatitis:
  • moderate to severe portal signs of inflammation
  • Significant border zone hepatitis
  • no bridge or panlobular necrosis
  • numerous acinar single cell necroses
  • isolated group necroses
• Grade 4 severe or high-grade hepatitis:
  • Severe portal inflammatory infiltrations
  • Border zone hepatitis
  • Severe acinar inflammation
  • Group necrosis
  • Possible bridge and panlobular necrosis (Piper 2013)

The blood of patients suffering from cryptogenic hepatitis is considered infectious (Kramer 2001).

Cryptogenic hepatitis is found in up to 20 % of people suffering from hepatitis (Herold 2025).

The frequency of cryptogenic hepatitis is estimated to be 5.4% overall. In patients with liver cirrhosis, 5 - 30 % are diagnosed with cryptogenic cirrhosis (Czaja 2011).

The cause of the disease is unknown. Kasper (2015) classifies it in the category of viral hepatitis.

The disease is often asymptomatic in the early stages. Only when liver function is impaired do symptoms such as fatigue, general weakness, loss of appetite, weight loss, nausea and jaundice occur.

Cryptogenic hepatitis is a diagnosis of exclusion.

Detection of autoantibodies such as LP, ANA, SMA, LKM, anti-SLA antibodies (Adler 2000)

A study by Akyüz et al. (2019) showed that there are high positive rates for anti-HEV IgG and HEV RNA in patients with cryptogenic cirrhosis.

- Autoimmune hepatitis

- Steatotic liver disease of unknown cause (Adler 2000)

• Chronic hepatitis
• Cirrhosis of the liver (Piper 2013)
• Protracted subacute liver failure in up to 90 % caused by cryptogenic hepatitis (Burchardi 2004)
• Fulminant liver failure (Adler 2000)
• Acute liver failure: 22% of patients with acute liver failure have cryptogenic hepatitis (Guidelines 2023)
• Hepatocellular carcinoma (Czaja 2011)

In a study of acute cryptogenic hepatitis, four patients with ALT values > 1,000 U/l and bilirubin values > 400 µmol/l successfully underwent immunosuppressive therapy with prednisolone and, in one case, azathioprine. This resulted in a drop in aminotransferases and rapid normalization of liver function. The response to therapy could indicate an autoimmune genesis of the disease (Potthoff 2007).

Cryptogenic hepatitis is an indication for liver transplantation (Czaja 2011).

The 1-year survival rate after liver transplantation is between 72-85%, the 5-year survival rate between 58-73% (Czaja 2011).

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