How do I differentiate between acute liver failure and acute hepatitis in a primary care setting?

In a primary care setting, differentiating acute liver failure (ALF) from acute hepatitis relies primarily on clinical features and initial investigations. Acute hepatitis typically presents with symptoms such as jaundice, malaise, anorexia, nausea, and right upper quadrant discomfort, but patients remain clinically stable without signs of encephalopathy or coagulopathy. In contrast, acute liver failure is characterised by rapid onset of jaundice, coagulopathy (INR >1.5), and hepatic encephalopathy in a patient without pre-existing liver disease, often within days to weeks of symptom onset.

Key clinical differentiators include: the presence of altered mental status or confusion indicating hepatic encephalopathy, which is a hallmark of ALF but absent in uncomplicated acute hepatitis. Additionally, signs of bleeding or bruising due to coagulopathy suggest ALF rather than isolated hepatitis.

Initial investigations in primary care should include liver function tests (LFTs), coagulation profile, and assessment of mental status. In acute hepatitis, LFTs show elevated transaminases (ALT and AST), often markedly raised, but coagulation parameters remain normal and there is no encephalopathy. In ALF, transaminases are also elevated but accompanied by prolonged prothrombin time (INR >1.5) and clinical or subclinical encephalopathy.

Referral criteria: Any patient suspected of ALF requires urgent hospital referral for specialist management due to the risk of rapid deterioration, whereas acute hepatitis without signs of liver failure can be managed conservatively with monitoring and supportive care in primary care or outpatient settings.

This approach aligns with UK clinical guidelines emphasising the importance of encephalopathy and coagulopathy in diagnosing ALF ¹, while recent literature further supports the rapid progression and need for early recognition of ALF to improve outcomes (Vasques et al., 2022; Maiwall et al., 2024).