Liver Involvement in POLG Disease-a Multicentre Cohort Study of 202 Patients

Area of Science:

• Genetics
• Hepatology
• Neurology

Background:

• Liver involvement is a frequent complication of Polymerase G (POLG) disease, often leading to severe outcomes.
• Limited large-scale studies exist on the characteristics and prognosis of liver involvement in POLG disease.

Purpose of the Study:

• To systematically describe the onset, clinical progression, and prognostic significance of liver involvement in a large cohort of POLG disease patients.
• To stratify liver involvement based on age of disease onset and identify associated risk factors.

Main Methods:

• A multinational, retrospective study analyzing clinical, genetic, and biochemical data from 202 confirmed POLG disease patients.
• Patients were categorized into early-onset (<12 years), juvenile/adult-onset (12-40 years), and late-onset (>40 years) groups.
• Analysis included the frequency, timing, and correlation of liver involvement with other clinical features like epilepsy and disease triggers.

Main Results:

• 54% (110/202) of patients exhibited liver involvement, more prevalent in early-onset disease (78%).
• Liver involvement occurred across all ages, with median onset ages of 7 years for females and 21 months for males.
• Infection-triggered onset significantly increased the risk of liver involvement; 85% of affected patients also had epilepsy.
• Liver involvement was a significant predictor of poor prognosis and reduced survival.

Conclusions:

• Liver involvement is a common and serious manifestation of POLG disease, strongly associated with poorer survival.
• POLG disease should be suspected in children with unexplained liver issues, and genetic testing is crucial for management.
• Vigilant monitoring for liver involvement is essential in all POLG patients, especially those with early-onset disease or during infections.