Non-Alcoholic fatty liver disease (NAFLD) and it progressive form, non-alcoholic steatohepatitis (NASH), represent a growing global health concern. These conditions are charactized by the accumulation of fat in the liver, potentially leading to inflammation, fibrosis, cirrhosis, and even liver failure. Accurate diagnosis and assessment of disease severity are crucial for effective management and resource allocation.

HCD Economics’ ‘Cost of non-alcoholic steatohepatitis in Europe and the USA: The GAIN study’ contributed to the evidence base providing global data on the diagnostic practices, disease severity, and socio-economic burden of NASH across six countries: Germany, Spain, France, the UK, Italy and the USA.

This article explores key findings from the GAIN study, highlighting differences in diagnostic approaches, comorbidities, and the economic burden of NASH.

Diagnostic Approaches: EU5 vs. USA

One notable finding from the GAIN study is the divergence in diagnostic practices between European countries (EU5) and the United States. In the EU5, routine clinical tests, including liver biochemistry, were commonly performed. Ultrasound imaging was the most frequently used diagnostic technique, with 68% of patients undergoing an ultrasound. In contrast, the USA relied less on imaging, with only 51% of patients receiving an ultrasound and a minority undergoing transient elastography.

Furthermore, serum biomarkers and non-invasive tests, recommended in clinical guidelines, were less commonly applied in both regions. The most frequently used serum biomarker was the AST/ALT ratio (23%), followed by the NAFLD fibrosis score (9%), the BARD score (3%), and the FIB-4 score (3%). The cytokeratin-18 biomarker, which detects apoptosis, was used in 3% of patients. Transient elastography (FibroscanTM) was the most commonly used imaging test to stage disease (33% of patients).

Comorbidities and Quality of Life

The GAIN study also revealed that NASH patients frequently experience comorbidities, with a higher prevalence in those with more advanced disease. Comorbidities such as obesity (35%), dyslipidemia (32%), type 2 diabetes mellitus (T2DM, 27%), and hypertension (27%) were common, reflecting the association of NAFLD/NASH with metabolic syndrome.

Depression was the most common mental and behavioural disorder, reported by 8% of patients overall. These comorbidities contribute to the overall burden of NASH, affecting patients' quality of life.

Health-Related Quality of Life (HRQoL)

The study assessed health-related quality of life (HRQoL) using the EQ-5D score and the Chronic Liver Disease Questionnaire - Non-Alcoholic Fatty Liver Disease (CLDQ-NAFLD) index. The EQ-5D score decreased with worsening fibrosis status in all countries except France, where similar scores were observed in both early and advanced fibrosis. The CLDQ-NAFLD index varied by country, with France having the highest score (5.7) and the USA the lowest (4.4).

Economic Burden

The economic burden of NASH was a key focus of the GAIN study. Despite the absence of drugs specifically licensed for NASH treatment, pharmacological therapy was a major component of NASH-related direct costs, including medications targeting obesity, metabolic syndrome components, and liver-directed therapies.

Non-medical and indirect costs, including professional and informal caregiving, transportation, disability allowances, alternative therapies, home alterations, and over-the-counter remedies, contributed substantially to the overall economic burden. Indirect costs, associated with work-related issues and early retirement, were particularly of note and correlated with disease severity.


The GAIN study provided valuable insights into the diagnostic practices, comorbidities, quality of life, and economic burden of NASH across US and EU5 markets. As the prevalence of NASH continues to rise, understanding its multifaceted impact is crucial for healthcare systems and policymakers to develop effective strategies for prevention, diagnosis, and management.

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