MetALD: Position statement by an expert panel

The expert position statement on Metabolic dysfunction- and Alcohol-related Liver Disease (MetALD) provides a comprehensive overview of the definition, diagnosis, and management of MetALD within the newly updated 2023 classification of steatotic liver diseases (SLD). Here are the key points highlighted in the paper:

### 1. **Purpose and Context**

The statement aims to clarify the terminology, diagnostic criteria, and management strategies for MetALD, a subtype of liver disease that arises from the combined impact of metabolic dysfunction and alcohol consumption. This is part of the broader reclassification of steatotic liver diseases (SLD) introduced in 2023.

### 2. **Redefinition of Steatotic Liver Diseases (SLD)**

The updated nomenclature divides SLD into three categories:

• **Metabolic dysfunction-associated steatotic liver disease (MASLD)**: Primarily driven by metabolic dysfunction.
• **MetALD**: Liver disease resulting from both metabolic dysfunction and alcohol consumption.
• **Alcohol-related liver disease (ALD)**: Liver disease predominantly caused by alcohol intake.

This framework acknowledges the overlapping spectra of these conditions, particularly between MASLD and ALD.

### 3. **Importance of Alcohol History**

A thorough assessment of alcohol consumption is essential for diagnosing MetALD. Both recent and lifetime alcohol intake must be evaluated to distinguish MetALD from MASLD and ALD. Tools like the AUDIT-C questionnaire and biomarkers such as phosphatidylethanol (PEth) are recommended to complement clinical history.

### 4. **Alcohol Intake Thresholds**

The paper endorses specific thresholds for alcohol consumption to define MetALD:

• **Women**: 140–350 grams per week.
• **Men**: 210–420 grams per week.

These thresholds help align alcohol exposure with metabolic dysfunction criteria.

### 5. **Challenges in Alcohol Quantification**

Accurate reporting of alcohol use is complicated by factors such as stigma, memory errors, and differing definitions of "standard drinks" across regions. These challenges can lead to misclassification of MetALD.

### 6. **Role of Biomarkers**

Phosphatidylethanol (PEth) is emphasized as a reliable biomarker for recent alcohol intake. It can detect alcohol use for up to six weeks and differentiate MetALD from MASLD and ALD.

### 7. **Histopathological Features**

While MASLD and ALD share overlapping histological patterns, specific features such as neutrophilic infiltration and Mallory-Denk bodies are more characteristic of alcohol-related liver injury.

### 8. **Fibrosis Progression**

Fibrosis progresses more rapidly in MetALD and ALD compared to MASLD. Fibrosis stage is the strongest predictor of mortality and liver-related outcomes.

### 9. **Interplay with Metabolic Syndrome**

Alcohol consumption exacerbates metabolic syndrome components—such as hypertension, hypertriglyceridemia, and hyperglycemia—further worsening liver injury in MetALD.

### 10. **Alcohol’s Dual Role**

Alcohol contributes to liver injury in two ways:

• **Direct hepatotoxicity**: Damage caused by alcohol itself.
• **Indirect effects**: Alcohol promotes obesity, insulin resistance, and poor metabolic health, which aggravate liver dysfunction.

### 11. **Screening Recommendations**

The paper recommends screening all individuals with suspected SLD for alcohol use and alcohol use disorder (AUD) using validated tools like AUDIT or AUDIT-C to ensure accurate classification under the new framework.

### 12. **Attributable Risk of Alcohol**

Alcohol is a significant contributor to liver-related morbidity and mortality worldwide. Even moderate alcohol consumption increases the risk of cirrhosis and hepatocellular carcinoma.

### 13. **Synergistic Risk with Obesity and Diabetes**

The combination of alcohol use and metabolic dysfunction (e.g., obesity or type 2 diabetes mellitus) exponentially increases the risk of liver fibrosis and cirrhosis.

### 14. **Complexity of Metabolic Criteria**

Alcohol influences metabolic parameters such as blood pressure, triglycerides, and glucose levels, complicating the diagnosis of MASLD or MetALD. Careful interpretation is required to avoid misclassification.

### 15. **Longitudinal Assessment**

Periodic reassessment of alcohol consumption and metabolic risk factors is recommended, especially after lifestyle changes or treatments, to better predict disease progression.

### 16. **Public Health Implications**

The paper emphasizes that there is no "safe" level of alcohol consumption for liver health. Population-level strategies to reduce alcohol use can significantly decrease the burden of alcohol-related liver disease.

### 17. **Clinical Management of MetALD**

MetALD requires a holistic management approach that addresses both metabolic dysfunction and alcohol consumption. Recommended strategies include:

• **Lifestyle modification**: Diet, exercise, and alcohol cessation.
• **Pharmacotherapy**: Medications targeting metabolic dysfunction or alcohol use disorder.
• **Behavioral interventions**: Counseling and support for alcohol cessation.

### 18. **Non-Invasive Fibrosis Assessment**

Non-invasive fibrosis tests are advocated for early identification of advanced liver disease, particularly in patients with MetALD or heavy alcohol use.

### 19. **Research Priorities**

Further studies are needed to:

• Quantify the individual contributions of alcohol and metabolic dysfunction to fibrosis progression.
• Validate diagnostic criteria for MetALD across diverse populations.

### 20. **Conclusion**

MetALD represents a critical intersection between metabolic dysfunction and alcohol-related liver injury. Accurate diagnosis, holistic management, and refined classification under the new steatotic liver disease framework can improve prognosis and guide future therapeutic strategies.

This position statement underscores the importance of recognizing MetALD as a distinct entity within the broader spectrum of liver diseases, offering a pathway for more precise diagnosis and better-targeted treatments.