Can Non-Alcoholic Steatohepatitis (NASH) cirrhosis cause non-anion gap metabolic acidosis?

NASH Cirrhosis and Non-Anion Gap Metabolic Acidosis

NASH cirrhosis does not directly cause non-anion gap metabolic acidosis, but cirrhosis from any etiology—including NASH—can lead to metabolic acidosis through multiple mechanisms, with hyperchloremic (non-anion gap) acidosis being one recognized pattern.

Acid-Base Disturbances in Cirrhosis

The primary acid-base disturbance in liver cirrhosis is respiratory alkalosis, not metabolic acidosis 1. However, metabolic acidosis is a well-documented complication in cirrhotic patients, particularly those who are critically ill 1, 2.

Types of Metabolic Acidosis in Cirrhosis

Cirrhotic patients can develop several forms of metabolic acidosis 1:

• Hyperchloremic (non-anion gap) metabolic acidosis occurs in cirrhosis and represents one of the pathophysiological mechanisms affecting acid-base equilibrium 1
• Hyponatremic metabolic acidosis develops as part of the complex electrolyte disturbances in cirrhosis 1
• Lactic acidosis (high anion gap) is common and carries the worst prognosis among all types of metabolic acidosis in cirrhotic patients 2
• Metabolic alkalosis can occur due to hypoalbuminemia and altered urea metabolism, sometimes coexisting with or compensating for other acid-base disorders 1

Prevalence and Clinical Significance

In critically ill cirrhotic patients admitted to intensive care units:

• 52% (506/975) had metabolic acidosis, with approximately half having decompensated metabolic acidosis at ICU admission 2
• The 28-day mortality rate in cirrhotic patients with metabolic acidosis was 41% (206/506) 2
• Metabolic acidosis is associated with significantly increased mortality risk in cirrhotic patients 2

NASH-Specific Considerations

While the provided guidelines extensively discuss NASH cirrhosis complications 3, they do not identify non-anion gap metabolic acidosis as a specific or characteristic complication of NASH cirrhosis per se 4, 5.

The most important complications of NASH cirrhosis are:

• Cardiovascular disease (the leading cause of death, not liver-related mortality) 4, 5
• Hepatocellular carcinoma (NASH is the third most common cause of HCC in the US) 5
• Liver transplantation need (NASH is the second most common indication for liver transplantation) 5
• Progressive fibrosis (30-40% of NASH patients develop fibrosis) 4

Clinical Pitfall: Complex Acid-Base Disorders

A critical caveat: Conventional acid-base models fail to identify and assess the underlying disorders in cirrhotic patients 1. Multiple simultaneous acid-base disturbances often coexist:

• Respiratory alkalosis (primary disorder) may be present alongside metabolic acidosis or alkalosis 1
• Hypoalbuminemia causes metabolic alkalosis that can mask concurrent metabolic acidosis 1
• Standard bicarbonate-based assessment may miss the true complexity of acid-base derangements 1

Practical Clinical Approach

When evaluating a NASH cirrhosis patient with suspected metabolic acidosis:

1. Calculate the anion gap to differentiate between high anion gap (lactic acidosis, uremia, ketoacidosis) and normal anion gap (hyperchloremic) acidosis 1, 2

2. Assess for lactic acidosis specifically, as this carries the worst prognosis and requires urgent intervention 2

3. Evaluate electrolytes carefully, looking for hyponatremia, hypokalemia, and hyperchloremia—all common in cirrhosis 6, 1

4. Consider physicochemical models (Stewart approach) rather than relying solely on traditional bicarbonate-based assessment, as these better capture the complex acid-base derangements in cirrhosis 1

5. Look for precipitating factors such as renal dysfunction, sepsis, gastrointestinal losses, or medications that may be contributing to the acidosis 2

Bottom Line

Non-anion gap metabolic acidosis can occur in NASH cirrhosis, but it is a complication of advanced cirrhosis in general rather than a specific feature of NASH etiology 1. The presence of metabolic acidosis in a cirrhotic patient signals severe illness and poor prognosis, particularly if lactic acidosis is present 2. Focus clinical attention on the established life-threatening complications of NASH cirrhosis: cardiovascular disease, hepatocellular carcinoma, and progressive liver failure 4, 5.