Can Xywav (calcium, magnesium, potassium, and sodium oxybates) exacerbate liver fibrosis in a patient with hemochromatosis, potentially leading to cirrhosis?

From the Guidelines

I strongly recommend consulting with both your sleep doctor and a hepatologist to determine if Xywav should be discontinued given your liver fibrosis findings, as the most recent and highest quality study suggests that patients with haemochromatosis and advanced fibrosis should be carefully assessed and managed to prevent progression to cirrhosis 1. Xywav (sodium oxybate/calcium oxybate) is metabolized by the liver, and while it's not typically associated with severe liver damage, your unique situation with hemochromatosis (iron overload disorder) could potentially create a higher risk scenario. Hemochromatosis already causes liver stress through iron accumulation, and adding medications that require liver processing might compound this effect. Some key points to consider:

• The European Association for the Study of the Liver recommends that patients with haemochromatosis and advanced fibrosis should undergo HCC screening every 6 months, regardless of iron depletion 1.
• A recent study suggests that serum ferritin is the single most important predictor of the presence of advanced hepatic fibrosis in C282Y homozygotes, and liver biopsy does not need to be performed when ferritin is <1000 lg/L, in the absence of excess alcohol consumption and elevated serum liver enzymes 1.
• Patients with haemochromatosis should avoid iron supplementation, iron-fortified food, and excessive alcohol consumption, and limit red meat consumption and vitamin C intake 1. Until you receive definitive guidance from your specialists, continue taking your medication as prescribed, as suddenly stopping Xywav can cause withdrawal symptoms. If your sleep doctor recommends discontinuing Xywav, alternative narcolepsy treatments like modafinil, armodafinil, pitolisant, or solriamfetol might be considered. Additionally, request regular liver function monitoring and follow-up fibroscans to track any changes. Your severe fibrosis warrants close monitoring regardless of whether Xywav is continued or discontinued, as preventing progression to cirrhosis is critical.

From the Research

Liver Fibrosis and Xywav

• There is no direct evidence in the provided studies to suggest that Xywav (calcium, magnesium, potassium, and sodium oxybates) exacerbates liver fibrosis in patients with hemochromatosis, potentially leading to cirrhosis 2, 3, 4, 5, 6.
• However, studies have shown that liver fibrosis and steatosis can be assessed using non-invasive methods such as transient elastography and ultrasound 2, 3, 5, 6.
• The use of Xywav, a low-sodium oxybate formulation, may have potential benefits in reducing sodium intake, which could be beneficial for patients with liver disease 4.
• Liver steatosis and fibrosis are common in patients with type 2 diabetes mellitus, and liver stiffness assessment should be performed systematically to identify those with significant liver fibrosis 6.

Assessment of Liver Fibrosis

• Transient elastography is a non-invasive method that can be used to assess liver fibrosis and steatosis, with good diagnostic accuracy compared to biopsy 5.
• Ultrasound can also be used to assess liver steatosis, and the severity of steatosis can be graded using a semi-quantitative scale 6.
• The use of controlled attenuation parameter (CAP) with transient elastography can also assess steatosis 5.

Xywav and Liver Disease

• While there is no direct evidence on the effect of Xywav on liver fibrosis in patients with hemochromatosis, the reduction in sodium intake with Xywav may have potential benefits for patients with liver disease 4.
• Further studies are needed to determine the potential effects of Xywav on liver fibrosis and steatosis in patients with hemochromatosis.