What Works for Itching?

Two recent articles delve into the issue of pruritus associated with cholestasis:

  • JE Squires et al. JPGN 2017; 64: 425-430.
  • Thebaut et al. JPGN 2017; 64: 431-35.

In the first study, a single-center retrospective review of 8 patients with FIC1 disease who underwent partial exernal biliary diversion (PEBD) showed that all patients had resolution of chronic cholestasis (T bili <2 mg/dL) but 7 of 8 experience episodic cholestatic events. Pruritus improved but did not resolve.  PEBD did not obviate the need for aggressive fat-soluble vitamin supplements.

In the second study, the authors added sertraline to patients who had ongoing pruritus despite ursodeoxycholic acid and rifampin therapy.  Patients had either Alagille syndrome or PFIC (progressive familial intrahepatic cholestasis). Two patients had undergone PEBD. Sertraline was started at 1 mg/kg/day and increased as needed every two weeks to max of 4 mg/kg/day (median daily dose 2.2 mg/kg/day).  6 patients had adverse effects, including agitation (2), skin reactions (2), alopecia (1) and vomiting (1). Key finding:

  • 14 of 20 children had improved “itching score” from 8/10 to 5/10.  This correlated with improved sleep and less skin scratch marks.

 

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

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Sertraline and Liver Disease

A recent case report (MA Conrad, HC Lin. J Pediatr 2016; 169: 313-5) on sertraline-associated cholestasis provided a good reason to take a quick review on the NIH Liver Toxicity website:

Hepatotoxicity with sertraline (zoloft)

Liver test abnormalities have been reported to occur in up to 1% of patients on sertraline, but elevations are usually modest and infrequently require dose modification or discontinuation.  Rare instances of acute, clinically apparent episodes of liver injury with marked liver enzyme elevations with or without jaundice have been reported in patients on sertraline.  The onset of injury is usually within 2 to 24 weeks and the pattern of serum enzyme elevations has varied from hepatocellular to mixed and cholestatic.  Autoimmune (autoantibodies) and immunoallergic features (rash, fever, eosinophilia) are uncommon.  Actue liver failure due to sertraline has been described but is very rare.

The case report describes a 15 yo who developed jaundice (peak bilirubin 33.7 mg/dL with a direct fraction of 29.2 mg/dL) after 6 months of treatment with 75 mg per day.  After negative blood tests, he had a liver biopsy which was notable for rare bile ducts.  A jaundice chip was negative for underlying disorders like Alagille syndrome.  Urine bile acids were negative as well.  His laboratories normalized completely four months after cessation of sertraline.

It is interesting to note that sertraline has been used therapeutically for patients with pruritus due to cholestasis (Understanding Cholestatic Pruritus | gutsandgrowth)

My take: This case report describes bile duct paucity (vanishing bile ducts) as a result of sertraline therapy.  For practitioners, the bottom line is that SSRIs rarely cause liver toxicity; however, for patients with persistently-abnormal liver chemistries on SSRI therapy, discontinuation and identification of a safe alternative medication may be warranted.

Castillo San Felipe del Morro

Castillo San Felipe del Morro