Liver Shorts -June 2020

SH Ibrahim et al. Hepatology 2020; 71: 1474-85.  Thorough review of liver diseases in the perinatal period and relationship of the maternal-infant interactions.  Liver diseases discussed include GALD which has “strikingly normal or near normal transaminases” despite liver failure (most common etiology).  Treatment for GALD includes IVIG (1 g/kg) along with subsequent double-volume exchange transfusion.  The review covers maternally-transmitted viral infections, fatty liver disease, and acute fatty liver disease of pregnancy (AFLP); AFLP is most commonly caused by LCHAD but can be caused by other defects in fatty acid oxidation.

RT Khalaf, RJ Sokol. Hepatology 2020; 71: 1486-98. This review focuses on intestinal failure-associated liver disease (IFALD).  The review provides an in-depth discussion of intravenous lipid emulsions and other factors implicated in the pathogenesis.

  • Risk factors: bacterial overgrowth, central line infections, recurrent sepsis, prematurity, parenteral nutrition composition, and micronutrient imbalances
  • Protective factors: early enteral nutrition, cycled parenteral nutrition, glucagon-like peptide 2, preservation of ileocecal valve, small bowel lengthening when appropriate
  • While the authors acknowledge that lipid minimization often improves cholestasis, they advise caution due to concern for both essential fatty acid deficiency and detrimental effects on brain growth.
  • Prevention of central line infections with use of ethanol locks is important and effectively reduces the rate by more than 80% (though currently costs of ethanol locks have skyrocketed: FDA Safety Initiative Complicit in Ethanol Costing $30,000 for 1 oz)
  • The authors note that long-term survival from intestinal transplantation is only 40% at 10 years indicating benefit of ongoing parenteral nutrition management if feasible.

Related blog posts:

PL Valentino et al. JPGN 2020; 70: 547-54. This article discusses potential management of Wilson disease diagnosed in infancy based on ATP7B genetic testing. Very little evidence presented.  Suggests starting Zinc therapy at an early age and monitoring for copper deficiency along with efficacy.  More precise recommendations regarding urine copper goals for children would be helpful as well.

Large (n=112, median age 38 years) prospective observational study of Acute Hepatic Porphyria. L Gouya et al. Hepatology 2020; 71: 1546-58. Key findings from EXPLORE group:

  • Chronic symptoms were noted in 65%; 46% had daily symptoms. Symptoms including body pains, trouble sleeping/tiredness, anxiety, GI symptoms (eg. nausea) and weakness.
  • During the 2-year study period, 88% experienced a total of 483 attacks; 77% of these attacks required treatment at a health care facility or hemin administration
  • Median annualized attack rate was 2.0
  • UrineDelta-aminolevulinic acid (ALA) and porphobilinogen (PBG) compared with upper limit of normal at baseline and increased further during attacks.
  • At baseline, 16% had elevations of liver aminotransferases
  • Related reference: M Balwani et al. Hepatology 2017; 66: 1314-22. Acute Hepatic Porphyrias -Review. Current recommendations include gene sequencing to confirm all biochemical cases. Biochemical tests are spot urine testing of porphobilinogen (PBG), 5-aminolevulinic acid (ALA), and porphyrins. A normal urine PBG in symptomatic patients “excludes the three most common acute hepatic porphyrias.”  For those with abnormal studies, this reference is a handy.

Automated ascites pump. F Wong et al. Liver Transplantation 2020; 26: 651-61. In this study with 30 patients, interventional radiology placement of an “alfapump” helped manage refractory ascites in cirrhosis.

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Data on Chelators for Wilson Disease

A recent retrospective analysis on 405 patients with Wilson disease analyzed the efficacy and safety of oral chelators for Wilson disease (Clin Gastroenterol Hepatol 2013; 11: 1028-35).

The authors noted that there were frequent changes in medication; in total, 471 monotherapies were analyzed: 326 patients with D-penicillamine (DPA) and 141 with trientine.  Trientine was a first line treatment in only 38 patients.  About 50% of patients presented with hepatic symptoms, about 20% neurologic symptoms, about 15% with combined hepatic/neurologic symptoms and the remainder, ~10%, were asymptomatic.

  • 9 of 326 with DPA and 3 of 141 with trientine underwent liver transplantation.
  • Adverse effects were more common with DPA, including arthralgias (8.9%), proteinuria (6.1%), ANA antibodies (6.7%), gastric complaints (2.5%) and polyneuropathy (1.8%).  28.8% of DPA stopped therapy due to adverse effects.
  • Adverse effects with trientine resulted in stopping treatment in 7.1% and included arthralgias in 2.8%, and gastric complaints in 1.4%.
  • Hepatic improvements were observed in >90%

The authors summarize their findings:

“Both DPA and trientine were equally and highly effective in controlling liver disease…In light of recent reports of hepatic deterioration under zinc therapy, the current data emphasize the role of these chelating agents in the treatment of symptomatic hepatic patients.”

Related blog post:

Finding the Right Specialist | gutsandgrowth This post has link to AASLD guidelines for Wilson disease.