Acute porphyria and liver health

What's UP Doc?
Written By Dr. Herbert Bonkovsky

What's UP Doc? Is a regular column where we feature a patient question along with a response from a member of the UPA Scientific Advisory Board.

Last week, a mom asked about her son and his liver. He had EPP. My daughter (now age 26) has AIP and I have a similar question about the health of her liver. How will acute porphyria attacks impact her liver as she ages? She was diagnosed a few years ago and her last attack was several months ago. I appreciate your response.

Thank you so much for the wonderful follow up question. UPA Scientific Advisory Board member Dr. Herbert L. Bonkovsky provided his response below.

“Most patients with AIP have normal or near-normal livers and they do not suffer from progressive liver disease or its complications. However, there is a modestly increased risk of their developing chronic liver disease and primary liver cancer [hepatocellular carcinoma, HCC], especially with advancing age. The risks of these disorders are likely greater among patients with biochemically active AIP: those who chronically over produce and over-excrete delta-aminolevulinic acid [ALA] and porphobilinogen [PBG]. It seems likely that the chief potential toxic intermediate is ALA, which causes increased oxidative stress.

We recommend that patients with AIP take good care of their livers: they should receive vaccinations to protect them from developing hepatitis A and B, for which there are safe and effective vaccines; they should not drink alcohol to excess—for women this means not more than one drink per day; for men, not more than two. They should avoid obesity and hyperlipidemia, both of which are associated with fatty liver disease, as is excess alcohol. Drugs and herbals and dietary supplements, especially concentrated extracts of green tea, are also hepatotoxic in some susceptible persons, so we recommend caution in their use and only for clearly indicated medical reasons, not for purposes of 'general health' or for 'weight loss.' Keeping other approved vaccinations complete and up-to-date, such as DPT, HPV, yearly flu, Covid-19 with boosters, etc, is strongly recommended.

Acute porphyric attacks should be treated promptly and vigorously, as recommended in our general guidelines:

  • Balwani M, Wang BD, Anderson KE, Bloomer JR, Bissell DM, Bonkovsky HL, Phillips JR, Desnick RJ, for the Porphyrias Consortium of the Rare Diseases Clinical Research Network. Acute hepatic porphyrias: recommendations for evaluation and long-term management. Hepatology 66: 1314-1322, 2017. [PMID: 28605040] [PMCID: PMC 5605422].

It is good medical practice for AIP patients to have yearly tests of hepatic and kidney status with comprehensive metabolic panels. If there are abnormalities detected, further assessments by hepatologists and/or nephrologists with knowledge of AIP are likely indicated. Beginning at age 50 years, we recommend regular and ongoing screening for the development of HCC with liver ultrasound, CT, or MRI every 6 months. Fortunately, if HCC develop in patients with AIP and it, they are detected early, before they have become very extensive or have spread to other organs, they generally can be removed surgically with good long-term survivals.

Thank you to Dr. Bonkovsky for this What's UP Doc? answer! Do you have a question for a porphyria expert? Send it to info@porphyria.org.

 

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Dr. Herbert Bonkovsky

Dr. Bonkovsky’s interest in the porphyrias began in medical school and was strengthened during his time studying under porphyria researcher D.P. Tschudy at the National Institutes of Health. Dr. Bonkovsky was among the first to show that hepatic porphyrin and heme synthesis is under the negative feedback regulatory control of heme itself, acting chiefly to down-regulate delta-aminolevulinic acid (ALA) synthase-1, the rate controlling enzyme for heme synthesis. This discovery was the basis for developing heme therapy for acute porphyria attacks, which is still today the treatment of choice for these life-threatening attacks. Dr. Bonkovsky was the first physician-investigator to purify heme and to administer it to a patient with severe acute intermittent porphyria.

Since that time, Dr. Bonkovsky has continued the search for new treatments for the porphyrias, administering clinical trials for potential new therapies at hospitals and medical centers in Massachusetts, Connecticut, and now at the Atrium Health--Wake Forest Baptist Medical Center in Winston-Salem, North Carolina. He is principal investigator of the Porphyria Center of Excellence at Wake Forest/NC Baptist Medical Center, which is a part of the Porphyrias Consortium of the USA, sponsored by the National Institute of Diabetes, digestive and Kidney Diseases and the National Center of Rare Diseases Research.

Dr. Bonkovsky also identified deficiency of ferrochelatase, the final enzyme in the heme synthetic pathway as the fundamental metabolic defect in EPP. Studies on the regulation of hepatic heme metabolism, especially the mechanisms and factors that regulate ALA synthase and heme oxygenase, have been the subject of a large number of studies, both in the basic research laboratory and the clinical research center during the past 50 years.

Dr. Bonkovsky has trained many medical students, residents, and sub-specialty fellows, especially in the fields of internal medicine, gastroenterology, and hepatology, as well as graduate students and junior faculty working on laboratory research.

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