Insight Into Alpha-1 Antitrypsin Heterozygosity

CV Schneider, K Hamesch et al. Gastroenterol 2020; 159: 534-548Liver Phenotypes of European Adults Heterozygous or Homozygous for Pi∗Z Variant of AAT (Pi∗MZ vs Pi∗ZZ genotype) and Noncarriers)

Key findings:

  • Ten percent of subjects with the Pi∗MZ genotype vs 4% of noncarriers had LSMs (liver stiffness measurements) of 7.1 kPa or more (adjusted odds ratio, 4.8; 95% confidence interval, 2.0–11.8)
  • Obesity and diabetes were the most important factors associated with LSMs ≥7.1 kPa in subjects with the Pi∗MZ genotype.
  • AAT inclusions were detected in liver biopsies of 63% of subjects with the Pi∗MZ genotype, vs 97% of subjects with the Pi∗ZZ genotype, and increased with liver fibrosis stages.

The associated editorial (pg 433-34) noted that Pi∗MZ genotype is a disease modifier in cystic fibrosis, alcoholic liver disease, and nonalcoholic liver disease.

My take: This study indicates that Pi∗MZ genotype for alpha-one antitrypsin are more likely to develop liver fibrosis in the presence of other risk factors like obesity and diabetes mellitus.

Related blog posts:

Liver Shorts March 2020 & COVID-19 Screenshots

Sofusbuvir and Ribavirin for children with hepatitis C infection (3-12 yrs, genotype 2 or 3) P Rosenthal et al. Hepatology 2020; 71: 31-43. n=54.  SVR12 was 98% (one patient did not complete treatment).

Alpha-one antitrypsin heterozygositiy contributes to cirrhosis in fatty liver disease. Liver Transplantation 2020; 26: 17-24. From the discussion: “unexpected PASD+ globules, in the context of advanced liver disease, are a specific finding that indicates the presence of a mutant A1AT allele.”  Of 196 explanted livers from NASH patients, 21 (11%) has PASD+ globules; however, among NASH patients the frequency was 47%.  Also, the Z allele was present in 10% of all tested liver explants, this exceeds the 2% rate in the general population.  Thus, in agreement with other studies, A1AT heterozygosity contributes to chronic liver failure, but may affect fatty liver disease more than other chronic liver diseases.

Durability of HBsAg Loss in Hepatitis B AS Alawad et al. Clin Gastroenterol Hepatol 2020;18: 700-09.  In this retorspective study form NIH, 89/787 HBsAg-positive patients cleared HBsA; 65 had confirmed clearance. (spontaneous in 19, post-interferon in 22, and post-NA treatment in 24). 62 of 65 remained negative after a mean time of 9.6 years. 3 patients had seroreversion at a mean of 20 months after stopping therapy, though this was transient in 2 of 3 and may have been a false-positive.

Are Medications Contributing to Obesity and Fatty Liver Disease? ~25% of U.S. adults take a prescription medication  that often produces obesity as an adverse effect. (Hales CM et al. Obesity Week 2019, Link to Abstract T-OR-2037). PRESCRIPTION MEDICATIONS THAT PROMOTE WEIGHT GAIN: Prevalence of Use Among U.S. Adults, 2013-2016 Common obesogenic medications in this cohort, (n=11,055), included all glucocorticoids, beta-blockers, and antihistamines and some agents among antidepressants, antipsychotics, antidiabetics and progestin-only contraceptives.  Medications were defined as promoting weight gain according to the Endocrine Society Clinical Practice Guideline for the Pharmacological Management of Obesity (J Clin Endocrinol Metab, 2015).


If you have not seen this on YouTube, highly recommend this virtual choir link: Rodean School -Hallelujah

More fallout from Coronavirus: NY Times: Coronavirus May Add Billions to Nation’s Health Care Bill Insurance premiums could spike as much as 40 percent next year, a new analysis warns, as employers and insurers confront the projected tens of billions of dollars in additional costs of treating coronavirus patients.

Topical (& Tasty) Tweets: