Among individuals with alpha-1 antitrypsin deficiency (AATD), the prevalence of fibrosis is high and rises incrementally with the number of Pi*Z mutations, according to findings from a systematic review and meta-analysis published in Alimentary Pharmacology & Therapeutics.
Although recent data imply that a considerable percentage of adults with AATD have significant liver fibrosis, the prevalence among those with the disorder due to Z homozygosity or Z heterozygosity has not been evaluated systematically. The most common cause of severe AATD is the homozygous Pi*Z (GLU342Lys) mutation (Pi*Z genotype) in the SERPINA gene, which is associated with a misfolded protein (Z-alpha-1 antitrypsin). This, in turn, leads to insufficient hepatic clearance, subsequent accumulation in hepatocytes, and liver injury. Heterozygous Pi*Z carriage is linked to fibrosis and hepatic injury as well, but to a lesser extent.
Among patients with AATD, the stage of fibrosis is a key factor in liver-related outcomes and mortality. The researchers sought to establish the prevalence of significant fibrosis (≥F2) and advanced fibrosis (F3 to F4) in individuals with AATD, according to the use of noninvasive imaging, including magnetic resonance elastography (MRE), vibration-controlled transient elastography (VCTE), and acoustic radiation force impulse (ARFI).
The primary study objective was to provide estimates of the pooled prevalence of significant fibrosis among patients with AATD, based on findings from ARFI, MRE, and VCTE. The coprimary study objective was to provide estimates of the pooled prevalence of advanced fibrosis, according to ARFI, MRE, and VCTE. Significant fibrosis and advanced fibrosis were defined as “a liver stiffness measurement by VCTE of ≥7.1 kPa and ≥9.5 kPa, respectively.” VCTE was selected as the noninvasive imaging test in the study objectives because it was used in the majority of articles included in the literature review.
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Among 214 articles originally identified, 8 were included in the meta-analysis. Overall, 5 of the 8 studies selected, which included 1359 patients, provided data on the presence of significant fibrosis, according to liver stiffness measurement by VCTE. The pooled prevalence of significant fibrosis was highest in Z homozygotes, (5 studies, 22.10%; 95% CI, 17.07-28.12), followed by Z heterozygotes (3 studies: 9.24%; 95% CI, 4.68-17.45), then by noncarriers (1 study, 5.38%; 95% CI, 3.27-8.73), yielding a statistically significant value of P <.0001.
The pooled prevalence of advanced fibrosis was as follows: Z homozygotes (5 studies, 8.13%; 95% CI, 4.60-13.96),
Z heterozygotes (3 studies: 2.96%; 95% CI, 1.49 to 5.81), and noncarriers (1 study, 1.08%; 95% CI, 0.35-3.28). In fact, the prevalence of advanced fibrosis was significantly more common in Z homozygotes compared with Z heterozygotes (P =.02) and noncarriers (P =.001).
“More than 1 in 5 adults with AATD and Z homozygosity harbor significant fibrosis, and nearly 1 in 10 harbors advanced fibrosis,” the researchers noted. “The risk for fibrosis increases incrementally with the frequency of Pi*Z mutations,” they concluded.
Huang DQ, Chan KE, Tan C, et al. Meta-analysis: prevalence of significant or advanced fibrosis in adults with alpha-1-antitrypsin deficiency. Aliment Pharmacol Ther. Published online April 23, 2023. doi:10.1111/apt.17516