High Prevalence of Viral Infection in Adults with Homozygous and Heterozygous Alpha₁-Antitrypsin Deficiency and Chronic Liver Disease

Abstract

Chronic liver disease in patients with alpha 1-antitrypsin deficiency is associated with a high prevalence of viral infection; this infection, rather than alpha 1-antitrypsin deficiency alone, may be the cause of the liver disease in such patients.

Increased risk of chronic liver failure in adults with heterozygous ?-antitrypsin deficiency

“…One of the largest studies of its kind was conducted by Propst et al at a tertiary care hospital in Austria. 34 This study showed that chronic liver disease in patients with ␣ 1 ATD is associated with a high prevalence of viral infection, in particular HCV. The authors suggested that carriers of at least one PI*Z allele are more susceptible to hepatic viral infections, and consequently to the development of chronic liver disease.…”

“…[29][30][31][32][33] An alternative explanation may be that individuals carrying a single PI*Z allele are more susceptible to other hepatic insults such as viral infection, toxins, or the coexistence of other liver diseases. [34][35][36][37][38] The aim of the present study was to determine the prevalence of heterozygous ␣ 1 ATD, particularly of PI MZ, in a population of adult patients with chronic end-stage liver disease who had been thoroughly evaluated for various etiologies of liver disease before orthotopic liver transplantation (OLT). We hypothesized that the finding of a greater prevalence of PI MZ heterozygotes within a disease category would suggest an interaction between the two conditions, resulting in an increased probability of developing end-stage liver disease in affected individuals.…”

Alpha-1-Antitrypsin Deficiency and Liver Disease

“…In these patients with AlATD-associated chronic liver disease, neither additive exoge nous risk factors such as alcohol nor addition al autoimmune liver disease were significant ly associated with chronic liver disease. The main finding of the investigation was the un expectedly high prevalence of markers of viral infections in patients with AlATD-associated chronic liver disease [44]. The finding of anti-HCV at different prevalences in several liver diseases is not surprising.…”

“…In another study involving adults with primary alcoholic liver disease, the incidence of the Pi Z phenotype was the same in cirrhotic patients as in a healthy blood donor population [42], Moreover, it has been shown that patients with the Pi ZZ phe notype and without clinical manifestation of chronic liver disease may exhibit the charac teristic PAS-positive globules in the liver, al though histology is otherwise normal [43], These findings suggest that the globules them selves are not responsible for hepatic damage and that there must be an additional agent triggering chronic liver disease. The possibili ty of other causally related factors in the A1ATD population with chronic liver disease has not been investigated until 1992 when we performed a study on a large population group with A1 ATD [44], With the availability of serological test methods for the detection of antibodies to the hepatitis C virus (HCV) and hepatitis B virus (HBV), it has finally become possible to test the hypothesis that A1ATD-associated liver disease observed is caused by coinfection in analogy to a proposed mouse hepatitis virus model [4], From the total population of 1,865 re ferred patients phenotyped for A1AT in our study, 164 (8.8%) were found to carry the homozygous or heterozygous phenotype. This prevalence is higher than has been reported in other studies and reflects the fact that our sample consisted of a select population seen in a specialist center.…”

Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency

“…An Austrian study of A1AT defi cient patients with chronic liver disease found that 62% of those with cirrhosis were HCV positive and 33% showed evidence of hepatitis B virus (HBV) infection. 48 Another study found that the odds of having a heterozygous Z phenotype increased in patients with HCV compared to a control population, where patients with hepatitis C or B virus were 3.6 times more likely to have a heterozygous Z phenotype than a normal phenotype. 49 Some studies, however, have found no association between hepatitis C infection and A1AT deficiency.…”