Future Perspectives in the Diagnosis and Treatment of Liver Disease Associated with Alpha-1 Antitrypsin Deficiency.

Alpha-1 antitrypsin deficiency (AATD) is one of the most common genetic diseases and is caused by mutations in the SERPINA1 gene. The homozygous Pi*Z variant is responsible for the majority of the classic severe form of alpha-1 antitrypsin deficiency, which is characterized by markedly decreased levels of serum alpha-1 antitrypsin (AAT) with a strong predisposition to lung and liver disease. The diagnosis and early treatment of AATD-associated liver disease are challenges in clinical practice. In this review, the authors aim to summarize the current evidence of the non-invasive methods in the assessment of liver fibrosis, as well as to elucidate the main therapeutic strategies under investigation that may emerge in the near future.

A deficiência de alfa-1 antitripsina é uma das doenças genéticas mais comuns e é causada por mutações no gene SERPINA1. A mutação Pi*Z em homozigotia é responsável pela maioria dos casos de apresentação clássica da deficiência de alfa-1-antripsina, que se caracteriza por uma diminuição significativa dos níveis séricos desta proteína com forte predisposição ao desenvolvimento de doença pulmonar e hepática. O diagnóstico precoce e tratamento da doença hepática representam importantes desafios na prática clínica. Nesta revisão, os autores têm como objetivo resumir a evidência atual dos métodos não invasivos na avaliação da fibrose hepática, bem como, elucidar as principais estratégias terapêuticas atualmente sob investigação e que poderão emergir num futuro próximo.

Infectious proctitis: what every gastroenterologist needs to know.

The incidence of sexually transmitted infections (STI) is rising, especially in high-risk groups, namely people living with human immunodeficiency virus (HIV), men who have sex with men, and people with multiple sexual partners. Additionally, the growing availability and use of pre-exposure prophylaxis to prevent HIV infection appears to be associated with an increased risk of infection by venereal agents. The correct recognition of these infections is crucial, not only for individual patients, but also in terms of public health. Furthermore, a diligent diagnostic assessment is key for an efficient therapeutic approach. Infectious proctitis (IP) predominantly occurs in individuals with a history of receptive anal exposure, being a frequent cause for referral to a gastroenterology specialist. The most frequently identified agents are Neisseria gonorrhoeae, Chlamydia trachomatis, Herpes simplex virus, and Treponema pallidum. This paper aims to provide a practice-oriented and up-to-date review regarding the diagnostic and therapeutic approaches to patients with suspected IP. The authors reviewed the most important issues in terms of clinical history, physical examination, and specific diagnostic and therapeutic methods. It is also highlighted the most important topics regarding vaccination, screening for other STIs and differential diagnosis with inflammatory bowel disease. Identification of high-risk groups, screening of potential STIs, and notification of diagnosed anorectal diseases are extremely important and essential to prevent transmission and other complications.

Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency.

OBJECTIVE: Alpha-1 antitrypsin deficiency (AATD) is a common, potentially lethal inborn disorder caused by mutations in alpha-1 antitrypsin (AAT). Homozygosity for the 'Pi*Z' variant of AAT (Pi*ZZ genotype) causes lung and liver disease, whereas heterozygous 'Pi*Z' carriage (Pi*MZ genotype) predisposes to gallstones and liver fibrosis. The clinical significance of the more common 'Pi*S' variant remains largely undefined and no robust data exist on the prevalence of liver tumours in AATD. DESIGN: Baseline phenotypes of AATD individuals and non-carriers were analysed in 482 380 participants in the UK Biobank. 1104 participants of a multinational cohort (586 Pi*ZZ, 239 Pi*SZ, 279 non-carriers) underwent a comprehensive clinical assessment. Associations were adjusted for age, sex, body mass index, diabetes and alcohol consumption. RESULTS: Among UK Biobank participants, Pi*ZZ individuals displayed the highest liver enzyme values, the highest occurrence of liver fibrosis/cirrhosis (adjusted OR (aOR)=21.7 (8.8-53.7)) and primary liver cancer (aOR=44.5 (10.8-183.6)). Subjects with Pi*MZ genotype had slightly elevated liver enzymes and moderately increased odds for liver fibrosis/cirrhosis (aOR=1.7 (1.2-2.2)) and cholelithiasis (aOR=1.3 (1.2-1.4)). Individuals with homozygous Pi*S mutation (Pi*SS genotype) harboured minimally elevated alanine aminotransferase values, but no other hepatobiliary abnormalities. Pi*SZ participants displayed higher liver enzymes, more frequent liver fibrosis/cirrhosis (aOR=3.1 (1.1-8.2)) and primary liver cancer (aOR=6.6 (1.6-26.9)). The higher fibrosis burden was confirmed in a multinational cohort. Male sex, age ≥50 years, obesity and the presence of diabetes were associated with significant liver fibrosis. CONCLUSION: Our study defines the hepatobiliary phenotype of individuals with the most relevant AATD genotypes including their predisposition to liver tumours, thereby allowing evidence-based advice and individualised hepatological surveillance.