Alpha-1 antitrypsin (A1AT) deficiency, particularly homozygous PiZZ genotype (severe defi...

Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.

ID	`RF-A1AT-DEFICIENCY-HCC-LUNG-PREVENTION`
Тип	Тривожна ознака
Статус	переглянуто 2026-05-18 \| очікує клінічного підпису
Хвороби	`DIS-HCC` `DIS-NSCLC`
Джерела	`SRC-AASLD-HCC-2023` `SRC-NCCN-BCELL-2025` `SRC-NCCN-NSCLC-2025`

Походження тривожної ознаки

Визначення	Alpha-1 antitrypsin (A1AT) deficiency, particularly homozygous PiZZ genotype (severe deficiency with serum A1AT typically <11 µM / <50 mg/dL), in an individual without a current HCC or lung cancer diagnosis. PiZZ confers elevated HCC risk in cirrhotic subset (~3-5%/year in adult cirrhotic A1AT-deficient cohorts; Pittelkow et al. JAMA 2014; Tanash et al. Gastroenterology 2016) and elevated lung cancer risk in smokers + non-smokers (Pittelkow JAMA 2014; observational cohorts SIR ~2-3 for lung cancer, multiplicatively higher with smoking). Underlying pathology: misfolded Z-A1AT polymerizes in hepatocytes (hepatic injury → fibrosis → cirrhosis → HCC) and absent circulating A1AT permits neutrophil-elastase-mediated alveolar destruction (emphysema → field-cancerization-mechanism lung cancer risk). PiSZ heterozygotes carry intermediate risk; PiMZ carriers near-population risk except with concu...
Клінічний напрям	investigate
Категорія	other

Логіка спрацьовування

{
  "any_of": [
    {
      "finding": "a1at_pizz_genotype_confirmed",
      "value": true
    },
    {
      "finding": "a1at_serum_level_severely_deficient",
      "value": true
    },
    {
      "finding": "a1at_deficiency_with_cirrhosis",
      "value": true
    },
    {
      "finding": "a1at_deficiency_with_copd_emphysema",
      "value": true
    }
  ],
  "type": "lab_value"
}

Нотатки

v0.3 chronic-condition prevention pilot — alpha-1 antitrypsin deficiency (PiZZ primarily) / HCC + lung cancer. Prevention-persona RedFlag (CHARTER §3 amended 2026-05-18 Path A, HCP-mediated). Fires when patient profile shows confirmed A1AT deficiency (PiZZ or severe serum deficiency) AND no confirmed HCC or lung cancer. Engine routes to PreventionPlan with 2 tracks: liver function + AFP q6-12mo + AASLD HCC surveillance if cirrhotic + smoking cessation imperative + HRCT chest if symptomatic (IND-A1AT-DEFICIENCY-HCC-LUNG-PREVENTION-SURVEILLANCE) as standard; hepatology/pulmonology-driven observation with imaging on symptom trigger only (IND-A1AT-DEFICIENCY-HCC-LUNG-PREVENTION-OBSERVATION) as alternative. Evidence base: - **HCC risk in cirrhotic A1AT:** Tanash et al. Gastroenterology 2016 (Swedish PiZZ cohort, HCC incidence in cirrhotic subset ~3-5%/year — meets AASLD surveillance threshold); Pittelkow JAMA 2014 (US cohort, SIR HCC ~3 overall). - **Lung cancer risk in A1AT:** Pittelkow JAMA 2014 (SIR ~2-3 lung cancer in PiZZ, multiplicatively higher in smokers); mechanism likely emphysema-driven field cancerization rather than direct A1AT-protective role on alveolar epithelium. - **S...

Де використовується

Indications

IND-A1AT-DEFICIENCY-HCC-LUNG-PREVENTION-OBSERVATION - IND-A1AT-DEFICIENCY-HCC-LUNG-PREVENTION-OBSERVATION
IND-A1AT-DEFICIENCY-HCC-LUNG-PREVENTION-SURVEILLANCE - IND-A1AT-DEFICIENCY-HCC-LUNG-PREVENTION-SURVEILLANCE