RESUMO
Liver cirrhosis development is a multifactorial process resulting from a combination of environmental and genetic factors. The aim of the study was to develop accurate non-invasive diagnostic and prognostic models for alcoholic cirrhosis. Consecutive subjects with at-risk alcohol intake were retrospectively enrolled (110 cirrhotic patients and 411 non-cirrhotics). At enrollment, the data about lifetime drinking history were collected and all patients were tested for Patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409, Transmembrane 6 Superfamily 2 (TM6SF2) rs58542926, and hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) rs72613567 variants. In cross-sectional analyses, models for the diagnosis of cirrhosis were developed using multivariate logistic regression. A predictive score for cirrhosis development over 24 years was built by evaluating time-dependent AUC curves. The best diagnostic accuracy was demonstrated by the model, which also includes daily alcohol consumption, duration of hazardous alcohol use, and genetic variants, with AUCs of 0.951 (95% CI 0.925-0.977) and 0.887 (95% CI 0.925-0.977) for cirrhosis and compensated cirrhosis, respectively. The predictive model for future cirrhosis development (AUC of 0.836 95% CI: 0.769-0.904) accounted for age at onset of at-risk alcohol consumption and the number of PNPLA3 and HSD17B13 variant alleles. We have developed accurate genetic and alcohol consumption models for the diagnosis of alcoholic cirrhosis and the prediction of its future risk.
RESUMO
In this article, we present an unusual case of granulomatosis with polyangiitis (GPA) in a 41-year-old man. The initial presentation of the disease was atypical, with persistent fever, cough, and fatigue, accompanied by elevated inflammatory markers in association with a large, solitary lung lesion observed at the chest X-ray. Despite the presence of an initial radiological picture suggesting pneumonia, the lack of response to antibiotics necessitated a more in-depth evaluation. The diagnosis was confirmed through a lung biopsy and serological tests positive for anti-neutrophil cytoplasmic antibodies (c-ANCA). GPA is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, a systemic autoimmune disease characterized by necrotizing granulomatous inflammation and pauci-immune small vessel vasculitis. This case posed diagnostic challenges due to the atypical presentation, initially mistaken for a respiratory tract infection versus cancer. However, the lack of improvement with antibiotics and persistent inflammation raised suspicions of an underlying complex condition. The diagnosis was confirmed through a lung biopsy and positive c-ANCA serological tests. The patient had reported a prior SARS-CoV-2 infection, raising questions about the possible connection between COVID-19 and GPA, as suggested by previous studies. The diagnostic workup ruled out common and rare pulmonary infections, autoimmune diseases, and neoplasms. However, the presence of positive c-ANCA antibodies was pivotal for the GPA diagnosis. Treatment involved the use of high-dose corticosteroids and rituximab to suppress the autoimmune response. Early diagnosis and timely treatment are essential for improving outcomes in patients with GPA.
