Background: Direct-acting antivirals (DAA) have revolutionized hepatitis C treatment, with high sustained virological response (SVR) rates reported, even in historically difficultto-treat groups. SVR is associated with a decreased risk of hepatocellular carcinoma (HCC), need for transplantation, and overall and liver-related mortality. Data from real-life cohorts on the medium-to long-term outcomes of patients with advanced liver disease and DAA-induced SVR are still missing. Objectives: To report and analyze the long-term Seguimento a longo prazo da doença hepática avançada após cura do vírus C com antivíricos de ação direta: dados de uma coorte Portuguesa Palavras ChaveAgentes antivirais · Carcinoma hepatocelular · Cirrose hepática · Hepatite C · Resposta virológica sustentada Resumo Introdução: Os antivíricos de ação direta (AAD) revolucionaram o tratamento da hepatite C ao atingirem elevadas taxas de resposta virológica sustentada (RVS), mesmo em grupos historicamente difíceis de tratar. A RVS associa-se a uma diminuição do risco de carcinoma hepatocelular (CHC), necessidade de transplantação e mortalidade, global e de causa hepática. São ainda insuficientes de coortes reais na literatura dados que permitam avaliar a extensão dos benefícios clínicos a médio-longo prazo do atingimento de uma RVS com os AAD. Objetivos: Reportar e analisar o impacto a longo prazo da RVS numa coorte real de doentes com doença hepática avançada, tratados com AAD. Métodos: Estudo unicêntrico, retrospetivo, longitudinal com inclusão de doentes com hepatite C crónica com cirrose ou fibrose avançada, que iniciaram tratamento com AAD de fevereiro de 2015 a janeiro de 2017. Resultados: Foram incluídos 237 doentes. Verificou-se uma taxa de retenção no tratamento de 98.7% com uma taxa de RVS de 97.8% (intention to treat: 96.6%). Dos 229 doentes curados, 67.2% eram cirróticos (64.2% Child-Pugh A, 3.1% Child-Pugh B) e 32.8% F3, com um seguimento médio de 28 meses. A taxa de mortalidade global foi de 19/1,000 pessoas-ano e de mortalidade associada à doença hepática de 9.5/1,000 pessoasano. A incidência de eventos de descompensação hepática foi de 25/1,000 pessoas-ano e a de CHC foi de 11.6/1,000 pessoas-ano. Verificou-se um aumento sustentado dos valores séricos de plaquetas até 2 anos de seguimento. A história de eventos de descompensação hepática, concentração de plaquetas e albumina prétratamento encontrou-se significativamente associada a eventos adversos hepáticos durante o seguimento. Conclusões: A cura virológica após tratamento com AAD é sustentada no tempo, encontrando-se associada a um excelente prognóstico clínico em doentes com doença hepática avançada compensada, e a uma melhoria ou estabilização da doença em doentes descompensados. O atingimento de RVS associa-se a um baixo risco de CHC, não o eliminando, e de progressão da doença, sobretudo perante a presença de outros cofatores de agressão hepática, recomendando-se a manutenção do seguimento destes doentes.

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Background and Aims C3 glomerulopathy (C3G) is a rare diagnosis, characterized by dysregulation of the alternative pathway of complement, classically presenting in children and young adults. Recently, it has been reported the association between the production of a monoclonal protein and the development of C3G, affecting a larger age span. Method We report the case of a 53-year-old male patient, that attended the emergency department due to persistent holocranial headache. He was an IV drug abuser with a history of treated Hepatitis C infection and free lambda light chain monoclonal protein, being studied by the Haematology Department. On admission, he was hypertensive (187/98 mmHg), and labs showed an acute on chronic kidney disease (serum creatinine 2.35 mg/dL from a basal of 1.5 mg/dL) with an active urinary sediment (38 erythrocytes/field, with dysmorphia), a urinary protein/creatinine ratio of 626 mg/g, and C3 consumption (0.52 g/L). The patient was admitted, and a kidney biopsy was performed. Results Further lab results confirmed a serum IgG Lambda monoclonal protein. Autoantibodies screening (ANCAs, ANAs, Anti-GBM), ASLO and Rheumatoid Factor were negative. Cryoglobulinemia was detected, and the cryoprecipitate's immunofixation revealed monoclonal proteins IgG Lambda and IgM Kappa. HCV viral load was negative. Bone marrow biopsy revealed a small population (< 3%) of plasma cells with Lambda light chain restriction. Kidney biopsy's light microscopy showed increased mesangial matrix and cells, endocapillary hypercellularity, and some glomeruli with lobulated appearance. Five out of 15 glomeruli presented fibrocellular crescents. Immunofluorescence showed C3 dominant staining on capillary walls and in the mesangium, with absent IgG and light chain deposits. A presumptive diagnosis of C3 glomerulopathy was made and the patient was empirically started on corticosteroids (3 pulses of intravenous methylprednisolone, followed by oral prednisolone 1mg/Kg/day), which was followed by paraprotein-directed chemotherapy with bortezomib, cyclophosphamide and dexamethasone (VCD). The patient is currently on the third VCD cycle, presenting both renal and haematological responses: recovery of serum creatinine to basal levels (1.54 mg/dL), resolution of haematuria and proteinuria, normalisation of C3 levels. Serum immunofixation is currently negative for monoclonal protein, with normal serum immunoglobulin levels. Electron microscopy revealed electron-dense deposits in the mesangium, and mesangium-capillary transition, supporting the diagnosis of C3 glomerulonephritis. Genetic testing of complement-related genes revealed a rare missense variation of unknown significance (c.4855A>C) on the C3 gene, that has been previously reported in association with C3 glomerulopathy and atypical Haemolytic-Uremic syndrome. Conclusion This case represents a monoclonal gammopathy associated-C3 glomerulonephritis with a favourable response to paraprotein-directed chemotherapy. Although the association between monoclonal gammopathy and C3G rests on epidemiologic findings, experimental evidence suggests that several monoclonal proteins have complement dysregulation features, which may enhance alternate complement pathway activation. Our patient's response is in line with observational data that have shown improved renal outcomes in patients who achieve a haematological response following clone-directed chemotherapy, which further supports the role of monoclonal gammopathy in C3G pathogenesis [1]. Interestingly, the genetic variation identified in our patient might have provided a favourable genetic background for the development of C3G, which is thought to rely upon a complex interaction of triggering events, such as a monoclonal gammopathy, and underlying complement abnormalities, such as genetic variants in complement genes.

Background and Aims Prior abdominal surgery may result in peritoneal membrane adhesions and fibrosis, compromising the success of peritoneal dialysis (PD). The impact of this factor on peritoneal membrane function and PD technique survival has not been adequately investigated. The aim of our study was to disclosure the effect of prior abdominal surgical procedures on PD technique survival (main outcome), efficacy rates and also evaluate the risk of infectious complications (secondaries outcomes). Method We performed a retrospective, longitudinal study, that included 155 PD patients followed at our unit, since September 2018 to September 2022. Two groups were created: G1 (without previous abdominal surgery) and G2 (with previous abdominal surgery). Demographic and clinical characteristics, such as age, gender, chronic kidney disease (CKD) etiology, time on PD program, dialytic efficacy (Kt/V), peritoneal equilibration test results and episodes of peritonitis were registered from our unit database. Statistical analyses were performed using SPSS statistics version 23,0. The statistical hypothesis tests with p-value <0,05 were considered significant. Results One-hundred and fifty-five patients (female: 50,9%) with a mean age of 55,4 ± 7 years were selected. The main CKD cause was glomerular diseases (n = 43, 27,7%), followed by uncertain etiology (n = 32, 20,6%) and autosomal dominant polycystic kidney disease (n = 21, 13,5%). G1 (n = 87; 56,1%) and G2 (n = 68; 43,9%) had similar distributions of gender (female: 50,6% vs 47,1%, p = 0,061), age (50,4± 9 vs 55,4 ±10 years, p = 0,076) and dialysis vintage (27,9 vs 28,2 months, p = 0,081). In G1, 62,1% of patients were on continuous ambulatory peritoneal dialysis (vs 55,9% in G2). The majority of patients were high-average transporters in both groups (58,6% vs 54,4%, p = 0,066). Previous comorbidities were (G1 vs G2): arterial hypertension (95,4% vs. 98,5%, p = 0,87), diabetes (27,6% vs. 26,5%, p = 0,83), heart failure (25,3% vs. 26,5%, p = 0,64), peripheral arterial disease (28,7% vs 35,3%, p = 0,082), body mass index >30 kg/m2 (20,7% vs 29,4%, p = 0,072) and dyslipidemia (64,4% vs. 64,7%, p = 0,91). In G1, Kt/V was inferior a 1,7 in 36,8% of patients (vs 66,2% in G2, p<0,001). Seven patients (8,1%) have reported more than one peritonitis during time in PD in group 1 (vs 32,4% in G2, p<0,001). We found no differences in PD technique survival between both groups. Transition to hemodialysis happened in 26,4% of patients in G1 (vs 26,5% in G2, p = 0,092). Mortality rate was similar in both groups (6,9% vs 10,3%, p = 0,063). Conclusion According to our results, prior abdominal surgical procedures do not appear to compromise technique survival in patients on PD. Although, abdominal surgical events places PD patients in a higher risk of infectious complications and lower efficacy rates. Thus, this group of patients deserve a more detailed evaluation before starting PD, in order to understand if they are good candidates for the technique, as this may not be the most advantageous for them in the long term.