Elimination of Hepatitis C in Portugal: An Urban Legend?

The burden of hepatitis C virus infection remains very high despite huge progress in the cure of the infection. The high prevalence of hepatitis C, especially in vulnerable groups and particularly drug users, may compromise the achievement of the 2030 WHO targets with a 90% reduction in new infections and a 65% reduction in mortality. Therapy with the latest pangenotypic direct-acting antivirals provides cure rates in the order of 97% with short-term oral treatment (8-12 weeks) and with an excellent safety and tolerability profile. Curing the infection causes significant health gains derived from preventing complications from cirrhosis, especially hepatocellular carcinoma, and from liver transplantation. Elimination of hepatitis seems feasible with the implementation of a massive therapy program, focusing particularly on vulnerable populations, through micro-elimination strategies, and in the general population with age-based screening. The reduction of the virus reservoir (humans are the only reservoir) is a determining factor in eradicating the virus.

O peso relativo da infecção pelo vírus da hepatite C permanece muito elevado apesar dos enormes progressos verificados na cura da infecção. A elevada prevalência da hepatite C, sobretudo nos nos grupos vulneráveis e em particular nos utilizadores de drogas, pode comprometer o atingimento das metas da WHO para 2030 com redução de 90% de novas infecções e redução de mortalidade em 65%. A terapêutica com os antivíricos de acção directa mais recentes, pangenotípicos, proporciona taxas de cura da ordem dos 97% com tratamento oral de curta duração (8-12 semanas), e com excelente perfil de segurança e tolerabilidade. A curada infecção ocasiona significativos ganhos em saúde derivados da prevenção das complicações da cirrose, sobretudo do carcinoma hepatocelular, e do transplante hepático. A eliminação da hepatite parece exequível com a aplicação de um programa de massificação da terapêutica, incidindo particularmente nas populaçõs vulneráveis, através de estratégias de microeliminação, e na população geral com rastreio baseado na idade. A redução do reservatório do vírus (o homem é o único reservatório), é determinante para a sua eliminação.

Fistula Recurrence: A Clinical Reality after Successful Endoscopic Closure of Laparoscopic Sleeve Gastrectomy Fistulas.

BACKGROUND AND AIMS: Laparoscopic sleeve gastrectomy (LSG)-related fistulas are important and potentially fatal complications. We aimed at determining the incidence, predictive factors, and management of recurrence of post-LSG fistulas. METHODS: This is a retrospective cohort study of 12 consecutive patients with LSG fistulas managed endoscopically between 2008 and 2013. We analyzed factors associated with recurrence of post-LSG fistulas and the efficacy of a primarily endoscopic approach to manage fistula recurrence. RESULTS: The average age at fistula detection after LSG was 43.3 ± 10.9 years, and 10 (83%) patients were female. The median interval between surgery and initial fistula detection was 14 (4-145) days. Fistulas were located at the gastric cardia in 9/12 patients. A median of 4 (1-10) endoscopies were performed per patient until all fistulas were successfully closed. The median follow-up was 30.5 (15-72) months. Fistula recurrence was detected in 3 (25%) female patients with an average age of 31.7 ± 7.9 years after a median of 119 (50-205) days of the initial fistula closure. Fistulas in all 3 patients recurred at the gastric cardia and were successfully managed endoscopically. There was a second recurrence in 1 patient after 6 months, and she was re-operated with anastomosis of a jejunal loop at the site of the fistula orifice at the gastric cardia. We did not find any factors at initial fistula detection that were significantly associated with fistula recurrence. There were no deaths related to initial fistula after LSG and fistula recurrence. CONCLUSIONS: A primarily endoscopic approach is an effective and safe method for the management of fistulas after LSG. Fistula recurrence occurred in 25% of patients and was managed endoscopically. KEY MESSAGES: Although we could not define predictive factors of post-LSG fistula recurrence, it is a clinical reality and can be managed endoscopically.

OBJECTIVOS: As fistulas pós-gastrectomia vertical (sleeve) laparoscópica (LSG) são complicações importantes e potencialmente fatais. O objectivo do estudo foi determinar a incidência, factores preditivos e manejo da recorrência de fistulas pós LSG. MÉTODOS: Estudo retrospectivo de 12 doentes com fistulas pós LSG manejados endoscopicamente entre 2008 e 2013. Analisámos factores associados à recorrência de fistulas pós LSG e a eficácia da abordagem endoscópica. RESULTADOS: Idade média na detecção das fistulas pós LSG foi de 43.3 ± 10.9 anos e 10 (83%) doentes eram mulheres. O intervalo mediano entre a cirurgia e a detecção da fistula inicial foi de 14 (4­145) dias. As fistulas localizaram-se no cárdia em 9/12 doentes. Foram realizadas em mediana 4 (1­10) endoscopias por doente até ao encerramento eficaz das fistulas. O tempo mediano de seguimento foi de 30.5 (15­72) meses. A recorrência das fistulas foi detectada em 3 (25%) doentes, todas mulheres, com idade média de 31.7 ± 7.9 anos, após um tempo mediano de 119 (50­205) dias após encerramento da fistula inicial. As recorrências das fistulas nas três doentes ocorreram no cárdia e foram manejados endoscopicamente.Houve uma segunda recorrência de fistula numa doente após 6 meses que foi reoperada com anastomose de ansa jejunal no local do orifício de fistula no cárdia. Não conseguimos determinar factores na altura da detecção da fistula inicial pós LSG significativamente associados com recorrência de fistulas. Não houve mortalidade associada às fistulas pós LSG (inicial ou recorrência). CONCLUSÕES: A abordagem primariamente endoscópica das fistulas pós LSG é um método eficaz e seguro. A recorrência de fistulas ocorreu em 25% dos doentes. As recorrências de fistulas pós LSG são manejáveis endoscopicamente. MENSAGENS CHAVE: Embora não tenhamos conseguido definir factores preditivos de recorrência de fistulas pós LSG, a recorrência de fistulas é uma realidade clínica e é manejável endoscopicamente.

Incidence, predictive factors and clinical significance of development of portal vein thrombosis in cirrhosis: A prospective study.

BACKGROUND AND AIMS: The role of portal vein thrombosis (PVT) in the natural history of cirrhosis is controversial. There are few prospective studies validating risk factors for development of PVT. We analysed the incidence, factors associated with PVT development and its influence on cirrhosis decompensations and orthotopic liver transplant (OLT)-free survival. METHODS: In this prospective observational study between January 2014 and March 2019, 445 consecutive patients with chronic liver disease were screened and finally 241 with cirrhosis included. Factors associated with PVT development and its influence on cirrhosis decompensations and OLT-free survival by time dependent covariate coding were analysed. RESULTS: Majority of patients belonged to Child-Pugh class A 184 (76.3%) and the average MELD score was 10 ± 5. Previous cirrhosis decompensations occurred in 125 (52.1%), 63 (26.1%) were on NSBB and 59 (27.2%) had undergone banding for bleeding prophylaxis. Median follow-up was 29 (1-58) months. Cumulative incidence of PVT was 3.7% and 7.6% at 1 and 3 years. Previous decompensation of cirrhosis and low platelet counts but not NSBB independently predicted the development of PVT. During follow-up, 82/236 (34.7%) patients developed cirrhosis decompensations. OLT-free survival was 100% and 82.8% at 3 years, with and without PVT respectively. MELD score, but not PVT, independently predicted cirrhosis decompensations (HR 1.14; 95%CI:1.09-1.19) and OLT-free survival (HR 1.16;95%CI:1.11-1.21). CONCLUSION: Previous decompensations of cirrhosis and thrombocytopenia predict PVT development in cirrhosis suggesting a pathophysiologic role for severity of portal hypertension. PVT development did not independently predict cirrhosis decompensations or lower OLT-free survival.

Gastric metastases of cervical carcinoma, rare cause of gastrointestinal bleeding / Metastatización gástrica por carcinoma del cuello del útero, una causa rara de hemorragia digestiva

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Anticoagulation in Cirrhosis and Portal Vein Thrombosis Is Safe and Improves Prognosis in Advanced Cirrhosis.

BACKGROUND: The role of portal vein thrombosis (PVT) in the natural history of cirrhosis is controversial. AIMS: We analyzed the safety and effect of anticoagulant therapy (AT) on PVT recanalization and orthotopic liver transplant (OLT)-free survival. METHODS: Eighty consecutive patients from a prospective registry of cirrhosis and non-tumoral PVT at a tertiary center were analyzed. AT effect on PVT recanalization and OLT-free survival was determined by time-dependent Cox regression analysis. RESULTS: Average MELD score was 15 ± 7. Portal hypertension-related complications at PVT diagnosis were present in 65 (81.3%) patients. Isolated portal vein trunk/branch thrombosis was present in 53 (66.3%) patients. AT was started in 37 patients. AT was stopped in 17 (45.9%) patients, in 4 (10.8%) due to bleeding events. No variceal bleeding occurred while on AT. Anticoagulation was restarted in 6/17 (35.2%) patients due to rethrombosis. In 67 patients with adequate follow-up imaging, AT significantly increased the rate of PVT recanalization compared with those who did not receive anticoagulation [51.4% (18/35) vs 6/32 (18.8%), p = 0.005]. OLT-free survival after a median follow-up of 25 (1-146) months was 32 (40%). Although there was no significant effect of AT on overall OLT-free survival, OLT-free survival was higher among patients with MELD ≥ 15 receiving AT compared to those who did not (p = 0.011). Baseline MELD at PVT detection independently predicted PVT recanalization (HR 1.11, 95% CI 1.01-1.21, p = 0.027) and mortality/OLT (HR 1.12, 95% CI 1.05-1.19, p < 0.001). CONCLUSIONS: Although AT did not improve overall OLT-free survival, it was associated with higher survival in advanced cirrhosis. Anticoagulation increased PVT recanalization and should be maintained after PVT recanalization to avoid rethrombosis.

A surprising "gastric" biopsy / Biopsia gástrica inesperada

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Endoscopic balloon dilation of oesophageal stenosis in a patient with recessive dystrophic epidermolysis bullosa / Dilatación endoscópica con balón de estenosis esofágica en paciente con epidermollis bulsosa distrófica recesiva

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Transient and persistent acute kidney injury in acute liver failure.

BACKGROUND: Acute Kidney Injury (AKI) is a very frequent complication in the Acute Liver Failure (ALF) population associated with negative outcomes. We aim to evaluate the impact of AKI duration on the outcomes of an ALF population. METHODS: A 20-year retrospective analysis of ALF patients admitted to an Intensive Care Unit (ICU) was performed. Chronic liver failure, chronic kidney disease on renal replacement therapy, dialysis requirement within the week prior or an ICU stay of less than 48 h after AKI diagnosis, were exclusion criteria. AKI was defined according to the KDIGO criteria and classified into transient (< 48 h duration) or persistent (48 h duration). RESULTS: A total of 51 patients were included in the analysis and most had AKI (66.7%). Persistent AKI patients (70.6%) presented more frequently with AKI at admission and a higher SOFA score than transient AKI and no AKI, p < 0.05. More severe AKI, sepsis, vasopressor support and mechanical ventilation were also more common (p < 0.05). Nineteen (55.9%) were classified as persistent AKI exclusively by serum creatinine and 15 (44.1%) by both serum creatinine and urine output criteria. Mean survival time at 30 days was 11.3 days for persistent AKI, 25.3 days for transient AKI and 27.0 days for no AKI, p = 0.01. Adjusted multivariate cox regression analysis showed that persistent AKI predicted in-hospital mortality but it lost significance when AKI severity was introduced in the model. CONCLUSION: Persistent AKI was common in ALF patients and associated with more severe AKI, worst systemic complications and a higher 30-day mortality, compared to transient and no AKI patients.

Serum vitamin D levels correlate with the presence and histological grading of colorectal adenomas in peri and postmenopausal women.

BACKGROUND & AIMS: Vitamin D is known to modulate immune function and proliferation. Higher vitamin D [25(OH)D3] serum levels have been reported to have protective effects on adenoma detection and colorectal cancer (CRC) development and survival. METHODS: This retrospective cohort study included 315 peri and post-menopausal women submitted to opportunistic colorectal and osteoporosis screening at the gynaecology outpatient clinic of a tertiary medical centre between 2004 and 2015. Colonoscopy findings were correlated with 25(OH)D3 and PTH serum levels, and subsequently adjusted in a multivariate logistic regression model. Confounding factors included demographic and colorectal risk factors, pharmacological therapies and bone densitometry metrics. RESULTS: A total of 77 lesions were identified in 66 patients. Vitamin D insufficiency (<30 ng/mL) and deficiency (<20 ng/mL) were identified in 79.4% and 35.2% of patients, respectively. In univariate analysis, lower levels of 25(OH)D3 were associated with polyp, adenoma and advanced adenoma detection. After adjusting for confounders, an association with polyps could not be observed, but a trend towards a negative correlation with adenoma detection was found (adjusted OR: 0.96; 95% CI 0.92-1.00; p = 0.083). Regarding advanced adenoma detection, 25(OH)D3 (adjusted OR: 0.86; 95% CI 0.77-0.97; p = 0.013) proved to be an independent predictive factor. No association was found between 25(OH)D3 levels and lesion detection site. CONCLUSION: The association of 25(OH)D3 serum levels with colorectal lesions seems to be restricted to adenomatous lesions and is influenced by histological grading. Vitamin D may be a valuable biomarker for optimization of risk stratification in group-specific CRC screening protocols.

Gastritis cystica profunda mimicking a GIST - A diagnostic challenge / Gastritis cystica profunda simulando GIST - un caso de desafío diagnóstico

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Epidemic history of hepatitis C virus genotypes and subtypes in Portugal.

Any successful strategy to prevent and control HCV infection requires an understanding of the epidemic behaviour among the different genotypes. Here, we performed the first characterization of the epidemic history and transmission dynamics of HCV subtypes in Portugal. Direct sequencing of NS5B was performed on 230 direct-acting antiviral drugs (DAA)-treatment naïve patients in Lisbon. Phylogenetic analysis was used for subtyping and transmission cluster identification. Bayesian methods were used to reconstruct the epidemic history of HCV subtypes. Sequences were analysed for resistance-associated substitutions (RAS). The majority of strains were HCV-GT1 (62.6%), GT3 (18.3%, all subtype 3a) and GT4 (16.1%). Among GT1, the most frequent were subtypes 1a (75.5%) and 1b (24.5%). Polyphyletic patterns were found in all but 12 lineages suggesting multiple introductions of the different subtypes in this population. Five distinct epidemics were identified. The first significant HCV epidemic in Portugal occurred between 1930s and 1960s, was caused almost exclusively by GT1b and was likely associated with blood transfusions. Rapid expansion of GT3a occurred in the 1960s and GT1a in the 1980s, associated with intravenous drug use. The most recent epidemics were caused by GT4a and GT4d and seem to be associated with the resurgence of opioid use. The C316N substitution was found in 31.4% of GT1b-patients. Close surveillance of patients bearing this mutation and undergoing dasabuvir-based regimens will be important to determine its impact on treatment outcome.

Lipids, glucose and iron metabolic alterations in chronic hepatitis C after viral eradication - comparison of the new direct-acting antiviral agents with the old regimens.

BACKGROUND: Hepatitis C virus (HCV) is a unique virus which interacts with cholesterol, iron and insulin metabolism. There is limited data on the effects of direct-acting antiviral agents (DAAs) on metabolic profiles. We aimed at evaluating the behavior of metabolic risk factors of chronically HCV-infected patients after sustained virologic response (SVR), comparing the outcomes with the new DAAs versus the old treatment regimen Peg-interferon ± ribavirin. METHODS: A total of 178 patients who achieved SVR and completed one year of follow-up were prospectively included in this study: group 1 with 105 patients treated with DAAs and group 2 with 73 patients treated with old regimens. Outcomes included lipid, glucose and iron metabolism variation after SVR. RESULTS: There was a significant increase in total cholesterol in both groups (group 1: p < .001, 95% CI: 0.41-0.78; group 2: p < .001, 95% CI: 0.24-0.69). Triglyceride levels significantly decreased (p = .015, 95% CI: -0.33-0.04) in group 1 and increased (p = .014, 95% CI: 0.07-0.59) in group 2. LDL levels increased in group 1 (p = .029, 95% CI: 0.05-0.88), but no significant variation was found in group 2. No significant variation in HDL, fast glucose and iron was seen in both groups. There was a significant increase of HOMA (p = .002, 95% CI: 0.17592-0.72317) only in group 2. Ferritin serum levels significantly decreased (p < .001, 95% CI:-138.3-74.4) in group 1 but no significant variation was found in group 2. CONCLUSION: Patients who have achieved SVR may have increased risk of cardiovascular outcomes due to development of hyperlipidemia and insulin resistance.

Prediction of acute kidney injury in cirrhotic patients: a new score combining renal, liver and inflammatory markers.

INTRODUCTION: Acute kidney injury (AKI) is common in hospitalized patients with cirrhosis and is associated with poor prognosis. A risk prediction score combining values easily measured at admission could be valuable to stratify patients for prevention, monitoring and early intervention, ultimately improving patient care and outcomes. The aim of this study was to develop a risk score for AKI in a cohort of cirrhotic patients. PATIENTS AND METHODS: We cross-examined the data from a retrospective analysis of 186 patients with cirrhosis admitted to the Gastroenterology and Hepatology Service of Centro Hospitalar Lisboa Norte from January 2003 to December 2005. AKI was defined as an increase in serum creatinine (SCr)≥0.3 mg/dL within 48 hours or a percentage increase in SCr≥50% from baseline. Neutrophil-to-lymphocyte ratio (NLR) was used as a marker for inflammation. A receiver operating characteristic (ROC) curve was produced to assess the discriminative ability of the variables. Cutoff values were defined as those with highest validity. The final AKI risk score model was assessed using the ROC curve. RESULTS: A total of 52 patients (28%) developed AKI. Higher baseline SCr (p<0.001), more severe liver disease as evaluated by the modified Model of End-stage Liver Disease (MELD)-Na score (p<0.001) and higher NLR (p=0.028) were independently associated with AKI. The area under the ROC (AUROC) curve for the prediction of AKI was 0.791 (95% CI 0.726-0.847) for SCr, 0.771 (95% CI 0.704-0.829) for modified MELD-Na and 0.757 (95% CI 0.689-0.817) for NLR. Cutoff values with the highest validity for predicting AKI were determined and defined as 0.9 for the SCr, 21.7 for the modified MELD-Na and 6 for the NLR. The risk score was created allowing 3 points if the SCr is higher than 0.9, 1 point if the modified MELD-Na is higher than 21.7 and 1 point if the NLR is higher than 6. The AUROC curve of the risk prediction score for AKI was 0.861. A risk score of ≥2 points predicts AKI in cirrhotic patients with a sensitivity of 88.5% and specificity of 72.4%. CONCLUSION: A new score combining SCr, MELD-Na and NLR demonstrated a strong discriminative ability to predict AKI in cirrhotic patients.

Identifying palliative care needs in a Portuguese liver unit.

BACKGROUND & AIMS: Chronic liver disease is a major worldwide cause of morbidity and mortality. Palliative care policies are not clearly established in chronic liver disease. The NECPAL CCOMS-ICO© (NECesidades PALiativas/Palliative Needs) is a tool to identify palliative care needs, including a section for liver disease. AIM: The aim of this study was to identify palliative care needs in liver patients hospitalised in a tertiary referral Liver Unit. METHODS: Single-centre prospective observational study. One hundred and twenty patients with cirrhosis were included and NECPAL questionnaire was applied to all patients in a 7-month period. RESULTS: 84.2% of patients were considered as requiring palliative intervention; however, clinicians identified those needs only in 65.8% of the cases and caregivers in 6.7% of the cases; less than 8% of the patients were referred for palliative care consultation. An excessive use of healthcare resources (positive answer to question 3) was strongly associated with a positive need for palliative care (positive NECPAL): OR 7.305, CI 95% 2.54-20.995, P < .001). An excessive use of healthcare facilities has a sensitivity of 84.2% and a specificity of 42.1% for prediction of a positive NECPAL result (AUC 0.710, 95% CI 0.570-0.850, P = .004). CONCLUSIONS: The NECPAL CCOMS-ICO© represents a feasible and easy-to-use tool to identify palliative care needs in patients with chronic liver disease.