Effectiveness of hepatitis C antiviral treatment and feasibility of hepatitis C elimination goal.

OBJECTIVES: Second-generation direct-acting antivirals (DAAs) have shown high efficacy in the treatment of chronic hepatitis C virus (HCV) infections in clinical trials. This study aimed to estimate the effectiveness in real-life conditions and their capacity to eliminate HCV infection in the general population. METHODS: In this observational cohort study, patients with active HCV infection who commenced DAA treatment between 2015 and 2020 in Navarre, Spain, were studied. Sustained virological response (SVR), defined as an undetectable viral load 12 weeks after the end of treatment, was evaluated until the end of 2021. RESULTS: Of a total 1366 HCV-infected patients that commenced treatment, 19.3% (n = 263) were HIV-coinfected. After the first DAA treatment, SVR was achieved in 96.6% (n = 1320/1366) of patients and in 97.7% (95% confidence interval [CI] 96.6%-98.3%) of those who completed treatment (per-protocol analysis; n = 1320/1351). SVR was achieved in 97.9% (n = 1066/1089) and 96.9% (n = 254/262) of mono-infected and HIV-coinfected patients, respectively. Thirty-one patients had virological failure due to non-response (n = 19), poor compliance (n = 9), and with adverse events (n = 3). Of 27 patients that received a second treatment, 24 attained SVR (one after a third treatment), two died, and one that did not achieve SVR declined a third treatment. Three patients were re-infected, re-treated, and achieved SVR. At the end of the study, 1344 patients (98.4%, 95% CI 97.6%-98.9%) had achieved SVR, and only 1.8% needed more than one course of treatment. All patients who completed the treatment and were followed-up achieved SVR. CONCLUSION: With DAAs, SVR was achieved in all patients with active HCV infection who completed follow-up, and a second course of treatment was only necessary in a small proportion of patients. Adherence to treatment is essential for HCV infection elimination.

Modification of liver fibrosis, glucose and lipid profile after hepatitis C virus clearance with direct-acting antiviral agents / Cambios en la fibrosis hepática, glucosa y perfil lipídico tras la eliminación del virus de la hepatitis C con antivirales de acción directa

INTRODUCTION: There is little information on whether direct-acting antiviral (DAA) treatment can improve liver fibrosis or change glucose and lipid profile in patients with chronic hepatitis C (CHC). We aimed to evaluate the impact of sustained virologic response (SVR) on liver stiffness, glucose and lipid levels. METHODS: 445 monoinfected CHC patients started treatment with interferon-free DAA therapy from January 2015 to February 2017. Transient elastography (TE), fibrosis scores, glucose and lipid levels were analyzed at baseline and 48 weeks post-treatment (SVR48). RESULTS: The SVR rate was 97.7%. Finally, we evaluated 369 patients who achieved SVR and had reliable TE measurements. Median liver stiffness significantly decreased from 9.3 (IQR 7.3-14.3) kPa at baseline to 6.4 (IQR 4.9-8.9) at SVR48 (p < 0.0001). 54.7% of the cohort presented fibrosis regression. Median FIB4 score regressed from 2.0 (IQR 1.1-3.3) to 1.3 (IQR 0.9-2.0) (p < 0.0001). Median APRI and Forns values significantly decreased from 0.9 (IQR 0.5-1.7) to 0.3 (IQR 0.2-0.4) and from 6.2 (5.0-7.5) to 4.9 (IQR 3.8-5.9) (p < 0.001), respectively. Mean levels of total cholesterol and LDL-C increased from 172mg/dL and 101.5mg/dL to 191mg/dL and 117.5mg/dL (p < 0.0001), respectively. In the sub-group of patients with pre-diabetes or diabetes, mean glucose levels decreased from 142.7mg/dL at baseline to 127.2mg/dL at SVR48 (p < 0.001). DISCUSSION: SVR reduces liver stiffness based on TE and fibrosis scores, in patients treated with DAA. Our results show elevated total cholesterol and LDL-C and decreased glucose levels at SVR48

INTRODUCCIÓN: Se desconoce el efecto a largo plazo de los antivirales de acción directa (AAD) sobre la fibrosis hepática y el perfil metabólico en pacientes con hepatitis crónica C (HCC). Nuestro objetivo fue evaluar el impacto de la respuesta viral sostenida (RVS) sobre la rigidez hepática, la glucosa y el perfil lipídico. MÉTODOS: Un total de 445 pacientes con HCC monoinfectados iniciaron tratamiento con AAD libres de IFN entre enero del 2015 y febrero del 2017. La ET, los marcadores serológicos de fibrosis, los niveles de glucosa y lípidos se analizaron basalmente y 48 semanas tras finalizar el tratamiento (RVS48). RESULTADOS: La tasa de RVS fue del 97,7%. Finalmente analizamos 369 pacientes que obtuvieron RVS y tenían medidas fiables en la ET. La mediana de la rigidez hepática descendió de forma significativa de 9,3 (IQR 7,3-14,3) basalmente a 6,4 (IQR 4,9-8,9) kPa en RVS48 (p < 0,0001). El 54,7% de la cohorte presentó una regresión de la fibrosis. La mediana del FIB4 disminuyó de 2,0 (IQR 1,1-3,3) a 1,3 (IQR 0,9-2,0) (p < 0,0001). Las medianas del APRI y del Forns descendieron significativamente de 0,9 (IQR 0,5-1,7) a 0,3 (IQR 0,2-0,4) y de 6,2 (IQR 5,0-7,5) a 4,9 (3,8-5,9) (p < 0,001), respectivamente. La media de los niveles de colesterol total (CT) y LDL-C aumentaron de 172mg/dL y 101,5mg/dL a 191mg/dL y 117,5mg/dL (p < 0,0001), respectivamente. En el subgrupo de pacientes con prediabetes o diabetes, los niveles de glucosa descendieron de 142,7mg/dL a 127,2mg/dL en RVS48 (p < 0,001). DISCUSIÓN: La RVS reduce la rigidez hepática determinada mediante ET y marcadores serológicos de fibrosis en pacientes tratados con AAD. Nuestros resultados muestran una elevación en el CT y LDL-C y un descenso en los niveles de glucosa en RVS48

Modification of liver fibrosis, glucose and lipid profile after hepatitis C virus clearance with direct-acting antiviral agents.

INTRODUCTION: There is little information on whether direct-acting antiviral (DAA) treatment can improve liver fibrosis or change glucose and lipid profile in patients with chronic hepatitis C (CHC). We aimed to evaluate the impact of sustained virologic response (SVR) on liver stiffness, glucose and lipid levels. METHODS: 445 monoinfected CHC patients started treatment with interferon-free DAA therapy from January 2015 to February 2017. Transient elastography (TE), fibrosis scores, glucose and lipid levels were analyzed at baseline and 48 weeks post-treatment (SVR48). RESULTS: The SVR rate was 97.7%. Finally, we evaluated 369 patients who achieved SVR and had reliable TE measurements. Median liver stiffness significantly decreased from 9.3 (IQR 7.3-14.3)kPa at baseline to 6.4 (IQR 4.9-8.9) at SVR48 (p<0.0001). 54.7% of the cohort presented fibrosis regression. Median FIB4 score regressed from 2.0 (IQR 1.1-3.3) to 1.3 (IQR 0.9-2.0) (p<0.0001). Median APRI and Forns values significantly decreased from 0.9 (IQR 0.5-1.7) to 0.3 (IQR 0.2-0.4) and from 6.2 (5.0-7.5) to 4.9 (IQR 3.8-5.9) (p<0.001), respectively. Mean levels of total cholesterol and LDL-C increased from 172mg/dL and 101.5mg/dL to 191mg/dL and 117.5mg/dL (p<0.0001), respectively. In the sub-group of patients with pre-diabetes or diabetes, mean glucose levels decreased from 142.7mg/dL at baseline to 127.2mg/dL at SVR48 (p<0.001). DISCUSSION: SVR reduces liver stiffness based on TE and fibrosis scores, in patients treated with DAA. Our results show elevated total cholesterol and LDL-C and decreased glucose levels at SVR48.

Long-term changes on health-related quality of life in patients with chronic hepatitis C after viral clearance with direct-acting antiviral agents

Background and aim: new direct-acting antivirals (DAAs) achieve high and sustained virological response (SVR) rates, although the long-term effect on patient health-related quality of life (HRQoL) is unknown. This study aimed to evaluate the impact of hepatitis C virus (HCV) clearance with DAAs on HRQoL after one year of follow-up. Methods: this was a prospective observational study of chronic hepatitis C patients who started DAA treatment between May 2016 and April 2017 and completed the EQ-5D-5L questionnaire at baseline, 12 (post-12) and 48 (post-48) weeks after the end of treatment. Patients with SVR were analyzed in order to investigate factors associated with changes in HRQoL. Results: a total of 199 patients were enrolled, 65% were male, 29% had cirrhosis and 32% had HIV co-infection. The proportion of patients with problems in mobility (from 35% to 21%, p = 0.002), usual activities (26% to 11%, p < 0.001), pain/discomfort (60% to 35%, p < 0.001) and anxiety/depression (57% to 35%, p < 0.001) decreased from the baseline to post-48. The median baseline and post-48 EQ-5D utility and visual analogue scale (VAS) score increased from 0.857 to 0.932 (p < 0.001) and from 70.0 to 90.0 (p < 0.001), respectively. HRQoL improvement was observed in all subgroups of patients. According to the multivariate analyses, patients with F2-F4 fibrosis had a higher utility and VAS score improvement at post-48 than F0-F1 patients, and females had a greater improvement in the VAS score. Age ≥ 65 years and HIV co-infection were associated with a lower gain in VAS score (all p < 0.05). Conclusions: hepatitis C virus clearance with DAAs is associated with important long-term improvements in HRQoL. Four of the five EQ-5D-5L dimensions, as well as the utility value and VAS score significantly improved one year after successful treatment with DAAs

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Long-term changes on health-related quality of life in patients with chronic hepatitis C after viral clearance with direct-acting antiviral agents.

BACKGROUND AND AIM: new direct-acting antivirals (DAAs) achieve high and sustained virological response (SVR) rates, although the long-term effect on patient health-related quality of life (HRQoL) is unknown. This study aimed to evaluate the impact of hepatitis C virus (HCV) clearance with DAAs on HRQoL after one year of follow-up. METHODS: this was a prospective observational study of chronic hepatitis C patients who started DAA treatment between May 2016 and April 2017 and completed the EQ-5D-5L questionnaire at baseline, 12 (post-12) and 48 (post-48) weeks after the end of treatment. Patients with SVR were analyzed in order to investigate factors associated with changes in HRQoL. RESULTS: a total of 199 patients were enrolled, 65% were male, 29% had cirrhosis and 32% had HIV co-infection. The proportion of patients with problems in mobility (from 35% to 21%, p = 0.002), usual activities (26% to 11%, p < 0.001), pain/discomfort (60% to 35%, p < 0.001) and anxiety/depression (57% to 35%, p < 0.001) decreased from the baseline to post-48. The median baseline and post-48 EQ-5D utility and visual analogue scale (VAS) score increased from 0.857 to 0.932 (p < 0.001) and from 70.0 to 90.0 (p < 0.001), respectively. HRQoL improvement was observed in all subgroups of patients. According to the multivariate analyses, patients with F2-F4 fibrosis had a higher utility and VAS score improvement at post-48 than F0-F1 patients, and females had a greater improvement in the VAS score. Age ≥ 65 years and HIV co-infection were associated with a lower gain in VAS score (all p < 0.05). CONCLUSIONS: hepatitis C virus clearance with DAAs is associated with important long-term improvements in HRQoL. Four of the five EQ-5D-5L dimensions, as well as the utility value and VAS score significantly improved one year after successful treatment with DAAs.

Progress in the elimination of hepatitis C virus infection: A population-based cohort study in Spain.

BACKGROUND: The World Health Organization set targets to eliminate hepatitis C virus (HCV) infection through detection and treatment of all cases by 2030. This study aimed to describe the progress and difficulties in the elimination of HCV infection in Navarra, Spain. METHODS: Using electronic healthcare databases, we performed a population-based prospective cohort study to describe changes in the prevalence of diagnosed active HCV infection at the beginning of 2015 and the end of 2017, the rate of new diagnoses and the rate of post-treatment viral clearance (PTVC) during this period. RESULTS: At the beginning of 2015 there were 1503 patients diagnosed with positive HCV-RNA, 2.4 per 1000 inhabitants, and at the end of 2017 the prevalence had decreased by 47%. In the study period, 333 (18 per 100,000 person-years) new positive HCV-RNA cases were detected, but only 76 (23%; 4.2 per 100,000 person-years) did not have anti-HCV antibodies previously detected. Prevalent cases and new diagnoses of active infection were more frequent in men, people born in 1950-1979, HIV-infected patients and in those with lower income levels. Among patients with HCV-RNA, 984 achieved PTVC (22.7 per 100 person-years). PTVC was less frequent in patients born before 1940, in immigrants and in patients with lower income levels. CONCLUSIONS: The prevalence of diagnosed active HCV infection has dropped by almost half over three years, because the number of patients with PTVC was much higher than the number of new diagnoses. Interventions specifically targeted at population groups with less favourable trends may be necessary.

Impact of successful treatment with direct-acting antiviral agents on health-related quality of life in chronic hepatitis C patients.

BACKGROUND: Direct-acting antivirals (DAA) have demonstrated high efficacy to achieve sustained virological response (SVR) in chronic hepatitis C patients. We aim to assess the change in health-related quality of life (HRQoL) among patients successfully treated, and to identify predictors of this variation. METHODS: In a prospective observational study, patients with chronic hepatitis C who started DAA therapy between May 2016 and April 2017 completed the EQ-5D-5L questionnaire at baseline and 12 weeks after the end of therapy before knowing the virological result. Analysis included all patients with SVR. RESULTS: Median baseline EQ-5D-5L scores of the 206 enrolled patients were 0.857 utility and 70.0 visual analogue scale (VAS). Following SVR, a reduction occurred in the proportion of patients with mobility problems (35% vs 24%, p = 0.012), pain/discomfort (60% vs 42%, p<0.001) and anxiety/depression (57% vs 44%, p = 0.012), with an increase in utility (+0.053, p<0.001) and VAS (+10, p<0.001). Score improvements were also observed in cirrhotic (+0.048 utility, p = 0.027; +15 VAS, p<0.001) and HIV co-infected patients (+0.039 utility, p = 0.036; +5 VAS, p = 0.002). In multivariate analyses, middle age (45-64 years) and baseline anxiety/depression were associated to greater improvement in utility after SVR, and moderate-advanced liver fibrosis and cirrhosis to greater increase in VAS score. Low baseline values were associated to greater improvements in utility value and VAS score. CONCLUSIONS: The cure of chronic hepatitis C infection with DAA has a short term positive impact on HRQoL with improvement in mobility, pain/discomfort, anxiety/depression, utility value and VAS score. Patients with poor baseline HRQoL were the most beneficed.

Anorectal melanoma: An atypical cause of rectorrhagia / Causa atípica de rectorragia: melanoma anorrectal

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Hipertensión portal idiopática no cirrótica y trombosis portal en paciente con infección por VIH / Idiopathic non-cirrhotic portal hypertension and portal vein thrombosis in a patient with HIV infection

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Safety of oral direct acting antiviral regimens for chronic hepatitis C in real life conditions.

OBJECTIVES: Direct acting antivirals (DAA) are extremely effective to treat chronic hepatitis C. The aim of this study was to evaluate, by using objective variables, the safety of DAA combinations under clinical practice conditions. METHODS: A retrospective study was carried out in mono-infected patients with chronic hepatitis C treated with DAA between January and December 2015 in our centre. Discontinuations, treatment modifications, deaths and laboratory parameters were studied (liver function tests, hemoglobin, creatinine and lipid profile at baseline, weeks 4, 8 and post 12). Temporal variation of laboratory parameters was analyzed by t-test for paired data, and comparison between groups was made by t-test for independent samples and ANOVA. RESULTS: 227 patients were included (40.5% cirrhotic). Sustained virological response (SVR) was achieved in 97.3% of patients. In only one case was the antiviral medication suspended due to toxicity, and there were no voluntary treatment discontinuations. The use of ribavirin (RBV) was associated with mild transient hyperbilirubinemia (41.2%) and anemia (32.6%, with RBV dose reduction in 7.9% of cases). There was an elevation in total cholesterol and LDL-cholesterol (LDL-C) during and after treatment: mean increase of 23 mg/dL (0.59 mmol/L) and 22 mg/dL (0.57 mmol/L), respectively in post 12 (p < .0001). An increment of 20% of patients with cholesterol levels over optimal figures was observed after DAA completion. CONCLUSION: DAA have an optimum safety profile in real life conditions, with infrequent discontinuation and minor laboratory alterations.

Unusual course of epiploic appendicitis.

Epiploic appendicitis is a benign and self-limited disease, due to inflammation of the epiploic appendices. The diagnosis is established by imaging techniques, avoiding treatments, interventions and unnecessary hospitalizations. Management is conservative. Complications are rare and chronicity is exceptional.

Descripción de un caso de evolución inusual de apendicitis epiploica / Unusual course of epiploic appendicitis

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Rescate con rituximab en paciente con liquen plano esofágico refractario / Rituximab as rescue therapy in refractory esophageal lichen planus

El liquen plano esofágico (LPE) es una entidad poco frecuente cuya prevalencia se desconoce, que puede en ocasiones estar subestimada por los hallazgos sutiles e inespecíficos en las exploraciones realizadas. Las lesiones orales rara vez se extienden para afectar a la mucosa esofágica pero, cuando lo hacen, provocan disfagia y odinofagia. Esta infrecuente afectación del liquen plano conlleva un retraso en el diagnóstico y un tratamiento inadecuado. Se presenta el segundo caso (en nuestro conocimiento) de una paciente de 59 años con LPE, con buena respuesta al tratamiento con rituximab, un anticuerpo monoclonal quimérico dirigido específicamente contra la proteína CD20 presente en los linfocitos B (AU)

Esophageal lichen planus (ELP) is a rare condition with unknown prevalence that can sometimes be underestimated due to the subtle and nonspecific findings of diagnostic workup. Oral lesions rarely extend to the esophageal mucosa, but when they do, the most frequent symptoms are dysphagia and odynophagia. There is often a significant delay in diagnosis and inadequate treatment. We report the case of a 59-year-old woman diagnosed with ELP, successfully treated with rituximab, a chimeric monoclonal antibody that depletes CD20+B cells. To our knowledge, this is only the second report of this treatment in ELP (AU)

[Rituximab as rescue therapy in refractory esophageal lichen planus]. / Rescate con rituximab en paciente con liquen plano esofágico refractario.

Esophageal lichen planus (ELP) is a rare condition with unknown prevalence that can sometimes be underestimated due to the subtle and nonspecific findings of diagnostic workup. Oral lesions rarely extend to the esophageal mucosa, but when they do, the most frequent symptoms are dysphagia and odynophagia. There is often a significant delay in diagnosis and inadequate treatment. We report the case of a 59-year-old woman diagnosed with ELP, successfully treated with rituximab, a chimeric monoclonal antibody that depletes CD20+B cells. To our knowledge, this is only the second report of this treatment in ELP.