RESUMEN
BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C. We analysed the use of different generations of DAAs over time in Switzerland and investigated factors predictive of treatment failure. METHODS: This retrospective study was conducted within the framework of the Swiss Association for the Study of the Liver and the Swiss Hepatitis C Cohort Study; it included all patients with chronic hepatitis C treated with DAAs between January 2015 and December 2019 at eight Swiss referral centres. RESULTS: A total of 3088 patients were included; 57.3% were male, and the median age was 54 years. Liver cirrhosis was present in 23.9% of the cohort, 87.8% of whom were compensated. The overall sustained virological response (SVR) rate (defined as undetectable HCV RNA at week 12 after the first course of DAA-based treatment) was 96.2%, with an increase over time. The rate of treatment failure dropped from 8.3% in 2015 to 2.5% in 2019. Multivariable analysis revealed that female sex, the use of the latest generation of pangenotypic DAA regimens, Caucasian origin, and genotype (gt) 1 were associated with SVR, whereas the presence of active hepatocellular carcinoma (HCC), gt 3, and increasing liver stiffness were associated with treatment failure. Notably, the presence of active HCC during treatment increased the risk of DAA failure by a factor of almost thirteen. CONCLUSIONS: SVR rates increased over time, and the highest success rates were identified after the introduction of the latest generation of pangenotypic DAA regimens. Active HCC, gt 3 and increasing liver stiffness were associated with DAA failure.
Asunto(s)
Antivirales , Hepatitis C Crónica , Cirrosis Hepática , Respuesta Virológica Sostenida , Humanos , Hepatitis C Crónica/tratamiento farmacológico , Suiza/epidemiología , Masculino , Femenino , Antivirales/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Hepacivirus/genética , Insuficiencia del Tratamiento , Genotipo , Carcinoma Hepatocelular , Neoplasias Hepáticas , AdultoRESUMEN
The etiology of autoimmune hepatitis (AIH) is unknown, though hepatotropic viruses may be potential triggers. Hepatitis E virus (HEV) infection, an increasingly recognized cause of acute hepatitis, has been misdiagnosed as AIH due to the occurrence of autoantibodies during its acute phase. It has also been suggested that HEV infection may lead to or unmask AIH. The HEV seroprevalence has been ascertained in patients with AIH, but the prevalence of AIH-related autoantibodies in patients with HEV infection has not been systematically tested. We aimed to investigate whether acute HEV infection is associated with the presence of AIH-relevant autoantibodies, following the liver autoimmune serology guidelines of the International AIH Group. We tested 48 patients with acute HEV infection. Half of them had at least one autoantibody, 17% two autoantibodies. Anti-nuclear antibody (ANA) were detected in 16 (33%), anti-smooth muscle antibody (SMA) in 10 (21%), and anti-neutrophil cytoplasmic antibody (ANCA) in 7 (14.6%). Of note, two patients showed SMA with VG or VGT patterns and five had ANA with homogeneous appearance, both being typical of AIH type 1. Other AIH-specific autoantibodies were negative. Atypical anti-mitochondrial antibody, without evidence of primary biliary cholangitis, was positive in one patient, disappearing at follow-up. Follow-up (median 12 months) serum was available from seven autoantibody positive patients: two became negative, while five remained positive, although no patient developed AIH to date. In conclusion, autoantibodies are frequently present during acute HEV infection, indicating that HEV should always be excluded before diagnosing AIH. Importantly, a minority of patients with acute hepatitis E develops AIH-specific autoantibodies, and, though they did not progress to autoimmune liver disease in the short-term, they warrant long-term monitoring.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/sangre , Anticuerpos Antinucleares/sangre , Autoantígenos/sangre , Hepatitis E/diagnóstico , Hepatitis Autoinmune/diagnóstico , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Hepatitis E/sangre , Hepatitis E/inmunología , Hepatitis E/virología , Virus de la Hepatitis E/inmunología , Virus de la Hepatitis E/patogenicidad , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/virología , Humanos , Sueros Inmunes/química , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The introduction of direct acting antivirals (DAAs) for the therapy of chronic hepatitis C (CHC) has revolutionised treatment and marks a paradigm shift in the approach to this disease, rendering interferon-based therapies obsolete. AIMS OF THE STUDY: We retrospectively and prospectively evaluated treatment results after the introduction of DAA in Switzerland in a cohort of patients with CHC. METHODS: We examined 565 patients who received DAA treatment for CHC between November 2013 and June 2016 with regard to HCV genotype, fibrosis stadium, treatment and outcome. In addition, outcome of re-treatment and resistance-associated substitutions (RAS) in patients that did not achieve sustained virological response (SVR) were evaluated. The majority of patients participate in the Swiss Hepatitis C Cohort Study. Data were evaluated in an intention-to-treat and a modified intention-to-treat analysis. RESULTS: Overall SVR rate for all patients was 94% (530 of 565, 95% CI 92-96%). Of 350 patients with HCV genotype 1 CHC, 335 achieved SVR, resulting in an SVR rate of 96% (335 of 350, 95% CI 94-98%). Patients with HCV genotype 2 achieved SVR in 94% (48 of 51, 95% CI 87-100%). Patients with HCV genotype 3 showed SVR of 92% (98 of 107, 95% CI 87-97%). In patients with HCV genotype 4, the SVR rate was substantially lower at 85% (49 of 57, 95% CI 76-94%). The rate of advanced liver fibrosis (Metavir F3/F4) assessed by means of liver biopsy or Fibroscan® in the entire patient population was 71% (404 of 565). Out of 35 patients that did not achieve SVR after DAA treatment, 32 had a relapse and 3 patients showed viral breakthrough. In 17 of 35 cases (49%) patients were treatment naïve and 21 of 35 patients (60%) were cirrhotic. RAS genotyping of HCV was performed in 14 patients. Nine of these 14 patients (60%) carried mutations in the NS5A region of the virus genome. Twenty-seven percent of patients who experienced treatment failure were not treated with recommended regimens as a result of drug availability and reimbursement limitations. CONCLUSION: In Switzerland, novel DAA treatments for CHC reflect the positive results from registration trials. Genotypes 2 and 4 remained more difficult to treat between 2014 and 2016. Patients who experienced a relapse after DAA treatment in Switzerland predominantly showed mutations in the NS5A region of the virus genome. DAA treatment limitations in Switzerland did prevent optimal treatment regimens in some patients.
Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/genética , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Suiza , Resultado del TratamientoRESUMEN
No data on primary biliary cholangitis (PBC) are available in Switzerland. We established a national patient cohort to obtain information on PBC phenotypes and disease course in Switzerland. Local databases in all university hospitals and in two large secondary centers were searched for case finding. In addition, all primary care physicians, gastroenterologists, rheumatologists, and dermatologists were invited to contribute patients from their own medical records. PBC diagnosis was centrally reviewed. Five hundred one PBC patients were identified, 474 were included in data analysis, and 449 of them were enrolled by tertiary centers. The catchment area accounts for approximately one third of the Swiss population or approximately 2.8 million inhabitants. The median age at diagnosis was 53 years, 84% were women, and 86% were anti-mitochondrial antibody positive. The median follow-up was 5.4 years, 12.6% experienced a liver-related endpoint. Splenomegaly was present at diagnosis in one quarter of patients and in half of male patients. Approximately one third were non-responders to ursodeoxycholic acid (UDCA). The median transplant-free survival at 10 years was 85%. The following variables were independently associated with poor outcome: low platelet count at baseline (HR = 0.99, p < 0.0001), elevated alkaline phosphatase at baseline (HR = 1.36, p < 0.0001), elevated bilirubin at baseline (HR = 1.11, p = 0.001), and elevated alanine aminotransaminase (HR = 1.35, p = 0.04) after 12 months of UDCA therapy. The AUROC for the UK-PBC risk score at 5, 10, and 15 years was 0.82. The AUROC for the Globe score at 5, 10, and 15 years was 0.77. Patients included in this study are currently being enrolled in a prospective nationwide registry with biobank, taking advantage of the collaboration network generated by this study. Our study provides the first snapshot of PBC in Switzerland, describing a diagnostic delay with one quarter of patients diagnosed when already in the cirrhotic stage. We were also able to externally validate the UK-PBC risk score and the Globe score. The ongoing nationwide prospective registry will be fundamental to improve disease awareness and interdisciplinary collaborations and will serve as a platform for clinical and translational research. TRIAL REGISTRATION NUMBER: clinicaltrials.gov : NCT02846896; SNCTP000001870.
Asunto(s)
Colangitis/epidemiología , Cirrosis Hepática Biliar/epidemiología , Trasplante de Hígado , Colangitis/tratamiento farmacológico , Colangitis/mortalidad , Estudios de Cohortes , Estudios Transversales , Diagnóstico Tardío , Resistencia a Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Cirrosis Hepática Biliar/tratamiento farmacológico , Cirrosis Hepática Biliar/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Suiza/epidemiología , Resultado del Tratamiento , Ácido Ursodesoxicólico/uso terapéuticoRESUMEN
BACKGROUND: Novel direct antiviral agents (DAA) targeting hepatitis C virus (HCV) have revolutionized the treatment of chronic hepatitis C infection (CHC). Rates of sustained virological response (SVR) to treatment have drastically improved since introduction of DAA. Transient Elastography (TE) is an ultrasound based, non-invasive technique to assess liver stiffness (LS). We examined the changes in TE values and fibrosis scores FIB-4 and APRI after DAA treatment of CHC. METHODS: 549 patients who received a DAA based treatment for CHC were screened and 392 were included. TE values recorded prior to therapy and within 18 months after therapy were evaluated. In addition, FIB-4 and APRI scores were calculated and histopathological results were recorded if available. RESULTS: Median TE prior to DAA treatment was 12.65 kPa (IQR 9.45-19.2 kPa) and decreased to 8.55 kPa (IQR 5.93-15.25) post-treatment. This finding is statistically significant (P<.001) and equals a TE regression of 32.4% after DAA treatment. Median FIB-4 and APRI values significantly decreased from 2.54 (IQR 1.65-4.43) and 1.10 (IQR 0.65-2.43) to 1.80 (IQR 1.23-2.84, P<.001) and 0.43 (IQR 0.3-0.79, P<.001) respectively. CONCLUSION: Patients with SVR after DAA therapy showed significant regression of TE values. Rapid decrease in TE was in concordance with regression of validated fibrosis scores FIB-4 and APRI. It remains to be examined whether this indicates a true regression of fibrosis or merely resolution of chronic liver inflammation with subsequent improvement of TE values and laboratory parameters.