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BACKGROUND AND AIMS: Biopsy-proven severe graft steatosis is associated with adverse outcomes after liver transplantation. The concomitant presence of metabolic risk factors might further increase this risk. We studied the association between graft steatosis and metabolic risk factors in the donor, with recipient outcomes after liver transplantation. METHODS: We analyzed data from all consecutive first adult full-graft donation after brain death (DBD) liver transplantations performed in the Eurotransplant region between 2010 and 2020. The presence of graft steatosis and metabolic risk factors was assessed through a review of donor (imaging) reports, and associations with recipient retransplantation-free survival were studied through survival analyses. RESULTS: Of 12 174 transplantations, graft steatosis was detected in 2689 (22.1%), and donor diabetes mellitus (DM), hypertension, and dyslipidemia were present in 1245 (10.2%), 5056 (41.5%), and 524 (4.3%). In multivariable Cox regression analysis, graft steatosis (adjusted HR [aHR] 1.197, p < 0.001) and donor DM (aHR 1.157, p = 0.004) were independently associated with impaired retransplantation-free survival. Graft steatosis and donor DM conferred an additive risk of retransplantation or death (DM alone, aHR: 1.156 [p = 0.0185]; steatosis alone, aHR: 1.200 [p < 0.001]; both steatosis and DM, aHR: 1.381 [p < 0.001]). Findings were consistent in sensitivity analyses focusing on retransplantation-free survival within 7 days. CONCLUSIONS: Graft steatosis and donor diabetes mellitus additively increase the risk of retransplantation or death in adult DBD liver transplantation. Future studies should focus on methods to assess and improve the quality of these high-risk grafts. Until such time, caution should be exercised when considering these grafts for transplantation.
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Hígado Graso , Supervivencia de Injerto , Trasplante de Hígado , Complicaciones Posoperatorias , Sistema de Registros , Donantes de Tejidos , Humanos , Femenino , Masculino , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Persona de Mediana Edad , Hígado Graso/patología , Hígado Graso/etiología , Hígado Graso/complicaciones , Hígado Graso/cirugía , Donantes de Tejidos/provisión & distribución , Factores de Riesgo , Estudios de Seguimiento , Pronóstico , Adulto , Europa (Continente)/epidemiología , Tasa de Supervivencia , Diabetes Mellitus , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Estudios Retrospectivos , Receptores de Trasplantes/estadística & datos numéricosRESUMEN
BACKGROUND AND AIMS: Since the introduction of SARS-CoV-2 vaccines, several cases of vaccine-induced immune thrombocytopenia and thrombosis (VITT) have been described, especially cerebral vein thrombosis. We aimed to retrospectively collect all new cases of acute onset first or recurrent splanchnic vein thrombosis (SVT) following a recent SARS-CoV-2 vaccination within the Vascular Liver Disease Group network. APPROACH AND RESULTS: New cases of SVT were identified from April 2021 to April 2022; follow-up was completed on December 31, 2022. Criteria to define VITT were derived from previous studies. Data from a pre-COVID cohort of patients with SVT (N=436) were used for comparison of clinical presentation, etiology, and outcome. Twenty-nine patients were identified with SVT occurring with a median of 11 days (range 2-76) after the first (48%), second (41%), or third (10%) vaccination (ChAdOx1 nCov-19 (n=12) or BNT162b2 (n=14), other (n=3) Only 2 patients(7%) fulfilled criteria for definite VITT. Twenty (69%) had SVT at multiple sites, including 4 (14%) with concomitant extra-abdominal thrombosis. Only 28% had an underlying prothrombotic condition, compared to 52% in the pre-COVID SVT cohort ( p =0.01). Five patients (17%) underwent bowel resection for mesenteric ischemia, compared with 3% in pre-COVID SVT ( p <0.001). Two patients died shortly after diagnosis (7%). CONCLUSIONS: Although definite VITT was rare, in 72% of cases, no other cause for SVT could be identified following SARS-CoV-2 vaccination. These cases were different from patients with nonvaccine-related SVT, with lower incidence of prothrombotic conditions, higher rates of bowel ischemia, and poorer outcome. Although SVT after SARS-CoV-2 vaccination is rare in absolute terms, these data remain relevant considering ongoing revaccination programs.
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Intrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension. Treatment is usually aimed at restoring the normal portal hemodynamics by obliterating the shunt. This report describes a case of idiopathic IAPF with severe portal hypertension complicated by portal enteropathy with vomiting, gastrointestinal hemorrhage and sepsis. The patient was successfully treated with portal embolization.
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Early detection of liver transplantation (LT) vascular complications enables timely management. Our aim was to assess if routine Doppler ultrasound (rDUS) improves the detection of hepatic artery thrombosis (HAT), portal vein thrombosis (PVT) and hepatic venous outflow obstruction (HVOO). We retrospectively analysed timing and outcomes, number needed to diagnose one complication (NND) and positive predictive value (PPV) of rDUS on post-operative day (POD) 0,1 and 7 in 708 adult patients who underwent primary LT between 2010-2022. We showed that HAT developed in 7.1%, PVT in 8.2% and HVOO in 3.1% of patients. Most early complications were diagnosed on POD 0 (26.9%), 1 (17.3%) and 5 (17.3%). rDUS correctly detected 21 out of 26 vascular events during the protocol days. PPV of rDUS was 53.8%, detection rate 1.1% and NND was 90.5. Median time to diagnosis was 4 days for HAT and 47 days for PVT and 21 days for HVOO. After intervention, liver grafts were preserved in 57.1%. In conclusion, rDUS protocol helps to detect first week's vascular events, but with low PPV and a high number of ultrasounds needed.
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Hepatopatías , Trasplante de Hígado , Trombosis , Trombosis de la Vena , Adulto , Humanos , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Trombosis/etiología , Ultrasonografía/efectos adversos , Trombosis de la Vena/etiología , Trombosis de la Vena/complicaciones , Arteria Hepática/diagnóstico por imagen , Vena Porta/diagnóstico por imagen , Ultrasonografía Doppler/efectos adversos , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/etiologíaRESUMEN
BACKGROUND AND AIMS: Historical paired liver biopsy studies are likely to underestimate current progression of disease in patients with chronic hepatitis C virus (HCV) infection. We aimed to assess liver disease progression according to the non-invasive Fibrosis-4 (FIB-4) index in patients with chronic HCV and early disease. METHODS AND RESULTS: Patients diagnosed with chronic HCV and FIB-4 <3.25 from four international liver clinics were included in a retrospective cohort study. Follow-up ended at start of antiviral therapy resulting in sustained virological response, at time of liver transplantation or death. Primary outcome of advanced liver disease was defined as FIB-4 >3.25 during follow-up. Survival analyses were used to assess time to FIB-4 >3.25.In total, 4286 patients were followed for a median of 5.0 (IQR 1.7-9.4) years, during which 41 071 FIB-4 measurements were collected. At baseline, median age was 47 (IQR 39-55) years, 2529 (59.0%) were male, and 2787 (65.0%) patients had a FIB-4 <1.45. Advanced liver disease developed in 821 patients. Overall, 10-year cumulative incidence of advanced disease was 32.1% (95% CI 29.9% to 34.3%). Patients who developed advanced disease showed an exponential FIB-4 increase. Among patients with a presumed date of HCV infection, cumulative incidence of advanced disease increased 7.7-fold from 20 to 40 years as opposed to the first 20 years after HCV infection. CONCLUSIONS: The rate of advanced liver disease is high among chronic HCV-infected patients with early disease at time of diagnosis, among whom liver disease progression accelerated over time. These results emphasise the need to overcome any limitations with respect to diagnosing and treating all patients with chronic HCV across the globe.
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Hepatitis C Crónica , Hepatitis C , Humanos , Masculino , Persona de Mediana Edad , Femenino , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/patología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Cirrosis Hepática/patología , Estudios Retrospectivos , Progresión de la EnfermedadRESUMEN
Hepatocellular carcinoma (HCC) and variceal bleeding are among the most common causes of liver-related mortality in patients with hepatitis C virus (HCV)-induced cirrhosis. Current guidelines recommend HCC and gastroesophageal varices (GEV) surveillance in patients with HCV infection and cirrhosis. However, since the recent introduction of direct-acting antivirals, most patients with cirrhosis are now cured of their chronic HCV infection. As virological cure is considered to substantially reduce the risk of cirrhosis-related complications, this review discusses the current literature concerning the surveillance of HCC and GEV in patients with HCV-induced cirrhosis with a focus on the setting following sustained virological response.
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Carcinoma Hepatocelular , Várices Esofágicas y Gástricas , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Várices , Antivirales/uso terapéutico , Carcinoma Hepatocelular/epidemiología , Várices Esofágicas y Gástricas/tratamiento farmacológico , Várices Esofágicas y Gástricas/epidemiología , Várices Esofágicas y Gástricas/etiología , Hemorragia Gastrointestinal/epidemiología , Hemorragia Gastrointestinal/etiología , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Várices/tratamiento farmacológicoRESUMEN
BACKGROUND & AIMS: HCV-infected patients with cirrhosis achieve high sustained virological response (SVR) rates with direct-acting antivirals (DAAs) even after hepatic decompensation. We aimed to assess the clinical outcome following DAAs among patients with compensated and decompensated cirrhosis in relation to SVR and changes in model for end-stage liver disease (MELD) score. METHODS: Consecutive DAA-treated chronic HCV-infected patients with cirrhosis from 4 hepatology clinics were included. The primary endpoint in survival analyses was clinical disease progression, defined as liver failure, hepatocellular carcinoma, liver transplantation or death. RESULTS: In total, 868 patients were included with a median age of 59 (IQR 54-65) years; 719 (83%) with Child-Pugh A cirrhosis and 149 (17%) with Child-Pugh B/C cirrhosis. SVR was attained by 647 (90%) Child-Pugh A patients and 120 (81%) Child-Pugh B/C patients. During a median follow-up of 28 (IQR 20-36) months, 102 (14%) Child-Pugh A patients and 96 (64%) Child-Pugh B/C patients experienced clinical disease progression. SVR was independently associated with an improved event-free survival in patients with Child-Pugh A cirrhosis (adjusted hazard ratio [HR] 0.47; 95% CI 0.27-0.82, p = 0.007), but not in patients with Child-Pugh B/C cirrhosis (adjusted HR 1.23; 95% CI 0.67-2.26; p = 0.51). Twelve weeks post-DAAs, 28 (19%) patients with Child-Pugh B/C cirrhosis had ≥2-point MELD decline, but their 2-year event-free survival did not differ from those with a stable MELD (47.9%; 95% CI 28.7-67.1 vs. 48.9%; 95% CI 38.1-59.7, respectively, p = 0.99). CONCLUSIONS: Among patients with chronic HCV infection, DAA-induced SVR was associated with a reduced risk of clinical disease progression in patients with Child-Pugh A cirrhosis but not in patients with Child-Pugh B/C cirrhosis. In Child-Pugh B/C cirrhosis, a ≥2-point MELD decline did not translate into improved clinical outcome. LAY SUMMARY: Chronic HCV infection can be cured with antiviral therapy. In this study, we evaluated the long-term effects of antiviral therapy on liver-related complications in patients with cirrhosis. Our results suggest that patients with compensated cirrhosis who were cured of their HCV infection have a lower rate of complications. In contrast, the rate of complications was not related to virological cure among those with decompensated cirrhosis. While these patients seem to remain in need of liver transplantation, antiviral therapy may lower their priority on the liver transplantation waiting list.
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Antivirales/uso terapéutico , Carcinoma Hepatocelular , Hepatitis C Crónica/tratamiento farmacológico , Fallo Renal Crónico , Cirrosis Hepática , Neoplasias Hepáticas , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/patología , Progresión de la Enfermedad , Femenino , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/etiología , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/virología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Cirrosis Hepática/cirugía , Fallo Hepático/diagnóstico , Fallo Hepático/etiología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/patología , Trasplante de Hígado/métodos , Trasplante de Hígado/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Respuesta Virológica Sostenida , Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Direct-acting antivirals for chronic hepatitis C (HCV) infection have reduced the need for on-treatment HCV RNA monitoring. We assessed the accuracy and cost implications of using HCV core antigen testing to replace HCV RNA testing for confirmation of diagnosis, on-treatment monitoring, and determination of sustained virological response (SVR). METHODS: In a retrospective screening cohort study, de-identified residual serum from unselected samples were obtained from commercial laboratories in Ontario, Canada. Samples from each 5-year age-sex band from birth years 1945-74 collected from Aug 1, 2014, to Feb 28, 2015, were included. All samples that tested positive for HCV antibodies, and 10% of samples that tested negative for HCV antibodies, were tested for HCV core antigen and HCV RNA. A retrospective clinical cohort study was also done using blood samples from patients with confirmed HCV infection collected at four tertiary academic centres: one in Canada, two in Germany, and one in the USA. For assessment of SVR, we included samples from patients who started direct-acting antiviral-based treatment (excluding telaprevir and boceprevir) with or without peginterferon, ribavirin, or both, from Jan 1, 2014, to March 31, 2015. To ensure inclusion of adequate numbers for analysis, patients who relapsed after any treatment regimen were included. Serum samples included in the study were from baseline, week 4 on-treatment (only for patients treated with direct-acting antivirals), end of treatment, and week 12 or 24 of follow-up. The sensitivity and specificity of core antigen testing as a diagnostic tool was assessed in the screening cohort, using HCV RNA as a reference. The sensitivity and specificity of core antigen testing as well as its concordance with HCV RNA testing in the clinical cohort was assessed at baseline, week 4 on-treatment, and at weeks 12 or 24 after the end of treatment in patients undergoing therapy with direct-acting antivirals. The cost-effectiveness of core antigen testing with and without confirmatory HCV RNA testing for negative samples was also assessed. FINDINGS: From 10â006 samples in the screening cohort, 75 of 80 viraemic (HCV RNA-positive) samples tested positive for HCV core antigen (sensitivity 94%, 95% CI 86-98), and none of the 993 HCV RNA-negative samples tested positive for HCV core antigen (specificity 100%, 95% CI 94-100). The five viraemic samples that tested negative for HCV core antigen had low corresponding HCV RNA concentrations. In the clinical cohort, two (1%) of 202 baseline samples tested negative for HCV core antigen; one had a low HCV RNA concentration (468 IU/mL), the other had a high HCV RNA concentration (>2â000â000 IU/mL). By week 4 of treatment, HCV core antigen concentrations decreased in all patients but were not predictive of SVR. Although there was good concordance between HCV RNA and HCV core antigen results at 12 weeks after the end of treatment (r=0·97; p<0·0001), three of the 148 patients who achieved SVR at 12 weeks tested HCV core antigen positive. 12 weeks after the end of treatment, HCV core antigen was undetectable in one (1%) of 71 samples from patients who were identified as having relapsed according to HCV RNA detection. On-treatment and end-of-treatment testing of core antigen or HCV RNA provided little clinical value. The use of HCV core antigen testing as a confirmatory diagnostic strategy was cost saving relative to HCV RNA testing, with a reduction of CAD$0·29-3·70 per patient screened depending on whether HCV RNA testing was used to confirm HCV core antigen-negative results. INTERPRETATION: These data support the use of HCV core antigen testing to document HCV viraemia in a cost-saving diagnostic algorithm. In a treatment setting, HCV core antigen testing can be used instead of HCV RNA testing for diagnosis and documentation of treatment adherence, but it might not be adequate to determine SVR. This approach might improve access to care, particularly in low-income and middle-income countries. FUNDING: Abbott Diagnostics and Toronto Centre for Liver Disease.
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Antivirales/uso terapéutico , Monitoreo de Drogas/economía , Monitoreo de Drogas/métodos , Antígenos de la Hepatitis C/sangre , Hepatitis C Crónica/sangre , Hepatitis C Crónica/tratamiento farmacológico , ARN Viral/sangre , Proteínas del Núcleo Viral/sangre , Adulto , Anciano , Ahorro de Costo , Femenino , Hepatitis C/genética , Hepatitis C/inmunología , Hepatitis C Crónica/diagnóstico , Humanos , Masculino , Tamizaje Masivo/economía , Tamizaje Masivo/métodos , Cumplimiento de la Medicación , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Viremia/sangre , Viremia/diagnóstico , Viremia/tratamiento farmacológicoAsunto(s)
Carcinoma Hepatocelular , Hepacivirus , Antivirales , Hepatitis C Crónica , Humanos , Neoplasias HepáticasRESUMEN
BACKGROUND & AIMS: Current guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in all patients with cirrhosis, regardless of etiology. However, HCC incidence is not well established for many causes of cirrhosis. We aimed to assess the disease-specific incidence of HCC in a large cohort of patients with cirrhosis and to develop a scoring system to predict HCC risk. METHODS: A derivation cohort of patients with cirrhosis diagnosed by biopsy or non-invasive measures was identified through retrospective chart review. The disease-specific incidence of HCC was calculated according to etiology of cirrhosis. Factors associated with HCC were identified through multivariable Cox regression and used to develop a scoring system to predict HCC risk. The scoring system was evaluated in an external cohort for validation. RESULTS: Of 2,079 patients with cirrhosis and ≥6months follow-up, 226 (10.8%) developed HCC. The 10-year cumulative incidence of HCC varied by etiologic category from 22% in patients with viral hepatitis, to 16% in those with steatohepatitis and 5% in those with autoimmune liver disease (p<0.001). By multivariable Cox regression, age, sex, etiology and platelets were associated with HCC. Points were assigned in proportion to each hazard ratio to create the Toronto HCC Risk Index (THRI). The 10-year cumulative HCC incidence was 3%, 10% and 32% in the low-risk (<120points), medium-risk (120-240) and high-risk (>240) groups respectively, values that remained consistent after internal validation. External validation was performed on a cohort of patients with primary biliary cirrhosis, hepatitis B viral and hepatitis C viral cirrhosis (n=1,144), with similar predictive ability (Harrell's c statistic 0.77) in the validation and derivation cohorts. CONCLUSION: HCC incidence varies markedly by etiology of cirrhosis. The THRI, using readily available clinical and laboratory parameters, has good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis. LAY SUMMARY: HCC incidence varies markedly depending on the underlying cause of cirrhosis. Herein, using readily available clinical and laboratory parameters we describe a risk score, THRI, which has a good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis.
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Chronic hepatitis C (HCV) infection remains a major public health problem with many infected individuals worldwide. The revolutionary discovery of highly effective direct-acting antivirals (DAAs) makes chronic HCV infection a curable disease, even in patients with advanced liver disease. Liver function may improve shortly after initiation of antiviral therapy in patients on the waiting list and could even obviate the need for transplantation. However, whether these short term benefits also result in a favorable prognosis on the long-term remains to be seen and this fuels the discussion whether DAAs should be used prior to liver transplantation in all patients. Following liver transplantation, DAA treatment is also highly effective so that postponing antiviral treatment to the post-transplant setting may be better for certain patients. Furthermore, the discussion whether HCV positive organ donors should be used now viral eradication is achieved in almost all patients has regained interest.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferones/uso terapéutico , Trasplante de Hígado/métodos , Hepatitis C Crónica/patología , HumanosRESUMEN
BACKGROUND & AIMS: The risk of hepatocellular carcinoma (HCC) is reduced but not eradicated among patients with hepatitis C virus (HCV)-induced advanced hepatic fibrosis who attained sustained viral response (SVR). We aimed to assess the risk of cirrhosis-related complications in this specific group of patients. METHODS: Data from previously reported Western cohort studies including patients with chronic HCV infection and bridging fibrosis or cirrhosis who attained SVR were pooled for survival analyses on the individual patient level. The primary endpoint was HCC and the secondary endpoint was clinical disease progression, defined as liver failure, HCC or death. RESULTS: Included were 1000 patients with SVR. Median age was 52.7 (IQR 45.1-59.7) years, 676 (68%) were male and 842 (85%) had cirrhosis. Median follow-up was 5.7 (IQR 2.9-8.0) years. Fifty-one patients developed HCC and 101 had clinical disease progression. The cumulative 8-year HCC incidence was 1.8 (95% CI 0.0-4.3) among patients with bridging fibrosis and 8.7% (95% CI 6.0-11.4) among those with cirrhosis (p=0.058). Within the cirrhosis group, the 8-year HCC incidence was 2.6% (95% CI 0.0-5.5) among patients <45years, 9.7% (95% CI 5.8-13.6) among patients from 45-60years, and 12.2% (95% CI 5.3-19.1) among patients >60years of age at start of therapy (p=0.006). Multivariable Cox analyses indicated that higher age, lower platelet count and diabetes mellitus were independently associated with development of HCC. After 8years 4.2% (95% CI 0.1-8.3) of patients with bridging fibrosis and 15.8% (95% CI 12.3-19.3) of patients with cirrhosis experienced clinical disease progression (p=0.007). CONCLUSIONS: Patients with HCV-induced cirrhosis and SVR showed an annual risk of approximately 1% for HCC and 2% for clinical disease progression. Therefore, to prevent HCC surveillance, chronic HCV infection should preferably be treated before cirrhosis has developed. LAY SUMMARY: Patients with cirrhosis who were able to eradicate their chronic HCV infection remain at substantial risk of primary liver cancer. The risk of liver cancer increases with higher age, laboratory makers suggesting more severe liver disease, and presence of diabetes mellitus. Also after successful antiviral therapy patients with HCV-induced cirrhosis should thus remain included in follow-up for early detection of liver cancer.
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Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Adulto , Anciano , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Incidencia , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Respuesta Virológica SostenidaRESUMEN
BACKGROUND & AIMS: Direct-acting antivirals (DAAs) have revolutionized treatment for patients with chronic hepatitis C virus (HCV) infection, leading to a high rates of sustained virologic response. This study assessed the real-world safety and effectiveness of DAA-based antiviral therapy for the treatment of cirrhotic patients with chronic HCV infection. METHODS: This international, multicenter cohort study included all consecutive patients with chronic HCV infection and cirrhosis who underwent antiviral therapy with second-generation DAAs. Data on all patients were analyzed to assess treatment response. Predictors of hepatic decompensation during antiviral therapy were assessed using Cox proportional hazards regression analyses. RESULTS: Until June 2015, 433 cirrhotic patients with chronic HCV infection started DAA-based treatment. Their mean age was 57.8 (±8.7) years, 277 (64.0%) patients were male, and 114 (26.3%) had a Child-Pugh (CP) score of B/C cirrhosis. The sustained virologic response rate at 12 weeks was similar among patients with a CP score of A (261 of 304 [85.9%]) and a CP score of B/C (83 of 101 [82.2%]; P = .37). A baseline albumin level less than 35 g/L (hazard ratio [HR], 3.11; 95% confidence interval [CI], 1.23-7.84; P = .005), baseline MELD score of 14 or higher (HR, 1.63; 95% CI, 1.03-2.61; P = .037), and HCV genotype 3 (HR, 2.05; 95% CI, 1.09-3.88; P = .033) were associated independently with hepatic decompensation during antiviral treatment among patients with a CP score of B/C. CONCLUSIONS: This large cohort study showed that therapy is safe and effective in patients with compensated (CP score of A) cirrhosis. For patients with decompensated (CP score of B/C) cirrhosis, albumin level less than 35 g/L, MELD score of 14 or greater, and HCV genotype 3 are important risk factors for hepatic decompensation during DAA-based treatment. Therefore, these patients require close monitoring during antiviral therapy or treatment should be deferred until after transplantation.
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Antivirales/efectos adversos , Antivirales/uso terapéutico , Insuficiencia Hepática/epidemiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Respuesta Virológica Sostenida , Anciano , Estudios de Cohortes , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Cooperación Internacional , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: Peginterferon (PegIFN) remains the backbone of therapy for chronic hepatitis C (CHC) in economically constrained regions. However, PegIFN may cause neutropenia and addition of a protease inhibitor can increase the likelihood of neutropenia. The aims of this study were to assess the occurrence of clinically relevant infections during first-generation protease inhibitor based therapy and its risk factors as well as the relation to treatment-induced neutropenia. METHODS: This multicenter (n=45) retrospective cohort study included CHC patients treated in the Netherlands. Based on absolute neutrophil count, categories of neutropenia were defined as: severe (<500/µL), moderate (500-750/µL) and mild (750-1500/µL). Likewise, infections were classified as severe (intravenous antibiotics/hospitalization) and moderate (anti-infective treatment). We assessed risk factors for infections using multivariable regression analysis with correction for multiple measurements. RESULTS: We included 467 CHC patients, 319 (68%) were male and 111 (24%) had cirrhosis. A total of 185 clinically relevant infections (34 severe) occurred in 145 patients (31%). During treatment 310 patients experienced neutropenia (34 severe). Multivariable analysis identified female sex (OR 1.7, 95%CI 1.2-2.5), chronic obstructive pulmonary disease (COPD) (OR 2.7, 95%CI 1.6- 4.5) and diabetes mellitus (OR 1.7, 95%CI 1.0-3.0) as risk factors for infections. Neutropenia at the previous visit was not associated with infection (univariable analysis: OR 0.9, 95%CI 0.6-1.3). CONCLUSION: This study shows that therapy with first generation protease inhibitors was complicated by an infection in 31% of patients. Not neutropenia, but female sex, COPD and diabetes mellitus were independent risk factors for infection. These patients should be monitored carefully once a PegIFN regimen is initiated.
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Antivirales/efectos adversos , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Huésped Inmunocomprometido , Neutropenia/inducido químicamente , Infecciones Oportunistas/inducido químicamente , Inhibidores de Proteasas/efectos adversos , Adulto , Anciano , Antiinfecciosos/administración & dosificación , Distribución de Chi-Cuadrado , Comorbilidad , Diabetes Mellitus/epidemiología , Quimioterapia Combinada , Femenino , Hepacivirus/enzimología , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/virología , Hospitalización , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Países Bajos/epidemiología , Neutropenia/epidemiología , Neutropenia/inmunología , Oportunidad Relativa , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/inmunología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Sofosbuvir (SOF) is active against all hepatitis C virus (HCV) genotypes, and SOF-based therapies lead to high rates of sustained virologic response (SVR). However, genotype 3 (GT3) HCV remains a challenge with lower SVR rates reported, particularly in patients with cirrhosis. This study reports the effectiveness and safety of SOF-based therapy in patients with GT3 HCV treated in clinical practice. METHODS: Hepatitis C Virus Therapeutic Registry and Research Network is an international, prospective observational study evaluating patients treated in usual clinical practice. Patients with GT3 HCV were analyzed to assess predictors of treatment response and adverse events using descriptive statistics and multivariable logistic regression. RESULTS: Treatment outcomes were available for 197 patients treated with SOF and ribavirin (RBV), with or without peginterferon, including 54% with cirrhosis and 49% who failed prior therapy. Of 178 patients treated with SOF/RBV, 60% achieved SVR at 12 weeks (SVR12), compared with 84% of 19 patients treated with SOF/peginterferon/RBV. For patients treated with SOF/RBV, the SVR12 rate was 58% in treatment-naive patients with cirrhosis, and 42% in those with cirrhosis who failed prior therapy. In noncirrhotic patients, SVR12 rates were 89% in treatment-naive and 88% in treatment-experienced patients. After controlling for age and sex, absence of cirrhosis (odds ratio [OR], 6.4; 95% confidence interval [CI], 2.78-14.74), albumin levels ≥3.2 g/dL (OR, 12.48; 95% CI, 3.86-40.33), and platelet count >10(5) cells/µL (OR, 7.44; 95% CI, 3.51-15.78) were associated with greater odds of SVR12 CONCLUSIONS: SVR rates were acceptable in patients with GT3 HCV without cirrhosis; however, in those with cirrhosis, treatment with SOF/RBV was suboptimal, highlighting the need for new therapies for this population.