RESUMEN

Lysyl oxidase-like 2 (LOXL2) mediates the crosslinking of extracellular collagen, reflecting qualitative changes in liver fibrosis. This study aimed to validate the utility of serum LOXL2 levels as a predictive biomarker for the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection who achieved a sustained virological response (SVR). This retrospective study included 137 patients with chronic HCV infection without history of HCC development and who achieved SVR via direct-acting antiviral therapy. Median LOXL2 levels decreased significantly after SVR achievement (pre-Tx, 2.33 ng/mL; post-Tx, 1.31 ng/mL, p < 0.001). Post-Tx LOXL2 levels, fibrosis-4 index, platelet counts, Wisteria floribunda agglutinin-positive human Mac-2 binding protein levels, and alpha-fetoprotein (AFP) levels were identified as independent predictive factors for post-SVR HCC development in the univariate analysis. The incidence of post-SVR HCC development was significantly higher in patients with post-Tx LOXL2 levels ≥ 2.08 ng/mL and AFP levels ≥ 5.0 ng/mL than in patients with elevated levels of either marker or with lower marker levels. Serum LOXL2 levels can serve as a predictive biomarker for HCC development after achieving SVR. The combination of serum LOXL2 and AFP levels provides robust risk stratification for HCC development after SVR, suggesting an enhanced surveillance strategy.

Asunto(s)

Aminoácido Oxidorreductasas , Carcinoma Hepatocelular , Hepatitis C Crónica , Neoplasias Hepáticas , Respuesta Virológica Sostenida , Femenino , Humanos , Masculino , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/análisis , Aminoácido Oxidorreductasas/sangre , Antivirales/uso terapéutico , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/virología , Hepacivirus , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/sangre , Hepatitis C Crónica/virología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/virología , Estudios Retrospectivos

RESUMEN

BACKGROUND: To investigate the trends in health-related quality of life (HRQoL) among hepatitis C virus (HCV) patients and to assess the longitudinal impact of antiviral therapy on their well-being. METHODS: In this prospective multicenter observational study in adults with HCV infection, sociodemographic, clinical characteristics and EQ-5D questionnaires were collected. Generalized estimating equation (GEE) models were used to assess the associations between these variables and changes in HRQoL over time. RESULTS: 456 patients were included, with a median age of 46.5 (36.5-57.0) years, of which 262 (57.5%) were males and 44 (9.6%) had cirrhosis. 335 patients (73.5%) receiving antiviral therapy and 61.8% achieved sustained virologic response (SVR). The baseline EQ-5D utility and EQ-VAS were 0.916 ± 0.208 and 80.6 ± 13.0. In multivariable analysis of GEE estimation, achieving SVR24 was positively associated with EQ-5D utility (p = 0.000) and EQ-VAS (p = 0.000) over time. Age and income were shown to be significant predictors of EQ-5D utility, while gender, age and genotype were associated with EQ-VAS over time. CONCLUSIONS: SVR improved long-term HRQoL in HCV patients in the first few years following viral clearance. Certain sociodemographic factors, such as gender, age, income as well as genotype, significantly influenced long-term changes in patients' quality of life. TRIAL REGISTRATION: NCT01594554. Registration date: 09/05/2012.

Asunto(s)

Hepatitis C Crónica , Hepatitis C , Adulto , Masculino , Humanos , Persona de Mediana Edad , Femenino , Hepatitis C Crónica/tratamiento farmacológico , Estudios Prospectivos , Calidad de Vida , Respuesta Virológica Sostenida , China , Hepacivirus/genética , Antivirales/uso terapéutico

RESUMEN

PURPOSE: Hepatitis C virus infection is a major health problem in hemodialysis patients. Occult HCV infection is defined as the presence of HCV-RNA in hepatocytes or peripheral blood mononuclear cells without the detection of HCV-RNA in the serum. We aimed to evaluate the prevalence and predictors of occult HCV infection among hemodialysis patients after treatment with direct-acting antiviral agents. METHODS: This research is a cross-sectional study that included 60 HCV patients maintained on regular HD patients who achieved 24 weeks of sustained virological response after treatment with direct-acting antiviral agents. Real-time PCR was performed to detect HCV-RNA in peripheral blood mononuclear cells. RESULTS: HCV-RNA was detected in peripheral blood mononuclear cells of three patients (5%). Occult HCV infection cases were treated by Interferon/ribavirin before direct-acting antiviral agents and two of them had raised pre-treatment alanine aminotransferase levels. Logistic regression analyses revealed that high pre-treatment viral load and raised pre-treatment alanine aminotransferase were associated with an increased risk of occult HCV infection with p value of 0.041 and 0.029, respectively. CONCLUSIONS: Occult HCV infection in hemodialysis patients who achieved sustained virological response after treatment with direct-acting antiviral agents may occur, and this may necessitate dual testing for HCV in both serum and peripheral blood mononuclear cells to ensure viral clearance. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT04719338.

Asunto(s)

Hepatitis C Crónica , Hepatitis C , Humanos , Antivirales/uso terapéutico , Hepacivirus/genética , Leucocitos Mononucleares/química , Alanina Transaminasa , Estudios Transversales , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Diálisis Renal/efectos adversos , ARN Viral , Quimioterapia Combinada

RESUMEN

The risk factors for hepatocellular carcinoma (HCC) development in patients whose duration of sustained virological response (SVR) is over 10 years are not fully understood. We compared the incidence of HCC development within and beyond 10 years after SVR. A total of 1384 patients who achieved SVR (714, interferon-based therapy; 670, direct-acting antiviral therapy) were enrolled. Factors associated with HCC development were analysed within and beyond 10 years after SVR by Cox proportional hazards models. The annual incidence rates of HCC development were 0.568% within 10 years after SVR and 0.190% beyond 10 years, and there was a significant difference in the incidence of HCC development between the 2 periods (p = 0.0242, log-rank test). Male gender (adjusted hazard ratio [aHR] 2.930; 95% confidence interval [CI] 1.508-5.693, p = 0.0015), fibrosis-4 (FIB-4) score > 3.25 (aHR 4.364; 95%CI 2.206-8.633, p < 0.0001) and alpha-fetoprotein ≥5.0 ng/ml (aHR 2.381; 95%CI 1.325-4.280, p = 0.0037) were independently associated with HCC development within 10 years after SVR. Male gender (aHR 4.702; 95%CI 1.366-16.190, p = 0.0141), presence of diabetes mellitus (aHR 2.933; 95%CI 1.240-6.935, p = 0.0143) and gamma-glutamyl transpeptidase (GGT) ≥ 56 U/l (aHR 4.157; 95%CI 1.400-12.350, p = 0.0103) were independently associated with HCC development beyond 10 years after SVR. The incidence of HCC development beyond 10 years after SVR was very low, and the associated factors were mainly extrahepatic, including DM and elevated GGT. Annual routine check-ups with abdominal ultrasound may be sufficient for such patients. (242 words).

Asunto(s)

Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Antivirales/uso terapéutico , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Incidencia , Masculino , Factores de Riesgo , Respuesta Virológica Sostenida

Asunto(s)

Carcinoma Hepatocelular , Hepatitis C Crónica , Hepatitis C , Neoplasias Hepáticas , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Humanos , Japón/epidemiología , Cirrosis Hepática/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , Medición de Riesgo , Respuesta Virológica Sostenida

RESUMEN

OBJECTIVES: Public Health England (PHE) aims meet the WHO target to eliminate hepatitis C as a public health concern by 2030. One aspect of this strategy is to use historical surveillance data of anti-HCV positive patients identified by PHE to re-engage with offers of PCR testing and treatment if RNA-positive. Operational Delivery Networks (ODN), who deliver Hepatitis C treatment across 22 regions in England, are responsible for enacting this initiative. This study aims to evaluate the effectiveness of using this data with regional PCR results to re-engage HCV-infected persons in the West Midlands region of England. STUDY DESIGN: A longitudinal prospective study using historical surveillance data. METHODS: A dataset of historical anti-HCV positive antibody patients provided to the ODN by PHE was cross-referenced with HCV RNA data from 01/01/1996 to 01/01/2019 from five laboratories across the West Midlands. Letters were sent to the general practitioner and to the patients who were HCV RNA positive to invite them for repeat testing and treatment to achieve cure. RESULTS: From a dataset of 4540 anti-HCV antibody results, 31.7% (n=1440) had a PCR result: 48.1% (n=693) were PCR positive for HCV RNA. 693 letters were sent to GPs with responses from 14.2% (n=99). By May 2021, only 212 patient letters were sent (due to significant interruption by the COVID-19 pandemic) and 11.3% (n=24) replied, 17 presented for PCR testing and 4 were found to be viraemic. To date, one patient has achieved cure and three have completed treatment awaiting confirmation of cure. CONCLUSION: The use of historical anti-HCV antibody results can be used to successfully re-engage people into testing and treatment for hepatitis C, albeit with modest gains.

RESUMEN

INTRODUCTION: In patients with hepatitis C virus (HCV) infection and decompensated cirrhosis (DC), it is uncertain whether viral clearance is clinically meaningful and whether it decreases liver-related and non-liver-related mortality. The aim of this study was to assess whether viral eradication reduced liver-related and non-liver-related mortality in patients with HCV infection and DC. METHODS: To clarify the impact of viral eradication on liver-related and non-liver-related mortality, 364 patients with DC who received direct-acting antivirals (DAAs) and achieved sustained virological response (SVR) in the UK (DAA group) were compared with 249 patients with DC who did not receive DAAs and who underwent symptomatic treatment in Japan (non-DAA group). Propensity score matching and inverse probability weighting (IPW) were performed to adjust the baseline characteristics in the DAA and non-DAA groups. Liver-related and non-liver-related mortality were analyzed using the competing risks IPW cumulative incidence functions estimator. RESULTS: The cumulative all-cause mortality rate in the DAA group was significantly lower than that in the non-DAA group (p < 0.0001, IPW-adjusted log-rank test). The cumulative incidence rates of both liver-related and non-liver-related mortality were significantly lower in the DAA group than those in the non-DAA group (p < 0.0001 for both). CONCLUSION: DAA-mediated viral eradication reduced not only liver-related mortality but also non-liver-related mortality in patients with HCV infection and DC.

RESUMEN

Objective Although most patients who obtain a sustained virological response (SVR) show an improved liver function, some show decreased platelet counts after the eradication of hepatitis C virus (HCV). The aim of this retrospective study was to clarify the association of the liver and spleen volumes with the platelet count after SVR achieved by direct-acting antiviral (DAA) treatment. Methods This study enrolled 36 consecutive patients treated by DAAs who obtained an SVR between September 2014 and December 2018. The liver and spleen volumes were derived from computed tomography scans obtained at pretreatment, SVR, and 48 weeks after SVR. No patient developed hepatocellular carcinoma during this study. Results Compared with pretreatment, the median aspartate aminotransferase, alanine aminotransferase, albumin serum levels, and platelet counts were significantly improved at SVR and 48 weeks after SVR. The liver/spleen volumes per body weight had decreased significantly from 22.5/4.2 mL/kg at baseline to 21.1/3.6 mL/kg at 48 weeks after SVR. The change in the liver volume was associated with the change in the platelet count, and the change in the spleen volume was negatively associated with the change in the serum albumin level. A multivariate analysis identified the change in the liver volume (≥95%, odds ratio 76.9, p=0.005) as the factor associated with improvement in the platelet count at 48 weeks after SVR. The patients with an increased liver volume at 48 weeks after SVR showed an increased platelet count. Conclusion Both the liver and spleen volume decreased significantly after the eradication of HCV. The patients with a re-increased liver volume showed a rapid increase in the platelet count.

Asunto(s)

Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Cirrosis Hepática/patología , Tamaño de los Órganos/fisiología , Recuento de Plaquetas/estadística & datos numéricos , Bazo/patología , Anciano , Anciano de 80 o más Años , Femenino , Hepacivirus , Hepatitis C/complicaciones , Humanos , Cirrosis Hepática/etiología , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Respuesta Virológica Sostenida

RESUMEN

Owing to the rapid development and wide clinical application of direct acting antiviral (DAA) drugs in the treatment of hepatitis C virus (HCV) infection, the era of interferon-based therapy has almost come to an end. Cumulative studies show that DAA therapy renders high cure efficiency (>90%) and good safety profile, and may even bring some unexpected benefits to the patients. However, some issues of concern arise, one of which is the resistance mutation of HCV genome leading to failure of treatment. With the aim of providing some meaningful references for the treatment of chronic hepatitis C (CHC), this article summarizes the research progress on benefits of DAA accompanied by viral clearance in the treatment of chronic hepatitis and the drug resistance.

Asunto(s)

Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Farmacorresistencia Viral/efectos de los fármacos , Glucosa/metabolismo , Hepacivirus/genética , Hepatitis C Crónica/metabolismo , Hepatitis C Crónica/fisiopatología , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/fisiología , Hígado/virología , Pruebas de Función Hepática

RESUMEN

We evaluated the changes of gadoxetic acid uptake of the liver parenchyma after hepatitis C virus (HCV) eradication by direct-antiviral agent (DAA) therapy. The increase rate of the liver-to-muscle signal intensity ratio, the skewness and the kurtosis were calculated in the hepatobiliary phase. After sustained virological response, gadoxetic acid uptake of the liver parenchyma increased, but became heterogeneous. Our study proved that HCV eradication by DAA therapy could significantly affect gadoxetic acid uptake.

Asunto(s)

Antivirales/uso terapéutico , Gadolinio DTPA/farmacocinética , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/diagnóstico por imagen , Hepatitis C Crónica/tratamiento farmacológico , Hígado/diagnóstico por imagen , Anciano , Femenino , Hepatocitos/patología , Hepatocitos/virología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Estudios Retrospectivos , Respuesta Virológica Sostenida

RESUMEN

BACKGROUND & AIMS: It is important to know which patients with hepatitis C are likely to develop liver-related complications after achieving a sustained virological response (SVR) to direct-acting antiviral (DAA) therapy. We aimed to describe the incidence of liver-related events in a population of patients with HCV-associated compensated advanced chronic liver disease (cACLD) who achieved SVR and to identify non-invasive parameters that predict the occurrence of liver-related events. METHODS: This 2-center prospective study included 572 patients with cACLD who had been treated with DAAs and had achieved SVR. Patients had liver stiffness measurement (LSM) ≥10 kPa at baseline and had never decompensated (Child-Pugh class A). Laboratory work-up and LSM were performed at baseline and at 1 year of follow-up. RESULTS: The median follow-up was 2.8 years during which 32 patients (5.6%) presented with a liver-related event. The incidence rate (IR) of portal hypertension-related decompensation was 0.34/100 patient-years. These patients all had baseline LSM >20 kPa, and LSM did not improve during follow-up in 4 out of 5 of them. Hepatocellular carcinoma (HCC) occurred in 25 patients (IR 1.5/100 patient-years). Albumin levels at follow-up (hazard ratio [HR] 0.08; 95% CI 0.02-0.25) and LSM <10 kPa at follow-up (HR 0.33; 95% CI 0.11-0.96) were independently associated with the risk of HCC. Combining both predictors identified 2 groups with differing risk of HCC occurrence: those with LSM ≥20 kPa at follow-up or those with LSM between 10-20 kPa and albumin levels <4.4 g/dl were at the highest risk (IR ≥1.9/100 patient-years). Visual nomograms predicting HCC risk based on LSM and albumin at 1 year of follow-up were constructed. CONCLUSION: In patients with HCV-related cACLD who have achieved SVR with DAAs, HCC is the most frequent liver-related event. Both albumin levels and LSM are useful for stratifying patients based on their risk of developing HCC during follow-up. LAY SUMMARY: New oral antivirals can cure chronic hepatitis C infection, however patients with advanced chronic liver disease are still at risk of presenting with liver-related complications. The most frequent complication after oral antiviral therapy in asymptomatic patients with advanced chronic liver disease was liver cancer. The use of simple parameters such liver stiffness and albumin levels after treatment can help to identify patients at higher or lower risk of liver cancer.

Asunto(s)

Antivirales/administración & dosificación , Carcinoma Hepatocelular/epidemiología , Diagnóstico por Imagen de Elasticidad/métodos , Hepacivirus/genética , Hepatitis C Crónica/sangre , Hepatitis C Crónica/tratamiento farmacológico , Hipertensión Portal/epidemiología , Neoplasias Hepáticas/epidemiología , Albúmina Sérica/análisis , Administración Oral , Anciano , Femenino , Estudios de Seguimiento , Hepatitis C Crónica/virología , Humanos , Incidencia , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Persona de Mediana Edad , Nomogramas , Estudios Prospectivos , ARN Viral/genética , Medición de Riesgo , Respuesta Virológica Sostenida

RESUMEN

Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860, which is favorable for interferon-based treatment regimens. This phase III clinical trial aimed to evaluate the efficacy and safety of the ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin regimen for 12 weeks in treatment-naïve mainland Chinese patients infected with HCV GT1 without cirrhosis. Methods: One hundred and forty-one treatment-naïve, non-cirrhotic HCV GT1 Chinese patients (age ≥18 years) were enrolled for this single-arm, multicenter, phase III MANASA study (NCT03020082). Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon α-2a (180 µg) and oral ribavirin (1000/1200 mg/day body weight <75/≥75 kg) for 12 weeks. The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment. The secondary end-points were safety outcomes, tolerability, virologic response over time and relapse rate. Results: All enrolled patients were HCV GT1-infected, and most among them (97.9%, 123/141) had the HCV GT1b subtype. Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2%, 123/141). Overall, 140 patients completed the 12-week treatment, and 97.1% (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group, 95% confidence interval: 92.9-99.2%). Only drug-related serious adverse event occurred. Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction. One patient discontinued treatment because of severe head injury in a car accident. Conclusions: The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon α-2a and ribavirin produced a sustained virologic response rate of 97.1% after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients, and was safe and well tolerated. Trial Registration Clinical-Trials.gov Identifier: NCT03020082.

RESUMEN

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the most important underlying causes for the development of hepatocellular carcinoma (HCC) worldwide. Determining the optimal approach for management of the viral infection and the HCC depends on the virus and the stage of the cancer. In patients with HCV-associated HCC, there are multiple reasons to first treat the HCC. Firstly, in case of a curable HCC, the urgency for HCC treatment is important to avoid progression during HCV treatment. Secondly, the presence of HCC itself appears to reduce the rates of sustained virological response (SVR) achieved with direct-acting antivirals (DAAs). And finally, the evidence does not support the concept of an increase in HCC recurrence due to DAAs, so a patient can safely be treated after HCC cure. For patients with very advanced HCC, the benefits of HCV therapy are questionable. In contrast, those who develop HCC in the setting of chronic HBV infection, treatment with nucleoside analogues (NAs) is recommended prior to treating HCC, to prevent further liver injury and reduce the risk for HCC recurrence. Ultimately, earlier diagnosis and treatment of HBV and HCV will hopefully reduce the incidence of HCC worldwide.

Asunto(s)

Antivirales/efectos adversos , Carcinoma Hepatocelular/terapia , Hepatitis C Crónica/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Recurrencia Local de Neoplasia/inducido químicamente , Carcinoma Hepatocelular/virología , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Humanos , Neoplasias Hepáticas/virología , Nucleósidos/uso terapéutico , Vigilancia de la Población , Respuesta Virológica Sostenida

RESUMEN

BACKGROUND AND AIM: To examine the effect on recurrence and survival of treatment by interferon (IFN)-free direct-acting antivirals (DAA) for patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) who underwent primary curative treatment. METHODS: This was a retrospective cohort study of 250 patients with HCV who had received curative treatment for primary HCC. As anti-HCV treatment after HCC treatment, 38 patients received IFN-free DAA therapy (DAA patients) and 94 received IFN-based therapy (IFN patients). The recurrence of HCC and overall survival of the patient groups were compared in a case-control study. RESULTS: The cumulative HCC recurrence rates at 1, 3, and 5 years were 5%, 39%, and 39% for DAA patients and 0%, 46%, and 62% for IFN patients, respectively (P = 0.370). Multivariate analysis of the HCC recurrence identified treatment responses (sustained virological response [SVR]: hazard ratio [HR] 2.237; P = 0.003) as an independent predictive factor. The cumulative overall survival rates at 3 and 5 years were 96%, 96% for DAA patients and 93%, 73% for IFN patients, respectively ( P = 0.163). Multivariate analysis identified treatment responses (SVR: HR 8.742; P < 0.001) as independent predictors of overall survival. Propensity score matching analysis showed no significant difference in HCC development rates and overall survival rates in the two groups. CONCLUSIONS: We found that SVR obtained after curative treatment for primary HCC suppressed recurrence and improved overall survival. And, IFN-free DAA therapy after curative treatment for primary HCC could predict improving overall survival and suppressed HCC recurrence.

Asunto(s)

Antineoplásicos/uso terapéutico , Antivirales/uso terapéutico , Carcinoma Hepatocelular/terapia , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Estudios de Casos y Controles , Femenino , Humanos , Interferones/uso terapéutico , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Respuesta Virológica Sostenida , Resultado del Tratamiento

RESUMEN

In Pakistan, the burden of the hepatitis C virus (HCV) infection is the second highest in the world with the development of chronic hepatitis. Interferon-based combination therapy with ribavirin was the only available treatment until a few years back, with severe side-effects and high failure rates against different genotypes of HCV. Interferon-free all-oral direct-acting antiviral agents (DAAs) approved by the FDA have revolutionized the HCV therapeutic landscape due to their efficiency in targeting different genotypes in different categories of patients, including treatment naïve, treatment failure and relapsing patients, as well as patients with compensated and decompensated cirrhosis. The availability and use of these DAAs is limited in the developing world. Sofosbuvir (SOF), a uridine nucleotide analogue and inhibitor of HCV encoded NS5B polymerase, is now a widely available and in-use DAA in Pakistan; whereas daclatasvir was recently added in the list. According to the documented results, there is hope that this disease can be effectively cured in Pakistan, although a few concerns still remain. The aim of this article is to review the effectiveness of DAAs and the current status of this treatment against HCV genotype 3 infection in Pakistan; various factors associated with SVR; its limitations as an effective treatment regime; and future implications.

Asunto(s)

Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/epidemiología , Interferones/uso terapéutico , Ribavirina/uso terapéutico , Sofosbuvir/uso terapéutico , Antivirales/efectos adversos , Antivirales/farmacología , Quimioterapia Combinada , Variación Genética , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/mortalidad , Humanos , Interferones/efectos adversos , Interferones/farmacología , Pakistán/epidemiología , Prevalencia , Recurrencia , Ribavirina/efectos adversos , Ribavirina/farmacología , Sofosbuvir/efectos adversos , Sofosbuvir/farmacología , Respuesta Virológica Sostenida

RESUMEN

Direct-acting antiviral agents (DAAs) are a safe and effective treatment for chronic hepatitis C (CHC). This may be particularly valuable for patients with severe comorbidities or baseline conditions, including non-liver solid organ transplant. We report cases of two heart transplant recipients with CHC treated with DAAs (sofosbuvir and daclatasvir) achieving sustained virological response. Treatment was well tolerated and no relevant side effects were observed. The drug-drug interactions and graft function were carefully monitored.

Asunto(s)

Antivirales/uso terapéutico , Trasplante de Corazón/efectos adversos , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Antivirales/efectos adversos , Antivirales/sangre , Comorbilidad , Quimioterapia Combinada , Femenino , Genotipo , Hepatitis C Crónica/virología , Humanos , Persona de Mediana Edad , Ribavirina/sangre , Ribavirina/uso terapéutico , Sofosbuvir/sangre , Sofosbuvir/uso terapéutico , Respuesta Virológica Sostenida , Resultado del Tratamiento

RESUMEN

INTRODUCTION: Chronic hepatitis C (HCV) infection is a systemic life-threatening condition that can lead to hepatic and extra-hepatic complications. Sustained virological response (SVR) is associated with a regression of most liver and non-liver manifestations, which reduce mortality. The history of HCV infection therapy radically changed in the last decade, with the introduction of the first generation direct acting antivirals (DAAs). Areas covered: The new regimens, based on the combination of 2 or 3 second-generation DAAs, allow SVR, namely hepatitis C infection cure, in more than 95% of cases. Antiviral treatment is generally well tolerated and its duration (8-16 weeks) varies depending on the stage of liver fibrosis, HCV genotype, prior treatment, baseline viral load, presence of resistance-associated variants (RAV). This review evaluates the cause, the efficacy and safety results in case of DAAs failure. Expert commentary: Despite the excellent efficacy of DAAs, a minority of patients (4-5%) still fail to eradicate HCV, mainly related to poor adherence but also to relapse or viral breakthrough. The main causes of a failure of DAAs are the presence of advanced liver disease, suboptimal treatment and NS5A mutations. Many questions regarding resistant associated substitutions (RASs) prevalence and clinical relevance in re-treatment remain unanswered.

Asunto(s)

Antivirales/uso terapéutico , Farmacorresistencia Viral , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Cumplimiento de la Medicación , Antivirales/efectos adversos , Farmacorresistencia Viral/genética , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/mortalidad , Hepatitis C Crónica/virología , Humanos , Retratamiento , Factores de Riesgo , Respuesta Virológica Sostenida , Insuficiencia del Tratamiento , Carga Viral

RESUMEN

BACKGROUND: Suppressive activity of recurrence by interferon-free direct-acting antivirals (DAA) is not elucidated after curative treatment of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 177 patients received DAA after curative manners of HCC: 89 patients underwent DAA therapy after initial HCC treatment, and the other 88 patients after repeated therapy of 2-10 times. Among a cohort of HCC patients with surgery and radiofrequency ablation, 89 patients were chosen adjusting age, gender, and Barcelona Clinic Liver Cancer (BCLC) staging with 89 patients with initial HCC therapy. RESULTS: HCC recurrence rates at the end of first and second year were 18.1 and 22.1% in patients with once of HCC therapy, 28.2 and 41.6% in those with 2-3 times of therapy, and 60.2 and 74.5% in those with 4 or more times of therapy, respectively (P < 0.0001). Recurrence rates were compared between 89 patients with DAA therapy after initial HCC therapy and 89 age-, gender-, and BCLC staging-matched patients without antiviral therapy after initial HCC therapy. HCC recurrence rates at first and second year were 18.1 and 25.0% in patients with DAA therapy and 21.8 and 46.5% in those without DAA therapy, respectively (P = 0.003). Multivariate analysis showed DAA therapy significantly decreased recurrence rate with a hazard ratio of 0.353 (confidence interval: 0.191-0.651) after adjustment with covariates of tumor multiplicity, alpha-fetoprotein value, and prothrombin time. CONCLUSIONS: DAA therapy significantly decreased recurrence rate when it was performed after initial HCC therapy.

Asunto(s)

Antivirales/administración & dosificación , Carcinoma Hepatocelular/terapia , Ablación por Catéter , Quimioembolización Terapéutica , Hepatectomía , Hepatitis C/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Recurrencia Local de Neoplasia , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/efectos adversos , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Ablación por Catéter/efectos adversos , Ablación por Catéter/mortalidad , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/mortalidad , Esquema de Medicación , Femenino , Hepatectomía/efectos adversos , Hepatectomía/mortalidad , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Hepatitis C/mortalidad , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

Cryoglobulinemia is a manifestation of hepatitis C virus (HCV) infection. Treatment of HCV is the mainstay of therapy for mixed cryoglobulinemia syndrome, and newer HCV therapies with direct-acting antiviral agents have achieved great success in treating HCV infection compared with pegylated interferon alfa and ribavirin. Recurrence of mixed cryoglobulinemia syndrome following successful treatment with direct-acting antiviral agents is uncommon, and when it occurs, it is most often due to relapse of HCV viremia. We report a case of recurrent mixed cryoglobulinemia syndrome following HCV treatment with a new direct-acting antiviral agent (sofosbuvir) and ribavirin, in which HCV RNA was undetectable in serum, but detectable in the cryoprecipitate.

Asunto(s)

Antivirales/uso terapéutico , Crioglobulinemia/tratamiento farmacológico , Crioglobulinemia/virología , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Ribavirina/uso terapéutico , Sofosbuvir/uso terapéutico , Respuesta Virológica Sostenida , Humanos , Masculino , Persona de Mediana Edad , Recurrencia

RESUMEN

Treatment of hepatitis C virus (HCV) with newer directly acting antivirals (DAAs) and lead to sustained viral response (SVR) in majority of patients and SVR has been documented to be associated with reversal of liver cirrhosis. The improved SVR rates and safety profiles of DAAs have led to the treatment of patients with decompensated cirrhosis awaiting liver transplantation (LT). Several clinical trials of DAAs in decompensated HCV patients have recently demonstrated SVR rates above 80%, which have been associated with significant improvements, in the Child-Pugh-Turcotte scores/or model for end-stage liver disease scores in a proportion of patients. Moreover, it has been shown that HCV RNA becomes negative after 2-4 weeks of treatment, and those who are transplanted after becoming HCV RNA negative will be have very low the risk of HCV recurrence after transplantation. Some of the patients may have reached the "point of no return" and may proceed to worsening of decomposition over time. To avoid the risk of worsening, there is an additional option of treating these patients after LT should they develop recurrent HCV infection. Currently there are no guidelines as to select patients who would benefit from treatment prior to LT as opposed to those who will be better off being treated after the transplant surgery. The article discusses a possible approach for such selection.