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BACKGROUND: There is limited literature describing the real-world practice of delayed initiation and shortened duration direct-acting antiviral (DAA) in kidney transplant recipients. We compared Hepatitis C virus (HCV) cure rates among kidney transplant recipients who received an HCV nucleic acid test positive (NAT +) kidney and were treated with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks or glecaprevir/pibrentasvir (G/P) for 8 weeks, a duration that is 4 weeks shorter than the guideline recommendation for treatment delay beyond 1-week post-transplant. METHODS: Retrospective study of HCV-negative adult patients who received a kidney transplant from an HCV NAT+ donor between April 2019 and April 2022 treated with either SOF/VEL for 12 weeks or G/P for 8 weeks. The primary outcome was sustained virologic response 12 weeks after completion of therapy (SVR12). Secondary outcomes included time to DAA initiation, renal function, graft loss, patient death, liver function tests, and opportunistic infections. RESULTS: 102 kidney transplant recipients were included with 36 treated with G/P and 66 treated with SOF/VEL. All 36 (100%) treated with G/P achieved SVR12. One patient in the SOF/VEL group failed to achieve SVR12 but received additional therapy and was cured. Time to DAA initiation was similar with a mean of 4 weeks. There was no difference in AST/ALT > 3x ULN or renal function. One rejection occurred in each group. No patient death or graft loss was observed. There was no difference in cytomegalovirus and BK viremia between groups. CONCLUSION: Delayed initiation of DAA therapy with 12 weeks of SOF/VEL or 8 weeks of G/P achieves SVR12 in kidney transplant recipients without significant adverse effects.
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Hepatitis C virus (HCV) belongs to the Flaviviridae family, and is a single-stranded RNA virus with positive polarity. It is the primary cause of hepatocellular carcinoma (HCC) worldwide. The treatment of HCV has entered a new era with the advent of direct-acting antiviral drugs (DAAs) and is associated with cure rates of more than 95â¯%, making HCV the only curable viral disease. The successful treatment of chronic hepatitis C has greatly reduced, but not eliminated, the risk of HCC. Certain individuals, especially those with cirrhosis already present, remain vulnerable to HCC after achieving a sustained virological response (SVR). This article systematically reviews the recent studies on the risk and mechanisms of HCC development after HCV viral cure, the screening and predictive value of biological markers, and patient surveillance. Factors such as older age, diabetes, hepatic fat accumulation, alcohol use, and lack of fibrosis reversal are linked to increased HCC risk after HCV cure. The mechanism of HCC development after DAAs treatment remains unclear, but the possible mechanisms include immune cell dysfunction during HCV infection, cytokine network imbalance, epigenetic alterations, and host factors. Several biological markers and risk prediction models have been used to monitor the risk of HCC in CHC patients who have achieved SVR, but most still require validation and standardization. The implementation of risk-stratified surveillance programs is becoming urgent from a cost-effective point of view, but the availability of validated biomarkers to predict HCC in cured patients remains an unmet clinical need. Additionally, managing CHC patients who achieve SVR is becoming a growing challenge as an increasing number of HCV patients are cured.
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To date, the effectiveness of direct-acting antivirals (DAAs) discontinued before 4 weeks has not been analysed in routine clinical practice. The study aimed to determine whether such a short therapy will enable achieving a sustained virological response under real-world experience. The study population of 97 patients who discontinued DAA therapy and had data enabling analysis of patient and disease characteristics, and assessment of treatment effectiveness was selected from 16,815 patients registered in the EpiTer-2 database. The most common reason for discontinuation was hepatic decompensation (20.6%) or the patient's personal decision (18.6%). Patients who discontinued treatment were significantly older, more frequently therapy-experienced, more likely to have cirrhosis, a history of decompensation and a Child-Pugh B or C classification than those who completed treatment. SVR was achieved by 93.5% of patients who discontinued treatment after 4 weeks, 60.9% if discontinued at 3 or 4 week and 33.3% at Week 1 or 2. Patients receiving pangenotypic but not genotype-specific treatment who discontinued after 4 weeks were as likely to achieve SVR as those who completed therapy. Patients who responded to treatment that lasted no longer than 2 weeks had a low baseline viral load (<400,000 IU/mL). Despite discontinuation of therapy after Week 4, the chances of SVR are high. Very early discontinuation does not preclude therapeutic success, especially in patients with low baseline viral load.
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Pharmacists are key players who can help to eliminate the hepatitis C virus (HCV) epidemic in the United States. This pilot retrospective study evaluated the impact of a pharmacist-led HCV treatment program in a federally qualified health center (FQHC) primary care clinic setting. The primary outcome was to assess sustained virologic response (SVR) rates 12 weeks after patients were initiated and completed their oral direct acting antiviral (DAA) treatment regimens. METHODS: This pilot retrospective study included historical analyses of patients who received DAA treatment in the pharmacist-led HCV treatment program in a FQHC clinic between 1 January 2019 and 31 January 2021. SVR was the primary outcome measure for treatment response. RESULTS: Sixty-seven patients with HCV mono- and HIV co-infection were referred, and 59 patients were initiated on DAA regimens after treatment. Fifty of those who were started on DAA regimens completed their treatment, and 38 achieved SVR (modified intention to treat [mITT] SVR rate of 76%). CONCLUSION: Our study's findings demonstrated SVR rates that were comparable with other pharmacist-directed HCV treatment services in the United States despite the impact of the COVID-19 pandemic. Our study included a higher proportion of individuals with HCV/HIV co-infection and of Hispanic ethnicity.
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BACKGROUND: Hepatitis C virus (HCV) infection affects 50 million people worldwide with around 242,000 deaths annually, mainly due to complications such as cirrhosis and hepatocellular carcinoma (HCC). Portal hypertension (PH) caused by cirrhosis leads to severe consequences, including esophageal varices (EV). This study aimed to evaluate the effectiveness and safety of direct-acting antiviral (DAA) treatment in patients with and without EV. METHODS: This retrospective analysis involved consecutive HCV-infected adults undergoing DAA therapy at 22 Polish hepatology centers from July 1, 2015, to December 31, 2022. Patients with cirrhosis were categorized based on the presence of EV diagnosed by gastroscopy. Treatment effectiveness was measured by sustained virologic response (SVR), with safety outcomes monitored for 12 weeks post-treatment. RESULTS: A population of 3393 HCV-infected patients with cirrhosis was divided into groups with (A, n = 976) and without (B, n = 2417) EV. Group A showed a significantly higher prevalence of comorbidities and concomitant medications. Genotype (GT)1b infections predominated in both groups, and GT3 infections were more common in the EV group. Group A exhibited more severe liver disease, and higher rates of decompensation, HCC, and HBV co-infection. SVR was significantly higher in group B (91.5% vs. 96.3%, p < 0.0001). Male gender, GT3, EV presence, and Child-Pugh grade B were identified as independent negative SVR predictors. Group A had a worse safety profile, with notably higher adverse event incidence and mortality. CONCLUSIONS: DAA therapies are highly effective and well tolerated in patients with cirrhosis, but EV presence predicts poorer virologic responses.
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Antivirales , Várices Esofágicas y Gástricas , Cirrosis Hepática , Respuesta Virológica Sostenida , Humanos , Masculino , Antivirales/uso terapéutico , Antivirales/efectos adversos , Femenino , Várices Esofágicas y Gástricas/etiología , Várices Esofágicas y Gástricas/virología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/virología , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Adulto , Resultado del Tratamiento , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Polonia/epidemiología , Genotipo , Hepatitis C/tratamiento farmacológico , Hepatitis C/complicacionesRESUMEN
We diagnosed six cases of acute hepatitis C virus (HCV) infection at our hospital between October 2003 and December 2022. During the same period, we diagnosed 402 cases of chronic HCV infection and 636 cases of acute hepatic injury. Acute HCV infection cases accounted for 1.4% of all HCV infections and 0.9% of all acute hepatic injury cases. The acute HCV infection group was younger, had more severe hepatitis, and exhibited higher levels of bilirubinemia compared to the chronic HCV infection group. Two acute HCV infection cases achieved spontaneous viral clearance, while the remaining four cases progressed to chronic infection and were treated with direct-acting antivirals (DAAs). Liver enzyme elevation and liver function deterioration did not differ significantly between the acute HCV and other acute liver injury groups. Notably, DAA treatment was equally effective for acute and chronic HCV cases (75% vs. 90%, p = 0.34). Early DAA treatment in acute cases might contribute to interrupting viral transmission among high-risk populations, such as people who inject drugs or men who have sex with men. While there are currently no specific guidelines for acute HCV infection treatment in Japan, our findings suggest that DAA therapy should be initiated immediately following diagnosis. Further studies with larger patient cohorts are warranted to confirm these observations.
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Background and Objectives: Chronic hepatitis C (CHC) can be cured with direct-acting antiviral (DAA) therapy. In Korea, sofosbuvir (SOF) and ledipasvir (LDV)/SOF were launched in 2016. Patients who achieve a sustained virologic response (SVR) following DAA treatment are predicted to have a favorable prognosis. Nevertheless, little is known regarding the prognosis of Korean CHC patients who receive SOF-based treatment and achieve SVR. Therefore, the purpose of this study was to look into the long-term outcomes for these patients. Materials and Methods: This was a prospective, multicenter observational study. CHC patients were enrolled who, following SOF or LDV/SOF treatment, had achieved SVR. The last day for follow-up was December 2023. The primary endpoint was HCC occurrence, which was checked at least once per year. Results: A total of 516 patients were included in this analysis, with a median follow-up duration of 39.0 months. Among them, 231 were male patients (44.8%), with a median age of 62.0 years. Genotypes were 1 (90, 17.4%), 2 (423, 82.0%), and 3 (3, 0.6%). The combination of SOF plus ribavirin was the most common treatment (394, 76.4%). In total, 160 patients were cirrhotic (31.0%), and the mean Child-Pugh score was 5.1. Within a maximum of 7 years, 21 patients (4.1%) developed HCC. Patients with HCC were older (69 vs. 61 years, p = 0.013) and had a higher cirrhosis incidence (81.0 vs. 28.9%, p < 0.001), higher AFP (6.0 vs. 3.3, p = 0.003) and higher APRI (0.8 vs. 0.5, p = 0.005). Age over 65 (p = 0.016) and cirrhosis (p = 0.005) were found to be significant risk factors for HCC by Cox regression analysis. Conclusions: Patients who achieved SVR with SOF-based treatment had a relatively favorable prognosis. However, the risk of HCC was not eliminated, especially in older and cirrhotic patients. Therefore, routine follow-up, surveillance, and early treatment are required.
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Antivirales , Hepatitis C Crónica , Sofosbuvir , Respuesta Virológica Sostenida , Humanos , Masculino , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Sofosbuvir/uso terapéutico , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Antivirales/uso terapéutico , República de Corea/epidemiología , Anciano , Pronóstico , Adulto , Neoplasias Hepáticas/epidemiología , Carcinoma Hepatocelular/epidemiologíaRESUMEN
BACKGROUND AND AIM: Understanding the dynamics of serum Mac-2 binding protein glycosylation isomer (M2BPGi) remains pivotal for hepatitis C virus (HCV) patients' post-sustained virologic response (SVR12) through direct-acting antivirals (DAAs). METHODS: We compared areas under receiver operating characteristic curves (AUROCs) of M2BPGi, FIB-4, and APRI and assess M2BPGi cutoff levels in predicting fibrosis stages of ≥F3 and F4 utilizing transient elastography in 638 patients. Variations in M2BPGi levels from pretreatment to SVR12 and their association with pretreatment alanine transaminase (ALT) levels and fibrosis stage were investigated. RESULTS: The AUROCs of M2BPGi were comparable to FIB-4 in predicting ≥F3 (0.914 vs 0.902, P = 0.48) and F4 (0.947 vs 0.915, P = 0.05) but were superior to APRI in predicting ≥F3 (0.914 vs 0.851, P = 0.001) and F4 (0.947 vs 0.857, P < 0.001). Using M2BPGi cutoff values of 2.83 and 3.98, fibrosis stages of ≥F3 and F4 were confirmed with a positive likelihood ratio ≥10. The median M2BPGi change was -0.55. Patients with ALT levels ≥5 times ULN or ≥F3 demonstrated more pronounced median decreases in M2BPGi level compared to those with ALT levels 2-5 times ULN and <2 times ULN (-0.97 vs -0.68 and -0.44; P < 0.001) or with < F3 (-1.52 vs -0.44; P < 0.001). CONCLUSIONS: Serum M2BPGi is a reliable marker for advanced hepatic fibrosis. Following viral clearance, there is a notable M2BPGi decrease, with the extent of reduction influenced by ALT levels and fibrosis stage.
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BACKGROUND: Clinic-based interventions are needed to promote successful direct acting antiviral (DAA) treatment for chronic hepatitis C virus (HCV) infection in patients with substance use disorders (SUDs) among rural Veterans. METHODS: We implemented a clinic-based intervention which used motivational interviewing (MI) techniques to promote medication adherence and treatment completion with 12 weeks of DAA treatment among rural Veterans with chronic HCV and SUDs. Patients received an MI session with a licensed psychologist at baseline and at each two-week follow-up visit during DAA treatment. Patients received $25 per study visit completed. Patients were to attend a laboratory visit 12 weeks after treatment completion to assess for sustained virologic response (SVR). RESULTS: Of the 20 participants who enrolled, 75% (n = 15) completed the planned 12-week course of treatment. Average adherence by pill count was 92% (SD = 3%). Overall SVR was 95% (19/20). CONCLUSIONS: We demonstrated that a clinic-based intervention which incorporated frequent follow up visits and MI techniques was feasible and acceptable to a sample of predominantly rural Veterans with chronic HCV and SUDs. CLINICAL TRIAL REGISTRATION: Registered at ClinicalTrials.gov (NCT02823457) on July 1, 2016. https://clinicaltrials.gov .
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Antivirales , Hepatitis C Crónica , Cumplimiento de la Medicación , Entrevista Motivacional , Población Rural , Trastornos Relacionados con Sustancias , Veteranos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Respuesta Virológica SostenidaRESUMEN
BACKGROUND & AIMS: Chronic HCV infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Herein, we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (Treg) cells from patients with chronic HCV infection before, during, and after DAA treatment. METHODS: Patients with chronic genotype 1b HCV infection who achieved sustained virologic response by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of Treg cells were investigated through flow cytometry analysis. Moreover, the transcriptomic and epigenetic landscapes of Treg cells were analyzed using RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin with sequencing) analysis. RESULTS: The Treg cell population - especially the activated Treg cell subpopulation - was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA sequencing analysis revealed that viral clearance did not abrogate the inflammatory features of these Treg cells, such as Treg activation and TNF signaling. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of Treg cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that Treg cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance. CONCLUSIONS: Overall, our results showed that during chronic HCV infection, the expanded Treg cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the Treg cell population after recovery from chronic HCV infection. IMPACT AND IMPLICATIONS: During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of direct-acting antivirals has led to high cure rates. Nevertheless, we have demonstrated that inflammatory features of Treg cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection.
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Despite achieving a high cure rate with direct-acting antivirals (DAAs) in hepatitis C treatment, further research is needed to identify additional benefits of the DAA therapy. The current study evaluated liver fibrosis improvement in 848 hepatitis C patients treated with DAAs, who also achieved sustained virologic response (SVR). Using the fibrosis-4 (FIB-4) index, patients were categorized based on their baseline fibrosis level, and improvements in fibrosis were analyzed in both the short-term (9-26 weeks) and long-term (≥ 36 weeks) follow-up. The results showed a significant decrease in the FIB-4 index, indicating an improvement in liver fibrosis, in 63.00% of the patients during the short-term follow-up and 67.56% during the long-term follow-up. Short-term improvement was associated with factors including ribavirin (RBV) usage, blood cholinesterase levels, alanine transaminase levels, albumin levels, and the baseline FIB-4 index. Additionally, long-term improvement was associated with factors such as aspartate transaminase levels, total protein level, and the baseline FIB-4 index. The current study emphasizes the importance of continuous assessment and post-treatment monitoring of liver fibrosis, providing crucial insights for enhancing patient care in hepatitis C management.
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Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving fixed-dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0-98.9) and 100% (95% CI: 66.4-100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed-dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9-100] vs. 97.1% [95% CI: 96.2-97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off-treatment week 12 among patients with HCV who are treated with fixed-dose pangenotypic DAAs.
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Antivirales , Hepacivirus , Hepatitis C Crónica , ARN Viral , Respuesta Virológica Sostenida , Humanos , Antivirales/uso terapéutico , Antivirales/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Hepacivirus/genética , Hepacivirus/efectos de los fármacos , Anciano , Adulto , ARN Viral/sangre , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Recurrencia , Estudios de Seguimiento , Resultado del Tratamiento , Hepatitis C/tratamiento farmacológico , Hepatitis C/virologíaRESUMEN
Objective: The aim of this study was to evaluate the glycated hemoglobin (HbA1c) levels before and after sustained virologic response (SVR) and investigate the baseline characteristics associated with improved glycemic control in patients with chronic hepatitis C (CHC) achieving SVR after directacting antivirals (DAA) therapy. Materials and methods: Consecutive adult patients with CHC who achieved SVR after DAA treatment between January 2016 and December 2017 at Hospital de Clínicas de Porto Alegre (RS, Brazil) were prospectively included. Levels of HbA1c were measured up to 24 weeks before DAA therapy and 12 weeks after SVR. Exclusion criteria were decompensated cirrhosis, HIV and/or hepatitis B virus, liver disease of other etiologies, and/or modification of prediabetes/ type 2 diabetes mellitus (PDM/T2DM) management. The primary outcome was a comparison of HbA1c levels before and after SVR. Secondary outcomes were the baseline variables associated with improved glycemic control. Results: The study included 207 patients with a mean age of 60.6±10.7 years, of whom 51.7% were women, 56% had cirrhosis, 37.7% had HCV genotype 3, and 54.5% had baseline T2DM or PDM. The median HbA1c level reduced significantly after SVR (5.5%, interquartile range [IQR] 4.9%-6.3%) compared with baseline (5.7%, IQR 5.3%-6.7%; p = 0.01). The baseline characteristics associated with improved HbA1c after SVR were cirrhosis, genotype 3, and age ≤ 60 years. Conclusion: Among patients with CHC, SVR after DAA was associated with HbA1c reduction, particularly in those with cirrhosis, genotype 3, and age ≤ 60 years.
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Antivirales , Glucemia , Hemoglobina Glucada , Hepatitis C Crónica , Respuesta Virológica Sostenida , Humanos , Femenino , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/sangre , Masculino , Persona de Mediana Edad , Hemoglobina Glucada/análisis , Glucemia/análisis , Glucemia/efectos de los fármacos , Anciano , Estudios Prospectivos , Resultado del Tratamiento , Hepacivirus/genética , Hepacivirus/efectos de los fármacos , Brasil , Adulto , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangreRESUMEN
Desde los años ochenta se ha explorado el tratamiento para el virus de la hepatitis C, aunque en ese entonces los medicamentos disponibles eran poco toleradas y poco eficaces. En el 2011, la introducción de antivirales de acción directa transformó significativamente el curso de la enfermedad, logrando tasas de curación superiores al 90 % en los pacientes. Este avance ha permitido prevenir complicaciones futuras con efectos adversos mínimos. La presente revisión aborda la línea de tiempo del descubrimiento de los antivirales, su mecanismo de acción, sus indicaciones y potencial impacto en la salud pública.
Since the 1980s, the treatment of hepatitis C has been explored, although at that time, the available medications were poorly tolerated and ineffective. In 2011, the introduction of direct-acting antivirals significantly transformed the course of the disease, achieving cure rates of over 90% in patients. This advance has made it possible to prevent future complications with minimal adverse effects. This review addresses the timeline of the discovery of antivirals, their mechanism of action, and their impact on medicine.
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BACKGROUND: Information on the dynamics of metabolic dysfunction-associated steatotic liver disease (MASLD) among hepatitis C virus patients achieving sustained virologic response (SVR12) with direct-acting antivirals (DAAs) is limited. METHODS: We enrolled 1512 eligible participants in this prospective study. MASLD was defined by a controlled attenuation parameter (CAP) of ≥248 dB/m utilizing vibration-controlled transient elastography in conjunction with presence of ≥1 cardiometabolic risk factor. The distribution of MASLD and the changes in CAP were evaluated before treatment and at SVR12. Forward stepwise logistic regression analyses were performed to determine factors significantly associated with the regression or emergence of MASLD. RESULTS: The prevalence of MASLD decreased from 45.0% before treatment to 36.1% at SVR12. Among 681 participants with MASLD before treatment, 144 (21%) exhibited MASLD regression at SVR12. Conversely, among 831 participants without MASLD before treatment, 9 (1.1%) developed MASLD at SVR12. Absence of type 2 diabetes (T2D) [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.13-2.65, p = 0.011], age > 50 years (OR: 1.73, 95% CI: 1.11-2.68, p = 0.015), and alanine transaminase (ALT) ≤ 2 times the upper limit of normal (ULN) (OR: 1.56; 95% CI: 1.03-2.37, p = 0.035) were associated with the regression of MASLD. Presence of T2D was associated with the emergence of MASLD (OR: 5.83, 95% CI: 1.51-22.56, p = 0.011). CONCLUSIONS: The prevalence of MASLD decreased after achieving SVR12 with DAAs. Patients with pre-existing T2D showed a diminished probability of MASLD regression and a heightened risk of MASLD emergence post-SVR12.
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Antivirales , Hígado Graso , Hepatitis C Crónica , Respuesta Virológica Sostenida , Humanos , Persona de Mediana Edad , Antivirales/uso terapéutico , Femenino , Masculino , Estudios Prospectivos , Anciano , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Diagnóstico por Imagen de Elasticidad , Adulto , Prevalencia , Factores de Riesgo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológicoRESUMEN
BACKGROUND: Direct-acting antiviral agents (DAAs) are highly effective treatment for chronic hepatitis C (CHC) with a significant rate of sustained virologic response (SVR). The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression. The assessment of fibrosis degree can be performed with transient elastography, magnetic resonance elastography or shear-wave elastography (SWE). Liver elastography could function as a predictor for hepatocellular carcinoma (HCC) in CHC patients treated with DAAs. AIM: To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus (HCV). METHODS: A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned. RESULTS: At baseline and after 12 wk of follow-up, a trend was shown towards greater liver stiffness (LS) in those who go on to develop HCC compared to those who do not [baseline LS standardized mean difference (SMD): 1.15, 95% confidence interval (95%CI): 020-2.50; LS SMD after 12 wk: 0.83, 95%CI: 0.33-1.98]. The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data. There was a statistically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not (0.64; 95%CI: 0.04-1.24). CONCLUSION: SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs. Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.
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Antivirales , Carcinoma Hepatocelular , Diagnóstico por Imagen de Elasticidad , Hepacivirus , Hepatitis C Crónica , Cirrosis Hepática , Neoplasias Hepáticas , Hígado , Valor Predictivo de las Pruebas , Respuesta Virológica Sostenida , Diagnóstico por Imagen de Elasticidad/métodos , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/virología , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/virología , Carcinoma Hepatocelular/patología , Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/diagnóstico por imagen , Hepacivirus/efectos de los fármacos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/virología , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: Mortality after sustained virological response (SVR) with interferon-free direct-acting antiviral (IFN-free DAA) therapy is crucial for optimizing post-SVR patient care, but it remains unclear, especially regarding non-liver-related mortality. METHODS: Consecutive post-SVR patients from 14 institutions were stratified into three cohorts: A (without advanced fibrosis and without prior HCC), B (with advanced fibrosis and without prior HCC), and C (curative HCC treatment). We assessed mortality (per 1000 person-years [/1000PY]) post-SVR. Mortality rates were compared between cohorts A and B and the general population using age- and sex-adjusted standardized mortality ratio (SMR). Comparison of survival between each cohort was performed using propensity-score (PS) matching with sex, age, and comorbidity. RESULTS: In cohort A (n = 762; median age, 65 years), 22 patients died (median follow-up, 36 months); all-cause mortality was 10.0/1000PY, with 86.4% non-liver-related deaths. In cohort B (n = 519; median age, 73 years), 27 patients died (median follow-up, 39 months); all-cause mortality was 16.7/1000PY, with 88.9% non-liver-related deaths. In both cohorts, malignant neoplasm was the most common cause of death; all-cause mortality was comparable to that of the general population (SMR: 0.96 and 0.92). In cohort C (n = 108; median age, 75 years), 15 patients died (median follow-up, 51 months); all-cause mortality was 36.0/1000PY, with 53.3% liver-related deaths. PS matching showed no significant survival differences between cohorts A and B, both of which had better survival than cohort C. CONCLUSIONS: Mortality varies based on HCC history in the DAA era; nevertheless, attention should be paid to non-liver-related deaths in all post-SVR patients.
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Carcinoma Hepatocelular , Hepatitis C Crónica , Neoplasias Hepáticas , Humanos , Anciano , Antivirales/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/etiología , Hepatitis C Crónica/tratamiento farmacológico , Respuesta Virológica Sostenida , FibrosisRESUMEN
A 69-year-old woman with chronic hepatitis C virus (HCV) infection was referred to our hospital due to liver enzyme abnormalities. Four years after anti-HCV therapy, the patient with sustained virologic response and no clinical symptoms developed an oval hepatic mass with mixed high and low internal echoes near the portal vein on ultrasound. Magnetic resonance imaging (MRI) of the liver lesion showed a slightly hypo intense pattern on T1-weighted images, a hyper intense pattern both on T2- and diffusion-weighted images, a slight rim enhancement pattern with no intra-lesional enhancement up to the late phase, and a very low intense pattern on hepatobiliary phase images. Positron emission tomography/computed tomography (PET / CT) showed no areas of avid radiotracer uptake in the liver. No tumor markers showed abnormally high values. All these images and laboratory findings led us to the assessment of the liver lesion as a non-neoplastic disorder. However, due to the patient's strong preference to get both definitive diagnosis and cure of the lesion, the patient underwent laparoscopic partial hepatectomy. Pathological study showed 2 necrotic areas surrounded by multiple lymph follicles, epithelioid cells, lymphocytes, collagen fibers, and plasma cells, leading to the diagnosis of focal coagulative necrosis of the liver (FCNL). Physicians should note that FCNL can occur without any symptoms and can be diagnosed at least as a non-neoplastic disorder with combined MRI and PET/CT analysis.
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Background and Aims: Direct-acting antiviral agents (DAAs) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection, resulting in a high sustained virologic response (SVR) rate. However, the published data from the Eastern Province of Saudi Arabia are limited to small patient groups and specific DAAs used for patients with genotype-4.(GT-4). This study aimed to investigate the effectiveness and safety of DAAs for treating HCV infection in Saudi Arabia in a real-life setting. Methods: This retrospective study from January 2015 to December 2019 included all HCV-infected patients who received DAAs at a tertiary university hospital in Saudi Arabia. Baseline characteristics and laboratory data were collected from health records, including HCV RNA level, genotype, and presence of liver cirrhosis or steatosis. The primary outcome was undetectable HCV RNA at 12 weeks posttreatment (SVR12). Results were stratified based on different DAAs and HCV genotypes. Treatment-related adverse events were recorded. Statistical analyses were performed using SPSS version 25.0. Results: Of the 117 patients included, 43.2% had advanced fibrosis or cirrhosis, and the majority (90.6%) were treatment-naïve. The mean age was 50.1 ± 15.5 years, with 57.3% females. The most common genotype was GT-4 (44.4%), followed by GT-1 (40.2%). Most patients (64.3%) received sofosbuvir and daclatasvir ± ribavirin, while the remaining patients received various DAAs. Overall, 98.3% of the patients achieved SVR12. The therapy was well tolerated, with fatigue and headache being the most common side effects. Conclusions: Treatment with DAAs is highly effective across different genotypes and various DDA regimens in the real world for treating HCV infection in the Eastern Province of Saudi Arabia, contributing to improved patient outcomes and the overall goal of HCV elimination.