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• W3048281202 abstract "Direct-acting antiviral (DAA)-induced HCV clearance conceivably leads to improved outcomes at all stages of liver disease. However, available data suggest that the maximum measurable benefit is obtained by treating patients before they reach the stage of compensated advanced chronic liver disease (cACLD). Ideally, all patients with chronic hepatitis C should be treated before they develop advanced fibrosis or cirrhosis, since even if sustained virologic response (SVR) reduces the risk of hepatic events (e.g. decompensation and hepatocellular carcinoma [HCC]) and improves survival, further progression of liver disease and adverse outcomes, including hepatic deaths, cannot be entirely avoided. The hepatic venous pressure gradient (HVPG) correlates closely with the stage of liver disease. Measurements of HVPG in patients with severe fibrosis or cirrhosis treated with DAAs show that those with the highest degree of portal hypertension have the lowest probability of a meaningful reduction of portal pressure after SVR, and remain at significant risk of decompensation. Reduced liver stiffness is commonly observed in patients with cACLD but its role in predicting prognosis is yet to be demonstrated. In patients with decompensated cirrhosis, prevention of further decompensation and of HCC is only weakly associated with SVR. Overall, the main clinical predictors of a high risk of HCC in patients who obtain SVR on DAAs are all indexes strongly reflecting advanced fibrosis and impaired hepatic function. Long-term follow-up of large real-life cohorts of patients treated at all stages of liver disease, but mainly those with mild to moderate fibrosis, will be needed to confirm the impact of SVR among diverse HCV-infected populations and, more importantly, to better stratify patients at higher risk of complications in order to define their correct surveillance. Direct-acting antiviral (DAA)-induced HCV clearance conceivably leads to improved outcomes at all stages of liver disease. However, available data suggest that the maximum measurable benefit is obtained by treating patients before they reach the stage of compensated advanced chronic liver disease (cACLD). Ideally, all patients with chronic hepatitis C should be treated before they develop advanced fibrosis or cirrhosis, since even if sustained virologic response (SVR) reduces the risk of hepatic events (e.g. decompensation and hepatocellular carcinoma [HCC]) and improves survival, further progression of liver disease and adverse outcomes, including hepatic deaths, cannot be entirely avoided. The hepatic venous pressure gradient (HVPG) correlates closely with the stage of liver disease. Measurements of HVPG in patients with severe fibrosis or cirrhosis treated with DAAs show that those with the highest degree of portal hypertension have the lowest probability of a meaningful reduction of portal pressure after SVR, and remain at significant risk of decompensation. Reduced liver stiffness is commonly observed in patients with cACLD but its role in predicting prognosis is yet to be demonstrated. In patients with decompensated cirrhosis, prevention of further decompensation and of HCC is only weakly associated with SVR. Overall, the main clinical predictors of a high risk of HCC in patients who obtain SVR on DAAs are all indexes strongly reflecting advanced fibrosis and impaired hepatic function. Long-term follow-up of large real-life cohorts of patients treated at all stages of liver disease, but mainly those with mild to moderate fibrosis, will be needed to confirm the impact of SVR among diverse HCV-infected populations and, more importantly, to better stratify patients at higher risk of complications in order to define their correct surveillance. Given their almost universal effectiveness and tolerability, as well as their rapidly reducing costs, direct-acting antivirals (DAAs) are considered standard of care for all individuals with chronic HCV infection, regardless of the stage of liver disease.[1]Pawlotsky J.-M. Negro F. Aghemo A. Berenguer M. Dalgard O. Dusheiko G. et al.EASL recommendations on treatment of hepatitis C 2018.J Hepatol. 2018; 69: 461-511Abstract Full Text Full Text PDF PubMed Scopus (980) Google Scholar While containment and ultimately control of HCV at a global level over the next decade has become a realistic goal, justifying expansion of treatment,[2]Ioannou G.N. Feld J.J. What are the benefits of a sustained virologic response to direct-acting antiviral therapy for hepatitis C virus infection?.Gastroenterology. 2019; 156: 446-460.e2Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar further evaluation of the clinical benefits of DAAs, especially in the long term, is still needed at the individual patient level. In fact, while the projected number of adverse liver disease outcomes over a relatively short period is high enough to make treatment benefits measurable in patients with fibrotic liver disease (Metavir F3/F4), patients with mild to moderate fibrosis (Metavir F1/F2), if left untreated, would only have a significant number of disease outcomes after years or even decades, and only after progressing to F3/F4 fibrosis. Herein, we re-evaluate the evidence of short and long-term benefit of DAAs for patients with HCV infection according to the stage of disease at the time of treatment. The main objective of obtaining HCV clearance in patients without advanced liver disease, excluding non-hepatic manifestations of HCV,[3]Negro F. Forton D. Craxì A. Sulkowski M.S. Feld J.J. Manns M.P. Extrahepatic morbidity and mortality of chronic hepatitis C.Gastroenterology. 2015; 149: 1345-1360Abstract Full Text Full Text PDF PubMed Scopus (217) Google Scholar is to avoid progression into fibrotic stages and ultimately prevent disease outcomes such as cirrhosis and hepatocellular carcinoma (HCC). Indeed, antiviral therapy in patients with HCV and mild to moderate fibrosis is usually easier since regimens can be shorter and ribavirin is never needed. Reducing the progression of fibrosis is not the only objective, since HCV clearance eliminates the risk of transmitting HCV, an issue of major relevance for people who inject drugs, men who have sex with men with high-risk sexual behaviour, incarcerated individuals, patients on long-term haemodialysis, or healthcare workers who perform invasive procedures.[4]Calvaruso V. Craxì A. Why do I treat my patients with mild hepatitis C.Liver Int. 2016; 36: 7-12Crossref PubMed Scopus (17) Google Scholar Younossi et al.[5]Younossi Z.M. Singer M.E. Mir H.M. Henry L. Hunt S. Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients.J Hepatol. 2014; 60: 530-537Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar performed a cost-effectiveness analysis to compare a staging-guided vs. treat all strategy with interferon-based vs. interferon-free regimens in patients with HCV genotype 1 and concluded that staging fibrosis in these patients is not cost effective for DAAs; thus, the indication to treat or not treat should not be based on the stage of liver disease. These data were later confirmed by Chhatwal et al.[6]Chhatwal J. Kanwal F. Roberts M.S. Dunn M.A. Cost-effectiveness and budget impact of hepatitis C virus treatment with sofosbuvir and ledipasvir in the United States.Ann Intern Med. 2015; 162: 397-406Crossref PubMed Scopus (254) Google Scholar who evaluated the cost effectiveness of sofosbuvir and ledipasvir, concluding that treatment not only reduces HCV-related outcomes but is cost-effective in the majority of patients. Avoidance of liver biopsy before and after treatment for HCV has nowadays become almost universal, hence we are left without direct proof that F1/F2 hepatic fibrosis actually regresses to an F0 stage with a complete restitutio ad integrum of liver architecture. Also, evidence on the non-invasive evaluation of fibrosis using Fibroscan is scarce in this group of patients. Knop et al.[7]Knop V. Mauss S. Goeser T. Geier A. Zimmermann T. Herzer K. et al.Dynamics of liver stiffness by transient elastography in patients with chronic hepatitis C virus infection receiving direct-acting antiviral therapy-results from the German Hepatitis C-Registry.J Viral Hepat. 2020; 27: 690-698Crossref PubMed Scopus (9) Google Scholar prospectively evaluated the dynamics of liver stiffness (LS) by transient elastography (TE) in patients with chronic HCV infection receiving DAA-based treatment. Stratified by fibrosis stage, like patients classified with F0–F1, patients with F2–F3 had only a marginal LS reduction between baseline and 24 weeks after end of treatment (5.3 vs. 5.2 kPa; p = 0.064) and (8.9 vs. 8.8 kPa; p = 0.060), respectively. Finally, data on the real-world effectiveness of new antivirals have been reported by Backus et al.[8]Backus L.I. Belperio P.S. Shahoumian T.A. Mole L.A. Direct-acting antiviral sustained virologic response: impact on mortality in patients without advanced liver disease.Hepatology. 2018; 68: 827-838Crossref PubMed Scopus (79) Google Scholar who evaluated 103,346 HCV-monoinfected patients without advanced liver disease identified from the Veterans Affairs Hepatitis C Clinical Case Registry. In patients who achieved SVR, with fibrosis-4 (FIB-4) <1.45 or 1.45–3.25, mortality rates were reduced by 46.0% and 63.2%, respectively, compared to patients who did not achieve SVR, and by 66.7% and 70.6%, respectively, compared to untreated patients. These data demonstrate that successfully treating HCV with DAAs in patients without clinically apparent advanced liver disease translates into a significant mortality benefit.Key pointHCV clearance is a major goal that can be achieved with DAAs regardless of the stage of liver disease. Patients achieving virological cure have better outcomes than non-responders at all disease stages. HCV clearance is a major goal that can be achieved with DAAs regardless of the stage of liver disease. Patients achieving virological cure have better outcomes than non-responders at all disease stages. Establishing the actual role of HCV clearance in terms of hepatic benefit for patients with advanced fibrosis or cirrhosis is a multifaceted task. While on one hand halting the progression of fibrosis even at a late stage of disease may prove beneficial in terms of prevention of liver decompensation and death, there is no clear evidence that F4 fibrosis may entirely revert. Moreover, when dealing with patients with compensated advanced chronic liver disease (cACLD), the risk of cirrhosis-related outcomes remains significant after HCV clearance. The disconnection between an easily obtainable virologic cure and a disease unmodified in its course is often disappointing for physicians and patients. Data on post-clearance disease course from studies carried out in the era of interferon-based therapies are scarcely significant nowadays, owing to the huge selection biases of these populations. Evidence on the medium- and long-term course of individuals with F3/F4 fibrosis is accumulating, but further follow-up is definitely still needed to assess the ultimate impact on different liver outcomes. Studies on interferon-based therapies have shown that liver fibrosis and even cirrhosis may regress in a large percentage of patients with HCV once SVR is achieved.[9]George S.L. Bacon B.R. Brunt E.M. Mihindukulasuriya K.L. Hoffmann J. Di Bisceglie A.M. Clinical, virologic, histologic, and biochemicaloutcomes after successful HCV therapy.Hepatology. 2009; 49: 729-738Crossref PubMed Scopus (303) Google Scholar,[10]D'Ambrosio R. Aghemo A. Rumi M.G. Ronchi G. Donato M.F. Paradis V. et al.A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis.Hepatology. 2012; 56: 532-543Crossref PubMed Scopus (266) Google Scholar In 2012, D'Ambrosio et al.[10]D'Ambrosio R. Aghemo A. Rumi M.G. Ronchi G. Donato M.F. Paradis V. et al.A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis.Hepatology. 2012; 56: 532-543Crossref PubMed Scopus (266) Google Scholar demonstrated regression of F4 to lesser stages of fibrosis in more than 60% of 38 patients treated with IFN plus ribavirin, a median of 5 years after SVR. With the arrival of DAAs and the validation of non-invasive tests (NITs) of liver fibrosis, the use of biopsy in patients with chronic HCV hepatitis has rapidly vanished. Thus, many studies have focused on the improvement of NITs after SVR. Bachofner et al.[11]Bachofner J.A. Valli P.V. Kröger A. Bergamin I. Künzler P. Baserga A. et al.Direct antiviral agent treatment of chronic hepatitis C results in rapid regression of transient elastography and fibrosis markers fibrosis-4 score and aspartate aminotransferase-platelet ratio index.Liver Int. 2017; 37: 369-376Crossref PubMed Scopus (130) Google Scholar have shown a rapid decrease in LS as measured by TE after treatment with DAAs. At the same time, fibrosis scores (aspartate aminotransferase to platelet ratio index [APRI] and FIB-4) improved significantly. More recently a Spanish study[12]Pons M. Rodríguez-Tajes S. Esteban J.I. Mariño Z. Vargas V. Lens S. et al.Non-invasive prediction of liver-related events in patients with HCV-associated compensated advanced chronic liver disease after oral antivirals.J Hepatol. 2020; 72: 472-480Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar evaluated the evolution of LS in more than 500 patients with HCV-associated cACLD who obtained SVR after oral antivirals. The authors observed that after 1 year of follow-up, mean LS after SVR decreased by nearly 30% from baseline. More than 70% of patients had an improvement of LS ≥20% and remarkably almost 40% of the patients achieved an LS <10 kPa at follow-up. This change in LS cannot be explained only by a decrease in actual fibrosis since the time course is too short for significant remodelling. Further long-term longitudinal evaluations of the dynamics of LS changes should be performed to consolidate results and to assess if they are associated with a better disease outcome. The first study showing an impact of SVR on hepatic venous pressure gradient (HVPG) was performed by Mandorfer et al. in 2016[13]Mandorfer M. Kozbial K. Schwabl P. Freissmuth C. Schwarzer R. Stern R. et al.Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension.J Hepatol. 2016; 65: 692-699Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar; the authors analysed 60 patients with an HVPG measurement before and after DAAs and stratified them according to baseline HVPG (6–9 mmHg; 10–15 mmHg, ≥16 mmHg). They showed that SVR ameliorates portal hypertension across all HVPG strata at baseline. However, an HVPG decrease was less likely in patients with HVPG ≥16 mmHg (more advanced liver dysfunction). Further evidence on this issue comes from a Spanish multicentre prospective study,[14]Lens S. Alvarado-Tapias E. Mariño Z. Londoño M.C. LLop E. Martinez J. et al.Effects of all-oral anti-viral therapy on HVPG and systemic hemodynamics in patients with hepatitis C virus-associated cirrhosis.Gastroenterology. 2017; 153: 1273-1283.e1Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar assessing 226 patients with HCV-related cirrhosis and clinically significant portal hypertension (CSPH). The portal pressure gradient was determined based on HVPG at baseline and 24 weeks after IFN-free therapy. Even if HVPG decreased by 10% or more from baseline in more than 60% of patients, CSPH persisted in 78% of patients, indicating a persistent risk of decompensation despite SVR. Both the Austrian and the Spanish study recorded LS by TE. In the first case, LS reduction was a predictor of an HVPG decrease of ≥10%, and follow-up LS had an AUROC of 0.931 for the diagnosis of CSPH.[13]Mandorfer M. Kozbial K. Schwabl P. Freissmuth C. Schwarzer R. Stern R. et al.Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension.J Hepatol. 2016; 65: 692-699Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar Conversely, in the second study, changes in LS did not correlate with HVPG and no reliable cut-off values were found to rule out CSPH after SVR.[14]Lens S. Alvarado-Tapias E. Mariño Z. Londoño M.C. LLop E. Martinez J. et al.Effects of all-oral anti-viral therapy on HVPG and systemic hemodynamics in patients with hepatitis C virus-associated cirrhosis.Gastroenterology. 2017; 153: 1273-1283.e1Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar More recently, Mandorfer et al.[15]Mandorfer M. Kozbial K. Schwabl P. Chromy D. Semmler G. Stättermayer A.F. et al.Changes in hepatic venous pressure gradient predict hepatic decompensation in patients who achieved sustained virologic response to interferon-free therapy.Hepatology. 2020; 71: 1023-1036Crossref PubMed Scopus (44) Google Scholar evaluated the change in HVPG after SVR as a tool to assess the prognosis of patients with pre-treatment CSPH. An HVPG decrease ≥10% was associated with a significant reduction in the likelihood of hepatic decompensation. Importantly, in the same study, NITs such as TE were inadequate for diagnosing an HVPG reduction ≥10%. NITs seem, at least up to now, relatively inconsistent and insensitive for predicting changes of HVPG after DAAs. That said, HVPG measurement, albeit accurate and reproducible, is an invasive technique with limited availability outside specialised centres; hence it cannot be broadly used to assess the ability of SVR to reduce portal hypertension (PHT). In this setting, the role of the best proxy for HVPG, i.e. assessment of gastroesophageal varices (GEVs) by endoscopy (which bears an intrinsic bias owing to intra- and interobserver variability), has only been explored in 2 studies. Thabut et al.[16]Thabut D. Bureau C. Layese R. Bourcier V. Hammouche M. Cagnot C. et al.Validation of Baveno VI criteria for screening and surveillance of esophageal varices in patients with compensated cirrhosis and a sustained response to antiviral therapy.Gastroenterology. 2019; 156: 997-1009.e5Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar evaluated the rate of PHT progression (development of medium/large EVs in patients with no or small EVs at baseline, or PHT-related bleeding) in a cohort of patients with HCV (most represented) or HBV infection. They found that viral suppression and an absence of EV at inclusion were associated with a reduced risk of PHT progression. The cumulative rates of PHT progression at 1, 3, and 5 years were 1.8%, 4.1%, and 4.1%, respectively, in patients with no EV at inclusion in whom viral suppression was achieved; 0%, 15.7%, and 15.7%, respectively, in patients with grade 1 EV at inclusion who obtained viral suppression; 2.2%, 7.7%, and 14.2%, respectively, in patients with no EV at inclusion in whom viral suppression was not achieved; and 2.7%, 31.7%, and 52.6%, respectively, in patients with grade 1 EV at inclusion without viral suppression (p <0.001). They also evaluated the role of Baveno VI criteria in predicting PHT progression which reached 0%, 0.8%, and 2.5% at 1, 3, and 5 years respectively, in the 136 patients with an initially favourable Baveno VI status vs. 3.9%, 15.9%, and 24.3%, respectively, among the 412 patients with an initially unfavourable Baveno VI status (p <0.001). Furthermore, the authors found that 17 out of 58 patients (28.3%) with HCV who achieved SVR, and had an unfavourable Baveno VI status at inclusion, subsequently developed a favourable Baveno VI status; none of these patients displayed any progression of PHT, while 5 (8.6%) patients whose Baveno VI status remained unfavourable during follow-up experienced progression. Puigvehi et al.[17]Puigvehí M. Londoño M.C. Torras X. Lorente S. Vergara M. Morillas R.M. et al.Impact of sustained virological response with DAAs on gastroesophageal varices and Baveno criteria in HCV-cirrhotic patients.J Gastroenterol. 2020; 55: 205-216Crossref PubMed Scopus (7) Google Scholar analysed 151 patients with HCV-related cirrhosis who had upper endoscopy before and after HCV clearance, showing that 12.5% of patients without GEVs at baseline developed them after SVR. This rate reached 24% for patients with baseline low-risk GEVs who developed high-risk GEVs. As for studies evaluating HVPG, GEV changes were also studied in relation to LS.[17]Puigvehí M. Londoño M.C. Torras X. Lorente S. Vergara M. Morillas R.M. et al.Impact of sustained virological response with DAAs on gastroesophageal varices and Baveno criteria in HCV-cirrhotic patients.J Gastroenterol. 2020; 55: 205-216Crossref PubMed Scopus (7) Google Scholar The rate of patients with baseline LS ≥25 kPa was significantly higher in those with GEV progression (64.7%) than in those without (39.4%) (p = 0.043). After SVR, the rate of patients with an LS ≥20 kPa was higher in those with GEV progression (66.7%) than in those without (41.9%) (p = 0.043).Key pointThe ultimate hepatic benefit of viral clearance is proportional to the functional class of liver disease reached by the patient at the time of treatment. The ultimate hepatic benefit of viral clearance is proportional to the functional class of liver disease reached by the patient at the time of treatment. In patients with cirrhosis, the likelihood of decompensation is closely related to the degree of portal hypertension. A significant reduction in decompensation rates has been demonstrated in prospective studies of patients with HCV infection and compensated cirrhosis who achieved SVR on IFN-based therapy and were followed-up for at least 5 years.[18]Di Marco V. Calvaruso V. Ferraro D. Bavetta M.G. Cabibbo G. Conte E. et al.Effects of eradicating hepatitis C virus infection in patients with cirrhosis differ with stage of portal hypertension.Gastroenterology. 2016; 151: 130-139.e2Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar,[19]Nahon P. Bourcier V. Layese R. Audureau E. Cagnot C. Marcellin P. et al.Eradication of hepatitis C virus infection in patients with cirrhosis reduces risk of liver and non-liver complications.Gastroenterology. 2017; 152: 142-156.e2Abstract Full Text Full Text PDF PubMed Scopus (285) Google Scholar These patients almost all had Child-Pugh A cirrhosis because of the intrinsic limits posed by interferon and thus had a lower probability of decompensation in the short/medium term, regardless of HCV clearance. The possibility of using DAAs to treat patients with the entire spectrum of liver disease regardless of residual liver function and of cytopenia sets a new stage for evaluating the ultimate relevance of HCV clearance in patients with cirrhosis. Due to the relatively short-term follow-up available since the inception of DAAs, only a few studies have assessed the rate of de novo liver decompensation in patients with cACLD after DAA-induced SVR. In the French Hepather cohort, Carrat et al.[20]Carrat F. Fontaine H. Dorival C. Simony M. Diallo A. Hezode C. et al.Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study.Lancet. 2019; 393: 1453-1464Abstract Full Text Full Text PDF PubMed Scopus (213) Google Scholar failed to demonstrate lower rates of decompensation in patients exposed to DAAs and followed for a median time of 33.4 months, after adjustment for numerous variables including comorbidities such as alcohol consumption, diabetes, and arterial hypertension. However in a cohort of 1,760 patients in South America, Mendizabal et al.[21]Mendizabal M. Piñero F. Ridruejo E. Wolff F.H. Anders M. Reggiardo V. et al.Disease progression in patients with hepatitis C virus infection treated with direct-acting antiviral agents.Clin Gastroenterol Hepatol. 2020; 18: 2554-2563.e3Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar found that SVR was significantly associated with a lower incidence of decompensation (hazard ratio [HR] 0.3; 95% CI 0.1–0.8; p = 0.016) in a cohort of 1,760 patients with HCV infection followed for a median follow-up period of 26.2 months. Other data come from our experience with the RESIST-HCV cohort, currently encompassing more than 15,000 patients with HCV treated with DAAs in Sicily. In an analysis of the outcomes of the first 5,000 treated patients, followed for a median of 18 months, decompensation only occurred after SVR in patients with a diagnosis of cirrhosis at baseline, which accounted for 75% of the cohort. In patients with Child-Pugh A cirrhosis achieving SVR made a significant difference to outcome (p = 0.001), while in those with Child-Pugh B cirrhosis the rate of liver decompensation was not associated with SVR (p = 0.44), suggesting that HCV clearance may be of less benefit in these patients.[22]Calvaruso V. Petta S. Cacciola I. Cabibbo G. Cartabellotta F. Di Rosolini M.A. et al.Disease outcomes after DAA-induced SVR: data from the resist-HCV cohort.J Hepatol. 2018; 68: S83Abstract Full Text PDF Google Scholar More data are available on the role of SVR on HCC, as most major international HCV cohorts have been analysed with this objective. After an initial warning about the possible relation between treatment with DAAs and a higher risk of HCC occurrence,[23]Conti F. Buonfiglioli F. Scuteri A. Crespi C. Bolondi L. Caraceni P. et al.Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals.J Hepatol. 2016; 65: 727-733Abstract Full Text Full Text PDF PubMed Scopus (544) Google Scholar most cohort studies did not support this relationship. A meta-analysis of the earlier studies available up to 2017 by Waziry et al.[24]Waziry R. Hajarizadeh B. Grebely J. Amin J. Law M. Danta M. et al.Hepatocellularcarcinoma risk following direct-acting antiviral HCV therapy: a systematic review, meta-analyses, and meta-regression.J Hepatol. 2017; 67: 1204-1212Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar excluded a higher rate of HCC in patients treated with DAAs vs. those receiving IFN-based therapies and confirmed the positive role of SVR on this outcome, indicating that HCV clearance significantly reduces the risk of HCC even if the oncogenic risk linked to fibrosis and cirrhosis persists in the long term, proportionally to the stage of liver disease. Some further large cohort studies confirm this statement. A retrospective analysis of registries from the Veterans Affairs system, evaluating the short/medium term occurrence of HCC in more than 62,000 patients with HCV receiving antivirals, of whom 21,948 were only treated with DAAs, demonstrated that SVR was associated with a significantly decreased risk of HCC in multivariable models irrespective of whether the antiviral treatment was DAA-only (adjusted HR 0.29; 95% CI 0.23–0.37), DAA + IFN (adjusted HR 0.48; 95% CI 0.32–0.73) or IFN-only (adjusted HR 0.32; 95% CI 0.28–0.37). The VA study concluded that eradication of HCV infection with DAAs reduces the risk of liver cancer by 71%.[25]Ioannou G.N. Green P.K. Berry K. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma.J Hepatol. 2017; 68: 25-32Abstract Full Text Full Text PDF Scopus (191) Google Scholar This result was later confirmed by Kanwal et al.[26]Kanwal F. Kramer J. Asch S.M. Chayanupatkul M. Cao Y. El-Serag H.B. Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents.Gastroenterology. 2017; 153: 996-1005.e1Abstract Full Text Full Text PDF PubMed Scopus (347) Google Scholar who focused only on patients treated with DAAs. The prospective study by Carrat et al.,[20]Carrat F. Fontaine H. Dorival C. Simony M. Diallo A. Hezode C. et al.Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study.Lancet. 2019; 393: 1453-1464Abstract Full Text Full Text PDF PubMed Scopus (213) Google Scholar in 7,344 French patients (ANRS CO22 Hepather cohort) treated with DAAs and followed for 33.4 months, also confirmed that antiviral treatment was associated with a reduced HCC risk (adjusted HR 0.66; 95% CI 0.46–0.93) after adjustment for several variables correlated to stage of liver disease and comorbidities. None of the examined cohorts reported a reduction of HCC cases to near zero, and a recent long-term evaluation of HCC occurrence in the Veterans cohort found that the incidence rate of HCC remained stable between 1.5 to 2.3/100 person-years (PY) in patients with cirrhosis, confirming that the risk of HCC had not regressed 3.6 years after DAA-induced SVR.[27]Kanwal F. Kramer J.R. Asch S.M. Cao Y. Li L. El-Serag H.B. Long-term risk of hepatocellular carcinoma in HCV patients treated with direct acting antiviral agents.Hepatology. 2020; 7: 44-55Crossref Scopus (55) Google Scholar Once it was ascertained that the risk of HCC is reduced but not altogether eliminated by DAA-induced HCV clearance, research has been devoted to identifying the potential predictors of HCC in order to tailor surveillance to risk classes. Our group[28]Calvaruso V. Cabibbo G. Cacciola I. Petta S. Madonia S. Bellia A. et al.Incidence of hepatocellular carcinoma in patients with HCV-associated cirrhosis treated with direct-acting antiviral agents.Gastroenterology. 2018; 155: 411-421.e4Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar analysed 2,249 DAA-treated patients with cirrhosis prospectively included in the RESIST-HCV cohort. We observed a cumulative incidence of HCC at 12 and 24 months of follow-up of 2.6% and 6.1%, respectively, in SVR patients vs. 8% and 23% in patients who did not achieve SVR. We stratified the residual risk of HCC as a function of liver function impairment and stratified patien" @default.
• W3048281202 created "2020-08-13" @default.
• W3048281202 creator A5091326593 @default.
• W3048281202 date "2020-12-01" @default.
• W3048281202 modified "2023-10-17" @default.
• W3048281202 title "Hepatic benefits of HCV cure" @default.
• W3048281202 cites W1998416778 @default.
• W3048281202 cites W2023149416 @default.
• W3048281202 cites W2078799829 @default.
• W3048281202 cites W2095348495 @default.
• W3048281202 cites W2139773897 @default.
• W3048281202 cites W2185218296 @default.
• W3048281202 cites W2266909385 @default.
• W3048281202 cites W2298389505 @default.
• W3048281202 cites W2325297898 @default.
• W3048281202 cites W2403969263 @default.
• W3048281202 cites W2406748516 @default.
• W3048281202 cites W2419146391 @default.
• W3048281202 cites W2467713285 @default.
• W3048281202 cites W2472585716 @default.
• W3048281202 cites W2474595113 @default.
• W3048281202 cites W2519498039 @default.
• W3048281202 cites W2524249329 @default.
• W3048281202 cites W2605644052 @default.
• W3048281202 cites W2605973763 @default.
• W3048281202 cites W2618797413 @default.
• W3048281202 cites W2736841222 @default.
• W3048281202 cites W2741420622 @default.
• W3048281202 cites W2742937844 @default.
• W3048281202 cites W2744914748 @default.
• W3048281202 cites W2748400966 @default.
• W3048281202 cites W2751505630 @default.
• W3048281202 cites W2773762333 @default.
• W3048281202 cites W2779756408 @default.
• W3048281202 cites W2794262809 @default.
• W3048281202 cites W2797952741 @default.
• W3048281202 cites W2800171985 @default.
• W3048281202 cites W2883468137 @default.
• W3048281202 cites W2898378712 @default.
• W3048281202 cites W2898673170 @default.
• W3048281202 cites W2903947257 @default.
• W3048281202 cites W2911964582 @default.
• W3048281202 cites W2913125611 @default.
• W3048281202 cites W2913385034 @default.
• W3048281202 cites W2914082649 @default.
• W3048281202 cites W2924974998 @default.
• W3048281202 cites W2928271725 @default.
• W3048281202 cites W2947814286 @default.
• W3048281202 cites W2950514720 @default.
• W3048281202 cites W2964678848 @default.
• W3048281202 cites W2965258952 @default.
• W3048281202 cites W2971513054 @default.
• W3048281202 cites W2980404810 @default.
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