Hepatitis C Virus Cure Rates Are Reduced in Patients With Active but Not Inactive Hepatocellular Carcinoma: A Practice Implication (original) (raw)
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Hepatoma Research, 2020
Aim: Patients with chronic hepatitis C virus (HCV) infection who develop hepatocellular carcinoma (HCC) soon after treatment with direct antiviral agents (DAA) may have been harboring hitherto hidden tumors. If this were true, they should have a lower sustained viral response (SVR) rate, since active HCC hampers DAA efficacy. We aimed to verify this hypothesis. Methods: We included all patients who attended an HCV clinic, provided that they: (1) had no previous history of HCC; (2) had received at least one DAA dose; and (3) had been followed-up clinically and ultrasonographically for at least six months after concluding DAA. Results: The study population included n = 789 patients (55% males, median age 62 years). A median of 9.3 months (8.8-11.9) after concluding DAA, n = 19 (2.4%) patients were discovered to harbor HCC. In comparison to all others, patients with HCC were more commonly male (84% vs. 54%, P = 0.009), obese (47% vs. 17%, P = 0.002), and cirrhotic (95% vs. 35%, P < 0.001) and had less commonly achieved an SVR (68% vs. 98%, P < 0.001). Moreover, they had a trend for being less commonly treatment naïve (58% vs. 67%, P = 0.051). Based on multivariate analysis, the independent predictors of HCC were male sex (P = 0.031), cirrhosis (P = 0.004), obesity (P = 0.006), and failure to achieve an SVR (P < 0.001). Conclusion: Lack of achieving SVR is a strong independent predictor of development of HCC early after treatment of hepatitis C with DAA. Treatment failure should further alert clinicians to the possibility of this dreadful complication.
Hepatoma Research, 2020
Aim: Despite the high cure rate of interferon-free directly acting antivirals (DAAs) for chronic hepatitis C (CHC) patients, the treatment efficacy for patients with preexisting hepatocellular carcinoma (HCC) remains undefined. We aimed in the present study to address the issue by using novel DAAs in treating CHC patients who were adherent to treatment in Taiwan. Methods: CHC patients with or without HCC were consecutively enrolled. The primary objective was sustained virological response (SVR) defined as undetectable HCV RNA throughout 12 weeks of a post-treatment follow-up period (SVR12). Only patients with available SVR12 were enrolled for final analysis. Results: A total of 1237 patients (1113 non-HCC, 101 inactive HCC and 23 active HCC) were enrolled. The overall SVR12 rate was 98.9%, and was similar between HCV patients with and without pre-existing HCC (98.4% vs. 98.9%, P = 0.64). While HCC patients were classified as those who had active or inactive HCC, the SVR12 was also similar between patients with and without active HCC (95.7% vs. 99.0%, P = 0.34). Among the 101 patients without viable HCC at the time of DAA initiation, eighty-four patients exhibited curative therapy and the other 17 patients experienced HCC recurrence before DAAs. Among the 23 patients with viable HCC at the time of DAA treatment, 10 patients had received curative therapy for HCC whereas the remaining 13 patients had HCC that was never cured. The SVR12 rates were also similar among the four subpopulations, being 98.8% (83/84), 100% (17/17), 90% (9/10) and 100% (13/13) respectively. Conclusion: CHC patients with HCC who were adherent to potent DAAs achieved similar SVR12 rate compared to those without HCC and could be effectively treated.
Hepatology Communications, 2019
Recent studies have suggested a negative impact of hepatocellular carcinoma (HCC) on sustained virologic response (SVR) to hepatitis C virus (HCV) direct acting antivirals (DAAs). We compared the effectiveness of DAAs in patients with cirrhosis, with and without HCC, and in those with HCC partially treated or untreated (PT/UT-HCC) versus completely treated (CT-HCC). HCC status was based on imaging 6 months before or 2 months after start of DAA therapy. Absence and presence of enhancing lesions after HCC treatment defined CT-HCC and PT/UT-HCC, respectively. Using minimally adjusted logistic regression, the association between the presence of HCC and SVR rates was estimated. Among the 1,457 patients with cirrhosis from HCV-TARGET with complete virologic data (per-protocol population) who did not undergo liver transplantation during treatment and followup, 1,300 were without HCC, 91 with CT-HCC, and 66 with PT/UT-HCC. Most patients were genotype 1 (81%) and treatmentexperienced (56%), 41% had history of prior decompensation, and the median pretreatment Model for End-Stage Liver Disease was 9 (range 6-39). The SVR rates were 91% for patients without HCC, 84% for CT-HCC, and 80% for PT/UT-HCC. The presence of HCC (versus not having HCC) was associated with significantly lower odds of achieving SVR (odds ratio [OR] = 0.51, 95% confidence interval [CI]: 0.33-0.81; P = 0.003). However, among those with HCC, HCC treatment status (PT/UT-HCC versus CT-HCC) did not show association with SVR (OR = 0.79, 95% CI: 0.35-1.79, P = 0.569). Conclusions: The presence of HCC reduces the likelihood of SVR by 50%, but with no evident difference in those with completely treated HCC versus partially treated/untreated HCC. (Hepatology Communications 2019;0:1-12). D irect-acting antiviral agents (DAAs) have dramatically improved the outcomes of patients with chronic hepatitis C virus (HCV) with overall sustained virologic response (SVR) rates of about 95%, including those with compensated cirrhosis.
Journal of Hepatocellular Carcinoma, 2021
Background: Direct-acting antivirals (DAA) have revolutionized the therapy of chronic hepatitis C (CHC) and have replaced previous PEG-interferon/ribavirin (PEG-IFN/RBV) treatment. Patients with CHC and advanced liver disease are at increased risk for hepatocellular carcinoma (HCC). However, the effects of DAA-based CHC treatment on subsequent HCC incidence remain poorly understood. Patients and Methods: This retrospective single-institution cohort study included 243 consecutive patients after PEG-IFN/RBV and 263 patients after DAA treatment. Multivariable cause-specific Cox proportional hazards models were used to compare time to HCC between treatment types, censoring patients who died or had an orthotopic liver transplantation (OLT) at the time of the competing event. Age, gender, BMI, viral load, cirrhosis, fibrosis stage, diabetes, virus genotype and previous PEG-IFN/RBV (before DAA) were used as covariates. In addition, we performed a propensity score-matched analysis. Results: Nineteen HCC cases were observed after DAA therapy compared to 18 cases after PEG-IFN/RBV treatment. Patients were followed for a median of 4.1 years (IQR: 3.5-4.7) for DAA and 9.3 years (IQR: 6.6-12.4) for the PEG-IFN/RBV group. In an unadjusted Cox model, a hazard ratio (HR) of 6.40 (CI: 2.20-18.61, p=0.006) for HCC following DAA vs PEG-IFN/RBV was estimated. In multivariable Cox proportional hazard models, age and liver cirrhosis were identified as further HCC risk factors but the HR estimates for DAA vs PEG-IFN/RBV still indicate a considerably increased hazard associated with DAA treatment (HR between 7.23 and 11.52, p≤0.001, depending on covariates). A HR of 6.62 (CI: 2.01-21.84, p=0.002) for DAA vs PEG-IFN/RBV was estimated in the propensity score-matched analysis. The secondary outcomes death and OLT did not differ between treatment groups. Conclusion: In a cohort study from a tertiary care hospital rates of HCC after the start of DAA treatment were higher compared to PEG-IFN/RBV treatment. Our data reinforce the recommendation that surveillance should be continued after successful CHC treatment.
Internal Medicine
Objective Owing to advances in direct-acting antiviral (DAA) therapy, a considerable number of patients with hepatitis C virus (HCV)-positive hepatocellular carcinoma (HCC) are now able to achieve a sustained viral response (SVR) after curative treatment of HCC. However, the beneficial effect of a DAA-SVR on the survival remains unclear. Methods A total of 205 patients with HCC who were HCV-positive with Child-Pugh A at the onset from 2008 to 2018 were categorized into 2 groups: 140 patients untreated for HCV throughout the entire course after HCC development (untreated group) and 65 patients treated for HCV with DAAs following HCC treatment who achieved an SVR (SVR group). After propensity score matching, 63 patients from each group were selected. Using these patients, the survival and maintenance of Child-Pugh A after HCC treatment were compared between the untreated group and SVR group. Results There was a significant difference in the overall survival (p<0.001) and the rate of maintaining Child-Pugh A (p<0.001) between the groups. The 5-year survival rates were 96% (SVR group) and 60% (untreated group), and the proportions of patients with Child-Pugh A at 5 years after HCC treatment were 96% (SVR group) and 38% (untreated group). Conclusion In patients with HCV-positive HCC, achieving a DAA-SVR after HCC treatment significantly improved the overall survival rate compared with HCV-untreated patients. The contribution of DAA-SVR during the course of HCC treatment to a longer survival is mainly due to the prevention of the progression of Child-Pugh A to B/C. Further research is needed to determine whether aggressive antiviral therapy is also effective for HCC patients with Child-Pugh B/C.
Scientific reports, 2017
This follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004-2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22-0.63) for those without cirrhosis and 0.54 (0.31-0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased ...
Hepatoma Research, 2024
Aims: The optimal timing for DAA therapy initiation in patients with chronic hepatitis C (CHC) and HCC is still debated. The aim of our study was to provide real-world data on virological response and overall survival in patients with hepatitis C-related HCC. Methods: Retrospectively, we included patients with HCV-related HCC between 2015 and 2020. The primary outcome was to compare the SVR rate in the patients with active or historical HCC who were treated with DAA therapy. The secondary outcome was to measure the overall survival of those patients. SVR is one of the main factors associated with mortality.
Digestive Diseases and Sciences, 2011
Background The effect of a sustained virological response (SVR) to interferon (IFN) on clinical outcomes of hepatitis C virus (HCV)-related cirrhosis is controversial. Aims: Evaluate the effect of SVR to IFN on the incidence of hepatocellular carcinoma (HCC) and mortality in patients with compensated HCV-induced cirrhosis. Methods A cohort of 130 consecutive patients (92 men, mean age 51.7 years) with histologically proven cirrhosis who received one or more courses of IFN monotherapy or combination therapy with ribavirin were analyzed. SVR was defined as undetectable serum HCV RNA by real-time polymerase chain reaction (PCR) 24 weeks after IFN discontinuation. HCC was assessed by alfa-fetoprotein and ultrasound every 6 months. Predictors of clinical outcomes, defined as HCC, orthotopic liver transplantation (OLT) and mortality, were assessed by Cox regression analysis. Results The mean follow-up was 6.4 ± 4.0 years (range 1-18). HCC developed in 21 patients: one with SVR versus 20 with non-SVR (P = 0.017). Logistic regression analysis showed that non-SVR (odds ratio [OR] = 27.0; confidence interval [CI], 1.6-452.1), male (OR = 11.6; CI, 1.8-75.4), and greater number of treatments (OR = 4.7; CI, 1.4-16.0) increased the probability of HCC development. Multivariate analysis found that SVR was associated with lower risk of HCC (HR 0.09; CI, 0.01-0.77), OLT (HR 0.04; CI, 0.003-0.63) and any event (HR 0.11; CI, 0.02-0.46) as compared to non-SVR. Conclusions In compensated HCV-related cirrhosis, SVR markedly reduces the risk of HCC and improves survival. Clearance of the virus should be intensively attempted in these patients.
Euroasian Journal of Hepato-Gastroenterology
Background: Chronic hepatitis C (CHC) management has changed tremendously after direct-acting antivirals (DAAs) availability. Sustained virological response (SVR) has improved significantly, but one of the major concerns is the chances of de novo hepatocellular carcinoma (HCC) development after DAAs. The objective of the study is to calculate the frequency of newly diagnosed cases of HCC after antiviral therapy for CHC in Pakistan. Materials and methods: This prospective, interventional research was conducted from June 2017 to September 2020. All patients after antiviral therapy for CHC were followed with an ultrasound abdomen and α-fetoprotein, six monthly. Multiphasic computed tomography (CT) of the abdomen was performed in suspected cases. For quantitative variables, the mean and standard deviations were calculated, whereas the qualitative variables were analyzed by frequencies and percentages. Results: Among 180 patients, 110 were men and 70 were women with a mean age of 45.52 ± 11.71 years. One hundred and twenty-six patients were noncirrhotic, 38 had compensated cirrhosis while 16 had decompensated cirrhosis. One hundred and sixty-four (91.11%) patients achieved SVR, of which 22 (12.22%) patients developed new HCC during follow-up. Compensated cirrhosis group had 10 patients, the decompensated group had 12 patients, and the noncirrhotic group had no new HCC cases. Among patients with the new HCC, 12 achieved SVR. Conclusion: The risk of the development of HCC after antiviral treatment is highly significant among patients with liver cirrhosis. So, a strict surveillance strategy should be adopted in every cirrhotic patient following treatment with DAA agents even if they achieve SVR. Clinical significance: • Chances of developing HCC are still significantly high even after achieving SVR with DAAs in patients with liver cirrhosis. • Patients with liver cirrhosis should be under surveillance for HCC even after achieving SVR after DAAs treatment.
Hepatology (Baltimore, Md.), 2017
Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in individuals treated with direct-acting antivirals (DAAs). However, making definitive conclusions has been challenging due to the heterogeneous populations and methodologies of these reports. We investigated whether DAA use is associated with higher rates of incident HCC compared to treatment with interferon-based regimens. We performed a retrospective population-based cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database. In a cohort of 17,836 persons, SVR was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. Among all treated persons, the risk of HCC was not higher in the DAA group compared to the IFN group (HR 1.07; [95% CI: 0.55, 2.08]). Among persons with cirrhosis who achieved SVR, neither the HCC incidence rate nor HCC-free survival were significantly different in the DAA group compared to the IFN group (21.2 vs. 22.8 per 1000 person y...