Incidence of Hepatocellular Carcinoma after Treatment with Sofosbuvir-Based or Sofosbuvir-Free Regimens in Patients with Chronic Hepatitis C

Advanced fibrosis/cirrhosis and related biomarkers have been recognized as useful predictors of the development of hepatocellular carcinoma (HCC) by patients with chronic hepatitis C (CHC) following hepatitis C virus (HCV) cure by direct-acting antivirals (DAAs). However, it remains unclear if DAAs themselves have an influence on or facilitate the development of HCC. This multicenter cohort study included CHC patients without a history of HCC who achieved HCV elimination by DAAs. Cohorts of 835 patients treated with a sofosbuvir (SOF)-based regimen and 835 treated with a SOF-free regimen were matched 1:1 by propensity scoring with nine variables to evaluate differences in HCC incidence. The median observation period was 3.5 years. Sixty-nine cases of HCC were found during 5483.9 person-years (PY) over the entire follow-up period. The annual incidence was similar for both groups (SOF-based 1.25 and SOF-free 1.27 per 100 PY, respectively: adjusted hazard ratio (HR) 1.26, 95% confidence interval (CI) 0.75–2.12, p = 0.39). However, the annual incidence within the first two years was higher for patients treated with SOF than for those without, but did not reach significance (1.50 and 0.97 per 100 PY incidence rates, respectively: adjusted HR 2.05, 95% CI 0.98–4.25, p = 0.06). In summary, DAA treatment with SOF was not associated with an increase in the development of de novo HCC.

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Interferon-free therapy of chronic hepatitis C with direct-acting antivirals does not change the short-term risk for de novo hepatocellular carcinoma in patients with liver cirrhosis

Alimentary Pharmacology & Therapeutics ◽

10.1111/apt.14427 ◽

2017 ◽

Vol 47 (4) ◽

pp. 516-525 ◽

Cited By ~ 30

Author(s):

F. Mettke ◽

B. Schlevogt ◽

K. Deterding ◽

A. Wranke ◽

A. Smith ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

De Novo ◽

Direct Acting Antivirals ◽

Short Term ◽

Direct Acting ◽

De Novo Hepatocellular Carcinoma

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Early development of de novo hepatocellular carcinoma after direct-acting agent therapy: Comparison with pegylated interferon-based therapy in chronic hepatitis C patients

Journal of Viral Hepatitis ◽

10.1111/jvh.12918 ◽

2018 ◽

Vol 25 (10) ◽

pp. 1189-1196 ◽

Cited By ~ 2

Author(s):

S. H. Yoo ◽

J. H. Kwon ◽

S. W. Nam ◽

H. Y. Kim ◽

C. W. Kim ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

De Novo ◽

Pegylated Interferon ◽

Acting Agent ◽

Direct Acting ◽

Chronic Hepatitis C Patients ◽

De Novo Hepatocellular Carcinoma

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Risk of De Novo Hepatocellular Carcinoma Following Use of Direct Acting Antiviral Medications for Treatment of Chronic Hepatitis C

Cancer Prevention Research ◽

10.1158/1940-6207.capr-19-0162 ◽

2019 ◽

Vol 12 (12) ◽

pp. 891-902

Author(s):

Samuel O. Antwi ◽

Holly K. Van Houten ◽

Lindsey R. Sangaralingham ◽

Tushar Patel

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

De Novo ◽

Direct Acting Antiviral ◽

Direct Acting ◽

Antiviral Medications ◽

De Novo Hepatocellular Carcinoma

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Development of Hepatocellular Carcinoma in Patients Aged 75–84 Years With Chronic Hepatitis C Treated With Direct-Acting Antivirals

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa359 ◽

2020 ◽

Cited By ~ 1

Author(s):

Eiichi Ogawa ◽

Hideyuki Nomura ◽

Makoto Nakamuta ◽

Norihiro Furusyo ◽

Eiji Kajiwara ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Propensity Score ◽

Propensity Score Matching ◽

Chronic Hepatitis C ◽

Multicenter Cohort Study ◽

Direct Acting Antiviral ◽

Significant Difference ◽

Direct Acting

Abstract Background Direct-acting antiviral (DAA) treatment has revolutionized hepatitis C virus (HCV) care. We aimed to evaluate the risk for the development of hepatocellular carcinoma (HCC) in patients aged 75–84 years with chronic hepatitis C after HCV elimination. Methods This multicenter cohort study included 2405 consecutive patients with chronic hepatitis C without a history of HCC who achieved HCV elimination by DAAs. Patients in whom HCC developed within 1 year of DAA initiation were excluded. Propensity score matching analysis was used to evaluate differences in HCC risk between patients aged 75–84 versus 60–74 years. Results The median observational period was 3.5 years. Among patients aged 75–84 years with a high Fibrosis-4 (FIB-4) index (≥3.25 at baseline), there was no significant difference in the annual incidence of HCCs between groups with an FIB-4 index ≥3.25 (2.75 per 100 person-years [PY]) versus <3.25 (2.16 per 100 PY) at 12 weeks after the end of treatment, unlike the results in those aged 60–74 years (3.61 and 1.51 per 100 PY, respectively) (adjusted hazard ratio, 2.20; P = .04). In 495 pairs matched by propensity score matching, in patients without cirrhosis, the cumulative HCC incidence was significantly higher in the 75–84-year than in the 60–74-year age group (P = .04). Conclusions Older patients aged 75–84 years remained at high risk for the development of HCC, even after HCV elimination and the improvement of the FIB-4 index to <3.25.

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Impact of Obesity and Heavy Alcohol Consumption on Hepatocellular Carcinoma Development after HCV Eradication with Antivirals

Liver Cancer ◽

10.1159/000513705 ◽

2021 ◽

pp. 1-11

Author(s):

Tatsuya Minami ◽

Ryosuke Tateishi ◽

Naoto Fujiwara ◽

Ryo Nakagomi ◽

Takuma Nakatsuka ◽

...

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Alcohol Consumption ◽

Chronic Hepatitis C ◽

Incidence Rates ◽

Multicenter Cohort Study ◽

Heavy Alcohol ◽

Heavy Alcohol Consumption

Background and Aims: It remains unclear whether obesity increases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C who achieved a sustained virological response (SVR) with antiviral therapy. Methods: In this multicenter cohort study, we enrolled patients with chronic hepatitis C who achieved SVR with interferon (IFN)-based therapy (IFN group) or direct-acting antiviral (DAA) therapy (DAA group) between January 1, 1990, and December 31, 2018. The patients underwent regular surveillance for HCC. Cumulative incidence of and the risk factors for HCC development after SVR were assessed using the Kaplan-Meier method and Cox proportional hazard regression analysis, respectively. Results: Among 2,055 patients (840 in the IFN group and 1,215 in the DAA group), 75 developed HCC (41 in the IFN group and 34 in the DAA group) during the mean observation period of 4.1 years. The incidence rates of HCC at 1, 2, and 3 years were 1.2, 1.9, and 3.0%, respectively. Multivariate analysis revealed that in addition to older age, lower albumin level, lower platelet count, higher alpha-fetoprotein level, and absence of dyslipidemia, obesity (body mass index ≥25 kg/m2) and heavy alcohol consumption (≥60 g/day) were independent risk factors for HCC development, with adjusted hazard ratio (HR) of 2.53 (95% confidence interval [CI]: 1.51–4.25) and 2.56 (95% CI: 1.14–5.75), respectively. The adjusted HR was not significant between the 2 groups (DAA vs. IFN; HR 1.19, 95% CI: 0.61–2.33). Conclusions: Obesity and heavy alcohol consumption increased the risk of HCC development after SVR.

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Assessment of Liver Stiffness Regression and Hepatocellular Carcinoma Risk in Chronic Hepatitis C Patients after Treatment with Direct-Acting Antiviral Drugs

Medicina ◽

10.3390/medicina57030210 ◽

2021 ◽

Vol 57 (3) ◽

pp. 210

Author(s):

Martynas Ridziauskas ◽

Birutė Zablockienė ◽

Ligita Jančorienė ◽

Artūras Samuilis ◽

Rolandas Zablockis ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Liver Stiffness ◽

Direct Acting Antiviral ◽

End Of Treatment ◽

Increased Risk ◽

Patients With Diabetes ◽

Direct Acting

Background and Objectives: Chronic hepatitis C virus infection affects about 71 million people worldwide. It is one of the most common chronic liver conditions associated with an increased risk of developing liver cirrhosis and cancer. The aim of this study was to evaluate changes in liver fibrosis and the risk of developing hepatocellular carcinoma after direct-acting antiviral drug therapy, and to assess factors, linked with these outcomes. Materials and Methods: 70 chronic hepatitis C patients were evaluated for factors linked to increased risk of de novo liver cancer and ≥ 20% decrease of ultrasound transient elastography values 12 weeks after the end of treatment. Results: The primary outcome was an improvement of liver stiffness at the end of treatment (p = 0.004), except for patients with diabetes mellitus type 2 (p = 0.49). Logistic regression analysis revealed factors associated with ≥ 20% decrease of liver stiffness values: lower degree of steatosis in liver tissue biopsy (p = 0.053); no history of interferon-based therapy (p = 0.045); elevated liver enzymes (p = 0.023–0.036); higher baseline liver stiffness value (p = 0.045) and absence of splenomegaly (p = 0.035). Hepatocellular carcinoma developed in 4 (5.7%) patients, all with high alpha-fetoprotein values (p = 0.0043) and hypoechoic liver mass (p = 0.0001), three of these patients had diabetes mellitus type 2. Conclusions: Liver stiffness decrease was significant as early as 12 weeks after the end of treatment. Patients with diabetes and advanced liver disease are at higher risk of developing non-regressive fibrosis and hepatocellular carcinoma even after successful treatment.

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Glucose Metabolism Changes in Patients with Chronic Hepatitis C Treated with Direct Acting Antivirals

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2018/6095097 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Sylvia Drazilova ◽

Martin Janicko ◽

Lubomir Skladany ◽

Pavol Kristian ◽

Marian Oltman ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Systemic Disease ◽

Direct Acting Antivirals ◽

Fasting Glycemia ◽

End Of Treatment ◽

History Of ◽

Direct Acting

Background and Aims. Chronic hepatitis C is a systemic disease and type 2 diabetes mellitus (T2DM) belongs to more common extrahepatic. The aim of this study was to (i) explore the prevalence of impaired fasting glucose (IFG) and T2DM in patients with chronic hepatitis C, (ii) explore the effect of direct acting antivirals (DAA) treatment on the glycemia, and (iii) explore the factors that modulate the effect of DAA treatment on glycemia in patients with chronic hepatitis C.Methods. We performed a longitudinal retrospective observational study focused on the patients undergoing DAA treatment of chronic hepatitis C. Data about glycemia, history of diabetes, hepatitis C virus, treatment, and liver status, including elastography, were obtained at baseline (before treatment start), at the end of treatment and 12 weeks after the end of treatment. Patients were treated with various regimens of direct acting antivirals.Results. We included 370 patients; 45.9% had F4 fibrosis. At baseline, the prevalence of T2DM increased with the degree of fibrosis (F0-F2 14.4%, F3 21.3%, and F4 31.8%, p=0.004). Fasting glycemia also increased with the degree of fibrosis (F0-F2 5.75±0.18 F3 5.84±0.17, and F4 6.69±0.2 mmol/L, p=0.001). We saw significant decrease of glycemia after treatment in all patients, but patients without T2DM or IFG from 6.21±0.12 to 6.08±0.15 mmol/L (p=0.002). The decrease was also visible in treatment experienced patients and patients with Child-Pugh A cirrhosis.Conclusion. We confirmed that the prevalence of either T2DM or IFG increases in chronic hepatitis C patients with the degree of fibrosis. The predictive factors for T2DM were, besides F4, fibrosis also higher age and BMI. Significant decrease of fasting glycemia after the DAA treatment was observed in the whole cohort and in subgroups of patients with T2DM, IFG, cirrhotic, and treatment experienced patients.

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