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

Author(s):  
Eiichi Ogawa ◽  
Hideyuki Nomura ◽  
Makoto Nakamuta ◽  
Norihiro Furusyo ◽  
Eiji Kajiwara ◽  
...  

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.

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 210
Author(s):  
Martynas Ridziauskas ◽  
Birutė Zablockienė ◽  
Ligita Jančorienė ◽  
Artūras Samuilis ◽  
Rolandas Zablockis ◽  
...  

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.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2602 ◽  
Author(s):  
Eiichi Ogawa ◽  
Hideyuki Nomura ◽  
Makoto Nakamuta ◽  
Norihiro Furusyo ◽  
Eiji Kajiwara ◽  
...  

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.


2019 ◽  
Vol 26 (12) ◽  
pp. 1489-1492 ◽  
Author(s):  
Clovis Lusivika‐Nzinga ◽  
Hélène Fontaine ◽  
Céline Dorival ◽  
Mélanie Simony ◽  
Stanislas Pol ◽  
...  

2020 ◽  
Vol 10 (8) ◽  
pp. 483
Author(s):  
Michele Fabrazzo ◽  
Rosa Zampino ◽  
Martina Vitrone ◽  
Gaia Sampogna ◽  
Lucia Del Gaudio ◽  
...  

In chronic hepatitis C (CHC) patients, interferon-based treatments showed toxicity, limited efficacy, and psychiatric manifestations. Direct-acting antiviral (DAA) agents appeared safer, though it remains unclear if they may exacerbate or foster mood symptoms in drug-naïve CHC patients. We evaluated 62 CHC patients’ mental status, before and 12 weeks after DAA therapy, by assessment scales and psychometric instruments. We subdivided patients into two groups, CHC patients with (Group A) or without (Group B) a current and/or past psychiatric history. After DAA treatment, Group A patients showed low anxiety and improved depression, no variation in self-report distress, but worse general health perceptions. No significant difference emerged from coping strategies. Depression and anxiety improved in Group B, and no change emerged from total self-reported distress, except for somatization. Moreover, Group B increased problem-focused strategies for suppression of competing activities, and decreased strategies of instrumental social support. Contrarily, Group B reduced significantly emotion-focused strategies, such as acceptance and mental disengagement, and improved vitality, physical and social role functioning. DAA therapy is safe and free of hepatological and psychiatric side effects in CHC patients, regardless of current and/or past psychiatric history. In particular, patients without a psychiatric history also remarkably improved their quality of life.


2020 ◽  
Vol 16 (11) ◽  
pp. 675-686
Author(s):  
Longteng Ma ◽  
Jiluo Liu ◽  
Wei Wang ◽  
Fan Yang ◽  
Ping Li ◽  
...  

Aim: It was controversial whether direct-acting antiviral (DAA) is better than interferon-based therapy (IBT) in preventing HCV-related hepatocellular carcinoma (HCC). Therefore, we accomplished this large, stepwise meta-analysis. Materials & methods: The PubMed, Cochrane and ScienceDirect were searched for studies published during January 2009–March 2019. Antiviral type, number of chronic hepatitis C (CHC) patients, number of HCC cases from CHC patients, sustained virological response (SVR) status and important covariate data were extracted from each study. Results & conclusion: It is demonstrated that antiviral treatment reduces the occurrence of HCC in patients with CHC; achieving SVR to antiviral treatment reduces HCC; DAA treatment is not better than IBT in the prophylaxis of HCC; DAA treatment and cirrhosis are independently associated with a higher incidence of HCC than IBT in middle-aged CHC patients who achieve SVR.


2019 ◽  
Vol 18 (3) ◽  
pp. 90-96
Author(s):  
N. A. Malinina ◽  
N. V. Mazurchik ◽  
O. I. Tarasova ◽  
P. P. Ogurtsov

Hepatocellular carcinoma (HCC) is one of the most common causes of death from cancer and is the final stage of chronic liver disease, usually occurring in patients with cirrhosis (CP). Chronic infection with hepatitis C virus (HCV) leads to progressive liver inflammation and cirrhosis because this virus specifically affects liver tissue. Previously used interferon therapy had a relatively low efficiency and very high risks of side effects. During the period of administration of interferon (IFN) schemes it was proved that elimination of the virus significantly reduced risk of liver cancer development. Discovery of direct-acting antiviral (DAA ) drugs have revolutionized HCV therapy with virus elimination rate of more than 95 % and an excellent safety profile. However, the risk of transformation of liver cirrhosis into hepatocellular carcinoma is still high even after complete eradication of the virus. Numerous studies have shown conflicting results on the possible relationship between the use of new antiviral drugs and the increase in the frequency of newly diagnosed or recurrent hepatocellular carcinoma. Thus, the long-term prognosis in terms of risk for HCC development among patients with sustained virological response (SVR) remains unclear.The purpose of the study was to analyze the literature on the effect of antiviral therapy of chronic hepatitis C with interferon-containing regimens and drugs of direct antiviral action on the risk of developing or recurring hepatocellular carcinoma.Material and Methods. We analyzed publications available from PubMed, S copus, E-library, Web of S cience using the key words “hepatocellular carcinoma”, “chronic hepatitis C”, “direct-acting antiviral drugs”, “liver cirrhosis”, “interferons”, and “sustained virological response”. Of the 99 studies found, 21 were used to write a systematic review.Results. Eradication of the virus reduces the risks of HCC. Despite reports on high risk of occurrence or recurrence of hepatocellular carcinoma in patients with cirrhosis after treatment with DAA s compared with interferon-containing regimens, there is not enough data confirming the direct link between the use of DAA s and the development of hepatocellular carcinoma. No statistically significant difference in the frequency of HCC between patients treated with interferon or DAA s was detected.Conclusion. Eradication of the virus is the most significant factor in the prevention of HCC; therefore, treatment of CHC should not be delayed due to the risk of HCC. Patients with liver cirrhosis require a long period of follow-up, even after successful treatment of chronic hepatitis C with DAA drugs. Stratification of HCC risk requires further research.


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