Advances in the era of direct-acting antivirals for hepatitis C in patients with unresectable hepatocellular carcinoma

2021 ◽  
Author(s):  
Li-Shu Chen ◽  
Shou-Wu Lee ◽  
Sheng-Shun Yang ◽  
Hsin-Ju Tsai ◽  
Teng-Yu Lee
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C ◽  
Virological Response ◽  
Factors Associated ◽  
Direct Acting Antiviral ◽  
Unresectable Hepatocellular Carcinoma ◽  
Multivariable Regression ◽  
Ifn Therapy ◽  
Direct Acting ◽  
To Receive

Background: In patients with unresectable hepatocellular carcinoma (HCC), the advances in direct-acting antiviral (DAA) therapy for chronic hepatitis C remain unclear. We aimed to investigate the characteristics of DAA therapy, when compared to interferon (IFN) therapy. Methods: In this hospital-based study, all HCC patients in Barcelona Clinic Liver Cancer (BCLC) stage B or C, who received pegylated IFN or DAA, were retrospectively screened from 2009 to 2020. Patients without viremia, without HCC, or with HCC in BCLC stage 0, A, or D prior to antiviral therapy, were excluded. Rates of, and odds ratio (OR) for sustained virological response (SVR) achievement were analyzed. Results: Nineteen and 78 patients were recruited into the IFN and DAA groups, respectively. The median age was significantly older in the DAA group (DAA vs. IFN: 69.5 [25%-75% IQR: 62.8-77.3] vs. 64.0 [25%-75% IQR: 61.0-68.0]; p< 0.05). The SVR rates were higher in the DAA group as per protocol (DAA vs. IFN: 94.5% vs. 76.5%; p< 0.05) and in BCLC stage B (DAA vs. IFN: 95.2% vs. 76.5%; p< 0.05). All patients in BCLC stage C received DAA therapy, with the SVR rate being 90.9%. In multivariable regression analysis, the 4-week virological response (OR 5.6, 95% CI: 1.3-25.4) and HCC within the up-to-7 criteria (OR 3.7, 95% CI: 1.1-12.9) were independent factors associated with SVR (all p< 0.05). Conclusions: Compared to IFN therapy, more elderly patients with unresectable HCCs were able to receive DAA therapy, while achieving a significantly higher SVR rate.

scholarly journals ERADICATION OF HCV INFECTION IN PATIENTS WITH LIVER CIRRHOSIS: FACTOR OF CANCER PREVENTION OR CARCINOGENESIS?

2019 ◽  
Vol 18 (3) ◽  
pp. 90-96
Author(s):  
N. A. Malinina ◽  
N. V. Mazurchik ◽  
O. I. Tarasova ◽  
P. P. Ogurtsov
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Sustained Virological Response ◽  
Chronic Hepatitis C ◽  
Virological Response ◽  
Antiviral Drugs ◽  
Direct Acting Antiviral ◽  
Direct Acting

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.

Efficacy of Direct-Acting Antiviral Combination Therapy in the Treat-ment of Hepatitis C Virus Among Kidney Transplant Patients

2020 ◽  
Vol 18 ◽  
Author(s):  
Mohammed Al Atbee ◽  
Saad Shaheen Al-Taher ◽  
Majid Alabbood
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Kidney Transplant ◽  
Virological Response ◽  
Hepatitis C Virus Infection ◽  
Direct Acting Antiviral ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Direct Acting

Background: Up to date, there is no consensus on the best combination of direct-acting antiviral to treat hepatitis C virus in kidney transplant recipients. Objective: This study aims to analyze the efficacy of combination of sofosbuvir and ledipasvir regimen for treatment of hepatitis C virus infected kidney transplant patients. Method: A cross-sectional study conducted in a nephrology clinic and the Nephrology Center in Basrah Teaching Hospital from June 2015 to June 2018. Ledifos (90 mg Ledipasvir and 400 mg Sofosbuvir fixed-dose) was given as a single daily dose for all the participants for 12 weeks. Response for therapy was tested by follow up hepatitis C virus load at the end of 12 weeks and 24 weeks. The sustained virological response was defined as negative viral load of hepatitis C virus (aviremia) at the end of therapy. This study was done according to the Helsinki Congress. Results: A total of 60 (16 females) patients with renal transplantation and hepatitis C virus infection were included. Mean age was 40±6.2 years. A sustained virological response observed in all of the patients who received Ledifos after 12 and 24 weeks of therapy for all genotypes (1a, 1b and 4); p= 0.0001. Genotype 1a was more prevalent among males, 34 (56.6%); p= 0.0001, and it was the most common genotype tested negative serologically, 11 (18.3%). Conclusion: Ledifos therapy is effective and safe option for the treatment of hepatitis C virus infection in the post–renal transplant setting.

scholarly journals Virological Factors Associated with Failure to the Latest Generation of Direct Acting Agents (DAA) and Re-Treatment Strategy: A Narrative Review

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 432
Author(s):  
Lorenzo Onorato ◽  
Mariantonietta Pisaturo ◽  
Mario Starace ◽  
Carmine Minichini ◽  
Alessandra Di Fraia ◽  
...  
Keyword(s):  
Liver Disease ◽  
Hepatitis C ◽  
Antiviral Agents ◽  
Clinical Problem ◽  
Narrative Review ◽  
Factors Associated ◽  
Direct Acting Antiviral ◽  
Direct Acting ◽  
The Impact ◽  
Direct Acting Antiviral Agents

The availability of all oral direct acting antiviral agents (DAAs) has revolutionized the management of HCV infections in recent years, allowing to achieve a sustained virological response (SVR) in more than 95% of cases, irrespective of hepatitis C Virus (HCV) genotype or staging of liver disease. Although rare, the failure to the latest-generation regimens (grazoprevir/elbasvir, sofosbuvir/velpatasvir, pibrentasvir/glecaprevir) represents a serious clinical problem, since the data available in the literature on the virological characteristics and management of these patients are few. The aim of the present narrative review was to provide an overview of the impact of baseline RASs in patients treated with the latest-generation DAAs and to analyze the efficacy of the available retreatment strategies in those who have failed these regimens.

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

Medicina ◽  
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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