scholarly journals Lymphocyte Landscape after Chronic Hepatitis C Virus (HCV) Cure: The New Normal

2020 ◽  
Vol 21 (20) ◽  
pp. 7473
Author(s):  
Alip Ghosh ◽  
Sara Romani ◽  
Shyam Kottilil ◽  
Bhawna Poonia
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune System ◽  
Virologic Response ◽  
Viral Clearance ◽  
Liver Pathology ◽  
Direct Acting Antiviral ◽  
Chronic Hcv ◽  
Direct Acting ◽  
Immune Defects ◽  
The Impact

Chronic HCV (CHC) infection is the only chronic viral infection for which curative treatments have been discovered. These direct acting antiviral (DAA) agents target specific steps in the viral replication cycle with remarkable efficacy and result in sustained virologic response (SVR) or cure in high (>95%) proportions of patients. These treatments became available 6–7 years ago and it is estimated that their real impact on HCV related morbidity, including outcomes such as cirrhosis and hepatocellular carcinoma (HCC), will not be known for the next decade or so. The immune system of a chronically infected patient is severely dysregulated and questions remain regarding the immune system’s capacity in limiting liver pathology in a cured individual. Another important consequence of impaired immunity in patients cleared of HCV with DAA will be the inability to generate protective immunity against possible re-infection, necessitating retreatments or developing a prophylactic vaccine. Thus, the impact of viral clearance on restoring immune homeostasis is being investigated by many groups. Among the important questions that need to be answered are how much the immune system normalizes with cure, how long after viral clearance this recalibration occurs, what are the consequences of persisting immune defects for protection from re-infection in vulnerable populations, and does viral clearance reduce liver pathology and the risk of developing hepatocellular carcinoma in individuals cured with these agents. Here, we review the recent literature that describes the defects present in various lymphocyte populations in a CHC patient and their status after viral clearance using DAA treatments.

scholarly journals Hepatocellular Carcinoma and Antiviral Therapies in HCV Chronic Infection

2021 ◽  
Author(s):  
Laura Iliescu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Infection ◽  
Medical Community ◽  
Systemic Complications ◽  
Direct Acting Antiviral ◽  
Antiviral Therapies ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting ◽  
The Impact

The development of direct-acting antiviral (DAA) therapies in chronic HCV infection has been associated with increased expectations regarding the prognosis of this infection in the medical community, as the possibility of HCV eradication is now in sight. While the cure of the HVC infection has been associated with a dramatic decrease in its systemic complications, the impact on the progression of the liver disease, especially in patients with cirrhosis, is still controversial. Furthermore, the risk of developing hepatocellular carcinoma (HCC) after direct-acting antiviral therapy is debatable, with studies presenting an increased prevalence of HCC early after the introduction of these therapies, as well as newer contradicting studies. This chapter aims to examine the current literature data available regarding the impact of new HCV therapies in the incidence and prognosis of hepatocellular carcinoma.

scholarly journals Hepatic resection for two giant hepatocellular carcinoma after oral direct-acting antiviral therapy: Is there a relationship?

2018 ◽  
Vol 8 (2) ◽  
pp. 32 ◽  
Author(s):  
Mohamed Abdel Wahab ◽  
Ahmed Shehta ◽  
Mahmoud Ali
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antiviral Drugs ◽  
Hcv Infection ◽  
Dramatic Improvement ◽  
Direct Acting Antiviral ◽  
Increased Risk ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting ◽  
The Relationship

Introduction: Direct-acting antiviral drugs have been recently introduced for management of chronic hepatitis C virus (HCV) patients. Those medications have achieved a dramatic improvement of sustained virologic response (SVR) reaching almost 90%. However, reports regarding the increased risk of occurrence or recurrence of hepatocellular carcinoma (HCC) in chronic HCV patients who achieved SVR after direct-acting antiviral drugs are controversial.Methods: We report two cases of giant HCCs complicating chronic HCV infection after direct-acting antiviral drugs-based therapies and were managed by major hepatic resection.Results: Two male patients with chronic HCV infection received several regimens oral direct acting antiviral drugs with a SVR for 3 and 6 months, respectively. They complained of progressive right hypochondrial pain and abdominal enlargement. Two large HCCs were diagnosed (16.2 cm * 17.6 cm * 16.9 cm, and 18 cm * 13 cm * 16.5 cm in dimensions) with markedly elevated serum alpha feto-protein (36,000 and 7,000 ng/ml, respectively). Due to the presence of adequate residual liver volume, the decision was to proceed for surgical resection. Central hepatectomy and extended right hemi-hepatectomy were performed, respectively. Patients had smooth postoperative course and were discharged after 10 and 9 days, respectively.Conclusion: The relationship between direct-acting antiviral drugs and HCC is controversial. Those cases add support to the accumulating literature suggesting the relationship of HCC development in chronic HCV patients receiving direct-acting antiviral drugs. Further prospective studies with adequate long term follow up are needed to prove or disprove this relationship.

scholarly journals Risk of Hepatocellular Carcinoma after HCV Clearance by Direct-Acting Antivirals Treatment Predictive Factors and Role of Epigenetics

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1351 ◽  
Author(s):  
Luca Rinaldi ◽  
Riccardo Nevola ◽  
Gianluigi Franci ◽  
Alessandro Perrella ◽  
Giusy Corvino ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Immune Surveillance ◽  
Liver Stiffness ◽  
Virologic Response ◽  
Direct Acting Antivirals ◽  
Direct Role ◽  
Direct Acting ◽  
The Impact

Direct-acting antivirals (DAAs) induce a rapid virologic response (SVR) in up to 99% of chronic hepatitis C patients. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC. In this review, we made an updated analysis of the literature data on the impact of SVR by DAAs on the risk of HCC as well as an assessment of risk factors and the role of epigenetics. Data showed that SVR has no impact on the occurrence of HCC in the short–medium term but reduces the risk of HCC in the medium–long term. A direct role of DAAs in the development of HCC has not been demonstrated, while the hypothesis of a reduction in immune surveillance in response to the rapid clearance of HCV and changes in the cytokine pattern influencing early carcinogenesis remains to be further elucidated. HCV induces epigenetic alterations such as modifications of the histone tail and DNA methylation, which are risk factors for HCC, and such changes are maintained after HCV clearance. Future epigenetic studies could lead to identify useful biomarkers and therapeutic targets. Cirrhosis has been identified as a risk factor for HCC, particularly if associated with high liver stiffness and α-fetoprotein values, diabetes and the male sex. Currently, considering the high number and health cost to follow subjects’ post-HCV clearance by DAAs, it is mandatory to identify those at high risk of HCC to optimize management.

scholarly journals Factors associated with hepatocellular carcinoma occurrence after HCV eradication in patients without cirrhosis or with compensated cirrhosis

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243473
Author(s):  
Kazumichi Abe ◽  
Hiroto Wakabayashi ◽  
Haruo Nakayama ◽  
Tomohiro Suzuki ◽  
Masahito Kuroda ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multivariate Analysis ◽  
Survival Rates ◽  
Virologic Response ◽  
Female Ratio ◽  
Factors Affecting ◽  
Direct Acting Antiviral ◽  
Compensated Cirrhosis ◽  
Male Female Ratio ◽  
Direct Acting

The present study aimed to investigate the incidence of hepatocellular carcinoma (HCC) and factors related to HCC occurrence after direct-acting antiviral (DAA) treatment in the Fukushima Liver Academic Group (FLAG). We conducted a multicenter retrospective cohort study of 1068 patients without cirrhosis (NC) or with compensated liver cirrhosis (LC) who achieved a sustained virologic response (SVR). First, we compared the cumulative HCC incidence and survival rates in NC (n = 880) and LC (n = 188) patients without a history of HCC treatment. Second, we performed multivariate analysis of factors related to HCC occurrence after DAA treatment. Overall, the average age was 65 years, and the male/female ratio was 511/557. Thirty-nine (4%) patients developed HCC. The cumulative 4-year HCC incidence and survival rates were 3.0% and 99.8% in NC patients and 11.5% and 98.5% in LC patients, respectively. The independent factors affecting HCC occurrence identified by multivariate analysis were the serum albumin (ALB) level before SVR for NC patients and the ALBI score, platelet count, and diabetes before SVR for LC patients. The factors related to HCC occurrence differed between NC and LC patients. Careful surveillance of post-SVR patients with these risk factors is needed.

Assessment of Liver Fibrosis after Direct-Acting Antiviral Therapy in Compensated and Decompensated HCV-related Liver Disease

2019 ◽  
Vol 4 (04) ◽  
Author(s):  
Mohammed Amin Mohammed ◽  
Nesreen Moustafa Omar
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Virologic Response ◽  
Post Treatment ◽  
Direct Acting Antiviral ◽  
Non Invasive ◽  
Apri Score ◽  
Fibrosis Regression ◽  
Chronic Hcv ◽  
Direct Acting

Background and Aim: Successful HCV eradication was associated with significant improvement in liver histology. Direct-acting antiviral (DAAs) therapy is associated with a significantly higher rate of sustained virologic response (SVR) compared to interferon-based therapies. Several non-invasive methods have been developed and validated with robust reliability and clinical applicability. Although these non-invasive tests are valuable in evaluating hepatic fibrosis prior to HCV therapy, use of these measures in monitoring fibrosis regression after HCV eradication with DAAs is currently limited. So, the aim was to assess the impact of DAAs on fibrosis regression in chronic HCV Egyptian patients with either compensated or decompensated liver disease. Patients and Methods: A total of 228 Egyptian chronic HCV patients eligible for treatment with DAAs were enrolled in this prospective study. All subjects selected from outpatient's Hepatology clinic of Mansoura university hospital received DAAs with different regimens after consent. The endpoint was a sustained virologic response at 12 (SVR12) weeks post-treatment. All participants were evaluated non-invasively by fibrosis-4 index (FIB-4), Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) score, and liver stiffness measurement (LSM) by fibroscan before DAAs treatment, at end of treatment (EOT), 6- and 12-months post-treatment. Results: SVR achieved by DAAs therapy was associated with significant improvement (p ˂0.05) of non-invasive fibrosis markers (FIB-4, APRI score, and LSM by fibroscan) from baseline compared to EOT, 6-and 12-months post-treatment among HCV patients with significant and advanced liver fibrosis. Conclusions: fibrosis regression after DAAs therapy regardless of fibrosis grade. Baseline LSM by fibroscan predicted fibrosis regression.

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