scholarly journals Hepatitis C Virus and Hepatocellular Carcinoma: When the Host Loses Its Grip

2020 ◽  
Vol 21 (9) ◽  
pp. 3057
Author(s):  
Kaku Goto ◽  
Armando Andres Roca Suarez ◽  
Florian Wrensch ◽  
Thomas F. Baumert ◽  
Joachim Lupberger

Chronic infection with hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC). Novel treatments with direct-acting antivirals achieve high rates of sustained virologic response; however, the HCC risk remains elevated in cured patients, especially those with advanced liver disease. Long-term HCV infection causes a persistent and accumulating damage of the liver due to a combination of direct and indirect pro-oncogenic mechanisms. This review describes the processes involved in virus-induced disease progression by viral proteins, derailed signaling, immunity, and persistent epigenetic deregulation, which may be instrumental to develop urgently needed prognostic biomarkers and as targets for novel chemopreventive therapies.

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 302
Author(s):  
Eui-Cheol Shin ◽  
Ji Won Han ◽  
Wonseok Kang ◽  
Takanobu Kato ◽  
Seong-Jun Kim ◽  
...  

Hepatitis C virus (HCV) infects ~71 million people worldwide, and 399,000 people die annually due to HCV-related liver cirrhosis and hepatocellular carcinoma. The use of direct-acting antivirals results in a sustained virologic response in >95% of patients with chronic HCV infection. However, several issues remain to be solved to eradicate HCV. At the 26th International Symposium on Hepatitis C Virus and Related Viruses (HCV2019) held in Seoul, South Korea, October 5–8, 2019, virologists, immunologists, and clinical scientists discussed these remaining issues and how we can achieve the elimination of HCV.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kao-Chi Chang ◽  
Shui-Yi Tung ◽  
Kuo-Liang Wei ◽  
Chen-Heng Shen ◽  
Yung-Yu Hsieh ◽  
...  

AbstractClinical trials showed pangenotypic direct-acting antivirals’ (DAAs) excellent efficacy and safety when treating hepatitis C virus (HCV). Two pangenotypic regimens were examined, glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a real-world Taiwanese setting, including all HCV patients treated with GLE/PIB or SOF/VEL from August 2018 to April 2020. The primary endpoint was sustained virologic response 12 weeks after treatment cessation (SVR12), including adverse events (AEs). A total of 1,356 HCV patients received pangenotypic DAA treatment during the study: 742 and 614 received GLE/PIB and SOF/VEL, respectively. The rates of SVR12 for GLE/PIB and SOF/VEL were 710/718 (98.9%) and 581/584 (99.5%), respectively, by per-protocol analysis, and 710/742 (95.7%) and 581/614 (94.6%), respectively, by evaluable population analysis. Eleven (GLE/PIB: 8, SOF/VEL: 3) did not achieve SVR12. The most common AEs for GLE/PIB and SOF/VEL were pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon; only < 1% exhibited elevated total bilirubin or aminotransferase levels with both regimens. Five drug discontinuations occurred due to AEs (bilirubin elevation: 3; dermatological issues: 2). Pangenotypic DAAs GLE/PIB and SOF/VEL are effective and well tolerated, achieving high SVR12 rates for patients with all HCV genotypes.


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3414
Author(s):  
Hye Won Lee ◽  
Dai Hoon Han ◽  
Hye Jung Shin ◽  
Jae Seung Lee ◽  
Seung Up Kim ◽  
...  

By pegylated interferon (PegIFN)-free direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection, a sustained virological response (SVR) rate >95% can be attained with a satisfactory tolerability and shorter treatment duration. However, it remains controversial whether there is any difference in prognosis depending on regimens—PegIFN or DAAs. We compared the probabilities of hepatocellular carcinoma (HCC) development between patients achieving an SVR by PegIFN/ribavirin (PegIFN group, n = 603) and DAAs (DAAs group, n = 479). The DAAs group was significantly older and had a higher proportion of cirrhosis than the PegIFN group. Before adjustment, the DAAs group had a higher HCC incidence than the PegIFN group (p < 0.001). However, by multivariate analyses, the DAAs (vs. PegIFN) group was not associated with HCC risk (adjusted hazard ratio 0.968, 95% confidence interval 0.380–2.468; p = 0.946). Old age, male, higher body mass index, cirrhosis, and lower platelet count were associated with increased HCC risk (all p < 0.05). After propensity score matching (PSM), a similar HCC risk between the two groups was observed (p = 0.372). We also compared HCC incidences according to sofosbuvir (SOF)-based and SOF-free DAAs, showing a similar risk in both groups before adjustment (p = 0.478) and after PSM (p = 0.855). In conclusion, post-SVR HCC risks were comparable according to treatment regimens; PegIFN- vs. DAA-based regimens and SOF-based vs. SOF-free DAA regimens. Further studies with a longer follow-up period are required.


2020 ◽  
pp. 106002802096411
Author(s):  
Anthony J. Gentene ◽  
Allison M. Bell ◽  
Alicia Pence ◽  
Kelly Thomas ◽  
Collin Jakubecz ◽  
...  

Background: Direct-acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) have resulted in great success through high attainment of sustained virologic response (SVR). Risk factors for DAA treatment failure are important to identify because of worsened outcomes with failure and high treatment cost. Objective: We sought to identify whether hospitalization during treatment affects SVR. The primary outcome was the difference in SVR at 12 weeks after treatment Methods: This multicenter, single health system retrospective cohort review compared achievement of SVR between patients hospitalized during DAA treatment for HCV with those not hospitalized during treatment. Results: Patients in the hospitalized cohort (n = 94) had more severe disease at baseline than nonhospitalized patients (n = 167) as indicated through higher Model for End-Stage Liver Disease (MELD) scores, Fibrosis-4 scores, and imaging-suggested or biopsy-confirmed cirrhosis. Patients hospitalized during treatment had lower SVR rates compared with those not hospitalized (87.2% vs 95.2%; P = 0.043) but failed to reach significance when inpatient mortality was excluded on secondary analysis (91.1% vs 95.2%; P = 0.195). Patients who were hospitalized and did not achieve SVR had higher MELD scores, were more likely to have intensive care unit stay, and had longer hospital stay compared with those who achieved SVR. Of 94 patients, 93 provided home supply of DAAs during hospitalization. Conclusion and Relevance: Patients hospitalized during DAA treatment for HCV had reduced rates of SVR. This reduced SVR rate may be driven by inpatient mortality and severity of liver disease. Patient education to bring home supply of medication for use during admission is an effective intervention.


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