scholarly journals A Review on Extrahepatic Manifestations of Chronic Hepatitis C Virus Infection and the Impact of Direct-Acting Antiviral Therapy

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2249
Author(s):  
Cesare Mazzaro ◽  
Luca Quartuccio ◽  
Luigi Elio Adinolfi ◽  
Dario Roccatello ◽  
Gabriele Pozzato ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Hcv Infection ◽  
Extrahepatic Manifestations ◽  
Direct Acting Antiviral ◽  
Chronic Hepatitis C Virus ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting

Extrahepatic manifestations are a feature of chronic hepatitis C virus (HCV) infection. In the course of chronic HCV infection, about 70% of patients have one or more extrahepatic manifestations. The latter are often the first and only clinical sign of infection. Experimental and clinical data support a causal association for many extrahepatic manifestations and HCV infection, which include mixed cryoglobulinemia, non-Hodgkin lymphomas (NHL), cardiovascular disease, insulin resistance, type 2 diabetes, neurological and psychiatric disease and other rheumatic diseases. All these extrahepatic conditions influence the morbidity, quality of life and mortality of HCV-infected patients. Currently, interferon-free therapeutic regimens with direct-acting antiviral agents (DAA) offer the possibility of treatment to almost the entire infected population, irrespective of stage of cirrhosis and associated serious comorbidities, always maintaining a high efficacy and tolerability. Several studies have shown a close association between HCV clearance by DAAs and an improvement or reduction in the risk of extrahepatic manifestations. Patients with HCV after a sustained virologic response (SVR) by DAA treatment have a lower risk than non-responders of developing cryoglobulinemic vasculitis and B-cell non-Hodgkin’s lymphomas. Furthermore, the SVR by DAA also reduces the risk of acute coronary syndrome, cardiovascular disease, insulin resistance and type 2 diabetes, and it improves atherosclerosis. HCV clearance by DAA also improves the quality of life and survival of patients with chronic HCV infection with associated extrahepatic diseases. Thus, DAAs should be initiated as early as possible in HCV patients with extrahepatic manifestations.

scholarly journals Virus Elimination by Direct-Acting Antiviral Agents Impacts Glucose Homeostasis in Chronic Hepatitis C Patients

2022 ◽  
Vol 12 ◽  
Author(s):  
Chun-Han Cheng ◽  
Chia-Ying Chu ◽  
Huan-Lin Chen ◽  
I-Tsung Lin ◽  
Chia-Hsien Wu ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Antiviral Agents ◽  
Hcv Infection ◽  
Treatment Experience ◽  
Factors Associated ◽  
Direct Acting Antiviral ◽  
Chronic Hcv Infection ◽  
Hcv Genotype 1 ◽  
Chronic Hcv ◽  
Direct Acting

Background and AimsChronic hepatitis C virus (HCV) infection is associated with dysregulation of glucose homeostasis, including insulin resistance (IR) and type 2 diabetes. However, independent risk factors associated with IR in chronic HCV-infected patients have not been detailly elucidated. Previous data regarding the impact of HCV elimination by direct-acting antiviral agents (DAAs) on glucose homeostasis is insufficient and controversial. This study aimed to analyze the independent factors associated with IR and to evaluate the changes in glucose homeostasis in chronic HCV-infected patients treated with DAAs therapies.MethodsWe screened 704 patients with chronic HCV infection who underwent treatment with interferon-free DAAs. Patients’ baseline characteristics, biochemical and virological data were collected. The outcome measurements were their IR and β-cell function assessed by the homeostasis model assessment (HOMA) method at baseline and 12-weeks post-treatment.ResultsHigh IR (HOMA-IR ≥ 2.5) was observed in 35.1% of the patients. Multivariable logistic regression analysis revealed that body mass index (BMI) >25 kg/m2, treatment experience, elevated baseline levels of alanine aminotransferase (ALT) and triglyceride, as well as Fibrosis-4 score >3.25 were independently associated with high IR. In patients who achieved sustained virological response (SVR), no significant change in mean HOMA-IR was observed from baseline to 12-weeks post-treatment (2.74 ± 2.78 to 2.54 ± 2.20, p = 0.128). We observed a significant improvement in β-cell secretion stress from 121.0 ± 110.1 to 107.6 ± 93.0 (p = 0.015). Subgroup analysis revealed that SVR was associated with a significant reduction in mean HOMA-IR in patients with baseline HOMA-IR ≥ 2.5 (5.31 ± 3.39 to 3.68 ± 2.57, p < 0.001), HCV genotype 1 (3.05 ± 3.11 to 2.62 ± 2.05, p = 0.027), and treatment experience (4.00 ± 3.37 to 3.01 ± 2.49, p = 0.039).ConclusionsThere were several independent factors associated with IR in patients with chronic HCV infection, including obesity, treatment experience, high serum ALT and triglyceride levels, as well as advanced hepatic fibrosis. After viral elimination by DAAs, we observed a significant reduction in mean HOMA-IR in patients with baseline high IR, HCV genotype 1, and treatment experience.

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 Hepatocellular carcinoma after direct-acting antiviral therapy for chronic HCV infection: Is it a real risk?

IDCases ◽  
2018 ◽  
Vol 14 ◽  
pp. e00450 ◽  
Author(s):  
Cátia Dias ◽  
Filipa Duarte-Ribeiro ◽  
Sara Pipa ◽  
Ana Rita Barbosa ◽  
Margarida Mota ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antiviral Therapy ◽  
Hcv Infection ◽  
Direct Acting Antiviral ◽  
Real Risk ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting

scholarly journals Immunological Mechanisms for Hepatocellular Carcinoma Risk after Direct-Acting Antiviral Treatment of Hepatitis C Virus Infection

2021 ◽  
Vol 10 (2) ◽  
pp. 221
Author(s):  
Pil Soo Sung ◽  
Eui-Cheol Shin
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
De Novo ◽  
Hcv Infection ◽  
Direct Acting Antiviral ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting

Direct-acting antiviral agents (DAAs) that allow for rapid clearance of hepatitis C virus (HCV) may evoke immunological changes. Some cases of rapid de novo hepatocellular carcinoma (HCC) development or early recurrence of HCC after DAA treatment have been reported. During chronic HCV infection, natural killer (NK) cells exhibited a deviant functional phenotype with decreased production of antiviral cytokines and increased cytotoxicity; however, DAA treatment rapidly decreased their cytotoxic function. Effective DAA therapy also suppressed the intrahepatic activation of macrophages/monocytes. This was followed by a decrease in mucosal-associated invariant T (MAIT) cell cytotoxicity without normalization of cytokine production. Rapid changes in the phenotypes of NK and MAIT cells after DAA treatment may attenuate the cytotoxicity of these cells against cancer cells. Moreover, DAA treatment did not normalize the increased frequencies of regulatory T cells even after clearance of HCV infection. Thus, the persistently increased frequency of regulatory T cells may contribute to a local immunosuppressive milieu and hamper the clearance of cancer cells. This review will focus on recent studies describing the changes in innate and adaptive immune responses after DAA treatment in patients with chronic HCV infection in the context of de novo occurrence or recurrence of HCC.

scholarly journals The efficacy and safety of direct-acting antiviral agents in patients with chronic HCV infection and UGT1A1*28 polymorphism

2020 ◽  
Vol 22 (1) ◽  
pp. 71-80
Author(s):  
S.P. Lukashyk ◽  
I.A. Karpov ◽  
M.G. Siniauskaya ◽  
N.G. Danilenko ◽  
L.A. Anisko ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Antiviral Agents ◽  
Hcv Infection ◽  
Efficacy And Safety ◽  
Svr12 Rate ◽  
Direct Acting Antiviral ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting ◽  
Direct Acting Antiviral Agents

Objective. To determine the efficacy and safety of direct-acting antiviral agents (DAA) in patients with chronic HCV infection and UGT1A1*28 polymorphism. Materials and Methods. An open-label, non-randomized, observational study to assess efficacy and safety of DAA in patients (n = 143) with chronic hepatitis C (CHC) and liver cirrhosis and UGT1A1*28 polymorphism was performed. A total of 139 patients with chronic HCV infection were included in the efficacy analysis (absence of HCV RNA in blood by PCR) by the rate of sustained virologic response at week 12 (SVR12). Results. The SVR12 rate in patients with CHC and HCV-CP was 92.5% and 87.9%, respectively (p = 0.508), regardless of the presence of UGT1A1*28 polymorphism. The SVR12 rate in patients with chronic HCV infection and (TA)7/(TA)7 was 84.8%, with (TA)6/(TA)7 – 92.2% compared with (TA)6/ (TA)6 – 90,5% (p = 0.518). The rate of SVR12 in patients with CHC and (TA)7/(TA)7 or (TA)6/(TA)7 was 80% and 95%, respectively, with (TA)6/(TA)6 – 95.2%. The rate of SVR12 in patients with liver cirrhosis and (TA)7/(TA)7 or (TA)6/(TA)7 was 92.3% and 87.5%, respectively, with (TA)6/(TA)6 – 85.7%. The rate of SVR12 in patients with 12- and 24-week treatment duration was 88.2% and 96.6%, respectively (p = 0.30). As many as 96.2% of patients with the previous treatment with interferon and ribavirin had SVR12 compared to 88.5% of patients who have not previously taken antiviral drugs (p = 0.486). Grade 1 adverse events (AE) occurred in 24% of patients with chronic HCV infection treated with DAA; two patients developed Grade 4 AE. Conclusions. The treatment with DAA was shown to be effective and safe in patients with chronic HCV infection and UGT1A1*28 polymorphism.

Favouring modulation of circulating lipoproteins and lipid loading capacity by direct antiviral agents grazoprevir/elbasvir or ledipasvir/sofosbuvir treatment against chronic HCV infection

Gut ◽  
2017 ◽  
Vol 67 (7) ◽  
pp. 1342-1350 ◽  
Author(s):  
Hung-Yu Sun ◽  
Pin-Nan Cheng ◽  
Chiung-Ying Tseng ◽  
Wei-Jen Tsai ◽  
Yen-Cheng Chiu ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Sustained Virological Response Rate ◽  
Antiviral Agents ◽  
Density Lipoprotein ◽  
Antiviral Agent ◽  
Hcv Infection ◽  
Direct Acting Antiviral ◽  
Chronic Hcv Infection ◽  
Chronic Hcv ◽  
Direct Acting

ObjectiveLipid homoeostasis is disturbed in patients with HCV infection. Direct-acting antiviral agent (DAA) treatment eradicates chronic HCV viraemia, but the dynamics of lipid components remain elusive. This study investigates the clinical manifestation and mechanistic relevance of plasma triglyceride (TG), cholesterol (Chol), lipoproteins and apolipoproteins (apos) after DAA treatment.DesignTwenty-four patients with chronic genotype 1 (GT1) HCV treated with elbasvir/grazoprevir or ledipasvir/sofosbuvir for 12 weeks, and followed-up thereafter, were recruited. Their TG, Chol, apoAI and apoB levels were quantified in plasma samples and individually fractionated lipoprotein of various classes. Liver fibrosis was evaluated using the FIB-4 Score. The TG and Chol loading capacities were calculated with normalisation to apoB, which represents per very low density lipoprotein (VLDL) and LDL particle unitResultsDAA treatment achieved a sustained virological response rate of 91.7% and reduced the FIB-4 Score. Relative to the baseline, the plasma TG level was reduced but the Chol level increased gradually. Plasma apoB levels and apoB/apoAI ratio were transiently downregulated as early as the first 4 weeks of treatment. The TG and Chol loading capacities in VLDL were elevated by ~20% during the period of DAA treatment and had steadily increased by 100% at follow-up. Furthermore, the TG-to-Chol ratio in VLDL was increased, while the ratio in LDL was reduced, indicating an efficient catabolism.ConclusionThe DAA treatment of patients with chronic hepatitis C might lead to efficient HCV eradication and hepatic improvement concomitantly evolving with favouring lipoprotein/apo metabolisms.

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