Enhanced immune responses, PI3K/AKT and JAK/STAT signaling pathways following hepatitis C virus eradication by direct-acting antiviral therapy among Egyptian patients: a case control study

Abstract The use of direct-acting antivirals (DAAs) therapy for the treatment of hepatitis C virus (HCV) results in a high sustained virological response (SVR) and subsequently alters liver immunologic environment. However, hepatocellular carcinoma (HCC) may occur after DAAs treatment. We aimed to clarify changes of immune responses, PI3K/AKT and JAK/STAT signaling pathways in HCV-induced liver diseases and HCC following DAAs treatment. Four cohorts are classified as chronic HCV patients, HCV-related cirrhosis without HCC, HCV-related cirrhosis and HCC, and healthy control group. The patient groups were further divided into treated or untreated with DAAs with SVR12. Increased percentages of CD3, CD8 and CD4, decreased CD4/FoxP3/CD25, CD8/PD-1 and CD19/PDL-1 were found in DAAs-treated patients in the three HCV groups. Following DAAs therapy, the levels of ROS, IL-1β, IL-6, IL-8 and TNF-α were significantly decreased in the three HCV groups. Treated HCV patients showed up regulation of p-AKT and p-STAT5 and down regulation of p-STAT3, HIF-1α and COX-2. In conclusion, DAAs enhance the immune response in chronic HCV and liver cirrhosis, hence our study is the first to show change in PI3K/AKT and JAK/STAT signaling pathways in different HCV-induced liver diseases after DAAs. In chronic HCV, DAAs have better impact on the immune response while in liver cirrhosis not all immune changes were prominent.

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Polymorphisms of α1-antitrypsin and Interleukin-6 genes and the progression of hepatic cirrhosis in patients with a hepatitis C virus infection

Balkan Journal of Medical Genetics ◽

10.1515/bjmg-2016-0034 ◽

2016 ◽

Vol 19 (2) ◽

pp. 35-44 ◽

Cited By ~ 4

Author(s):

T Motawi ◽

OG Shaker ◽

RM Hussein ◽

M Houssen

Keyword(s):

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Interleukin 6 ◽

Liver Diseases ◽

Multivariate Regression Analysis ◽

Nucleotide Polymorphisms ◽

Cirrhotic Patients ◽

Chronic Hcv

AbstractHepatitis C virus (HCV) infection represents a serious health problem. The –174 G/C mutation in the pro inflammatory cytokine interleukin-6 (IL-6) is associated with developing liver diseases. Likewise, the S and Z mutations in the serine protease inhibitor α1-antitrypsin (A1AT) are associated with pulmonary emphysema and/or liver cirrhosis. We explored the distribution of the single nucleotide polymorphisms (SNPs) ofIL-6andA1ATgenes in chronic HCV-infected patients and evaluated their impact on the progression of liver cirrhosis.One hundred and fifty Egyptian HCV-infected patients together with 100 healthy controls were enrolled in this study. The patient groups were subdivided into chronic hepatitis patients (n= 85) and cirrhotic patients (n= 65). The SNP of IL-6 (–174 G/C, rs1800795), A1AT Z mutation (342 Glu/Lys, rs28929474) and A1AT S mutation (264 Glu/Val, rs17580) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Cirrhotic patients exhibited significantly increased frequency of the A1AT S allele compared with the controls (34.6vs. 5.0%), while the chronic hepatitis patients showed a higher frequency of the A1AT Z allele compared with the controls (14.7vs. 2.5%). Remarkably, IL-6 (CC genotype) was detected only in the chronic hepatitis patients. Multivariate regression analysis showed that aspartate transaminase (AST) and the S alleles of A1AT, represented as SS+MS genotypes, were significantly independent predictors for development of liver cirrhosis. We concluded that inheritance of deficient S and Z alleles of theA1ATgene but not IL-6 (–174 G/C), were associated with progressive liver diseases.

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The Beginning of Ending Hepatitis C Virus: A Summary of the 26th International Symposium on Hepatitis C Virus and Related Viruses

Viruses ◽

10.3390/v12030302 ◽

2020 ◽

Vol 12 (3) ◽

pp. 302

Author(s):

Eui-Cheol Shin ◽

Ji Won Han ◽

Wonseok Kang ◽

Takanobu Kato ◽

Seong-Jun Kim ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

International Symposium ◽

Virologic Response ◽

Direct Acting Antivirals ◽

Chronic Hcv Infection ◽

Chronic Hcv ◽

Direct Acting

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.

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Sa1525 – Visne Analysis of Hepatitis C Virus-Specific Cd8 T Cells from Direct Acting Antiviral-Treated Chronic Hcv Patients and Hcv Resolvers

Gastroenterology ◽

10.1016/s0016-5085(19)40073-5 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-1232

Author(s):

Jihad Aljabban ◽

Pierre Tonnerre ◽

Dan Kvistad ◽

Max Robidoux ◽

Joelle Brown ◽

...

Keyword(s):

T Cells ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Cd8 T Cells ◽

Direct Acting Antiviral ◽

Chronic Hcv ◽

Direct Acting

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Characteristics of patients with hepatitis C virus-related chronic liver diseases just before the era of oral direct-acting antiviral therapy in Italy

European Journal of Gastroenterology & Hepatology ◽

10.1097/meg.0000000000001390 ◽

2019 ◽

Vol 31 (4) ◽

pp. 549

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Therapy ◽

Liver Diseases ◽

Chronic Liver ◽

Chronic Liver Diseases ◽

Direct Acting Antiviral ◽

Direct Acting

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Impact of Sustained Virological Response for Gastroesophageal Varices in Hepatitis-C-Virus-Related Liver Cirrhosis

Journal of Clinical Medicine ◽

10.3390/jcm9010095 ◽

2019 ◽

Vol 9 (1) ◽

pp. 95 ◽

Cited By ~ 1

Author(s):

Yukihisa Yuri ◽

Hiroki Nishikawa ◽

Hirayuki Enomoto ◽

Kazunori Yoh ◽

Yoshinori Iwata ◽

...

Keyword(s):

Liver Cirrhosis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Sustained Virological Response ◽

Virological Response ◽

P Value ◽

Gastroesophageal Varices ◽

Direct Acting Antiviral ◽

Direct Acting

We aimed to clarify the relationship between sustained virological response (SVR) and gastroesophageal varices (GEVs) progression among hepatitis C virus (HCV)-related liver cirrhosis (LC) patients treated with interferon (IFN)-based therapies (n = 18) and direct-acting antiviral (DAA)-based therapies (n = 37), and LC patients with no SVR (n = 71) who had already developed GEVs. Factors influencing GEVs progression were also examined. During the follow-up period, GEVs progression was observed in 50 patients (39.7%). The 3-year cumulative GEVs progression rates in the DAA-SVR group, the IFN-SVR group, and the non-SVR group were 32.27%, 5.88%, and 33.76%, respectively (overall p value = 0.0108). Multivariate analysis revealed that sex (p = 0.0430), esophageal varices (EVs) F2 or more (p < 0.0001), and DAA-SVR (p = 0.0126, IFN-SVR as a reference) and non-SVR (p = 0.0012, IFN-SVR as a reference) were independent predictors for GEVs progression. The proportion of GEVs progression in patients with no or F1 EVs was significantly lower than that in patients with F2 or F3 EVs (33.9% (38/112) vs. 85.7% (12/14), p = 0.0003). In conclusion, IFN-based therapies can have a favorable impact for preventing GEVs progression in HCV-related LC patients with GEVs. Clinicians should be aware of a point of no return where SVR is no longer capable of avoiding GEVs progression.

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Direct-acting Antivirals for Hepatitis C Virus in Patients on Maintenance Dialysis

The International Journal of Artificial Organs ◽

10.5301/ijao.5000613 ◽

2017 ◽

Vol 40 (10) ◽

pp. 531-541 ◽

Cited By ~ 6

Author(s):

Fabrizio Fabrizi ◽

Francesca M. Donato ◽

Piergiorgio Messa

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Severe Renal Impairment ◽

Controlled Trial ◽

Hcv Infection ◽

Direct Acting Antivirals ◽

Safety And Efficacy ◽

Maintenance Dialysis ◽

Chronic Hcv ◽

Direct Acting

The frequency of hepatitis C virus (HCV) infection remains high in patients with chronic kidney disease (CKD) and plays a detrimental role in mortality in this population. According to the latest survey, the adjusted hazard ratio for HCV-positive versus HCV-negative patients on long-term dialysis was 1.12 (95% CI, 1.05 to 1.20) and 1.10 (95% CI, 0.98 to 1.22) for all-cause and cardiovascular mortality, respectively. An impairment on quality of life has also been documented in HCV-infected patients undergoing regular dialysis. Most clinicians have been so far reluctant to treat hepatitis C in patients with advanced CKD, due to concerns regarding low efficacy and safety of interferon-based regimens. The advent of all-oral, direct-acting antivirals (DAAs) has revolutionized treatment paradigms for HCV, including patients with other comorbidities such as CKD. Two combinations of DAAs have been recently approved for the treatment of HCV in advanced CKD: elbasvir/grazoprevir (evaluated in 1 randomized controlled trial) and ombitasvir/paritaprevir/ritonavir/dasabuvir with or without ribavirin (examined in some observational, single-arm studies). These antiviral combinations have provided high safety and efficacy (SVR12 rates >90%) in HCV-infected patients with stage 4–5 CKD. Sofosbuvir, a nucleotide analogue inhibitor of the HCV NS5B polymerase, is the cornerstone of most anti-HCV current regimens but is not currently recommended for patients with severe renal insufficiency (eGFR <30 mL/min per 1.73 m2). However, several small-sized studies have been published on the safety and efficacy of sofosbuvir-based regimens for patients with hepatitis C on maintenance dialysis>; overall, the viral response was satisfactory (SVR12 rates ranging between 58% and 100%) with a few drug-related drop-outs. Studies are in progress to assess whether ribavirin-free antiviral combinations with novel DAAs are a viable option for patients with severe renal impairment and chronic HCV infection.

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Sustained Virological Response after 8-Week Treatment of Simeprevir with Peginterferon α-2a plus Ribavirin in a Japanese Female with Hepatitis C Virus Genotype 1b and IL28B Minor Genotype

Case Reports in Gastroenterology ◽

10.1159/000437138 ◽

2015 ◽

Vol 9 (2) ◽

pp. 215-220 ◽

Cited By ~ 2

Author(s):

Tatsuo Kanda ◽

Masato Nakamura ◽

Reina Sasaki ◽

Shin Yasui ◽

Shingo Nakamoto ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Adverse Events ◽

Sustained Virological Response ◽

Virological Response ◽

Hcv Infection ◽

Direct Acting Antivirals ◽

Chronic Hcv ◽

Direct Acting ◽

Peginterferon Α

Direct-acting antivirals with or without peginterferon α (PEG-IFN α) plus ribavirin are now available for the treatment of hepatitis C virus (HCV) infection. Direct-acting antivirals are potent inhibitors of HCV replication, but some of them occasionally possess serious adverse events. We experienced a 64-year-old female with chronic HCV genotype 1b infection who showed elevated alanine aminotransferase of 528 IU/l at week 9 after the commencement of treatment of simeprevir with PEG-IFN α-2a plus ribavirin. However, she achieved sustained virological response at week 24 after the end of treatment. In Japan, we also have to treat elderly patients infected with HCV and/or advanced hepatic fibrosis. Until an effective interferon-free regimen is established, direct-acting antivirals with PEG-IFN plus ribavirin may still play a role in the treatment for certain patients. To avoid serious results from adverse events, careful attention and follow-up will be needed in the treatment course of simeprevir with PEG-IFN plus ribavirin for chronic HCV infection.

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Liver Cirrhosis as a Risk Factor for Direct-Acting Antiviral Therapy Failure in Real-Life Hepatitis C Virus/Human Immunodeficiency Virus Coinfection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx158 ◽

2017 ◽

Vol 4 (3) ◽

Cited By ~ 17

Author(s):

Christoph Boesecke ◽

Patrick Ingiliz ◽

Florian Berger ◽

Thomas Lutz ◽

Knud Schewe ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Liver Cirrhosis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Treatment Guidelines ◽

Real Life ◽

Direct Acting Antiviral ◽

Hiv Coinfection ◽

Immunodeficiency Virus ◽

Direct Acting

Abstract Current hepatitis C virus (HCV) treatment guidelines recommend treating HCV/human immunodeficiency virus (HIV)-coinfected individuals similar to HCV-monoinfected individuals. Recently inferior response rates to direct acting antiviral (DAA) therapy in HCV/HIV coinfection have been reported. Our German hepatitis C cohort (GECCO) cohort data show that coinfected patients with liver cirrhosis are less likely to achieve viral eradication.

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