Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C

Brzdęk, Michał; Zarębska-Michaluk, Dorota; Invernizzi, Federica; Cilla, Marta; Dobrowolska, Krystyna; Flisiak, Robert

doi:10.3748/wjg.v29.i6.949

Cited by 11 publications

(5 citation statements)

References 128 publications

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“…Importantly, we documented a significantly higher SVR rate among women than men of the same age. In multivariate analysis, liver cirrhosis and GT3 infection turned out to be negative predictors of response to DAA treatment in both sexes, and this conclusion from our study confirms the findings of other researchers, both from clinical trials and RWE studies 47 . However, despite GT3 infection and the presence of cirrhosis, in the current study, women of reproductive age were still more likely to achieve virological clearance than men, with a treatment response of 97% compared with 93% in men for both cirrhosis and GT3 infections.…”

Section: Discussionsupporting

confidence: 91%

“…In multivariate analysis, liver cirrhosis and GT3 infection turned out to be negative predictors of response to DAA treatment in both sexes, and this conclusion from our study confirms the findings of other researchers, both from clinical trials and RWE studies. 47 However, despite GT3 infection and the presence of cirrhosis, in the current study, women of reproductive age were still more likely to achieve virological clearance than men, with a treatment response of 97% compared with 93% in men for both cirrhosis and GT3 infections. It is worth noting that in our research, both GT3 HCV infection and liver cirrhosis were diagnosed significantly more often in men, which is in line with the findings from other RWE studies.…”

Section: Discussioncontrasting

confidence: 49%

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Direct‐acting antivirals in women of reproductive age infected with hepatitis C virus

Dobrowolska,

Pawłowska,

Zarębska‐Michaluk

et al. 2024

Journal of Viral Hepatitis

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Eliminating hepatitis C virus (HCV) infection in the population of women of reproductive age is important not only for the health of women themselves but also for the health of newborns. This study aimed to evaluate the implementation of this goal by analysing the effectiveness of contemporary therapy in a large cohort from everyday clinical practice along with identifying factors reducing therapeutic success. The analysed population consisted of 7861 patients, including 3388 women aged 15–49, treated in 2015–2022 in 26 hepatology centres. Data were collected retrospectively using a nationwide EpiTer‐2 database. Females were significantly less often infected with HCV genotype 3 compared to males (11.2% vs. 15.7%) and less frequently showed comorbidities (40.5% vs. 44.2%) and comedications (37.2% vs. 45.2%). Hepatocellular carcinoma, liver transplantation, HIV and HBV coinfections were reported significantly less frequently in women. Regardless of the treatment type, females significantly more often reached sustained virologic response (98.8%) compared to males (96.8%). Regardless of gender, genotype 3 and cirrhosis were independent factors increasing the risk of treatment failure. Women more commonly reported adverse events, but death occurred significantly more frequently in men (0.3% vs. 0.1%), usually related to underlying advanced liver disease. We have demonstrated excellent effectiveness and safety profiles for treating HCV infection in women. This gives hope for the micro‐elimination of HCV infections in women, translating into a reduced risk of severe disease in both women and their children.

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 49%

Direct‐acting antivirals in women of reproductive age infected with hepatitis C virus

Dobrowolska,

Pawłowska,

Zarębska‐Michaluk

et al. 2024

Journal of Viral Hepatitis

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“…The introduction of DAAs was a breakthrough in the treatment of patients with HCV, including those with cirrhosis, signi cantly improving treatment effectiveness and safety pro le [25]. There is a notable dearth of studies comparing the e cacy and safety of IFN-free therapies in patients with and without CSPH [26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Real-world experience with direct-acting antiviral therapy in HCV-infected patients with cirrhosis and esophageal varices

Brzdęk,

Zarębska-Michaluk,

Kukla

et al. 2024

Preprint

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Background Hepatitis C virus (HCV) infection affects 58 million people worldwide with around 290,000 deaths annually, mainly due to complications such as cirrhosis and hepatocellular carcinoma (HCC). Portal hypertension (PH) caused by cirrhosis leads to severe consequences, including esophageal varices (EV). To evaluate the effectiveness and safety of DAA treatment in patients with and without EV. Methods This retrospective analysis involved consecutive HCV-infected adults undergoing DAA therapy at 22 Polish hepatology centers from July 1, 2015, to December 31, 2022. Patients with cirrhosis were categorized based on presence of EV diagnosed by gastroscopy. Treatment effectiveness was measured by sustained virologic response (SVR), with safety outcomes monitored during and for 12 weeks post-treatment. Results The population of 3393 HCV-infected patients with cirrhosis was divided into groups with (A, n = 976) and without (B, n = 2417) EV. Group A showed a significantly higher prevalence of comorbidities and concomitant medications. Genotype (GT)1b infections predominated in both groups, and GT3 infections were more common in the EV group. Group A exhibited more severe liver disease, and higher rates of decompensation, HCC, and HBV co-infection. SVR was significantly higher in group B (91.5% vs. 96.3%, p<0.0001). Male gender, GT3, EV presence, and Child-Pugh grade B were identified as independent negative SVR predictors. Group A had a worse safety profile, with notably higher adverse event incidence and mortality. Conclusions DAA therapies are highly effective and well tolerated in patients with cirrhosis, but EV presence predicts poorer virologic responses.

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“…The continuous interplays between IL-1b and IFN in the microenvironment of HCV-infected cells may contribute to immune tolerance, IFN resistance, an extended inflammation state and the development of liver cirrhosis and HCC (73, 74) (Figure 2). This may also be the reason why the interferon therapy does not generate sustained virological response in the great majority of HCV patients (75).…”

Section: Hcv-induced Inflammasome and Innate Immune Responsementioning

confidence: 99%

HCV-induced autophagy and innate immunity

Lee,

2024

Front. Immunol.

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The interplay between autophagy and host innate immunity has been of great interest. Hepatitis C virus (HCV) impedes signaling pathways initiated by pattern-recognition receptors (PRRs) that recognize pathogens-associated molecular patterns (PAMPs). Autophagy, a cellular catabolic process, delivers damaged organelles and protein aggregates to lysosomes for degradation and recycling. Autophagy is also an innate immune response of cells to trap pathogens in membrane vesicles for removal. However, HCV controls the autophagic pathway and uses autophagic membranes to enhance its replication. Mitophagy, a selective autophagy targeting mitochondria, alters the dynamics and metabolism of mitochondria, which play important roles in host antiviral responses. HCV also alters mitochondrial dynamics and promotes mitophagy to prevent premature cell death and attenuate the interferon (IFN) response. In addition, the dysregulation of the inflammasomal response by HCV leads to IFN resistance and immune tolerance. These immune evasion properties of HCV allow HCV to successfully replicate and persist in its host cells. In this article, we discuss HCV-induced autophagy/mitophagy and its associated immunological responses and provide a review of our current understanding of how these processes are regulated in HCV-infected cells.

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Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C

Cited by 11 publications

References 128 publications

Direct‐acting antivirals in women of reproductive age infected with hepatitis C virus

Direct‐acting antivirals in women of reproductive age infected with hepatitis C virus

Real-world experience with direct-acting antiviral therapy in HCV-infected patients with cirrhosis and esophageal varices

HCV-induced autophagy and innate immunity

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