Progression of hepatitis C in the haemophiliac population in Ireland, after 30 years of infection in the pre‐<scp>DAA</scp> treatment era

Murphy, Niamh; O’Mahony, Brian; Flanagan, Paula; Noone, Declan; White, Barry; Bergin, Colm; Norris, Suzanne; Thornton, Lelia

doi:10.1111/hae.13244

Cited by 7 publications

(22 citation statements)

References 12 publications

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“…As compared to the group without haemophilia, the greater rate of platelet transfusion in the group with haemophilia may relate to their greater bleeding risk with concomitant thrombocytopenia. While alcoholism and substance abuse are infrequent in this population, only alcoholism contributed to HCC risk as previously shown …”

Section: Discussionsupporting

confidence: 71%

“…HCV was identified in this analysis as the most important predictor of HCC in haemophilic men, similar to other risk groups, 5 9 only alcoholism contributed to HCC risk as previously shown. 4,15 Despite the increase in HCC rates in this NIS database, only 40%-50% of haemophilic men with HCV infection were reported to have received antiviral agents in this time period. 9,15 It is, however, anticipated that with the highly effective and well-tolerated directacting antiviral agent (DAA) treatment, associated with a 95% or greater response rate in haemophilic men, 16 that more patients will agree to be treated.…”

Section: Discussionmentioning

confidence: 98%

“…Despite the increase in HCC rates in this NIS database, only 40%‐50% of haemophilic men with HCV infection were reported to have received antiviral agents in this time period . It is, however, anticipated that with the highly effective and well‐tolerated direct‐acting antiviral agent (DAA) treatment, associated with a 95% or greater response rate in haemophilic men, that more patients will agree to be treated.…”

Section: Discussionmentioning

confidence: 99%

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Incidence and risk factors for hepatocellular cancer in individuals with haemophilia: A National Inpatient Sample Study

et al. 2019

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Introduction Among haemophilic (H) men, hepatitis C virus (HCV) is the leading cause of liver disease and mortality, but demographics and risks of hepatocellular carcinoma (HCC) in H are not well known. Methods Adult discharges in H and non‐haemophilic (NH) men, with and without HCC were identified in the National Inpatient Sample (NIS) between 1998 and 2014, using ICD‐9 codes. Analyses included NIS‐provided discharge‐level weights to reflect national estimates. Categorical variables were assessed by Rao‐Scott chi‐square and continuous variables by weighted simple linear regression. HCC predictors were determined by weighted multivariable logistic regression. Results Of 18 098 H, 144 (0.79%) had HCC between 1998 and 2014. Adjusted rates of HCC increased 3.0‐fold in H vs 1.7‐fold in NH (P = 0.484). Among HCV+, HCC rates adjusted for HIV, increased 2.2‐fold in H vs 1.7‐fold in NH (P = 0.740), while among HIV+, HCC increased 1.4‐fold in H vs 0.2‐fold in NH (P = 0.448). Among those with HCC, H were older than NH (P < 0.001), Caucasian (P = 0.006), platelet transfusion recipients (P < 0.001), with greater comorbidity (P < 0.001) and mortality (P < 0.006). H with HCC also had greater rates of HCV and HIV (each P < 0.001), lower rates of alcoholism and hyperlipidemia (each P < 0.001), and similar rates of HBV (P = 0.866), smoking (P = 0.507) and obesity (P = 0.502). In multivariable logistic regression, HCV was a strong predictor for HCC in haemophilia, (OR: 15.42, 95% CI: 8.75‐27.16). Discussion Haemophilic men have increasing rates of HCC, similar to men without haemophilia. HCV is the major predictor of HCC in haemophilia. Future trends in HCC will depend on the impact of newer HCV antiviral therapy.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Incidence and risk factors for hepatocellular cancer in individuals with haemophilia: A National Inpatient Sample Study

et al. 2019

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“…Chronic hepatitis C is the main co‐morbidity in adult patients with haemophilia treated with plasma‐derived concentrates before 1990 . It causes progressive liver fibrosis with increased risk of end‐stage liver disease and hepatocellular carcinoma (HCC) . Eradication of HCV infection is the only therapeutic approach that can halt progression of liver disease and prevent cirrhosis and hepatocellular carcinoma .…”

Section: Introductionmentioning

confidence: 99%

High rate of sustained virological response with direct‐acting antivirals in haemophiliacs with HCV infection: A multicenter study

Mancuso

Linari²,

Santagostino

et al. 2020

Liver International

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Background and Aims: Chronic hepatitis C is the main co-morbidity in adult patients with haemophilia (PwH). It causes progressive liver damage leading to end-stage liver disease and/or hepatocellular carcinoma. Eradication of HCV was possible with interferon (IFN)-based regimens in the past and direct-acting antivirals (DAAs) more recently. PwH have been considered "difficult-to-treat" because of several bad predictors of response. The advent of DAAs has provided high rates of sustained virological response (SVR) despite bad prognostic factors. Here, we present the results of antiviral treatment with DAAs in PwH treated in 2 large Italian Hemophilia Treatment Centers. Methods: PwH and chronic hepatitis C sustained by any HCV genotype were eligible for therapy with DAAs, including those with compensated cirrhosis, HIV infection and/or previous failure to IFN-based antiviral therapy. Patients received DAAs for 8-24 weeks according to existing guidelines. SVR was defined as persistent negative serum HCV-RNA at 12 weeks after treatment completion (SVR12). patients aged 21-84 years (median: 50.5) received DAAs. HCV genotype 1 was the most prevalent (158, 79%). Forty patients (20%) were HIV positive, 56 (28%) had cirrhosis and 91 (46%) previously failed interferon-based treatment. Ribavirin was used in 70 (35%). HCV-RNA was undetectable at week 4 in 124/192 (65%) and SVR12 was achieved in 193/195 (99%). No patient had serious side effects related to DAAs.Conclusions: DAAs were safe and highly effective in PwH irrespective of HIV status, stage of liver disease severity and/or previous failure to IFN-based therapy.

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“…Hepatitis C virus (HCV) infection in humans has two major outcomes: eradiation in a minority of individuals or chronic infection causing hepatitis that can progress to cirrhosis and hepatocellular carcinoma. Some individuals are able to forestall clinical disease for decades with mild hepatitis while remaining infected and viremic with HCV, which presumably reflects an ability of the host response to prevent liver failure (75). There is considerable evidence that liver damage leading to cirrhosis is a consequence of chronic inflammation and that progression to end-stage liver disease is associated with strong inflammatory responses to persistent hepatocyte infection.…”

Section: Individual Susceptibility and The Damage-response Frameworkmentioning

confidence: 99%

What Is a Host? Attributes of Individual Susceptibility

Casadevall

Pirofski

2018

Infect Immun

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In every epidemic some individuals become sick and some may die, whereas others recover from illness and still others show no signs or symptoms of disease. These differences highlight a fundamental question of microbial pathogenesis: why are some individuals susceptible to infectious diseases while others who acquire the same microbe remain well? For most of human history, the answer assumed the hand of providence. With the advent of the germ theory of disease, the focus on disease causality became the microbe, but this did not explain how there can be different outcomes of infection in different individuals with the same microbe. Here we examine the attributes of susceptibility in the context of the "damage-response framework" of microbial pathogenesis. We identify 11 attributes that, although not independent, are sufficiently distinct to be considered separately: microbiome, inoculum, sex, temperature, environment, age, chance, history, immunity, nutrition, and genetics. We use the first letter of each to create the mnemonic MISTEACHING, underscoring the need for caution in accepting dogma and attributing disease causality to any single factor. For both populations and individuals, variations in the attributes that assemble into MISTEACHING can create an enormity of combinations that can in turn translate into different outcomes of host-microbe encounters. Combinatorial diversity among the 11 attributes makes identifying "signatures" of susceptibility possible. However, with their inevitable uncertainties and propensity to change, there may still be a low likelihood for prediction with regard to individual host-microbe interactions, although probabilistic prediction may be possible.

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Progression of hepatitis C in the haemophiliac population in Ireland, after 30 years of infection in the pre‐DAA treatment era

Cited by 7 publications

References 12 publications

Incidence and risk factors for hepatocellular cancer in individuals with haemophilia: A National Inpatient Sample Study

Incidence and risk factors for hepatocellular cancer in individuals with haemophilia: A National Inpatient Sample Study

High rate of sustained virological response with direct‐acting antivirals in haemophiliacs with HCV infection: A multicenter study

What Is a Host? Attributes of Individual Susceptibility

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