Estimating the impact of hepatitis C virus therapy on future liver-related morbidity, mortality and costs related to chronic hepatitis C

doi:10.1016/j.jhep.2004.12.031

Journal of Hepatology

Volume 42, Issue 5, May 2005, Pages 639-645

https://doi.org/10.1016/j.jhep.2004.12.031 Get rights and content

Background/Aims

Chronic Hepatitis C virus (HCV) infection is common and often produces a progressive disease. Some studies suggest that HCV related complications will increase in the future. Our aim was to estimate the future morbidity, mortality and costs of chronic HCV infection in a cohort of patients infected by HCV and to evaluate the impact of HCV therapy.

Methods

A mathematical model was used to project over the next 30 years, the HCV related complications and costs in a cohort of 419,895 infected patients representing the HCV infected population in Spain. The impact of HCV therapy with peginterferon and ribavirin in this population was also projected.

Results

A gradual decline in the infected population is expected in the future, however, the proportion of patients with cirrhosis will increase by up to 14% and morbidity associated with HCV infection by up to 10% by the year 2030 with a subsequent increment in HCV related costs. However, treating from 10 to 50% of the HCV population will result in a reduction of 6 and 26% in morbidity and 4 and 20% in mortality, respectively. The cost per year of life gained ranges from 6078 € for a 29-year-old patient to 8911 € for a 59-year-old patient.

Conclusions

In the future, HCV infection mortality, morbidity and associated costs will increase. Treatment of the chronic HCV infected population can eradicate the infection, increase patients' survival and reduce the need for liver transplantation, making this a cost-effective strategy.

Introduction

Hepatitis C virus (HCV) infection is a global health problem. Although the prevalence in the European population is estimated as 3%, the real HCV prevalence is still unknown [1]. There are a significant number of undiagnosed cases and it is unknown whether the distribution of the infection is uniform among the estimated 200 million carriers worldwide [2].

The majority of people infected by HCV acquired the infection 10–20 years ago, before the identification of the virus and the availability of HCV tests for screening and diagnosis. Most patients with chronic hepatitis C are asymptomatic until HCV related complications develop [1]. When complications such as decompensated cirrhosis and hepatocellular carcinoma appear, patients require an increased number of clinical visits, drug therapies and diagnostic tests. Hospitalisation and liver transplantation are also often required. These costs are related to the type of HCV complications and have a direct impact on health care resources. Currently, in developed countries, cirrhosis due to HCV infection and hepatocellular carcinoma are the leading causes of liver transplantation, accounting for 30% of all liver transplantations [2], [3]. The total number of liver transplantations is limited by the shortage of organs and in the future, if the number of patients requiring transplantation grows, the shortage will become a major problem despite the increasing number of liver related donors.

Considering the high prevalence of HCV infection, the current cost to the National Health Care System of managing HCV infection is relatively low due to the small number of patients receiving HCV therapy and the high number of asymptomatic patients, but it is clear that these costs will rise in the future.

The purpose of this study is to estimate, using a mathematical model, the morbidity, mortality, and costs of chronic hepatitis HCV infection in Spain over the next 30 years and to evaluate the potential impact of HCV therapy on these projections.

Section snippets

Decision analytic model: Markov model

A Markov computer simulation was used to model prognosis by following over time a representative cohort of the HCV infected patients for each age group. The Markov model used the software DATA 3.5 (TreeAge software, Williamstown, MA, USA).

The Markov model describes disease progression and determines the long-term morbidity, life expectancy, mortality, and lifetime costs for cohorts of HCV infected subjects. The model (described elsewhere) uses probabilities of progression from chronic hepatitis

Cohort definition

The total population of Spain, the age distribution, the total number of anti-HCV and HCV RNA cases, those with elevated ALT and the distribution of liver lesions are shown in Table 2. Overall, 699,823 subjects were estimated to have active HCV disease and 419,895 to have elevated ALT levels and therefore progressive liver disease. These figures were used in the model.

Base case scenario

The expected burden of hepatitis C infection for the base case and for the alternative scenario is shown in Table 3. Hepatitis C

Discussion

Our study shows that the increase in morbidity and mortality associated with uncomplicated chronic hepatitis C infection is going to increase in the near future without any type of therapeutic intervention, and how this phenomenon will translate into an important increase in the costs of the disease. The large pool of patients with chronic hepatitis C and progressive liver disease will require bigger Health Care System budgets. The projected HCV disease scenario used in this study is quite

Acknowledgements

Supported in part by a project Red Tematica Cooperativa C03/02 from Ministerio de Sanidad y Consumo, and Schering Plough Spain.

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Analizar la evolución analítica, clínica y de la fibrosis en pacientes F3-F4 curados con antivirales de acción directa (AAD).
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Se trataron 169 pacientes: 123 (72,8%) hombres, edad 57,5 ± 12 años; 117 (69,2%) presentaban cirrosis, 99 (84,6%) Child A. El 96,4% consiguieron respuesta virológica sostenida (RVS).
La mediana de seguimiento fue de 46,14 (2,89-62,55) meses. Durante el seguimiento se observó precozmente un aumento significativo de plaquetas (155 × 10³/μl [VB]; 163 × 10³/μl [12s]), colesterol (158 mg/dl [VB]; 179 mg/dl [12s]) y albúmina (4,16 g/dl [VB]; 4,34 g/dl [12s]), y un descenso significativo de GPT (82 UI/l [VB]; 23 UI/l [12s]), GOT (69 UI/l [VB]; 26 UI/l [12s]), GGT (118 UI/l [VB]; 48 UI/l [12s]), y bilirrubina (0,9 mg/dl [VB]; 0,7 mg/dl [12s]). La fibrosis disminuyó, también inicialmente, tanto con métodos serológicos como Fibroscan (19,9 KPa [VB]; 14,8 KPa [12s]); p < 0,05).
El 8,1% de los pacientes con cirrosis compensada presentaron alguna descompensación. El 4,5% desarrollaron varices esofágicas.
Nueve (5,52%) pacientes presentaron hepatocarcinoma de novo; seis (3,68%) lo presentaban basalmente, y el 40% sufrieron recidiva.
Durante el seguimiento la mortalidad fue del 9,2%.
Existe mejoría de los parámetros analíticos y de la fibrosis hepática medida por métodos no invasivos en los pacientes F3-F4 curados con AAD. Sin embargo, el riesgo de descompensación y de hepatocarcinoma persiste, por lo que se debe mantener el seguimiento.
To analyze laboratory parameters, clinical and fibrosis evolution in F3-F4 patients cured with direct-acting antivirals (DAA).
Unicenteric, observational and prospective study. All F3–F4 hepatitis C patients cured with DAA from 01/11/2014 to 31/08/2019 were included. A basal visit (BV) was performed and at 12 weeks (12w), 1, 2, 3 and 4 years after treatment.
Demographic and laboratory variables, fibrosis measured by non-invasive tests, indirect markers of portal hypertension, the presence of esophageal varices, cirrhosis decompensation and hepatoceullar carcinoma were collected.
169 patients were treated: 123 (72.8%) men, age 57.5 ± 12 years; 117 (69.2%) with cirrhosis, 99 (84.6%) Child A. 96,4% achieved SVR.
The study was conducted for a median follow-up of 46.14 (2.89-62.55) months. It was observed a significant increase in platelets [155 × 10³/μL (BV); 163 × 10³/μL (12w)], cholesterol [158 mg/dL (BV); 179 mg/dL (12w)] and albumin [4.16 g/dL (BV); 4.34 g/dL (12w)] and a significant decrease in ALT [82 UI/L (BV); 23 UI/L (12w], AST [69 UI/L (BV); 26 UI/L (12w)], GGT [118 UI/L (BV); 48 UI/L (12w)] and bilirrubin [0.9 mg/dL (BV); 0.7 mg/dL (12w)]. Fibrosis also improved early in follow-up, both by serological methods and Fibroscan [19.9 kPa (BV); 14.8 kPa (12w; P < .05].
8.1% of compensated cirrhosis patients had some decompensation. 4.5% developed esophageal varices.
Nine patients (5.52%) had de novo hepatocellular carcinoma; 6 (3.68%) had hepatoceullar carcinoma in BV and 40% had a recurrence.
During follow-up mortality was 9.2%.
There is an improvement in laboratory parameters and fibrosis measured by non-invasive methods in F3-F4 patients cured with DAA. However, the risk of decompensation and the incidence/recurrence of hepatocellular carcinoma still remain, so there is a need to follow these patients.
Real life experience with direct-acting antivirals agents against hepatitis C infection in elderly patients
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There is scarce data about the clinical evolution in elderly patients after HCV cure [16]. Several mathematical natural history models predict an increasing tendency in liver decompensation and deaths related to HCV over the next 10 years [17,18]. However, this tendency might be modified with the recent introduction of DAAs.
New direct-acting antivirals agents (DAAs) are very safe and well tolerated.
The purpose of this study is to analyse the efficacy and safety of DAAs in elderly patients, who have co-morbidities and are on chronic medications.
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Cost-effectiveness analysis of sofosbuvir, peginterferon and ribavirin in patients with chronic hepatitis C: Early treatment in the initial stage of fibrosis vs. delayed treatment in advanced fibrosis
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Modelo de Markov para estimar costes y resultados en salud (años de vida ganados [AVG] y años de vida ajustados por calidad [AVAC]), con una tasa de descuento del 3% anual de dos estrategias: SOF/PEG-IFN/RBV en fases precoces (fibrosis leve-moderada, F2-F3) o tardías (cirrosis compensada, F4). La eficacia (respuesta virológica sostenida), probabilidades anuales de transición, costes del manejo de la enfermedad y utilidades se obtuvieron de la literatura. Se consideraron costes directos expresados en € 2014. Se realizó un análisis de sensibilidad probabilístico (ASP).
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SOF/Peg-IFN/RBV therapy at F2-F3 was more effective (19.12 LYGs and 14.14 QALYs) compared to F4. In a cohort of 1,000 patients, SOF/Peg-IFN/RBV prevented 66 cases of decompensated cirrhosis, 60 hepatocellular carcinomas and 4 liver transplantations compared with therapy in advanced fibrosis. The total lifetime cost of early therapy (€ 43,263) was less than the cost of treatment in the advanced stage (€ 49,018). Early therapy was a dominant strategy, more effective and less costly in all simulations. In the PSA analysis, administration of SOF/PEG-IFN/RBV at F2-F3 was dominant in all simulations.
Starting SOF/Peg-IFN/RBV therapy at F2-F3, compared with therapy at F4, reduced the incidence of liver disease complications and was associated with cost savings for the Spanish NHS in CHC-GT1 patients.
Reversion of disease manifestations after HCV eradication
2016, Journal of Hepatology
Chronic infection with the hepatitis C virus (HCV) may lead to hepatic fibrosis and eventually cirrhosis, at which stage, patients have a substantial risk of liver failure, hepatocellular carcinoma (HCC) and liver-related death. Moreover, HCV infection is associated with several extrahepatic manifestations which impact the quality of life and increase the non-liver-related mortality rate. For patients with compensated liver disease, interferon (IFN)-based antiviral therapy has been a treatment option for over two decades. Long-term follow-up studies indicated that among those with sustained virological response (SVR) the extend of hepatic fibrosis can regress and that their risk of cirrhosis-related complications (including HCC) is reduced, also in case of cirrhosis. Recent population-based studies extended these observations for solid extrahepatic outcomes, such as end-stage renal failure and cardiovascular events. Most importantly, SVR has been associated with prolonged overall survival. These results highlight the importance of the development of new direct-acting antivirals (DAAs), by which almost all patients are able to eradicate HCV in a comfortable manner. Based on the excellent first experiences with the DAAs, physicians gained confidence to use these drugs among patients with decompensated cirrhosis on a more regular basis as well. This was not possible with interferon therapy. Also in this high risk population the DAAs show high SVR rates with improvements in biochemical parameters of liver function shortly after therapy, especially in case of SVR. In fact, some patients could actually be removed from the liver transplantation waiting list due to clinical improvement following DAA therapy. How these short-term results translate into a prolonged (long-term) survival has yet to be determined, as well as which patients with decompensated liver disease are likely or not to benefit from viral eradication. Here we review the current data regarding the beneficial clinical outcome with antiviral therapy as well the remaining uncertainties in this field, both for patients with compensated liver disease and patients with decompensated liver disease.
Cost-effectiveness of telaprevir in patients with genotype 1 hepatitis C in australia
2014, Value in Health
Citation Excerpt :
Therefore, it appears that the choice of a three-state fibrosis model does not substantially alter the overriding interpretation of the analysis. In many other models [21–23], patients achieving an SVR have the same annual rate of disease progression irrespective of whether they had mild, moderate, or cirrhotic disease before commencing treatment (i.e., patients achieving an SVR were considered to be cured of their virus irrespective of their fibrosis status before treatment). Our model, however, conservatively assumes that patients with cirrhosis achieving an SVR experience disease progression to HCC (albeit at a slower rate than do those who do not achieve an SVR).
Protease inhibitors such as telaprevir (Incivo) are reimbursed in Australia for the treatment of patients with genotype 1 hepatitis C virus (HCV) infection in combination with pegylated interferon and ribavirin (PR).
To assess the cost-effectiveness of telaprevir plus PR compared with PR alone in 1) previously untreated patients and 2) patients who had received treatment with PR earlier.
Sustained virological response rates and average treatment durations of telaprevir and PR (given with or without telaprevir) were taken from the telaprevir ADVANCE and REALIZE clinical trials but were modified to take account of differences in prescribing rules between the trials and Australian clinical practice. The probability of transitioning between Markov disease states was based on data from the Australian Kirby Institute where possible and supplemented using data from the published literature. Utility values obtained from the EuroQol five-dimensional questionnaire data collected in the ADVANCE and REALIZE trials were used to represent the utility during HCV treatment. Utility values for Markov health states were taken from the published literature. Unit costs (2014 AU $) were taken from Australian sources.
In treatment-naive patients, the discounted cost per life-years gained was AU $37,706 and the discounted cost per quality-adjusted life-year was AU $19,283. In treatment-experienced patients, the discounted cost per life-year gained was AU $23,855 and the discounted cost per quality-adjusted life-year was AU $14,948.
Telaprevir plus PR in the Australian setting is cost-effective when compared with PR alone in patients infected with genotype 1 HCV.

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^☆: The authors state that they received funding from the manufacturers Schering-Plough to carry out their research.

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Estimating the impact of hepatitis C virus therapy on future liver-related morbidity, mortality and costs related to chronic hepatitis C☆

Background/Aims

Methods

Results

Conclusions

Introduction

Section snippets

Decision analytic model: Markov model

Cohort definition

Base case scenario

Discussion

Acknowledgements

J Hepatol

J Hepatol

Am J Med

N Engl J Med

Lancet

Liver Transpl

Hepatology

Natural history of chronic hepatitis C

Hepatology

Estimates of the cost-effectiveness of a single course of interferon alfa-2b in patients with histologically mild chronic hepatitis C

Ann Intern Med

Pretreatment evaluation of chronic hepatitis C: risks, benefits, and costs

J Am Med Assoc

Cost-effectiveness analysis of therapeutic strategies for patients with chronic hepatitis C previously not responding to interferon

Aliment Pharmacol Ther

A cost-effectiveness analysis of peginterferon alfa-2b plus ribavirin for the treatment of naïve patients with chronic hepatitis C

Aliment Pharmacol Ther

Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients

Gastroenterology

Survival and prognostic factors of cirrhotic patients with ascites: a study of 134 outpatients

Am J Gastroenterol

Prognosis after the first episode of gastrointestinal bleeding or coma in cirrhosis. Survival and prognosis factors

Scand J Gastroenterol

Cost effectiveness of combination therapy for hepatitis C: a decision analytic model

Gut