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Editorial
Viral hepatitis: towards the eradication of HCV and a cure for HBV
Tarik Asselah and
Patrick Marcellin
Article first published online: 22 DEC 2014
DOI: 10.1111/liv.12744
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Issue
Liver International
Special Issue: Proceedings of the 8th Paris Hepatitis Conference International Conference on the Management of Patients with Viral Hepatitis
Volume 35, Issue Supplement s1, pages 1–3, January 2015
Abbreviations
CHC
chronic hepatitis C
DAA
direct acting antivirals
EMA
The European medicine agency
FDA
The federal drug authorities
PEG-IFN
pegylated-interferon
RBV
ribavirin
SVR
sustained virological response
This supplement of Liver International for the 8th Paris Hepatitis Conference (PHC) includes review articles by outstanding international experts with the most up-to-date information and their applications to the clinical care of patients with not only hepatitis B and hepatitis C but also hepatocellular carcinoma (HCC) and end-stage liver diseases, which were presented at this meeting.
Approximately 170 million people are chronically infected with HCV and 350 million are chronically infected with HBV worldwide. It is estimated that more than 1 million patients die from complications related to chronic viral hepatitis, mainly HCC which is one of the most frequent cancers in many countries, especially Africa, the Middle East and Asia. In France, despite a relatively low prevalence of chronic hepatitis B and C, mortality related to chronic viral hepatitis has been shown to be around 5000 deaths per year [1]. In addition, HBV- and HCV-related cirrhosis and HCC are the most common causes of liver transplantation.
The eradication of HCV: an achievable goal
Rapid progress, the availability of new direct-acting antivirals (DAAs) and new therapeutic strategies have increased the need for an update on the management of patients with viral hepatitis. Therefore, it is extremely important to educate and advise clinicians, allowing them to exploit available results and optimize management of these patients. Last year, more than 1300 doctors, specialized in managing patients with viral hepatitis from nearly 70 countries, attended the PHC meeting to update their knowledge and discuss clinical practices.
The primary goal of treatment is to achieve an SVR which is usually defined as undetectable serum HCV RNA 24 weeks after the end of treatment. Twelve-week post-treatment follow-up appears to be as relevant as 24 weeks to determine an SVR [2]. The SVR has been shown to be durable on long-term follow-up and associated with the eradication of HCV infection confirmed by undetectable HCV RNA in serum and the liver [3]. An SVR indicates that viral infection has been cured. In addition, viral eradication is associated with the regression of fibrosis, the possible reversibility of cirrhosis as well as significant improvement of the clinical outcome and survival with a decreased incidence of complications, especially HCC.
Thanks to the development of DAAs, spectacular innovations have recently been made in the management of hepatitis C [4-12]. However, in most countries, the current standard of care is still a pegylated interferon (PEG-IFN) based regimen. Significant progress was made in the treatment of chronic HCV genotype 1 infection with triple therapy combining PEG-IFN and ribavirin with a protease inhibitor (telaprevir, boceprevir or simeprevir) or a nucleotide (sofosbuvir). Interestingly, simeprevir is being evaluated in HCV genotype 1-infected patients without cirrhosis, for a 12-week short treatment based on an early virological response. Even if these triple therapies are associated with side effects, mainly related to PEG-IFN and ribavirin, the SVR rates in treatment-naïve patients with HCV genotype 1 infection have significantly increased by 30% (from 40% to 70%).
Strong predictors of response to treatment with the combination of PEG-IFN and ribavirin have been identified. Some are related to the virus and others to the host [13]. The relationship between HCV infection and insulin resistance is another fascinating avenue of research. It has been shown that HCV interferes with intracellular metabolic pathways (such as endoplasmic reticulum stress) that induce insulin resistance and increase the risk of diabetes [14, 15]. Genetic factors are an additional area of investigation, in particular the predictive value of IL28B polymorphism [16].
In other studies, IFN-stimulated genes have been shown to be highly expressed in non-responders, thus pre-activation of the IFN system appears to limit the effect of IFN therapy [17, 18].
Several, all oral, IFN–free DAAs combinations are now able to cure HCV in more than 90% of HCV genotype 1-infected patients after 12 weeks of treatment [5-12]. The SVR rate is very high with several of these regimens and they are all well tolerated. Real life data on treatment efficacy, tolerability and adherence are needed. Compliance to drug regimens will become a major issue to avoid relapse. We can expect a decrease in the SVR of 5 to 10% in real life data compared to clinical trials, because of compliance or other factors (disease severity, drug exposure, drug–drug interactions, etc.).
The programme to eradicate HCV must include increased screening as well as increased access to treatment in highly endemic regions such as eastern Europe, Latin America, as well as certain countries in Africa (Cameroon), the Middle East and South Asia [19, 20]. Egypt has the highest rate of HCV in the world (around 6–8 million), and several other African countries have a prevalence of more than 3%. Most HCV genotype 4-infected patients are still treated with PEG-IFN/RBV therapy, thus trials with DAAs are urgently needed in this specific population [19, 20].
HBV cure
Simultaneously, the PHC 2015, as in the past, will address major issues associated with hepatitis B. There is cumulative evidence that complete long-term suppression of HBV replication by the most potent drugs (entecavir and tenofovir) results in an improved long-term outcome with a decreased risk of progression to cirrhosis and complications such as liver failure, HCC and improved survival. In addition, a recent study assessing liver histology in patients treated with tenofovir for 5 years demonstrated that fibrosis regressed in most patients [21, 22]. Moreover, unlike what is generally believed, the reversal of cirrhosis was observed during treatment in 75% of patients with cirrhosis, probably associated with a decreased risk of HCC and improved survival.
Quantifying HBsAg is certainly an important new tool for predicting the severity of disease, to distinguish inactive carriers from patients with HBeAg-negative chronic active hepatitis and thus help tailor follow-up and treatment management [23, 24]. In addition, a decline in quantitative HBsAg during therapy is a strong predictor of SVR after PEG-IFN therapy and of the probability of HBsAg loss, which is the ultimate goal of therapy [25]. In patients treated with analogues, a decline in HBsAg levels is also a predictor of HBsAg loss, allowing therapy to be discontinued. Finally, optimal management of special populations and difficult situations needs to be improved: in particular pregnancy, co-infections with HIV and/or HDV and HCV and cirrhosis, immunosuppression.
This up-to-date special issue including comprehensive reviews covers every aspect of hepatitis C and hepatitis B management. Nowadays, with the availability of highly efficient and well-tolerated drugs, the challenge is to define the best therapeutic strategies and facilitate access to therapy. Because of the complexity and costs of treatment, there is now a need to develop optimal cost-effective strategies to provide the best chance of cure to as many patients as possible worldwide.
Acknowledgements
Conflict of interest: Tarik Asselah is a speaker and investigator for AbbVie, BMS, Janssen, Gilead, Roche and MSD. Patrick Marcellin is a speaker and investigator for AbbVie, BMS, Janssen, Gilead, Roche and MSD.
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发表于 2014-12-23 16:53
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