More people die from hepatitis C than from HIV. Half of hepatitis C sufferers are unaware of their infection. Individuals born in the 1960s are at increased risk for hepatitis C. Hepatitis C can be cured in over 90% of cases with modern interferon-free treatment combinations, but there are profound medical and ethical concerns due to pricing and limitations of use.
In Switzerland, an estimated 60,000-80,000 people have chronic hepatitis C, only half of whom have been tested, and less than 10% have been treated to date [1,2]. Infection occurs through blood-to-blood contact. Blood transfusions, invasive medical procedures, hemodialysis, and i.v. drug use are the main routes of transmission, although the first three have become rare thanks to routine testing of blood products and today’s high medical hygiene standards. Tattoos and piercings under inadequate hygienic conditions and sharing tubes when snorting drugs are other possible routes of infection. 70-80% of infections are chronic, and approximately one-third of chronic infections progress to cirrhosis or liver cancer over the years [3]. Hepatitis C (HCV) is a systemic infectious disease, all organs can be affected. Nonspecific extrahepatic manifestations such as fatigue, impaired concentration, and listlessness are common and are not infrequently identified by patients as HCV-associated only in retrospect during recovery.
Hepatitis C is referred to as a “silent disease” not only because of the frequent absence of specific symptoms, but also because of a lack of awareness and knowledge both at the medical and public health levels and in the general population. This is despite chronic hepatitis C infections being a relevant public health problem. Today, more people in Switzerland die from the consequences of viral hepatitis than from HIV. Hepatitis C is the leading cause of liver transplantation. Mathematical modeling analyses predict an increase in hepatitis C-induced liver sequelae with corresponding individual, social, and economic consequences if HCV incidence rates remain constant or decrease [4].
Transaminases insufficient for HCV screening
The screening test for hepatitis C is performed with HCV antibody detection. If positive, HCV RNA is used to determine active viral replication as an expression of chronic hepatitis C as well as the genotype. Transaminase determination as a marker for hepatitis C is not recommended. Up to one-third of hepatitis C patients with normal transaminases have relevant liver fibrosis or even cirrhosis [5,6].
Testing: vintage as a “new risk factor
More consistent risk-stratified testing is needed to address the high incidence of undetected HCV infection [7]. New findings regarding additional risk factors may be helpful in this regard.
Individuals born 1955-1974 represent 60% of the Swiss hepatitis C population but only 30% of the total population [8]. Individuals born in the mid-1960s have a threefold increased likelihood of being infected with hepatitis C. Accordingly, special attention should be paid to these vintages.
Immigrants from high-prevalence countries constitute a relevant proportion of the hepatitis C population in Switzerland. For example, HCV antibody prevalence in southern Italy is as high as 30% in people over 60 years of age. This is due to reused glass syringes and dental procedures in the 1970s [9].
These findings should be considered in practice when considering hepatitis C testing.
New therapies
Hepatitis C therapy is currently undergoing a revolution. Interferon-based HCV therapy is largely a thing of the past. These are replaced by combination therapies with Direct Acting Antivirals (DAA) with or without the addition of ribavirin, known from Interfon-based therapies. With these new hepatitis C drugs, a quantum leap was made in this field of medicine within a very short time. The new DAA combinations will not only achieve unprecedented efficacy in HCV therapy, but at the same time significantly increase the safety and tolerability of therapy, simplify the mode of administration, and shorten the duration of therapy.
The sum of developments and improvements in medication mean that the new HCV therapies will have a relevant impact not only on the individual affected, but also on public health. In the future, there will hardly be any sufferers who have to be excluded from therapy because of potential side effects of the medication and their accompanying circumstances. The acceptance of the therapy by patients will increase strongly, so will the demand for adequate testing, clarification and subsequent treatment.
Currently, treatment recommendations for hepatitis C are changing so rapidly that printed versions are no longer produced [10]. Currently, there are five DAA resp. fixed DAA combinations approved, or they are in the process of being approved. DAAs can be broadly divided into three classes according to their mode of action: Protease inhibitors, NS5B polymerase inhibitors, and NS5A inhibitors. They all inhibit virus replication directly in the host cell. Sofosbuvir (Sovaldi®), an NS5B polymerase inhibitor, is the only substance currently approved for use by health insurers. The fixed combinations of ombitasvir (NS5A inhibitor), paritaprevir (protease inhibitor), and ritonavir (Viekirax®) plus dasabuvir (Exviera®), a polymerase inhibitor, as well as sofosbuvir and the NS5A inhibitor ledipasvir (Harvoni®) have been approved by Swissmedic, but health insurance approval is pending (as of Jan. 15, 2015). The protease inhibitor simeprevir (Olysio®) and the NS5A inhibitor daclatasvir (Daklinza®) are still in the approval process.
Drug prices limit supply
The new HCV drugs, which can be combined without interferon, have the potential to cure the vast majority of patients with chronic hepatitis C thanks to their high efficacy, good tolerability and simple and comparatively short application. The use of interferon-based treatments was self-limiting because of the potential for side effects, associated anxiety, and the complexities of use and care during therapy. This drug-related high barrier to accessing therapy could be overcome with DAAs. However, current pricing and subsequently imposed use restrictions by health authorities significantly reduce this potential. DAA-based treatment combinations cost around 100,000 euros for a twelve-week course of treatment in Germany, where they have been mandatory for some time. If the therapy has to be extended to 24 weeks due to negative predictors, it is over 200,000 euros.
The medically and ethically questionable limitatio
The high price of Sovaldi®, which costs more than 600 Swiss francs per tablet in Switzerland, led the FOPH to restrict prescribing to patients with already severe liver fibrosis or liver cancer. already present cirrhosis limited, notwithstanding the increased risk of liver failure and liver cancer even with successful HCV therapy. Patients who have waited years for interferon-free treatment options must now be put off because their livers have not yet suffered enough damage. From a medical and ethical point of view, this is an untenable situation, the origin of which is to be found in the very high prices of the new hepatitis C drugs.
HCV therapy: looking to the future
The variety of DAA will increase in the coming years. Thus, the combination and treatment options will become even greater. Since the DAAs available today have cure rates of over 90%, there is no longer much potential for development in the area of efficiency. The only exception is small subgroups such as genotype 3 patients with liver cirrhosis and prior unsuccessful therapies. Additional improvement in hepatitis C therapy is expected with duration of therapy. There are good prospects that the current therapy duration of 12-24 weeks can be shortened even further, possibly even to a few weeks in well-treatable patient groups. With a broader range of drugs, the use of ribavirin, which is still responsible for some side effects, will continue to decline in the future.
Swiss Hepatitis Strategy
The new hepatitis C drugs have the potential to eliminate this epidemic. Due to the inadequate supply situation and prohibitive pricing, this goal is also a long way off in Switzerland. The hepatitis C treatment revolution has not solved the problem of hepatitis C care. In addition to treatment rates, testing and screening rates as well as awareness and knowledge are still insufficient.
A Swiss hepatitis strategy is currently being developed in Switzerland by a broad-based network of medical professionals, patient organizations, industry and payers. The network is supported by SEVHep (Swiss Experts in Viral Hepatitis), the Association of Hepatologists (SASL), the Swiss Society of Gastroenterology (SGGSSG), the Swiss Society of Infectious Diseases (SGINF) and the Global Health Program of the Graduate Institute.
A coordinated plan of action is being developed, covering the fields of action “education and prevention”, “testing and monitoring”, “therapy”, “risk groups”, “financing and prices”, and “policy”. The goal of the strategy is to limit the individual, medical and socioeconomic consequences of the hepatitis epidemic in Switzerland with patient-oriented, cost-effective and implementable measures.
Literature:
- Bruggmann P, et al: Historical epidemiology of hepatitis C virus (HCV) in selected countries. J Viral Hepat 2014 May; 21 Suppl 1: 5-33.
- Lettmeier B, et al: Market uptake of new antiviral drugs for the treatment of hepatitis C. J Hepatol 2008 Oct; 49(4): 528-536.
- Lavanchy D: Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect 2011 Feb; 17(2): 107-115.
- Razavi H, et al: The present and future disease burden of hepatitis C virus (HCV) infection with today’s treatment paradigm. J Viral Hepat 2014 May; 21 Suppl 1: 34-59.
- Shiffman ML, et al: Chronic hepatitis C in patients with persistently normal alanine transaminase levels. Clin Gastroenterol Hepatol 2006 May; 4(5): 645-652.
- Puoti C: Hepatitis C virus with normal transaminase levels. Dig Dis 2007; 25(3): 277-278.
- Fretz R, et al: Hepatitis B and C in Switzerland – healthcare provider initiated testing for chronic hepatitis B and C infection. Swiss Med Wkly 2013; 143: w13793.
- Bruggmann P, Richard JL: Birth year distribution in reported hepatitis C cases in Switzerland. Eur J Public Health 2014 Jul 23.
- Lavanchy D, McMahon BJ: Worldwide prevalence and prevention of hepatitis C. Hepatitis C. San Diego: Academic Press 2000; 185-202.
- SASL SSI Expert Opinion Statement: Treatment of Chronic Hepatitis C – September 2014 Update https://sasl.unibas.ch/guidelines/SASL-SSI_HepC_EOS_Sept2014.pdf. 2014.
HAUSARZT PRAXIS 2015; 10(2): 10-12
