Hepatitis C treatment gap in Europe: France doing well but Italy treated fewer than one in a hundred patients in 2010

France led the world in the proportion of its hepatitis C patients who received treatment in 2010, but some countries in southern and eastern Europe had treatment rates that were almost tenfold lower, according to research presented last month at the International Liver Congress in Amsterdam.

However, European epidemiologists and physicians cautioned that the results should be treated as indicative rather than hard estimates, and that far more research is needed into hepatitis C prevalence in order to arrive at reliable estimates of treatment need in the European region.

The study, carried out by the Center for Disease Analysis in Colorado, USA, sought to develop estimates of the number of people who received treatment with pegylated interferon and ribavirin in 2010. This was the last year in which all European countries had access to a comparable regimen for the treatment of hepatitis C. In 2011, the HCV protease inhibitors telaprevir (Incivo) and boceprevir (Victrelis) began to become available in some European countries following European marketing approval.

Glossary

pegylated interferon

Pegylated interferon, also known as peginterferon, is a chemically modified form of the standard interferon, sometimes used to treat hepatitis B and C. The difference between interferon and peginterferon is the PEG, which stands for a molecule called polyethylene glycol. The PEG does nothing to fight the virus. But by attaching it to the interferon (which does fight the virus), the interferon will stay in the blood much longer. 

systematic review

A review of the findings of all studies which relate to a particular research question and which conform to pre-determined selection criteria. 

trend

In everyday language, a general movement upwards or downwards (e.g. every year there are more HIV infections). When discussing statistics, a trend often describes an apparent difference between results that is not statistically significant. 

exclusion criteria

Defines who cannot take part in a research study. Eligibility criteria may include disease type and stage, other medical conditions, previous treatment history, age, and gender. For example, many trials exclude women who are pregnant, to avoid any possible danger to a baby, or people who are taking a drug that might interact with the treatment being studied.

HIV-associated neurocognitive disorder (HAND)

HIV-associated neurocognitive disorder (HAND) describes the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the central nervous system (CNS) during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. Cognitive impairment in people with HIV is not necessarily due to HAND; other possible causes include alcohol or drug abuse, depression, anxiety, vascular cognitive impairment and Alzheimer’s disease.

The study compared treatment rates in 22 European countries (Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, Slovakia, Spain, Switzerland, Sweden and the United Kingdom) using data supplied from a variety of sources including key opinion leaders and national surveys, as well as international databases on pharmaceutical sales. The Baltic states and Ukraine were excluded due to a lack of robust data on drug purchases.

Treatment rates were calculated using the following parameters:

  • Estimates of the total number of units of pegylated interferon and ribavirin sold in each country between 2004 and 2010, adjusted for probable use in hepatitis B treatment.
  • Estimates of chronic, viremic hepatitis C infections for each country, derived from calculations of global burden published in the journal Liver International in 2011.
  • Country-specific genotype distribution, used to adjust the duration of treatment (the higher the prevalence of difficult-to-treat genotypes, the fewer patients would be treated with a given volume of interferon, because treatment courses would last for 48 weeks rather than 24 weeks).
  • The proportion of patients who were estimated to complete a full course of treatment and the average duration of treatment of all patients who started treatment.

Estimates of HCV prevalence remain the subject of controversy among public health specialists and epidemiologists owing to a lack of robust national surveys.

Session chair Prof. Daniele Prati warned that some estimates of HCV prevalence in Italy are questionable. In particular, he warned, they may over-estimate prevalence through reliance on population surveys which over-represent southern Italy and older populations. Both these populations had a higher HCV prevalence.

Epidemiologist Prof. Matthew Hickman of Bristol University voiced similar concerns about the United Kingdom. “The bound of uncertainty for the United Kingdom alone might be anywhere between 100,000 and 500,000 – that’s just one country,” he said.

Homie Razavi of the Center for Disease Analysis defended the prevalence estimates, pointing out that they were based on the best available data, identified through a systematic review of the published literature on HCV prevalence.

Taking into account these uncertainties, some clear European trends were evident nevertheless.

While the total number of patients treated had grown substantially between 2004 and 2010 in the United Kingdom, Russia and Romania, Germany and Spain, the number of patients treated had fallen in Italy and France. This, said Homie Razavi, indicated that liver specialists had already begun 'warehousing' patients in anticipation of the availability of more effective hepatitis C treatments in the future. This trend was already evident by 2008, he said.

The rate of hepatitis C treatment within the viremic population differed enormously between some countries in northern and western Europe and most countries in southern and eastern Europe. Whereas an estimated 6.7% of French hepatitis C patients underwent treatment in 2010, only 0.8% of Italian patients were treated in the same year. Even if the prevalence of hepatitis C in Italy and France were the same, the treatment rate in France would still be several times higher than in Italy.

The treatment rate was also very low in Poland (0.4%), Romania (1%) and Russia (0.3%), perhaps due to the cost of treatment. Yet it was also substantially lower in Belgium (1.1%), Finland (1.1%) and Ireland (1.5%) when compared to Germany (4.3%), Sweden (4.3%) and the United Kingdom (3.4%), suggesting that resource allocation for hepatitis C treatment in countries at similar levels of economic development remains highly variable.

Prof. Daniele Prati cautioned that any comparison of treatment rates needed to take into account two factors: the age distribution of the viremic population, and the proportion of people in the population who had already experienced failure of a treatment regimen and who were waiting for new treatment.

HCV epidemics in eastern Europe may be 'younger' than in northern Europe and the Mediterranean. More recently infected people may not need treatment yet. On the other hand, high rates of HIV/HCV co-infection in eastern European populations, particularly in Russia, could diminish this difference, by causing rapid progression of liver disease.

Similarly, even though almost twice as many people received treatment in Italy in 2004 compared to France, with the gap disappearing by 2010, a very high proportion of these patients and those treated in subsequent years would have to fail treatment for this argument to explain the difference in treatment rates between Italy and France.

References

Razawi H. HCV treatment rate in select European countries, 2004-2010. 48th International Liver Congress (EASL 2013), Amsterdam abstract 51, 2013.