REPORT
Highlights from Barcelona 2012 International Liver Congress and EASL meeting
Destaques del Congreso Internacional del Hígado y reunión de la EASL, Barcelona 2012
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Julio C Aguilar
Departamento de Vacunas, Dirección de Investigaciones Biomédicas, Centro de Ingeniería Genética y Biotecnología, CIGB. Ave. 31 e/ 158 y 190, Cubanacán, Playa, CP 11600, La Habana, Cuba.
The International Liver Congress 2012 took place at the Centre de Convencions Internacional de Barcelona (CCIB), Spain, on April 18-22. This venue was the 47th annual meeting of the European Association for the Study of the Liver (EASL). The most important novelties of these two events are summarized in the present report.
Keywords: International Liver Congress 2012, EASL, hepatitis C virus, hepatitis therapy, diabetes, gut microbiota.
]]> RESUMEN
El Congreso Internacional del Hígado del año 2012 se celebró en el Centro de Convenciones Internacional de Barcelona (CCIB), España, del 18 al 22 de abril. En esta ocasión coincidió con la 47 Convención Anual de la Asociación Europea para el Estudio del Hígado (EASL). Se describen en este reporte las novedades más relevantes de estos dos importantes eventos.
Palabras clave: Congreso Internacional del Hígado 2012, EASL, virus de la hepatitis C, terapia de la hepatitis, diabetes, flora microbiana.
INTRODUCTION
The International Liver Congress 2012 organized by the European Association for the Study of the Liver (EASL) was held in Barcelona, Spain, at the Centre de Convencions Internacional de Barcelona (CCIB), on April 18-22, 2012.
The meeting evidenced the consolidation of the interferon-free revolution in hepatitis C virus (HCV) treatment as most outstanding topic. The studies related to the true impact that liver disease has across Europe in terms of mortality and costs were also highlighted. At preclinical level, studies in mice significantly evidenced that gut microbiota transplantation may prevent the development of diabetes and fatty liver disease.
NEW DATA SUGGESTS INTERFERON-FREE THERAPY AROUND THE CORNER FOR HEPATITIS C PATIENTS
]]> The much anticipated data from a number of clinical trials [1-6] confirmed that combinations of antivirals offer the hope of shorter, more effective treatment with fewer side effects compared to the 2012 standard of care using interferon.The new studies cover the treatment of patients infected with hepatitis C virus (HCV) genotypes (GT) 1 to 3, who were administered ribavirin (RBV) without interferon (IFN) and either one or two other drugs: direct-acting antivirals, such as HCV nucleotide analogues, HCV protease inhibitors, non-nucleoside RNA polymerase inhibitors, or host-targeting antivirals like the inhibitor cyclophilin A.
The combination of pegylated interferon alpha (PegIFN-α) and RBV is the current standard of care for chronic HCV [7], but it is associated with a number of side effects - including flu-like symptoms, psychiatric manifestations, autoimmune reactions, and hematologic toxicities [8, 9]. Between 20-40 % of patients require a dose reduction or temporary interruption in their PegIFN-α and RBV treatment [10], and in 10-14 % the side effects are so severe that treatment must be interrupted [8, 9].
Studies have shown that PegIFN-α free therapy is highly anticipated by healthcare professionals and patients alike. The EASL’s Secretary General, Professor Mark Thursz commented on the exciting new data being showcased at the congress: “In the future, patients can look forward to all oral treatment regimens with high success rates and low side effects. Furthermore, there is a large cohort of patients with more advanced liver disease who will now be able to access treatment that was previously impossible due to the side effects of Interferon-alpha. Over the last five years we have seen an evolution in HCV treatment, with direct antivirals used in combination with Pegylated Interferon and Ribavirin. Interferon-free regimes truly represent a revolution in treatment.”
Separate data presented at the congress may provide a further option. New results from a phase IIb study show a different form of interferon: PegIFN-λ, administered with RBV for 24 weeks in HCV GT2 & 3 patients give comparable undetectable HCV RNA levels 24 weeks after treatment as those treated with PegIFN-α-2a and RBV, but with fewer side effects (musculoskeletal and flu-like symptoms, hematologic toxicity) and dose modifications for PegIFN or RBV. Professor Thursz commented: “It remains possible that a number of patients will still need interferon based therapy for their HCV infection. Interferon-lambda, with a better side effect profile, looks like an excellent option in this group of patients, who are likely to have more advanced disease.”
Some of the above studies, together with the most relevant works on this topic presented in the meeting are summarized in the table [1-3, 6, 11-16].
Definitively, the development of interferon free therapies will impact in the currently established guidelines for chronic hepatitis C therapy in the next two or three years.
GUT MICROBIOTA TRANSPLANTATION PREVENTS DEVELOPMENT OF DIABETES AND FATTY LIVER DISEASE IN PRECLINICAL STUDIES
The factors leading to non-alcoholic fatty liver disease (NAFLD) are poorly understood, but it is known that NAFLD and type 2 diabetes are characterized by liver inflammation and metabolic disorders like insulin resistance, respectively. New data presented at the meeting showed the gut microbiota as having a causal role in the development of diabetes and NAFLD, independent of obesity [17].
]]> Though at an early stage of animal model development, a French study highlights the possibility of preventing diabetes and NAFLD with gut microbiota transplantation, the engrafting of new microbiota, usually through administering faecal material from a healthy donor into the colon of a diseased recipient [18].In the 16 weeks of the study, two groups of germ free mice received gut microbiota transplants; one set from donor mice displaying symptoms of insulin resistance and liver steatosis (responders), and the other from normal mice (non responders). The donor mice were selected due to their response to feeding with a high fat diet. The germ free group that received microbiota from symptomatic mice showed higher levels of fat concentrations in the liver and was insulin resistant. The germ-free group that received microbiota from healthy mice maintained normal glucose levels and sensitivity to insulin. This study showed that different microbiota cause different metabolic responses in animals. It was possible to prevent development of liver inflammation and insulin resistance by implanting microbiota from healthy mice, both indications of liver disease and diabetes, respectively. This type of treatment could have a therapeutic outcome in the future. At present, the intestinal microbiota is considered to be a “microbial organ”, with pivotal roles in the body’s metabolism and immune functions. Therefore gut transplantation aims to restore gut functionality and re-establish the state of intestinal flora to certain extent.
CHRONIC HEPATIC DISEASES GENERATE HIGH COSTS TO EUROPE
Two studies presented at the International Liver Congress 2012 showed the true impact that liver disease has across Europe, one the financial cost of liver disease and the other the high mortality rates associated with cirrhosis.
The former comprised a multicenter, retrospective cost of illness study (COME), to assess costs occurring in 1088 patients over six months. Patients enrolled had liver diseases including hepatitis C, cirrhosis, hepatitis B, hepatic carcinoma and other hepatic diseases (cholestasis, nonalcoholic steatohepatitis, etc.). The study found that liver disease costs in the European Union on average at least €644.77 per patient per month [19]. Hospitalizations account for 50.6 % of the overall mean direct costs per month, with treatment accounting for 41.2 % of costs. In addition, patients and family caregivers lost an average of 1.15 days per patient per month of productivity, an important indirect cost.
The study concluded that although treatment costs account for just over 40 % of direct costs, the use of efficient treatments is required to reduce worsening of patients’ health, and the increase of direct and indirect costs. These results demonstrate the real life costs of the treatment and ongoing management of patients with liver disease, a condition increasingly frequent and requiring impact estimates to aid on planning more effective treatment strategies. This might engage health authorities more on investing in preventive actions like reducing harmful alcohol consumption and fighting obesity.
In a separate study, the EASL-CLIF consortium reported that mortality for Acute-on-Chronic liver failure (ACLF) was 35.5 % on day 28 [20]. The consortium set out to address questions around ACLF, a poorly defined syndrome characterized by acute deterioration of cirrhosis, representing a main cause of hospitalization and death. At present, no diagnostic criteria and information on prevalence, pathogenesis or prognosis are available.
Overall, the meeting was useful on discussing emerging approaches for treating hepatitis viruses-related conditions and liver diseases such as diabetes and hepatic fat depot-related diseases, and the impact of current and emerging therapies on a population-wide perspective of the occurrence of hepatic diseases.
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20. Moreau R, Gines P, Jalan R, Pavesi M, Durand F, Angeli P, et al. Diagnosis, prevalence, and prognosis of acute-on-chronic liver failure (ACLF): results of the EASL-chronic liver failure (CLIF) consortium canonic study. J Hepatol. 2012;56(Suppl 2):S552-S53.
Julio C Aguilar. Departamento de Vacunas, Dirección de Investigaciones Biomédicas, Centro de Ingeniería Genética y Biotecnología, CIGB. Ave. 31 e/ 158 y 190, Cubanacán, Playa, CP 11600, La Habana, Cuba. E-mail: julio.aguilar@cigb.edu.cu.
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