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patients with hepatitis C treated with direct-acting antivirals (Gastroenterology 2018; 154:976-988). In this same line of work there has been an in vitro assessment of the resistance of certain strains of virus C to lethal mutagenesis. This could explain the persistence of the virus in complex clinical situations such as after diverse cycles of failed treatment (Virology 2018;523:100- 109). Lastly, there has also been progress in the genomic characterisation of the delta virus, taking advantage of mass sequencing techniques (Virus Res. 2018 Jan 2; 243:52-59).
As done every year, it is important to underline the participation of researchers from the
Hepatic and Digestive Oncology
Coordinator:
Bruno Sangro Gómez-Acebo
Hepatobiliopancreatic and digestive system cancer is a frequent cause of death in the general population,represents a great care burden at hospitals and health centres,and very high healthcare and pharmaceutical costs. For this reason the CIBEREHD has a programme on this pathology. But tackling this goes beyond the programme itself and involves other CIBEREHD programmes in transversal lines of work focussing on partial aspects of the problem. Knowledge of this is contributed by molecular biology,genetics, immunology,epidemiology or clinical intervention.
Researchers from the Programme have taken part in drawing up the guidelines for handling for the management of hepatocellular carcinoma prepared at the request of the European Association for the Study of the Liver and the European Society for Medical Oncology. They have also taken part in defining a new international system for classifying the in-depth invasion of colorectal polyps.
In liver cancer they have helped to define how the risk of developing the more aggressive forms of hepatocellular carcinoma is temporarily increased in a percentage of patients after eradicating the infection by hepatitis virus C with direct-acting antivirals. The debate in this field has not been settled but the work done and the research lines undertaken from these clinical observations will enable progress in knowledge to be made.
programme in the preparation of Clinical Guidelines (Guidelines on treatment of hepatitis C virus infection. Spanish Association for the Study of the Liver, Gastroenterol Hepatol. 2018;41:597-608 and EASL Recommendations
on Treatment of Hepatitis C 2018 https://doi. org/10.1016/j.jhep.2018.03.026) In the teaching field, different researchers from the programme have taken part in the postgraduate course of the Asociación Española y Europea para el Estudio del Hígado (2018) and have been organisers
of international-scale events (International Hepatitis Meeting, Barcelona 2018).
From the therapeutic stance the first studies have been started in a line of work intended
to identify the mechanisms of hepatocellular carcinoma’s resistance to immunotherapy agents based on blocking checkpoints and developing combinations increasing their effectiveness. In this respect it has been shown in animal models that epigenetic modulators such as Belinostat
can synergise with CTLA-4 and PD-1inhibitors; and the TGFbeta pathway has been identified
as a probable fundamental aspect of resistance to these drugs. In large-scale international studies the groups from the Programme have furthermore contributed to defining the utility of new drugs in liver cancer.
In the field of bowel cancer progress has been made in learning the performance of hereditary risk markers for developing digestive cancer. These enable individuals at risk to be identified for them to participate in follow-up plans enabling the disease to be detected in early stages in which potentially curative treatment can be applied.
The role of advanced dysplastic alterations in the risk of metachronous colon cancer has been reassessed in patients with small polyps.
Lastly, research work in cholangiocarcinoma has been consolidated, with the identification
of circulating metabolites which could act as markers for the early diagnosis of the disease in patients with primary sclerosing cholangitis, a pre-cancerigenous entity, and for the distinction between the histology of cholangiocarcinoma or hepatocarcinoma in small-sized nodules of cirrhotic livers.
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CIBEREHD | ANNUAL REPORT 2018