248 research outputs found
Review article: immune checkpoint inhibitors and the liver, from therapeutic efficacy to side effects
No full textBackground: Immune checkpoint inhibitors have revolutionised the oncological landscape in the last few years. Possible applications include the treatment of hepatocellular carcinoma and cholangiocarcinoma. Unfortunately, new immune-related adverse effects have been associated with the use of these agents and the liver is one of the organs most frequently involved. Aims: To provide a general overview of the potential impact of immune checkpoint inhibitors on the liver. Methods: We reviewed the literature and abstracts/presentations on immune checkpoint inhibitors at most relevant hepatology meetings over the last 5 years. Results: The role of immune checkpoint inhibitors has been investigated both for the treatment of viral hepatitis and primary liver cancer. Hepatocellular carcinoma and chronic hepatitis B show the greatest potential for treatment with these drugs in the near future. However, immune-related adverse events involving the liver are a growing concern related to their widespread use. Conclusions: Immune checkpoint inhibitors represent an exciting new class of drugs with currently limited application in malignant and non-malignant liver disease. Caution must be exercised on the emergence of potentially severe immune adverse reactions
Production of human monoclonal antibodies to hepatitis C virus and their characterization
No full text: Human monoclonal antibodies (hMAb) provide novel ways to probe the B-cell repertoire in health and disease. However, the development of hMAb technology has met with several difficulties owing to the instability of the cell lines, the low level of specific antibody secretion, and the poor cloning efficiency, particularly when using lymphoblastoid cells (1,2). In order to overcome these problems, some investigators have fused human B lymphocytes with human/mouse myeloma heterohybrids. However, in such systems, human chromosomes are unstable and may occasionally be deleted. Despite the potential emergence of technical pitfalls, B-cell immortalization with EBV has been extensively used for hMAb production, because of its simplicity and because EBV can bind to and penetrate in virtually all B lymphocytes, theoretically allowing the exploration of the whole B-cell repertoire. The most recent protocols have made use of techniques aimed at expanding the population of antigen-specific B-cell precursors and improving the capacity of B-cells to grow at low density. These methods will be discussed below
Hepatitis C: Is eradication possible?
No full textHepatitis C has a relevant global impact in terms of morbidity, mortality and economic costs, with more than 70 million people infected worldwide. In the resolution, “Transforming our world: the 2030 Agenda for Sustainable Development” was included as a focus area in the health-related goal with world leaders pledging to “combat” it by 2030. In response, WHO drafted the Global Viral Hepatitis Strategy carrying the ambitious targets to reduce the number of deaths by two-thirds and to increase treatment rates up to 80%. Despite the availability of highly effective therapeutic regimens based on direct-acting antivirals many barriers to HCV eradication still remain. They are related to awareness of the infection, linkage to care, availability of the therapeutic drug regimens and reinfection. Overall, if an effective prophylactic vaccine will not be available, HCV eradication appears difficult to achieve in the future
Does the immune response play a role in the pathogenesis of chronic liver disease?
No full textThe pathogenesis and perpetuation of hepatocellular injury in chronic inflammatory liver disease is still unclear. Several pieces of circumstantial evidence point to the importance of antigen-specific immune responses. In chronic hepatitis B virus infection, the hepatitis B virus nucleoprotein appears to be a major target antigen for both helper and cytotoxic T lymphocytes. In autoimmune chronic active hepatitis, several autoantibodies have been identified that are associated with different disease subgroups and that may be helpful to distinguish this form of chronic active hepatitis from that caused by non-A, non-B agents. In primary biliary cirrhosis, antimitochondrial antibodies are almost invariably present and have now been characterized at the molecular level
Elimination of hepatitis C in Europe: can WHO targets be achieved?
No full textBackground: Chronic hepatitis C virus (HCV) infection affects 71 million people worldwide. The availability of highly efficient direct-acting antivirals has revolutionized the treatment landscape with over 95% cure rates. The WHO has launched a global programme to achieve rather ambitious HCV elimination targets for 2030. Objectives: This article aims to provide a critical overview of the current HCV elimination programmes in Europe highlighting the elements that should be implemented to achieve elimination and those that are already in place to promote this process. Sources: Review of the recently published literature and opinion of experts in the field. Content: Elimination of hepatitis C as a public health threat appears to be a difficult task, which should be subdivided into smaller targets, the so-called micro-elimination goals, to increase chances of success. Macro-elimination strategies based on mass-screening are difficult to implement. Evidence supporting the efficacy of micro-elimination comes from key populations, such as people who inject drugs. HCV elimination is proceeding at different speeds in Europe. Some countries are on target with the WHO's objectives whereas others lack economic support and political advocacy, and have insufficient infrastructures to achieve this. The absence of an effective prophylactic vaccine is hampering the process and should be overcome. Implications: Elimination of hepatitis C worldwide appears plausible, but in several countries probably not within the time frame suggested by the WHO. In the absence of vaccination, universal access to HCV treatment would act as a ‘therapeutic’ option to reduce transmission, especially in high-risk populations
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