Interpreting liver stiffness in the cirrhotic range: What are we measuring?

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Wone-Watch Extension

Projecte wonewatch extension. El proyecto trata de crear un sistema de para monitorización y configuración de elementos de una red óptica

Extrahepatic manifestations associated with Chronic Hepatitis C Virus Infection

Chronic hepatitis C virus (HCV) infection has been associated with both organ-specific and systemic autoimmune diseases, with cryoglobulinemia being the most frequent associated disease. Experimental, virologic, and clinical evidence have demon-strated a close association between HCV infection and some systemic autoimmune diseases, especially Sjögren's syndrome, but also rheumatoid arthritis and lupus. A higher prevalence of hematological processes has also been described in patients with HCV infection, including cytopenias and lymphoproliferative disorders (B-cell lymphoma). In addition, patients with chronic HCV infection have a higher frequency of other extrahepatic manifestations including endocrine, metabolic and cardiovascular disorders that may worse the prognosis of patients, along with neuropsychiatric manifestations and general symptoms that have a significant influence on the quality of life of the patient. Direct-acting antiviral therapies (DAAs) that have recently begun to be used are providing the opportunity to effectively cure chronic HCV infection and reduce the burden of both hepatic and extrahepatic complications

A Gaussia luciferase cell-based system to assess the infection of cell culture- and serum-derived hepatitis C virus

Robust replication of hepatitis C virus (HCV) in cell culture occurs only with the JFH-1 (genotype 2a) recombinant genome. The aim of this study was to develop a system for HCV infection quantification analysis and apply it for the selection of patient sera that may contain cell culture infectious viruses, particularly of the most clinically important genotype 1. Initially, a hepatoma cell line (designated Huh-7.5/EG(4A/4B)GLuc) was generated that stably expressed the enhanced green fluorescent protein (EGFP) fused in-frame to the secreted Gaussia luciferase via a recognition sequence of the viral NS3/4A protease. Upon HCV infection, NS3/4A cleaved at its signal and the Gaussia was secreted to the culture medium, thus facilitating the infection quantification. The Huh-7.5/EG(4A/4B)GLuc cell line provided a rapid and highly sensitive quantification of HCV infection in cell culture using JFH-1-derived viruses. Furthermore, the Huh-7.5/EG(4A/4B)GLuc cells were also shown to be a suitable host for the discovery of anti-HCV inhibitors by using known compounds that target distinct stages of the HCV life cycle; the Ź-factor of this assay ranged from 0.72 to 0.75. Additionally, eighty-six sera derived from HCV genotype 1b infected liver transplant recipients were screened for their in vitro infection and replication potential. Approximately 12% of the sera contained in vitro replication-competent viruses, as deduced by the Gaussia signal, real time quantitative PCR, immunofluorescence and capsid protein secretion. We conclude that the Huh-7.5/EG(4A/4B)GLuc cell line is an excellent system not only for the screening of in vitro replication-competent serum-derived viruses, but also for the subsequent cloning of recombinant isolates. Additionally, it can be utilized for high-throughput screening of antiviral compounds

Incidence of depression in patients with hepatitis C treated with direct-acting antivirals

Depression has been associated with hepatitis C, as well as with its treatment with proinflammatory cytokines (i.e., interferon). The new direct-acting antiviral agents (DAAs) have minimal adverse effects and high potency, with a direct inhibitory effect on non-structural viral proteins. We studied the incidence and associated factors of depression in a real-life prospective cohort of chronic hepatitis C patients treated with the new DAAs. The sample was recruited from a cohort of 91 patients with hepatitis C, of both sexes, with advanced level of fibrosis and no HIV coinfection, consecutively enrolled during a 6-month period for DAA treatment; those euthymic at baseline (n=54) were selected. All were evaluated through the depression module of the Patient Health Questionnaire (PHQ-9-DSM-IV), at three time points: baseline, 4 weeks, and end-of-treatment. The cumulative incidence (95%CI) of major depression and any depressive disorder during DAA treatment was 13% (6.4-24.4) and 46.3% (33.7-59.4), respectively. No differences were observed between those patients with and without cirrhosis or ribavirin treatment (p > 0.05). Risk factors for incident major depression during DAA treatment included family depression (relative risk 9.1 [1.62-51.1]), substance use disorder (11.0 [1.7-73.5]), and baseline PHQ-9 score (2.1 [1.1-3.1]). The findings of this study highlight the importance of screening for new depression among patients receiving new DAAs, and identify potential associated risk factors

Lack of a 5.9 kDa peptide C-terminal fragment of fibrinogen α chain precedes fibrosis progression in patients with liver disease

Early detection of fibrosis progression is of major relevance for the diagnosis and management of patients with liver disease. This study was designed to find non-invasive biomarkers for fibrosis in a clinical context where this process occurs rapidly, HCV-positive patients who underwent liver transplantation (LT). We analyzed 93 LT patients with HCV recurrence, 41 non-LT patients with liver disease showing a fibrosis stage F≥1 and 9 patients without HCV recurrence who received antiviral treatment before LT, as control group. Blood obtained from 16 healthy subjects was also analyzed. Serum samples were fractionated by ion exchange chromatography and their proteomic profile was analyzed by SELDI-TOF-MS. Characterization of the peptide of interest was performed by ion chromatography and electrophoresis, followed by tandem mass spectrometry identification. Marked differences were observed between the serum proteome profile of LT patients with early fibrosis recurrence and non-recurrent LT patients. A robust peak intensity located at 5905 m/z was the distinguishing feature of non-recurrent LT patients. However, the same peak was barely detected in recurrent LT patients. Similar results were found when comparing samples of healthy subjects with those of non-LT fibrotic patients, indicating that our findings were not related to either LT or HCV infection. Using tandem mass-spectrometry, we identified the protein peak as a C-terminal fragment of the fibrinogen α chain. Cell culture experiments demonstrated that TGF-β reduces α-fibrinogen mRNA expression and 5905 m/z peak intensity in HepG2 cells, suggesting that TGF-β activity regulates the circulating levels of this protein fragment. In conclusion, we identified a 5.9 kDa C-terminal fragment of the fibrinogen α chain as an early serum biomarker of fibrogenic processes in patients with liver disease

Community-based screening enhances hepatitis B virus linkage to care among West African migrants in Spain

Hepatitis B virus; Community approach; Screening programsVirus de l'hepatitis B; Abordatge comunitari; Programes de deteccióVirus de la hepatitis B; Abordaje comunitario; Programas de detecciónBackground: Chronic infection with HBV is responsible for >50% of all hepatocellular cancer cases globally and disproportionately affects sub-Saharan African (sSA) countries. Migration from these countries to Europe has increased substantially in recent years, posing unique challenges to health systems. The aim of this study was to carry out a community-based intervention to increase HBV screening, vaccination, and linkage to care among sSA migrants in Catalonia, Spain. Methods:This was a prospective cohort study. Participants ≥18 years were offered community-based HBV screening between 20/11/20 and 21/01/22. Rapid HBV testing and blood sample collection utilizing plasma separation cards were carried out and linkage to care was offered to all participants. HBV vaccination and post-test counseling were performed at a second visit in the community. The main outcome was the odds of those with current HBV infection being successfully linked to hepatology. Rates of completing the care cascade of this model were analyzed. Results: In the present study, 444 people undergo screening, with 50.6% of participants showing evidence of past or current HBV infection, including an HBsAg prevalence of 9.2%. Migrants with current HBV infection exhibit 5.2 times higher odds of successful linkage to care compared to those in need of post-test counseling or vaccination. The study achieves a successful linkage to care rate of 72% for all participants, with specialist appointments arranged within 15.5 days.Conclusions:This community-based HBV screening program provides evidence of a successful model for identifying and providing care, including vaccination, to west African migrants at high risk of HBV infection who may otherwise not engage in care.Antecedents: La infecció crònica pel VHB és responsable del >50% de tots els casos de càncer hepatocel·lular a nivell mundial i afecta desproporcionadament els països de l'Àfrica subsahariana (SAS). La migració d'aquests països a Europa ha augmentat substancialment en els últims anys, plantejant reptes únics per als sistemes de salut. L'objectiu d'aquest estudi va ser dur a terme una intervenció basada en la comunitat per augmentar la detecció del VHB, la vacunació i la vinculació amb l'atenció entre els migrants de SSA a Catalunya, Espanya. Mètodes: Es tractava d'un estudi de cohort prospectiu. Als participants ≥18 anys se'ls va oferir un cribratge comunitari del VHB entre el 20/11/20 i el 21/01/22. Es van dur a terme proves ràpides de VHB i recollida de mostres de sang mitjançant targetes de separació de plasma i es va oferir vinculació a l'atenció a tots els participants. La vacunació contra el VHB i l'assessorament post-test es van realitzar en una segona visita a la comunitat. El resultat principal van ser les probabilitats que les persones amb infecció actual pel VHB estiguin vinculades amb èxit a l'hepatologia. Es van analitzar les taxes de completar la cascada assistencial d'aquest model. Resultats: En el present estudi, 444 persones se sotmeten a cribratge, amb el 50.6% dels participants que mostren evidència d'infecció passada o actual pel VHB, inclosa una prevalença de VHB del 9.2%. Els migrants amb infecció actual pel VHB presenten 5,2 vegades més probabilitats d'èxit en l'atenció en comparació amb aquells que necessiten assessorament o vacunació post-prova. L'estudi aconsegueix una taxa de vinculació reeixida a l'atenció del 72% per a tots els participants, amb cites amb especialistes concertades en un termini de 15,5 dies. Conclusions: Aquest programa de cribratge del VHB basat en la comunitat proporciona proves d'un model reeixit per identificar i proporcionar atenció, inclosa la vacunació, als migrants de l'Àfrica occidental amb alt risc d'infecció pel VHB que d'altra manera podrien no dedicar-se a l'atenció.C.A.P., J.V.L. and Lv.S. acknowledge support to ISGlobal from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and from the Government of Catalonia through the “CERCA Program”. C.A.P. acknowledges support from the Secretaria d’Universitats i Recerca de la Generalitat de Catalunya and the European Social Fund as an AGAUR-funded PhD fellow. E.M. thanks the CERCA Program/Generalitat de Catalunya for their support to the Germans Trias i Pujol Research Institute (IGTP). This study was carried out by ISGlobal with competitive funding through the Gilead Sciences global HBV-CARE program (IN-ES-988–5799)