Hepatocellular Carcinoma and Antiviral Therapies in HCV Chronic Infection

The development of direct-acting antiviral (DAA) therapies in chronic HCV infection has been associated with increased expectations regarding the prognosis of this infection in the medical community, as the possibility of HCV eradication is now in sight. While the cure of the HVC infection has been associated with a dramatic decrease in its systemic complications, the impact on the progression of the liver disease, especially in patients with cirrhosis, is still controversial. Furthermore, the risk of developing hepatocellular carcinoma (HCC) after direct-acting antiviral therapy is debatable, with studies presenting an increased prevalence of HCC early after the introduction of these therapies, as well as newer contradicting studies. This chapter aims to examine the current literature data available regarding the impact of new HCV therapies in the incidence and prognosis of hepatocellular carcinoma

The impact of improving hepatitis B and C antiviral therapy on hepatocellular carcinoma

Background Hepatocellular carcinoma (HCC) is the commonest primary liver cancer, and is one of the leading causes of cancer related death worldwide. Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are the major aetiologies of HCC. The improving HBV and HCV antiviral therapies may have played an impact on the incidence and survival of HCC. Aims This PhD thesis aimed to evaluate: 1. The incidence of HCC in HBV infected population and risk factors associated with HCC incidence; 2. Comparison of HBV antiviral treatments on HCC incidence, and risk factors associated with HCC incidence; 3. Effectiveness of HCV direct-acting antiviral agents (DAAs) in patients with HCC; 4. Survival of HCV-related HCC, and the factors associated with survival. Methods Chapter 4 is a systematic review and meta-analysis using published data captured from bibliographic and conference databases; Chapter 2, 3 and 5 are populational studies using New South Wales administrative databases of HBV and HCV notifications (1993-2007), HCC diagnosis (2001-2008), HBV, HCV and HCC treatments (2001-2018), HIV notifications (1994-2017), and mortality (1993-2018) to assess the incidence and survival of HCC among individuals with an HBV or HCV notification and a diagnosis of HCC. Results The incidence of HBV related HCC in overall HBV population showed a decline; HBV antiviral treatment regimens showed no significant differential effect on HCC incidence; male, older age, and decompensated cirrhosis were associated with an increased risk of HBV related HCC; the survival following HCC diagnosis in HCV infected population has improved in the DAA era, curative HCC management and DAA treatment were the strongest predictors of an improved survival, while male, older age, and decompensated cirrhosis exhibited association with a decreased survival; DAA treatment effect in terms of sustained virologic response (SVR) decreased in patients with HCV related HCC but remained reasonably high; SVR was particularly lower in patients with genotype 3 HCV infection, patients who received suboptimal DAA regimens, and patients who had active HCC. Conclusion The incidence of HBV related HCC has shown a decline over the study period; current HBV antiviral treatment options (entecavir and tenofovir) had similar effectiveness in attenuating the risk of HCC; the survival of HCV related HCC has improved in the DAA era; DAA treatment was safe and efficacious in patients with HCC, despite a lower SVR rate than in patients without HCC

2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.ope

New Therapies of Liver Diseases

In this Special Issue of the journal, advancements in the treatment of liver diseases are illustrated by international experts in the field. New treatment options for primary biliary cirrhosis and, hopefully, primary sclerosing cholangitis are discussed. Up-to-date pharmacological therapy for preventing liver cirrhosis decompensation and treating acute-on-chronic liver failure is highlighted. Furthermore, new treatments for cholangiocarcinoma, based on biological and tissue markers, will be available in the near future, aiming to surpass the current unsatisfactory results of traditional therapies. Immunotherapy has been applied to hepatocellular carcinoma (HCC). The new first-line treatment, combining atezolizumab plus bevacizumab for HCC in the intermediate and advanced stages, will allow for an increase in patient survival in the near future. Liver transplantation (LT) remains the preferred treatment for many patients with end-stage liver diseases and HCC. The selection criteria for LT in patients with HCC moved from morphological to dynamic criteria, such as those derived from the assessment of tumor responses to locoregional and/or systemic treatments before transplantation. This allowed many patients who would have been excluded from a transplantation with the old selection criteria to access one. Finally, a very interesting issue regarding new indications for liver transplantation is illustrated

Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV

Developed by the National Institutes of Health, the Centers for Disease Control and Prevention, and the HIV Medicine Association of the Infectious Diseases Society of America Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV\u2014A Working Group of the NIH Office of AIDS Research Advisory Council (OARAC).The Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV document is published in an electronic format and updated as relevant changes in prevention and treatment recommendations occur.All changes are developed by the subject-matter groups listed in the document. (Changes in group composition also are posted promptly.) These changes are reviewed by the editors and by relevant outside reviewers before the document is altered.How to Cite the Adult and Adolescent Opportunistic Infection Guidelines: Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Available at https://clinicalinfo.hiv.gov/en/guidelines/adult-and- adolescent-opportunistic-infection. Accessed (insert date) [include page numbers, table number, etc., if applicable].Publication date from document properties.guidelines-adult-adolescent-oi.pd

Efectividad y seguridad a largo plazo de los antivirales de acción directa en pacientes con hepatitis C crónica de un hospital terciario

La hepatitis crónica por virus hepatitis C (VHC) constituye un problema de salud de primer nivel, con 71 millones de personas afectadas, responsable de una importante morbimortalidad hepática y extrahepática. La infección por el VHC puede progresar a enfermedad hepática avanzada, cirrosis y carcinoma hepatocelular (CHC).El tratamiento para la infección por VHC ha cambiado radicalmente en los últimos años debido a la aparición de fármacos antivirales de acción directa (AAD) de segunda generación que se combinan entre sí y actúan sobre diferentes dianas terapéuticas claves para la replicación del virus, consiguiéndose tasas de respuesta viral sostenida (RVS) superiores al 95% en la mayor parte de los pacientes. Son regímenes de tratamiento de corta duración, administrados por vía oral y con escasos efectos adversos asociados, lo que se traduce en mayor comodidad y adherencia al tratamiento por parte de los pacientes.Después del tratamiento con AAD se espera la erradicación del virus y la mejora de la función hepática, grado de fibrosis y disminución de riesgo de desarrollo de CHC y otros tumores extrahepáticos.

Ultrasound Elastography

Elastography, the science of creating noninvasive images of mechanical characteristics of tissues, has been rapidly evolving in recent years. The advantage of this technique resides in the ability to rapidly detect and quantify the changes in the stiffness of soft tissues resulting from specific pathological or physiological processes. Ultrasound elastography is nowadays applied especially on the liver and breast, but the technique has been increasingly used for other tissues including the thyroid, lymph nodes, spleen, pancreas, gastrointestinal tract, kidney, prostate, and the musculoskeletal and vascular systems. This book presents some of the applications of strain and shear-wave ultrasound elastography in hepatic, pancreatic, breast, and musculoskeletal conditions

Characterising Mer and Axl receptor tyrosine kinase expression and transcriptomic profiling of myeloid cells in hepatocellular carcinoma

Background: TAM receptor tyrosine kinases attenuate pro-inflammatory signalling in myeloid cells and maintain tissue homeostasis through apoptotic cell clearance (efferocytosis). Two members of the TAM-RTK family, MerTK and Axl, are overexpressed in human cancers; MerTK+ macrophages display a regulatory phenotype (M2c) similar to tumour associated macrophages (TAMs). MerTK+ and Axl+ macrophages contribute to immune paresis in liver disease. Little is known about MerTK and Axl expressing myeloid cells in HCC. In this thesis I characterise their expression and phenotype in circulating and tissue-resident myeloid cells, explore drivers for their expansion and function in vitro and utilise transcriptomics to interrogate wider TAM phenotype in human HCC. Methods: Tissue and blood were collected from patients undergoing surgery or awaiting treatment for HCC. TAM-RTK expressing myeloid cells were identified using immunohistochemistry. Flow cytometry of isolated immune cell populations was utilised to understand their abundance and phenotype; in vitro conditioning and co-culture experiments were devised to recapitulate the tumour microenvironment, identify potential drivers for MerTK and Axl expression and assay their function. Serum and tissue homogenates were analysed for levels of TAM-RTK ligands. Transcriptomic analysis of tumour and liver derived myeloid cells was undertaken. Results: MerTK+ macrophages are evident within inflammatory infiltrates in HCC. There is modest expansion of myeloid cells expressing MerTK and Axl in the tumour microenvironment, however gene expression is not upregulated and neither are downstream signalling cascades. In vitro conditioning does stimulate Axl but not MerTK expression and promotes immune-regulatory cytokine production. TAMs exhibit a ‘post-phagocytic’ phenotype with upregulation of C1Q, scavenger receptor Stabilin-1 and APOE. Conclusions: TAM-RTK signalling is not activated within the tumour microenvironment. Transcriptomic analysis has identified an immune regulatory post-phagocytic and efferocytotic phenotype; further work is needed to evaluate the significance of this in the tumour biology of HCC, if it is not mediated through MerTK and Axl signalling.Open Acces