Liver Safety Assessment in Special Populations (Hepatitis B, C, and Oncology Trials)

Abstract The FDA guidance for industry in the premarketing clinical evaluation of drug-induced liver injury (DILI) is the most specific regulatory guidance currently available and has been useful in setting standards for the great majority of clinical indications involving subjects with a low risk of liver disorders. However, liver safety assessment faces challenges in populations with underlying liver disease, such as viral hepatitis or metastatic cancer. This is an important issue because there are currently many promising anti-viral and oncologic therapies in clinical development, with a trend toward oral therapies with reduced side effects. Without clearer guidelines, questions regarding liver safety may become a major factor in regulatory approval and ultimately physician uptake of the new treatments. The lack of consensus in defining stopping rules based on serum alanine aminotransferase (ALT) levels underscores the need for precompetitive data sharing to improve our understanding of DILI in these populations and to allow evidence-based rather than empirical definition of stopping rules. A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials.
Source: Drug Safety - Category: Drugs & Pharmacology Source Type: research

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Basel, 18 September 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the European Medicines Agency ’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Tecentriq® (atezolizumab) in combination with Avastin® (bevacizumab) for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have not received prior systemi c therapy. Based on this recommendation, a final decision regarding approval of Tecentriq in combination with Avastin in this disease setting, along with the full details of the approved indication, is expe...
Source: Roche Investor Update - Category: Pharmaceuticals Source Type: news
Conclusion: In conclusion, Baishouwu extract exhibited potent effect on the development of HCC by altering TLR4/MyD88/ NF-κB signaling pathway in the sequence of hepatic inflammation-fibrosis-cancer, which provided novel insights into the mechanism of Baishouwu extract as a candidate for the pretreatment of HCC in the future. Introduction Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third cause of cancer-related deaths (Jemal et al., 2011). Chronic inflammation, caused by chemical, biological and physical factors, is found to be related to certain human cancers. The effe...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
AbstractThe treatment of patients with chronic hepatitis C virus (HCV) infection has changed tremendously over the past 2  years, with an increasing variety of all-oral direct-acting antiviral (DAA) treatment regimens available for different HCV genotypes and distinct clinical settings. These treatments have significantly improved safety in patients with advanced liver disease compared with interferon (IFN)-based regi mens. HCV modifies the human immune system to escape immunosurveillance via several mechanisms. One of the basic mechanisms of HCV is the ability to “switch” the immune response by reducing t...
Source: Archivum Immunologiae et Therapiae Experimentalis - Category: Allergy & Immunology Source Type: research
Conclusion: Marked reduction in liver disease mortality by widespread use of antiviral treatments against HBV may increase the life expectancy and number of patients at risk of developing liver cancer, inadvertently leading to increased burden of liver cancer in a HBV‐endemic population. The competing nature between death from liver disease and that from liver cancer should be carefully considered in establishing a health care policy. This article is protected by copyright. All rights reserved.
Source: Hepatology - Category: Internal Medicine Authors: Tags: Viral Hepatitis Source Type: research
Background: Periodontal disease, a common disorder of the tissue surrounding and supporting the teeth, is a major cause of tooth loss in adults. Periodontal infection by oral microorganisms may have systemic effects and has been associated with several types of cancer. However, its association with liver cancer has only been examined in two prospective studies, both of which had very small number of liver cancer cases (n
Source: Cancer Epidemiology Biomarkers and Prevention - Category: Cancer & Oncology Authors: Tags: Improving Cancer Risk Prediction for Prevention and Early Detection: Poster Presentations - Proffered Abstracts Source Type: research
Non‑infective occupational risk factors for hepatocellular carcinoma: A review (Review). Mol Med Rep. 2016 Dec 14;: Authors: Ledda C, Loreto C, Zammit C, Marconi A, Fago L, Matera S, Costanzo V, Fuccio Sanzà G, Palmucci S, Ferrante M, Costa C, Fenga C, Biondi A, Pomara C, Rapisarda V Abstract Liver cancer is the second leading worldwide cause of cancer‑associated mortalities. Hepatocellular carcinoma, which accounts for the majority of liver tumors, ranks fifth among types of human cancer. Well‑established risk factors for liver cancer include the hepatitis B and C viruses, aflatoxins, alc...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
ConclusionsLong‐term viral suppression with nucleoside analogues leads to HBsAg loss in a substantial proportion of patients, particularly if HBeAg‐negative. Serious outcomes during the first 10–20 years of treatment occur largely among patients with pre‐existing cirrhosis who do not clear HBsAg with therapy.
Source: Alimentary Pharmacology and Therapeutics - Category: Drugs & Pharmacology Authors: Tags: Original Article Source Type: research
ConclusionsLong‐term viral suppression with nucleoside analogues leads to HBsAg loss in a substantial proportion of patients, particularly if HBeAg‐negative. Serious outcomes during the first 10–20 years of treatment occur largely among patients with pre‐existing cirrhosis who do not clear HBsAg with therapy.
Source: Alimentary Pharmacology and Therapeutics - Category: Drugs & Pharmacology Authors: Tags: Original Article Source Type: research
Abstract Although a considerable number of studies have been undertaken to date, it is still controversial as to whether or not coinfection with schistosomiasis increases the susceptibility to or progression from Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection. This review is a closer examination of the key studies conducted on human populations on clinical factors that were published in English between 1975 and January 2015. Our review is mainly based on tables containing the salient information, which are arranged first by study population, country of study and publication date. We provide further e...
Source: Advances in Parasitology - Category: Parasitology Authors: Tags: Adv Parasitol Source Type: research
Conclusions The high rate of detectable HPV DNA by oncogenic types suggests that periodic cytological screening and clinical evaluation may be necessary since transsexuals are at high risk of anogenital cancer. Also promoting HPV vaccination in younger subjects may be advisable.
Source: Sexually Transmitted Infections - Category: Sexual Medicine Authors: Tags: Liver disease, Drugs: infectious diseases, Hepatitis and other GI infections, HIV/AIDS, Vaccination / immunisation, Screening (oncology), Sexual and gender disorders, Hepatitis (sexual health), HIV / AIDS, Sexual and gender disorders, Syphilis, HIV infect Source Type: research
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