Immunotherapies for hepatocellular carcinoma

Nature Reviews Clinical Oncology, Journal Year: 2021, Volume and Issue: 19(3), P. 151 - 172

Published: Nov. 11, 2021

Language: Английский

---

Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

Journal of the National Comprehensive Cancer Network, Journal Year: 2021, Volume and Issue: 19(5), P. 541 - 565

Published: May 1, 2021

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, cancer bile ducts (intrahepatic extrahepatic cholangiocarcinoma). Due to multiple modalities that can be used treat disease complications arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential determining an optimal treatment strategy. A team should include hepatologists, diagnostic radiologists, interventional surgeons, medical oncologists, pathologists with hepatobiliary expertise. In addition surgery, transplant, intra-arterial therapies, there have been great advances in systemic HCC. Until recently, sorafenib was only therapy option patients advanced 2020, combination atezolizumab bevacizumab became first regimen show superior survival sorafenib, gaining it FDA approval as new frontline standard unresectable or metastatic This article discusses recommendations

Language: Английский

---

Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification

Advances in cancer research, Journal Year: 2020, Volume and Issue: unknown, P. 1 - 61

Published: Nov. 28, 2020

Language: Английский

---

Changing global epidemiology of liver cancer from 2010 to 2019: NASH is the fastest growing cause of liver cancer

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(7), P. 969 - 977.e2

Published: June 3, 2022

Language: Английский

---

Global Epidemiology and Genetics of Hepatocellular Carcinoma

Gastroenterology, Journal Year: 2023, Volume and Issue: 164(5), P. 766 - 782

Published: Feb. 2, 2023

Language: Английский

---

Global epidemiology of alcohol-associated cirrhosis and HCC: trends, projections and risk factors

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2022, Volume and Issue: 20(1), P. 37 - 49

Published: Oct. 18, 2022

Heavy alcohol consumption is a major cause of morbidity and mortality. Globally, per-capita rose from 5.5 litres in 2005 to 6.4 2016 projected increase further 7.6 2030. In 2019, an estimated 25% global cirrhosis deaths were associated with alcohol. The age-standardized death rate (ASDR) alcohol-associated was 4.5 per 100,000 population, the highest lowest ASDR Africa Western Pacific, respectively. annual incidence hepatocellular carcinoma (HCC) among patients ranged 0.9% 5.6%. Alcohol approximately one-fifth HCC-related 2019. Between 2012 2017, for declined, but liver cancer increased. Measures are required curb heavy reduce burden HCC. Degree intake, sex, older age, obesity, type 2 diabetes mellitus, gut microbial dysbiosis genetic variants key factors development this Review, we discuss epidemiology, projections risk

Language: Английский

---

Pathophysiological Aspects of Alcohol Metabolism in the Liver

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(11), P. 5717 - 5717

Published: May 27, 2021

Alcoholic liver disease (ALD) is a globally prevalent chronic caused by or binge consumption of alcohol. The the major organ that metabolizes alcohol; therefore, it particularly sensitive to alcohol intake. Metabolites and byproducts generated during metabolism cause damage, leading ALD via several mechanisms, such as impairing lipid metabolism, intensifying inflammatory reactions, inducing fibrosis. Despite severity ALD, development novel treatments has been hampered lack animal models fully mimic human ALD. To overcome current limitations studies therapy development, necessary understand molecular mechanisms underlying alcohol-induced injury. Hence, provide insights into progression this review examines previous conducted on in liver. There particular focus occurrence hepatotoxicity originating from metabolism.

Language: Английский

---

Prevention of NAFLD-associated HCC: Role of lifestyle and chemoprevention

Journal of Hepatology, Journal Year: 2021, Volume and Issue: 75(5), P. 1217 - 1227

Published: July 31, 2021

In many countries worldwide, the burden of hepatocellular carcinoma (HCC) associated with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) is increasing. Preventive strategies are needed to counteract this trend. review, we provide an overview evidence on preventive in NAFLD-associated HCC. We consider impact lifestyle factors such as weight loss, physical activity, smoking, dietary patterns food items, including coffee alcohol, both HCC NAFLD/NASH. Furthermore, chemopreventive treatments, aspirin, antidiabetic treatments statins summarised. The role adjuvant therapies for tertiary prevention briefly reviewed.

Language: Английский

---

ACG Clinical Guideline: Alcohol-Associated Liver Disease

The American Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 119(1), P. 30 - 54

Published: Sept. 1, 2023

ABSTRACT Alcohol-associated liver disease (ALD) is the most common cause of advanced hepatic and frequent indication for transplantation worldwide. With harmful alcohol use as primary risk factor, increasing over past decade has resulted in rapid growth ALD-related healthcare burden. The spectrum ALD ranges from early asymptomatic injury to with decompensation portal hypertension. Compared those other etiologies disease, patients progress faster more often present at an stage. A unique phenotype alcohol-associated hepatitis (AH) presenting onset or worsening jaundice, acute on chronic failure severe forms conveying a 1-month mortality 20%–50%. model end stage score accurate stratify AH severity (>20 defined disease). Corticosteroids are currently only available therapeutic proven efficacy AH, providing survival benefit 1 month 50%–60% patients. Abstinence use, crucial determinant long-term outcomes, challenging achieve concurrent disorder (AUD). As rarely treated AUD, strategies needed overcome barriers AUD treatment promote multidisciplinary integrated care hepatology, addiction medicine providers, social workers comprehensively manage dual pathologies AUD. Liver transplantation, definitive option cirrhosis, should be considered selected who unresponsive medical therapy have low relapse posttransplant use. Level evidence strength recommendations were evaluated using Grading Recommendations, Assessment, Development, Evaluations system. This guideline was developed under American College Gastroenterology Practice Parameters Committee.

Language: Английский

---

Oxidative Stress–Induced Liver Damage and Remodeling of the Liver Vasculature

American Journal Of Pathology, Journal Year: 2023, Volume and Issue: 193(10), P. 1400 - 1414

Published: June 23, 2023

As an organ critically important for targeting and clearing viruses, bacteria, other foreign material, the liver operates via immune-tolerant, anti-inflammatory mechanisms indispensable to immune response. Stress stress-induced factors disrupt homeostatic balance in liver, inflicting tissue damage, injury, remodeling. These include oxidative stress (OS) induced by viral infections, environmental toxins, drugs, alcohol, diet. A recurrent theme seen among stressors common multiple diseases is induction of mitochondrial dysfunction, increased reactive oxygen species expression, depletion ATP. Inflammatory signaling additionally exacerbates condition, generating a proinflammatory, immunosuppressive microenvironment activation apoptotic necrotic that integrity morphology. pathways initiate significantly contribute development steatosis, inflammation, fibrosis, cirrhosis, cancers. In addition, hypoxia OS directly enhance angiogenesis lymphangiogenesis chronic diseases. Late-stage consequences these conditions often narrow outcomes transplantation or result death. This review provides detailed perspective on various specific focus role different with special emphasis molecular mechanisms. It also highlights how resultant changes vasculature correlate pathogenesis. Stress-induced health issues are one major challenges modern society. Stress, which defined "conditions where demand exceeds natural regulatory capacity organism, particular situations unpredictability uncontrollability,"1Koolhaas J.M. Bartolomucci A. Buwalda B. de Boer S.F. Flugge G. Korte S.M. Meerlo P. Murison R. Olivier Palanza Richter-Levin Sgoifo Steimer T. Stiedl O. van Dijk Wohr M. Fuchs E. revisited: critical evaluation concept.Neurosci Biobehav Rev. 2011; 35: 1291-1301Crossref PubMed Scopus (982) Google Scholar can alter normal homeostasis human physiological psychological status.2Vere C.C. Streba C.T. L.M. Ionescu A.G. Sima F. Psychosocial disease status.World J Gastroenterol. 2009; 15: 2980-2986Crossref (65) Scholar,3Joung J.Y. Cho J.H. Kim Y.H. Choi S.H. Son C.G. literature injury.Brain Behav. 2019; 9e01235Crossref (43) Both experimental clinical studies show impacts hepatic physiology contributes Furthermore, it worsen patients cardiovascular diseases, cancer, HIV/AIDS.2Vere Scholar, 3Joung 4Cohen S. Janicki-Deverts D. Miller G.E. Psychological disease.JAMA. 2007; 298: 1685-1687Crossref (1952) Liver, largest solid body, center metabolism detoxification, site complex immunologic activity controlled diverse cells populations, as well nonhematopoietic cells.5Robinson M.W. Harmon C. O'Farrelly Liver immunology its inflammation homeostasis.Cell Mol Immunol. 2016; 13: 267-276Crossref (598) receives digested products, microbial agents, antigens from body through portal vein, elicit cell cause persistent regulated inflammation.6Racanelli V. Rehermann The immunological organ.Hepatology. 2006; 43: S54-S62Crossref (967) Prolonged exposure high-fat diet, hormones causes leading diseases.7Ozkan Stolley Cressman E.N.K. McMillin DeMorrow Yankeelov T.E. Rylander M.N. influence vasculature: liver-on-a-chip review.Micromachines (Basel). 2020; 11: 487Crossref Episodes such physiological, psychological, have negative impact long-term pre-existing conditions, hepatitis B virus (HBV),8Kunkel E.J. J.S. Hann H.W. Oyesanmi Menefee L.A. Field H.L. Lartey P.L. Myers R.E. Depression Korean immigrants related diseases.Psychosomatics. 2000; 41: 472-480Crossref (57) C (HCV),9Nagano J. Nagase Sudo N. Kubo stress, personality, severity C.Psychosomatics. 2004; 45: 100-106Crossref (38) alcoholic hepatitis,10Fukudo Suzuki Tanaka Y. Iwahashi Nomura Impact injury; histopathological study.J Psychosom Res. 1989; 33: 515-521Crossref nonalcoholic steatohepatitis,11Elwing J.E. Lustman P.J. Wang Clouse Depression, anxiety, steatohepatitis.Psychosom Med. 68: 563-569Crossref (100) (OS), endoplasmic reticulum (ER) hepatocellular carcinoma (HCC).12Luna-Marco Ubink Kopsida Heindryckx Endoplasmic carcinoma.Am Pathol. 2023; 193: 1377-1388Abstract Full Text PDF Scholar,13Brahma M.K. Gilglioni E.H. Zhou L. Trepo Chen Gurzov E.N. Oxidative obesity-associated carcinoma: sources, therapeutic challenges.Oncogene. 2021; 40: 5155-5167Crossref (16) stress-mediated damages, both hepatocytes nonparenchymal cells, present vasculature, impacted.7Ozkan current principal contributing damage progression disease. highly vascularized dense network blood vessels, bile ducts, lymphatic vessels. plays transforming toxic substances into form be eliminated. Compared organs has high receive cardiac output, up 25% output at rest.14Abdel-Misih S.R. Bloomston anatomy.Surg Clin North Am. 2010; 90: 643-653Abstract (179) first nutrient-rich intestines participates response.15Gibert-Ramos Sanfeliu-Redondo Aristu-Zabalza Martinez-Alcocer Gracia-Sancho Guixe-Muntet Fernandez-Iglesias sinusoid disease: optimal milieu cancer.Cancers 5719Crossref (4) unique because superimposition two inlet networks (ie, artery vein), running parallel; outlet composed central veins, veins.16Lorente Hautefeuille Sanchez-Cedillo functionalized vascular structure.Sci Rep. 1016194Crossref (28) vein play maintaining supply liver. divided hexagonal lobules, consist triads, resident cells. triad artery, ducts7Ozkan Scholar,17Fleischer J.R. Jodszuweit C.A. Ghadimi De Oliveira Conradi L.C. Vascular heterogeneity microenvironment.Front Physiol. 11591901Crossref (Figure 1). collects digestive tract, pancreas, spleen, approximately 75% liver's supply, whereas remaining supplied artery. venous mixes oxygenated flows sinusoid, microvascular bed sinusoids send vein.7Ozkan sinusoidal endothelial (LSECs) morphologically functionally they clustered fenestrations sieve plates,16Lorente discontinuous arrangement, lack typical basement membrane, attenuated extracellular matrix fibronectin component.18Xu Broome U. Uzunel Nava Ge X. Kumagai-Braesch Hultenby K. Christensson Ericzon B.G. Holgersson Sumitran-Holgersson Capillarization cell-reactive autoantibodies cirrhosis hepatitis.Am 2003; 163: 1275-1289Abstract adult length 250 μm, their diameter varies between 7 15 μm.19Vollmar Menger M.D. microcirculation: mechanistic contributions targets injury repair.Physiol 89: 1269-1339Crossref (368) Under arrangement LSECs facilitates exchange large molecules pathogens blood.18Xu Bile ducts carry gallbladder direction opposite sinusoids.20Du Khandekar Llewellyn Polacheck W. C.S. Wells R.G. duct-on-a-chip organ-level functions.Hepatology. 71: 1350-1363Crossref (41) Along system maintenance fluid homeostasis, response.21Burchill M.A. Goldberg A.R. Tamburini B.A.J. Emerging roles lymphatics disease.Front 10: 1579Crossref (11) Scholar,22Roy Banerjee Ekser Bayless Zawieja Alpini Glaser S.S. Chakraborty Targeting lymph node metastasis cancer.Am 191: 2052-2063Abstract (0) Recent murine models organized segmentally, intrahepatic vessels populated around triad.23Frenkel N.C. Poghosyan Verheem Padera T.P. Rinkes I. Kranenburg Hagendoorn drainage patterns follow segmental anatomy model.Sci 1021808Crossref Lymphatic capillaries, thin-walled single layered (LECs), collect lymph, rich cellular proteins, lipoproteins, lymphocytes, drain collecting Collecting unlike covered muscle pump nodes.21Burchill Scholar,24Tanaka Iwakiri system: structure, function, markers, lymphangiogenesis.Cell Gastroenterol Hepatol. 2: 733-749Abstract About 70% 80% parenchymal hepatocytes. Hepatocytes crucial metabolism, innate regulation, protein synthesis, secretion circulation.25Schulze R.J. Schott M.B. Casey Tuma McNiven biology hepatocyte: membrane trafficking machine.J Cell Biol. 218: 2096-2112Crossref (80) Scholar,26Zhou Z. Xu M.J. Gao Hepatocytes: key type immunity.Cell 301-315Crossref (247) main proteins secreted α-fetoprotein, serum albumin, transferrin, plasminogen, fibrinogen, α-1-antitrypsin, C-reactive protein, clotting (except factor VIII).25Schulze initiation acid (BA) then transported canaliculi. BAs take part emulsification, digestion dietary fats, removal metabolic wastes.25Schulze series ductules eventually transferred stored there until being hormonally stimulated released intestines. However, retained impaired toxicity.27Fang Han S.I. Mitchell Gupta Studer Grant Hylemon P.B. Dent acids induce ROS, promote receptor tyrosine kinases rat hepatocytes.Hepatology. 961-971Crossref (106) pathologic enhanced level BAs, deoxycholic acids, taurodeoxycholic (ROS) production, which, turn, activates downstream signal-regulated kinase 1/2 AKT pathways.27Fang ROS-mediated damage. High ROS stimulates hypertonicity, release cytochrome c hepatocyte apoptosis.28Wei Ma Zhao Mechanism hydrophobic acid-induced drug discovery.Front Pharmacol. 1084Crossref (26) three-dimensional duct, biliary tree, lined heterogeneous, dynamic population epithelial cholangiocytes, represent only 3% 5% total population.29Banales Huebert R.C. Karlsen Strazzabosco LaRusso N.F. Gores G.J. Cholangiocyte pathobiology.Nat Rev 16: 269-281Crossref (237) cholangiocytes responsible 30% flow humans, produced hepatocytes.29Banales Cholangiocytes activated several stimuli, xenobiotic cholestasis, ischemia, OS. Activated altered proliferation secrete variety profibrotic proinflammatory factors.29Banales Scholar,30Ostrycharz Wasik Kempinska-Podhorodecka Banales Milkiewicz Melatonin protects proapoptotic stimuli miR-132 miR-34.Int Sci. 21: 9667Crossref (13) Hepatic stellate (HSCs), 10% liver-specific fibroblasts reside space Disse, healthy HSCs primary storage sites vitamin A.15Gibert-Ramos case get activated, differentiate myofibroblasts, produce components, fibrosis Interestingly, plethora cytokines chemokines, monocyte chemoattractant 1, IL-6, growth factor-β, enable leukocyte recruitment Recruited leukocytes response further HSCs.31Winau Quack Darmoise Kaufmann Starring immunology.Curr Opin 2008; 20: 68-74Crossref (70) OS, activate quiescent long run, HCC.32Ramos-Tovar Muriel Molecular link liver.Antioxidants 9: 1279Crossref (99) Kupffer (KCs) macrophages adherent wall KCs serves line defense against bacterial infection host response.33Fox E.S. Thomas Broitman S.A. Comparative endotoxin uptake isolated peritoneal cells.Infect Immun. 1987; 55: 2962-2966Crossref 34Bilzer Roggel Gerbes A.L. Role disease.Liver Int. 26: 1175-1186Crossref (651) 35Bleriot Dupuis Jouvion Eberl Disson Lecuit Liver-resident macrophage necroptosis orchestrates 1 microbicidal type-2-mediated repair during infection.Immunity. 2015; 42: 145-158Abstract (309) differentiated M1-like (classic) M2-like (alternative) macrophages. sources cytokines, damage.36Liu Tao Q. Sun Wu J.Z. Yang Jian Peng Hu Liu associated apoptosis, fibrotic effects rats.Lab Invest. 1805-1816Abstract (109) Scholar,37Zhang Zhu X.D. H.C. Xiong Y.Q. Zhuang P.Y. H.X. Kong L.Q. W.Z. Tang Z.Y. Depletion tumor-associated enhances effect sorafenib metastatic cancer antimetastatic antiangiogenic effects.Clin Cancer 3420-3430Crossref (313) oxidized low-density lipoprotein, lipopolysaccharide, infiltrating NADPH oxidase 2 (Nox2), stimulate [eg, tumor necrosis (TNF)-α, IL-1β].38Kim S.Y. Jeong S.J. Seo M.H. W.M. Yoo Lee Shim Y.R. Yi H.S. Y.S. Eun B.S. Chun Kang S.C. Kunos H.M. W.I. Pro-inflammatory generate endocytosis monomeric TLR4-MD2 complex.Nat Commun. 2017; 8: 2247Crossref (147) specialized interface lumen contrast display clusters plates.39Wisse Zanger R.B. Charels Van Der Smissen McCuskey R.S. sieve: considerations concerning structure function fenestrae, Disse.Hepatology. 1985; 5: 683-692Crossref (581) Because permeable membrane.40Braet Wisse Structural functional aspects fenestrae: review.Comp 2002; 1: 1Crossref (572) selectively control diffusion substrate Disse.41Poisson Lemoinne Boulanger Durand Moreau Valla Rautou P.E. cells: diseases.J 66: 212-227Abstract (549) Scholar,42Geraud Evdokimov Straub B.K. Peitsch W.K. Demory Dorflinger Schledzewski Schmieder Schemmer Augustin H.G. Schirmacher Goerdt Unique type-specific junctional complexes endothelium sinusoids.PLoS One. 2012; 7e34206Crossref (48) phenotypes maintained factor-A (VEGF-A) stimulation nitric oxide–dependent oxide–independent signaling.43Xie Atkinson R.D. Kanel G.C. Gaarde W.A. Deleve L.D. differentiation regression rats.Gastroenterology. 142: 918-927.e6Abstract (259) keep quiescent. source fibrillar collagens components scar.44Wells Cellular fibrosis.Clin Dis. 12 (viii): 759-768Abstract (146) Scholar,45Kisseleva Brenner regression.Nat 18: 151-166Crossref (594) diseased damaged factor-β hepatocytes, damage.7Ozkan Scholar,34Bilzer lymph-producing system.46Tanaka Lymphatics liver.Curr 2018; 53: 137-142Crossref plasma component filtered fenestrae Disse. mall, enters interstitial triad, finally capillaries.24Tanaka primarily located nearby draining nodes outside liver.47Ohtani Ohtani Lymph circulation liver.Anat Rec (Hoboken). 291: 643-652Crossref (138) Inside LECs, identified markers vessel hyaluronan (Lyve-1), prospero homeobox (Prox1), podoplanin, absence α-smooth actin–positive (smooth cells/pericytes). express Lyve-1, Prox1.48Truman Bentley K.L. Smith E.C. Massaro Gonzalez D.G. Haberman A.M. Hill Jones Min Krause D.S. Ruddle N.H. ProxTom reporter mice reveal Prox1 expression adrenal medulla, megakaryocytes, platelets.Am 180: 1715-1725Abstract Thus, co-existence above three identifies LECs. livers, LECs required maintain fat cholesterol scavenger class I.49Lim H.Y. Thiam C.H. Yeo K.P. Bisoendial Hii McGrath K.C. Tan K.W. Heather Alexander Angeli essential peripheral tissues SR-BI-mediated transport HDL.Cell Metab. 2013; 17: 671-684Abstract (217) Scholar,50Martel Randolph Atherosclerosis transit HDL vasculature.Curr Atheroscler 354Crossref (22) Several report that, under production increases expansion lymphangiogenesis.24Tanaka Scholar,51Banerjee Kumaravel Roy Gaddam Odeh K.J. Conjugated modulation species-p90RSK-vascular 3 pathway.Cells. 12: 526Crossref 52Singla Aithabathula R.V. Kiran Kapil Kumar Singh U.P. Reactive regulating function.Cells. 2022; 1750Crossref Schola

Language: Английский

---