cord-000083-3p81yr4n	2009	R. China Background: The objective of this study was to evaluate the early virologic response for prediction of achievement of HBeAg seroconversion and hepatitis B virus (HBV) DNA negativity after two years of lamivudine treatment in chronic hepatitis B (CHB) patients. Methods: A total of 620 patients who tested positive for hepatitis B surface antigen and were referred to Chiba University Hospital between February 1985 and March 2008 were included in the study, and their following characteristics were analyzed: age, gender, the status of HBeAg, ALT, HBV-DNA level, and PLT. Methods: A total of 60 patients with chronic hepatitis B, 32 (53.3%) were HBeAg positive (group A) while 28(46.7%) were HBeAg negative (group B) were included in this study after meeting the following criteria: age 18 to 60 years, HBsAg positive for more than 6 months, serum HBV-DNA was >5 log(10) copies/mL and ALT more than two times the upper normal limit.
cord-001567-3bw7jbzq	2015	title: Proteome mapping of epidermal growth factor induced hepatocellular carcinomas identifies novel cell metabolism targets and mitogen activated protein kinase signalling events Importantly, 11 out of 54 mouse tumour specific proteins were likewise uniquely expressed in human HCC and 49 disease regulated proteins identified in EGF induced liver cancer were similarly regulated in human HCC, as determined by immunhistochemistry using different antibodies and the information given in the publically available Human Protein Atlas depository. Likewise, the genes coding for igals3, i.e. a beta-galactoside-binding protein frequently overexpressed in cancers and pcbp1 that is involved in transcription and functions as an inhibitor of invasion [65] were up-regulated in transgenic nontumour livers (ur-Tr-nT) whereas transcript expression of aars, a member of tRNA synthases and anaxa6, a calcium-dependent, phospholipid-binding protein with important roles in the tumour microenvironment and metastasis were repressed (dr-Tr-nT).
cord-002272-c7f1l13s	2016	title: Macrophage colony-stimulating factor (CSF1) controls monocyte production and maturation and the steady-state size of the liver in pigs Combined with earlier data from the mouse, this study supports the existence of a CSF1-dependent feedback loop, linking macrophages of the liver with bone marrow and blood monocytes, to mediate homeostatic control of the size of the liver. The expected increase in half-life was confirmed, and CSF1-Fc administration to mice produced substantial increases in circulating monocyte and tissue macrophage numbers, at much lower doses than the native protein. Cluster 2 (Fig. 9B) , the set of genes reduced in the CSF1-Fc-treated pigs, most likely reflects the functional zonation of the liver between periportal and perivenous regions of liver lobules (8, 19, 48) and the selective proliferation of cells derived from portal progenitors that has been observed in regenerating liver (15, 34, 36) .
cord-003921-8r8z0otz	2019	PURPOSE OF REVIEW: Hepatic ischemia-reperfusion injury (IRI), an inevitable event during liver transplantation, represents a major risk factor for the primary graft dysfunction as well as the development of acute and chronic rejection. In IRI-LT pathophysiology, both Kupffer cells (donor-origin) and liver-infiltrating bone marrow-derived macrophages (recipient-origin) play dominant roles in priming innate immune responses [9] [10] [11] , with the majority of studies focusing on macrophage regulation [12, 13] . Indeed, hepatocyte-specific HMGB1 deficient mice showed decreased hepatic necrosis and neutrophil accumulation, whereas the number of their macrophages remained unchanged in acetaminophen-induced liver injury model [28] . In addition, CXCL1 blocking antibody alleviated hepatic infiltration in necrotic cellinduced neutrophil mobilization model [31] , whereas in a carbon tetrachloride (CCl4)-induced acute liver injury, defective CXCL2 expression in TLR2-knockout or S100A9-knockout mice was accompanied by suppressed hepatic neutrophil recruitment [32] . CD4 T cells promote tissue inflammation via CD40 signaling without de novo activation in a murine model of liver ischemia/reperfusion injury
cord-005892-3yuznrdv	2017	Acute-on-chronic liver failure (ACLF) is an emerging clinical syndrome in patients with underlying liver disease that is usually triggered by one or multiple insults and characterized by progressive hepatic and nonhepatic organ failure, a significant risk of infections, and high short-term mortality rates. Im Rahmen dieses ärztlichen Entscheidungsprozesses müssen neben der unmittelbaren Schwere der Erkrankung beispielsweise auch der mutmaßliche Patientenwunsch, jeweilige lokale und nationale Überlebensraten, eine potenzielle Reversibilität der Or-Das akut-auf-chronische Leberversagen als diagnostische und therapeutische Herausforderung der Intensivmedizin Zusammenfassung Das akut-auf-chronische Leberversagen ("acute-on-chronic liver failure", ACLF) ist ein emergentes Krankheitssyndrom, das durch einen oder mehrere akute Trigger bei vorgeschädigter Leber ausgelöst wird und vom progressiven hepatalen und nichthepatalen Organversagen, einem gravierenden Risiko infektiöser Komplikationen sowie hoher kurzfristiger Letalität gekennzeichnet ist. Leberversagen · Zirrhose · Infektion · Organversagen · Transplantation Acute-on-chronic liver failure: a diagnostic and therapeutic challenge for intensive care Abstract Acute-on-chronic liver failure (ACLF) is an emerging clinical syndrome in patients with underlying liver disease that is usually triggered by one or multiple insults and characterized by progressive hepatic and nonhepatic organ failure, a significant risk of infections, and high short-term mortality rates.
cord-005949-8po9xe5g	2013	Die amerikanische "acute liver failure study group" unterscheidet in Bezug auf die Zeit zwischen dem Auftreten von Koagulopathie und beginnender hepatischer Enzephalopathie weiterhin zwischen dem hyperakuten (<7 Tage), dem akuten (7-28 Tage) und dem subakuten (28 Tage -6 Monate) Leberversagen [9] . Die etablierte Therapie des häufigen paracetamolinduzierten ALV besteht in der intravenösen Gabe von N-Acetylcystein (NAC) in Form eines 72-stündigen Reduktionsschemas (NAC: 150 mg/kg/h für 1 h, dann 12,5 mg/kg/h für 4 h und 6,25 mg/kg/h für 67 h). Interessanterweise wurde in einer prospektiven multizentrischen Studie gezeigt, dass es beim nicht durch Paracetamol bedingtem ALV unter Gabe von NAC zumindest bei Patienten mit niedriggradiger hepatischer Enzephalopathie (°I-II) ebenfalls zu einer Verbesserung des transplantatfreien Überlebens kommt [10] . Hier wurde gezeigt, dass 84% der Patienten mit ALV nach Erhalt einer frühen Transplantation überlebten, während die Überlebensrate ohne Lebertransplantation bei nur 34% lag.
cord-006391-esnsa4u5	1982	In our parallel tests using an excision-sample technique [2] which is considerably more sensitive than the DGHM procedure, we have observed the following mean reductions in the counts of accessible bacteria: iodine in ethanol, 96%; povidone-iodine, 89%; chlorhexidine in ethanol, 88%; iso-propanol, The purpose of this study was to compare radiation injury in Guinea Pig small bowel (1) devoid of contents (2) containing bile (3) containing pancreatic juice. Studies in vitro employing isolated perfused rat pancreas and stomach revealed following results: Mean basal pancreatic somatostatin release in normal, diabetic and transplanted rats were 12___3, 24-t-7, and 17__+4 pg/ml, respectively. As these changes appear closely correlated to the blood glucose levels which show a 30 % decrease at 4 h and progressive restoration towards normal values up to 24 h, attempts have been made to alter the insulin/glucagon ratio by glucose infusion after PH and study its relation to liver regeneration.
cord-009987-biop7gyd	2017	& Thonn., Salvia miltiorrhiza Bunge., Astragalus membranaceus (Fisch.) Bunge, Capparis spinosa (L.), Cichorium intybus (L.), Solanum nigrum (L.), Sapindus mukorossi Gaertn., Ginkgo biloba (L.), Woodfordia fruticosa (L.) Kurz, Vitex trifolia (L.), Schisandra chinensis (Turcz.) Baill., Cuscuta chinensis (Lam.), Lycium barbarum, Angelica sinensis (Oliv.) Diels, and Litsea coreana (H. Herbal medicines are claimed to both treat and prevent diseases, which adds to a deep belief that these Abbreviations: ALT, alanine aminotransaminase; ASP, Angelica sinensis polysaccharides; AST, aspartate transaminase; EGF, epidermal growth factor; HBV, Hepatitis B virus; LBPs, Lycium barbarum polysaccharides; WF4, Woodfordia fruticosa flower extract.
cord-014770-cgtzlra1	1995	The volume combines some basic reviews, such as chapters on the pathophysiology of viral diarrhea and gastrointestinal tract immunology, with detailed exploration of more focused topics, such as rotavirus proteins. While interesting and one of the more clinically applicable sections of the book, the inclusion of a chapter on bacterial diarrhea in a volume dedicated to viral gastroenteritis is somewhat puzzling. While this book has certain outstanding features, there are some shortcomings which warrant mention, most notably a paucity of references beyond 1990 in some chapters and the failure to recognize viral pathogens which, through gastrointestinal tract infection, cause significant disease other than diarrhea. The final chapter in the book is devoted to the therapeutic aspects of gastrointestinal motility, including biofeedback training for fecal incontinence. Once again, adequate references are provided for those who desire more in-depth study, The next several chapters begin at the oropharynx and proceed through the gastrointestinal tract, presenting a discussion of the motility of each area.
cord-016130-5q9ufu28	2010	Our clinical research demonstrates that daily supplementation with a flavored cod liver oil (which meets European purity standards) and a children''s multivitamin-mineral with trace metals, including Se, can decrease morbidity from upper respiratory tract illnesses, otitis media, and sinusitis in young children living in the United States. This chapter discusses the role of essential fatty acids, vitamins, and trace metals in the pathophysiology of inflammation; reviews our clinical research on the use of a lemon-flavored cod liver oil (which meets European purity standards) and a children''s chewable multivitamin-mineral with Se for the prevention and adjunctive treatment of these disorders; reviews the history of cod liver oil, including its importance in the discovery of vitamin D and the anti-infective properties of vitamin A; and discusses the current clinical use of these supplements.
cord-016757-3d320c0a	2008	Hepatic coma can be subdivided according to its aetiology as follows: (1.) hepatocyte disintegration coma (Ï­ endogenous coma due to the loss of parenchyma), (2 ( ( .) liver cell failure coma (Ï­ exogenous coma due to metabolic disorders, almost always in the presence of cirrhosis), (3.) electrolyte coma (Ï­ so-called "false" coma due to dyselectrolytaemia, almost always iatrogenic), and (4.) mixed forms of coma. Acute liver failure (ALF) is defined as an acute clinical picture with jaundice due to a most severe disorder in the liver function and/or massive liver cell necrosis which, without any pre-existing liver disease, culminates in hepatic coma (Ï­ endogenous coma) within 8 weeks. 11) Consequently, severe damage to liver cells and widespread necrosis are usually the result of a network of altered cellular and humoral reactions, which for their part are often the initial cause of acute liver failure due to their synergistic and interactive effects (H. Fulminant hepatic failure caused by acute fatty liver of pregnancy treated by orthotopic liver transplantation
cord-016880-q44623s8	2015	Uit analyse van patiënten die getransplanteerd zijn terwijl ze buiten de Milaan-criteria vielen, blijkt dat met name micro-angio-invasie een slechte prognostische marker is en dat de overleving bij grotere of meer dan drie tumoren nog goed kan zijn als er geen micro-angio-invasie is. [29] Bij een hemodynamisch instabiele patiënt kan OLT -of auxiliaire levertransplantatie met een grote resectie van de natieve lever [30] -beter zijn omdat resectie van de necrotische lever het toxic liver-syndroom -door cytokines -kan tegengaan. [48] Het Epstein-Barr-virus (EBV) kan (bij 1% van de levertransplantaties) leiden tot posttransplantatielymfomen (PTLD); die zijn tegenwoordig vaak curatief te behandelen en voor een deel mogelijk te voorkomen door EBV-DNA-metingen in het eerste jaar, met zonodig aanpassen van de immuunsuppressie. Bij de levende donor wordt een resectie verricht van de linkslaterale segmenten van de lever, die vervolgens gebruikt worden voor transplantatie bij het kind.
cord-017603-wq4cgqs2	2018	Trying to address this issue, Bhaduri and Vergani defined ALF in children as "a rare multisystem disorder in which severe impairment of liver function, with or without encephalopathy, occurs in association with hepatocellular necrosis in a patient with no recognized underlying chronic liver disease" [2] . They used the following criteria to define acute liver failure (ALF) in children: (1) hepatic-based coagulopathy defined as a prothrombin time (PT) ≥ 15 s or international normalized ratio (INR) ≥ 1.5 not corrected by vitamin K in the presence of clinical hepatic encephalopathy (HE) or a PT ≥ 20 s or INR ≥ 2.0 regardless of the presence or absence of clinical hepatic encephalopathy (HE), (2) biochemical evidence of acute liver injury and (3) no known evidence of chronic liver disease [3] . A similar study in children failed to show any benefit, and Paediatric Acute Liver Failure study group does not recommend routine use of in non-acetaminophen-induced ALF in children [33] .
cord-018225-dozmy3lb	2008	The paper by Harrison and co-workers, again from the King''s Liver Unit, investigates the effects of n-acetylcysteine in patients with acute liver failure, and the findings of this study have resulted in widespread use of this agent in this setting. The incidence of hypoxic hepatitis was prospectively studied for 1 year in a group of high-risk patients suffering from low cardiac output in a coronary care unit. In intensive care patients, a rapid decrease in MEGX test values is associated with increased risk of developing multiple organ failure, and a poor outcome, and consequently may have a role in investigation of the role of the liver in the multiple organ failure syndrome. We studied the effect of acetylcysteine on systemic hemodynamics and oxygen transport in 12 patients with acetaminophen-induced fulminant hepatic failure, and 8 patients with acute liver failure from other causes. The increase in oxygen delivery and consumption in response to acetylcysteine may account for its beneficial effect on survival in patients with fulminant hepatic failure induced by acetaminophen.
cord-018318-vzzrsqsn	2017	They focussed on serum bilirubin (SB) and prothrombin time (PT) as important prognostic markers of postoperative liver functional status and proposed the ''50-50'' criteria for the defi nition of PLF, i.e. the combination of PT >50 % of baseline normal and SB >50 μmol/L on postoperative day (POD) 5 (the ''50-50'' criteria) was found to be strongly predictive of mortality. In a study, mortality was signifi cantly higher in patients who had resection of hepatocellular carcinoma (HCC) in cirrhosis associated with active hepatitis (8.7 versus 1.5 %; p < 0.05) [ 13 ] . PLF and postoperative renal dysfunction are independent predictors of 90-day mortality following liver resection but the predictive value for mortality is significantly higher when both systems fail simultaneously. The patient''s liver status, hepatic reserve potential and functional aspect need to be investigated along with the metabolic and haematological derangements, which may lead to PLF.
cord-018414-6ffhm895	2016	
cord-018620-3kqx8arn	2016	
cord-018801-amet0wx4	2018	Depending on acuity, patients with decompensated chronic or acute fulminant liver failure generally require preoperative intensive care unit admission to manage organ dysfunction. Depending on acuity, patients with decompensated chronic or acute fulminant liver failure generally require preoperative intensive care unit (ICU) admission to manage organ dysfunction. In patients that develop AKI post-liver transplantation, treatment includes the prevention of hypotension and decreased use of unnecessary blood products. Early postoperative infections in liver transplant patients are typically bacterial and related to the donor''s status (previous infections from advanced cirrhosis), the surgical procedure itself, prolonged use of invasive catheters, and duration of mechanical ventilation. The resulting lack of blood flow and developing ischemia and necrosis from hepatic artery thrombosis present with signs and symptoms similar to fulminant liver failure patients with elevated liver serum tests, coagulopathy, and severe metabolic acidosis.
cord-022300-9w0lehal	2009	Several different types of congenital PSS occur in young dogs and cats, including but not limited to (1) persistent patent fetal ductus venosus, (2) direct portal vein to caudal vena cava, (3) direct portal vein to azygos vein, (4) combination of portal vein with caudal vena cava into the azygos vein, (5) left gastric vein to vena caval shunt, (6) portal vein hypoplasia or atresia with secondary anomalous vessel, and (7) anomalous malformation of the caudal vena cava (Center et aI, 1995) . Ultrasonographic findings in puppies with congenital PSS include small liver, reduced visibility of intrahepatic portal vasculature, and an anomalous blood vessel draining into the caudal vena cava or sometimes into the azygos vein (Lamb, 1996) . A chronic active liver disease associated with an age-related accumulation of hepatic copper occurs in Bedlington terrier dogs (Hultgren et al, 1986 ).
cord-022483-hdmwv540	2009	In the neonatal period, commonly reported causes of abdominal pain are meconium impaction, small-intestinal volvulus, enteritis or colitis, uroperitoneum, intussusception, gastric ulcers, and ileus secondary to prematurity, septicemia, or neonatal encephalopathy. Lower-intestinal contrast studies (i.e., barium enema) have been reported to have 100% sensitivity and 100% specificity for identifying mechanical obstruction (meconium impaction, atresia coli) of the transverse colon or small colon in foals less than 30 days of age ( Figure 11-14) . The only published study on 20 foals less than two weeks of age with acute abdominal pain reported that an exploratory celiotomy revealed functional ileus (45%), meconium impaction (25%), large-colon displacement (15%), small intestine displaced around the base of the cecum (10%), ruptured gastric ulcer, and small colon obstructed by the ovarian ligament. 8 These reports underscore the difficulty in definitively identifying the cause of abdominal pain prior to exploratory celiotomy in neonatal foals, as clearly some of these cases, such as enteritis and functional ileus, would not be considered to be predominantly surgical diseases.
cord-022555-a7ie82fs	2011	One study found that, of cats investigated for gastrointestinal disease, 9 of 33 cats (27%) had no pathology recognized proximal to the jejunum (i.e., the effective length of diagnostic endoscopes would have precluded diagnosis), and other organs were affected in 9 of 10 cats with inflammatory bowel diseases and 7 of 8 cats with intestinal small cell lymphoma. 60, 64 Quantification of serum cobalamin levels is recommended in cats with clinical signs of small bowel diarrhea, ones suspected to have an infiltrative disease of the small intestine (inflammatory bowel disease or gastrointestinal lymphoma), or ones with pancreatic dysfunction. Survey radiographs may be normal in cats with esophagitis and strictures, but are useful to rule out other causes for the clinical signs, such as a foreign body, or to detect related problems, such as aspiration pneumonia. 8, 29 Other non-neoplastic causes reported for gastric or gastroduodenal ulceration in cats include parasites (e.g., Ollulanus tricuspis, Toxocara cati, Aonchotheca putorii, Gnathostoma spp.), bacterial infections, toxins, inflammatory bowel disease, and foreign bodies.
cord-022754-ehq9qnoo	2012	Conversely, in cases of chronic end-stage liver disease, such as cirrhosis, serum hepatic enzyme activities may not be markedly increased, or may even be within the reference interval as a result of the replacement of hepatocytes with fibrous tissue. World Small Animal Veterinary Association (WSAVA) Standards for the Clinical and Histological Diagnosis of Canine and Feline Liver Disease suggest that the cytologic evaluation of bile forms part of the minimum diagnostic requirement for cats with extrahepatic cholestasis and for dogs guidance. 32 Hyperglobulinemia can be seen in dogs with cirrhosis, but it remains to be determined whether this corresponds with increased autoantibodies as occurs in humans with autoimmune hepatitis, or whether it reflects nonspecific systemic antibody production in response to antigens from the portal blood which bypass the liver through acquired PSSs. 83 Mild nonregenerative anemia may be a reflection of chronic disease.
cord-023017-k6edtg58	2006	14/55 (25%) patients in AC who did not discontinue by week 24 received ribavirin dose reduction in comparison to 31/108 ( The clinical outcome in response to combination therapy for treatment of chronic hepatitis C virus (HCV) infection appears to be different for Caucasian versus African American patients. Over the period of combination therapy, most patients in which serum virus titers were reduced to non detectable levels had significant increases in T cell responses to HCV proteins. CHRONIC Background: Recent large prospective trials demonstrated that the combination therapy of interferon (1FN)-alphalribavirin significantly increased the ratio of a sustained virological response in patients with chronic hepatitis C in comparison with IFN monotherapy, especially in patients with high HCV-RNA titer and genotype lb. Results: Patients with chronic HCV infection showed higher MxA gene expression levels than healthy controls, indicating that hepatitis C virus induces IFN production.
cord-023033-tgt69ir6	2006	Methods: We performed a retrospective analysis comparing outcomes, and the incidence, timing, and severity of histologic recurrence of HCV following transplantation in patients who underwent living donor liver transplant compared to recipients of cadaveric organs. Local liver immune responses are thought to play a major role in chronic autoimmune diseases directed at biliary epithelium.Using the apical sodium dependent bile acid transporter (ASBT) promoter to drive biliary epithelial cell -specific expression of a membrane form of ovalbumin (OVA), we have previously developed OVA-BIL transgenic mice. Thus, our AIM was to ascertain whether Kupffer cells express death ligands and contribute to hepatocyte apoptosis and liver fibrosis in the bile duct ligated mouse, an animal model of cholestasis. Control experiments confirmed that Y2 protein inhibited IFNa-induced ISRE-mediated signaling in Huh-T7 cells; relative luciferase activity was reduced from 653 (pH771 IFNP nAb increased HCV core Ag replication by 42% and 23% compared to no treatment (p=O.O1).
cord-025168-be7zube4	2020	Adipose tissue-derived mesenchymal stem cells (AD-MSCs) are isolated from adipose tissue by liposuction, are capable of differentiation to hepatocytelike cells in the presence of HGF, FGF-1, and FGF-4 factors and participate in the regeneration of hepatocytes and vasculogenesis [61] . Several studies have shown that MSCs secrete tropic factors and can be effective in reducing inflammation, fibrosis and apoptosis of liver cells as well as repairing damaged tissue by stimulating angiogenesis [74] . It can be argued that the beneficial effects of MSCs in liver diseases (including ALF) are not limited to hepatocyte repair, but rather the tropical factors released by Fig. 1 Mesenchymal stem cells and its effects on acute liver failure them modulate the deleterious effects of the immune response [142] . Bone marrow-derived mesenchymal stem cells inhibits hepatocyte apoptosis after acute liver injury In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: therapeutic effect on liver fibrosis/cirrhosis
cord-029138-avfvpqs5	2020	Initial reports examining the use of liver grafts from DCD described inferior longterm outcomes when compared with donation after brain death donors (DBD). More recent single center publications from high volume DCD programs have demonstrated equivalent outcomes between DCD and DBD liver transplantation (LT), with appropriate donor and recipient selection [5] [6] [7] . A previous publication demonstrated that after the implementation of the Share 35 policy, more HCC patients have received livers from DCD donors [22] , potentially as the result of the highest quality organs being preferentially utilized by higher MELD recipients with broader sharing. As the collective experience with DCD LT increased, a concept of functional donor warm ischemic time (fDWIT) arose from the notion that individual events during DCD procurement, such as variations in hemodynamics, mandatory wait period, time from incision to cannulation of the aorta and cross-clamp, all of which are included in total DWIT, may have different impacts on the outcome of the liver graft [25, 26] .
cord-030369-4dn02a35	2019	Once pulmonary infection is present, the disease condition will likely deteriorate, directly causing death; (3) a majority of infections are nosocomial infection, and pathogens are usually resistant to common antibiotics, making therapy challenging; (4) the pathogens causing infection are diverse but mainly Gram-negative bacteria, although the incidence of Gram-positive and fungal infections is increasing; (5) infection is closely related to the prognosis for liver failure patients. Although their clinical manifestation differ significantly, the "coexistence of acute and chronic failures" is shared by failures of all those organs; (2) CLF classification has been generally recognized at home and abroad, and the necessity of classification are further proved by the difference between CLF and the other three types; (3) CLF cases are relatively large in proportion (nearly 30%), which is still increasing (since the proportion of ALF/SALF are lowering); (4) Complications of CLF are common and are found in various forms, with bad prognosis; (5) In CLF patients with correlation to HBV, virus replication are commonly found, which is closely related to decompensation.
cord-032131-ghgciqfk	2013	16.2) handelt es sich um eine Erkrankung des frühen Säuglingsalters, bei der insbesondere die großen Gallengänge außerhalb der Leber (extrahepatische Gallengangatresie) zerstört werden, es können aber auch die intrahepatischen Gallenwege mit betroffen sein. Bislang wurden keine verlässlichen immunologischen Parameter identifiziert, die ein komplettes Absetzen der Immunsuppression nach einigen Therapiejahren bei selektiven Patienten rechtfertigen würden, so dass derzeit von einer lebenslangen immunsuppressiven Therapie ausgegangen werden muss. Durch eine frühzeitige Vorstellung von Kindern mit akutem oder chronischem Leberversagen in einem geeigneten Transplantationszentrum und unter Ausnutzung sämtlicher möglicher Transplantationstechniken sollte es möglich sein, die Mortalität auf der Lebertransplantationswarteliste für Kinder auf Null zu senken. So ist eine Autoimmunhepatitis, vor allem bei jüngeren Kindern, mit einer schlechten Prognose (selbst nach Lebertransplantation) assoziiert, wenn diese nicht kurzfristig auf eine immunsuppressive Therapie (Steroid, Azathioprin) anspricht (Vogel et al.
cord-032181-gmcugd8h	2019	3. Hepatorenal syndrome, which is characterized by renal failure, hemodynamic changes in arterial circulation and abnormalities in the endogenous vascular system, is a common clinical complication of end-stage liver disease, and one of the important indicators for the prognosis of patients with severe hepatitis. The latest report indicated that basic laboratory examinations for coagulation function testing in common use at present, such as PT, APTT, international normalized ratio (INR) etc., have little correlation with occurrence of gastrointestinal bleeding in these patients, thereby revealing the importance to search and pay close attention to those complicating disease upregulating bleeding risk, such as bacterial infection, renal failure, hemodynamic change after portal hypertension, dysfunction of endotheliocyte as well as macrophagocyte and so on [107] .
cord-033821-i14dmmps	2020	11 Treatment based on the etiology may not completely attenuate all fibrosis patients, as there are currently no effective managements for eliminating the cause of certain liver diseases, such as autoimmune hepatitis. In a multicenter, randomized, placebo-controlled trial, 19 patients with NASH exhibited improvements of liver histological features after treatment with OCA (25 mg, 72 weeks). Currently, two active phase II clinical trials (NCT03486912, NCT03486899) are investigating the efficacy and safety of pegbelfermin in patients with NASH-related fibrosis as determined by liver biopsy. A phase II clinical trial 51 showed that pirfenidone (1200 mg daily, 24 months) improved inflammation, fibrosis, and steatosis in patients with hepatitis C virusrelated cirrhosis. 52 A phase II clinical trial (NCT02499562) has explored the effective dose and safety of hydronidone capsules in patients with liver fibrosis induced by hepatitis B virus infection in Shanghai General Hospital, Shanghai, China.
cord-033914-a9e3rncp	2020	His paternal grandmother, Josepha, and his father, Johann van Beethoven, suffered from alcohol use disorder, which led to his father''s death when Ludwig was 21 years old. 1 Numerous pathologies in the differential diagnosis have been proposed for Beethoven''s sensorineural hearing loss, and the most sustainable are: 1) lead poisoning, based on the presence of residuals of lead 100 times higher than normal in his hair and bones, according to an analysis performed in the United States in the mid 1990s, 4 2) Cogan''s syndrome, characterized by bilateral sensorineural hearing loss and interstitial keratitis secondary to vasculitis, albeit there is no evidence of vestibular dysfunction in Beethoven''s texts; that syndrome can be associated with idiopathic inflammatory bowel disease and reactive arthritis, 5 and 3) Paget''s disease is supported by the frontal bone prominence, tinnitus, and headache. Alcohol consumption appears to be the most probable cause of Beethoven''s cirrhosis of the liver, despite the macronodular appearance described in the autopsy.
cord-261608-4sjlg0p0	2020	title: COVID-19-INDUCED LIVER INJURY: A CLINICAL DISTRACTION? His hospital course was also complicated by acute renal failure requiring renal replacement therapy, coagulopathy, and encephalopathy which coincided with liver injury trailing behind the peak of inflammatory markers. Emerging data support the hypothesis that liver injury in COVID-19 is often the result of SARS-CoV-2 directly binding to ACE2+ cholangiocytes, leading to cholangiohepatitis. In addition, cytokine storm may further exacerbate the hepatic injury in COVID-19 (2). Hepatic congestion in ventilated patients, shock liver and particularly, drug-induced liver injury (DILI) remains an important consideration in COVID-19 patients. CONCLUSIONS: COVID-19 induced viral hepatitis is now being increasingly identified as a self-resolving complication and the physician should be mindful of it and in the right setting, it may only be a clinical distraction. We should be cognizant of other potential causes of liver injury in COVID-19 patients like concurrent infection, sepsis-induced and DILI. Liver injury in COVID-19: The current evidence COVID-19 and the liver: little cause for concern.
cord-262152-gdnc51m5	2020	title: Liver Function Test Abnormalities Are Associated With A Poorer Prognosis In Covid-19 Patients: Results Of A French Cohort AIM: To assess the impact of liver function test (LFT) abnormalities on the prognosis of patients with coronavirus disease 2019 (COVID-19) in a French cohort of hospitalized patients. Similar results were obtained for patients with cholestatic liver injury (Table Table 5 shows the association of factors with the composite severity endpoint (admission to ICU, respiratory failure requiring mechanical ventilation, CT scan injury >50% and global mortality). Severe infection is known to be more frequent among those patients, but they had mostly imbalanced diabetes or hypertension, which was not the case in our study Global mortality was also similar (16.0%), yet the number of admissions to ICU (15.3%) was higher than previously reported 1 .
cord-271635-tydlyc1q	2018	They can inhibit the liver cancer development and progression in several ways as protecting against liver carcinogens, enhancing effects of chemotherapeutic drugs, inhibiting tumor cell growth and metastasis, and suppression of oxidative stress and chronic inflammation. The co-treatment with LPP, orally, in NAFLD in rats, showed a significant improvement in the hepatic histology, reduction in the fibrosis, oxidative stress, inflammation, accumulation of fats and apoptosis, through modulating the transcriptional factors NF-κB and activator protein-1 (AP-1). The major polyphenol of green tea, epigallocatechin-3-gallate (EGCG), was used in CCl 4 -treated mice and showed a significant therapeutic potential in hepatic damage, inflammation and oxidative stress induced by CCl 4 in a dose-dependent manner at both biochemical and histological levels [34] . It was also reported that co-treatment of the whole green tea extract with alcohol administration showed an effective reduction of the hepatic oxidative stress and reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase systems in experimental alcohol-induced liver injury [35] .
cord-275637-ea6w2kqv	2020	Conclusions UK Biobank data demonstrated an association between pre-existing liver disease and obesity with severe COVID-19, with higher proportions of liver fat in obese individuals a likely risk factor for symptomatic disease and severity. The aim of this study was to test the hypothesis that liver disease, and specifically liver fat accumulation, is a risk factor for developing symptomatic COVID-19. . https://doi.org/10.1101/2020.06.04.20122457 doi: medRxiv preprint Furthermore, the 32.7% of obese patients with liver fat ≥10% had a higher likelihood of being symptomatic and testing positive for COVID-19 (OR: 2.96, p=0.02). Our study demonstrates that in addition to the previouslyreported risk factors of male gender, non-white-British ethnicity, and obesity (1-3), liver fat is also a significant risk factor for having symptomatic COVID-19, with a person testing positive for COVID-19 being 1.85 times more likely to have pre-existing severe fatty liver disease.
cord-277535-u283k70i	2020	Additionally, drugs can also modify how the liver functions and cause dysfunction or even failure of the organ both by a direct effect on the liver or by alteration in liver blood flow. Furthermore, once a patient has been recognized to be suffering with liver dysfunction or failure drug choice and dosing regime will need to be rationalized. After reading this article you should: C understand the mechanisms of drug metabolism by the liver C have an appreciation of alterations to drug choice and dosing regimens in patients with liver disease due to their altered pharmacokinetics C know the management of a patient with paracetamol overdose There are many different isoforms of CYP450, classified according to their amino acid sequencing into families, subfamilies and individual genes. NSAIDS are contraindicated for systemic use in most liver disease patients, because of increased bioavalibilty, the high risk of precipitating gastrointestinal bleeding and renal failure.
cord-279667-ikfduu2k	2020	title: Complicated COVID-19 in pregnancy: a case report with severe liver and coagulation dysfunction promptly improved by delivery Severe COVID-19 promptly improved by the termination of the pregnancy or atypical HELLP (Hemolysis, Elevated Liver Enzymes and Low Platelet Count) exacerbated by concomitant COVID-19 infection could not be ruled out. CONCLUSIONS: This case adds to the growing body of evidence which raises concerns about the possible negative maternal outcomes of COVID-19 infection during pregnancy and advocates for pregnant women to be recognized as a vulnerable group during the current pandemic. We report a case of severe COVID-19 during in third trimester pregnancy, which led to an emergency Caesarean section and preterm delivery at 32 + 6 weeks of gestational age. Atypical presentation of HELLP could not be ruled out and the importance of a multidisciplinary team in the treatment and management of severe COVID-19 during pregnancy is critical for positive patient outcome.
cord-280234-anlytu3q	2020	Although several typical manifestation of novel coronavirus disease 2019 (COVID-19) including respiratory symptoms, weakness, fever, and fatigue have been reported, some rare and novel manifestations have also been observed, particularly in children. In this study, we report a novel pediatric case of fulminant hepatic failure associated with COVIDAlthough there have been a significantly smaller number of reported cases of COVID-19 in the pediatric population compared with the adults, the number of infected children has seen a moderate increase [2, 7] . Owing to the acute fulminant hepatic failure in our patient, the only treatment option was liver transplantation; however, because of the progressive course of the disease and its rapid progression to stage 4 with encephalopathy and brain death, he died. In conclusion, in patients with fulminant hepatic failure, especially in cases with symptoms including fever, respiratory distress, and diarrhea, we should rule out COVID-19 infection as the underlying cause.
cord-283120-hyzk59qv	2020	In this meta-analysis, we aim to study the occurrence and association of liver injury, comorbid liver disease and elevated liver enzymes in COVID-19 confirmed hospitalizations with outcomes. MATERIALS AND METHODS: Data from observational studies describing comorbid chronic liver disease, acute liver injury, elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and outcomes of COVID-19 hospitalized patients from December 1, 2019, to June 30, 2020 was extracted following PRISMA guidelines. The aim of the study is to evaluate the role of the comorbid chronic liver disease (CM-CLD), elevated liver enzymes and COVID-19 associated acute liver injury (COVID-19 ALI) in predicting the outcomes in confirmed COVID-19 hospitalized patients. The Maentel-Haenszel formula was used to calculate dichotomous variables to obtain odds ratios (ORs) along with its 95% confidence intervals to describe the association of comorbid liver disease, elevated liver enzymes, acute liver injury and outcomes of COVID-19 patients in each study.
cord-284693-mgpxnnk0	2020	Advanced recipient age, diabetes mellitus, severe liver disease (Child Pugh >10), IL-28B polymorphism, high HCV RNA >10 7 IU/ml, ischemic/reperfusion injury, CMV, donor age >65 years, cold ischaemic time over 8 hours and warm ischemia over 90 minutes, marginal graft, DCD donor, higher immunosuppression in particular high dose corticosteroids for acute cellular rejection, use of anti-thymocyte globulin were significantly associated with rHCV in the liver allograft 15, 16 . Initial studies with sofosbuvir and ribavirin combination therapy for post-transplant rHCV showed poor drug tolerance, however, the main adverse event was anaemia related to ribavirin in 62% of patients, and subsequent hepatic decompensation related to the low haemoglobin 38 . A study by Pellicelli et al., showed significant adverse events including hepatic decompensation and 25% mortality in those with advanced disease following treatment with daclatasvir and sofosbuvir for post-transplant rHCV 51 .
cord-288721-3bv3aak6	2019	Thus, single-organelle and multi-parameter resolution allows to explore altered energy metabolism and antiviral defence by tagged mitochondria selectively in virus-infected cells and will be instrumental to identify viral immune escape and to develop and monitor novel mitochondrial-targeted therapies. When challenged with high concentrations of calcium (100 µM), mitochondria isolated from virus-infected livers are much more fragile shown by time-dependent loss of membrane potential and change of their morphology indicated by decrease in side-scatter (Fig. 2F ). Number of viable mitochondria detected per second by flow-cytometry declined after calcium challenge, consistent with loss of mitochondrial integrity, and did so much faster in samples from virus-infected livers (Fig. 2F ). In order to further evaluate mitochondrial functionality, we challenged mitochondria with Ca 2+ as stress test and performed time kinetic measurements of DilC 1 (5) fluorescence and side-scatter of mito-DsRed + and mito-DsRed − mitochondria isolated from Ad-CMV-mitoRL infected livers.
cord-290412-m6fesoyb	2014	In this article, we introduce TCM herbal preparations from the Chinese materia medica (such as Fuzheng Huayu) that are typically used for the treatment of liver diseases. TCM is widely applied in the treatment of liver diseases in China by both Chinese medicine doctors and Western medicine doctors because its ability to protect hepatocytes, inhibit hepatic inflammation and reduce fibrosis in the liver. Several patent drugs (Chinese herbal formulas) for treatment Clinical observations showed that FZHYC can effectively improve liver function and decrease the expression of fibrosis biomarkers such as serum hyaluronic acid, collagen type IV, procollagen type III and laminin, in chronic liver disease patients with fibrosis or cirrhosis [43, 44] . Randomized controlled multicenter clinical trial for integrated treatment of community-acquired pneumonia based on traditional Chinese medicine syndrome differentiation Optimized project of traditional Chinese medicine in treating chronic kidney disease stage 3: a multicenter double-blinded randomized controlled trial
cord-291851-xesef17i	2020	Our meta-analysis aims to compare the risks and clinical outcomes of COVID-19 associated liver injury among adults with severe and non-severe COVID-19. The objective of this meta-analysis is to compare the risk and clinical outcome of COVID-19 associated liver injury between COVID-19 patients with severe and non-severe COVID-19. In this meta-analysis, we included all studies that met the following inclusion criteria: (1) population: adult patients infected with the COVID-19, (2) reported outcome data on liver enzymes derangement (3) reported outcome data on the risk or severity of liver injury between severe and non-severe COVID-19. We extracted data on the demographic of study populations (age, gender, sample size, the proportion of subjects with baseline chronic liver disease and the use of Lopinavir/ritonavir) as well as the pattern of COVID-19 associated liver injury (ALT, AST, bilirubin, albumin and GGT) from all included studies. and performed a meta-analysis on the severity and risk of COVID-19 associated liver injury in these patients.
cord-292501-2jv7xkfn	2020	Multivariable regression showed that the number of concomitant medications (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.05-1.21) and the combination treatment of lopinavir/ritonavir and arbidol (OR: 3.58, 95% CI: 1.44-9.52) were risk factors for liver injury in non-critically ill patients. Multivariable regression showed that the number of concomitant medications (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.05-1.21) and the combination treatment of lopinavir/ritonavir and arbidol (OR: 3.58, 95% CI: 1.44-9.52) were risk factors for liver injury in non-critically ill patients. In the non-critically ill group, the univariate logistic analyses showed that the combination treatment of lopinavir/ritonavir and arbidol and the number of concomitant medications were significantly associated with liver injury ( Table 4) . Drug factors, including the combination treatment of lopinavir/ritonavir and arbidol and the number of concomitant medications were independent risk factors for liver injury in non-critically ill patients with COVID-19, which may be due to drug interactions at the metabolic level.
cord-300187-fr6tme32	2009	Although bacterial infections are probably the most common cause of infectious hepatitis, the clinician should be aware of other potential organisms and other commonly involved systems. Therefore, this article includes a description of common bacterial, mycobacterial, viral, fungal, protozoal, parasitic, and rickettsial diseases in dogs and cats. Mycobacterial disease is often subclinical in dogs and cats, but signs may be associated with granuloma formation in various organs. 39, 40 Nontuberculous mycobacterium, including those in the Mycobacterium avium complex, are saprophytic opportunistic organisms primarily implicated in disseminated disease in cats [41] [42] [43] [44] [45] and occasionally in dogs. No clear dissemination pattern has been identified because of low case numbers, but affected organs include the internal lymph nodes, liver, lungs, eyes, bone, muscles, and CNS. Infection results in disseminated disease, including protozoal hepatitis. Bacterial culture results from liver, gallbladder, or bile in 248 dogs and cats evaluated for hepatobiliary disease: 1998-2003
cord-303046-unksl7p4	2020	As a result of lockdowns and suspension of usual clinical care activities for the benefit of patients with COVID-19, the SARS-CoV-2 pandemic is having a major effect on the management of patients with chronic liver diseases, in particular those with cirrhosis, hepatocellular carcinoma and in liver transplantation programmes. The COVID-19 pandemic will also negatively affect the care and management of patients with hepatocellular carcinoma, generating delayed diagnosis, deferred treatment (including medical and surgical, such as access to liver transplantation), loss to follow-up and, ultimately, increased mortality. Most COviD-19-induced liver-mortality will be delayed, resulting from deferred care for liver diseases, reduced funding for public health interventions and the global economic crisis, which will lead to increases in alcohol and drug use and in blood-borne virus transmissions, while access to care and funding are reduced.
cord-305956-l02xdq87	2020	These reports highlighted that beyond severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a complicated course of the disease or even viral infection itself can lead to involvement of other organs and multiorgan failure. The current review summarizes the pathophysiology and potentially specific role of COVID-19 in liver disease based on the available data and case series published, ahead of print and non-peer-reviewed preprints as of 2 April. In this study, 47.3% of the discharged patients showed elevated LFTs at baseline, and 23.7% developed abnormalities during hospitalization, suggesting emerging liver injury from drugs or during the course of the infection. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series
cord-309795-2kozsv4z	2020	NAFLD, which affects about 25% of the population [3] , comprises a broad range of abnormalities ranging from simple fatty liver (steatosis) to non-alcoholic steatohepatitis (NASH), characterized by inflammation, necrosis, and hepatocellular ballooning, and progression to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) [2] . In general, both hyperglycemia and toxic lipids such as ceramides, DAG, FFA, and cholesterol can induce deleterious effects on liver cells (glucolipotoxicity), which might initiate NAFLD progression from simple steatosis to NASH and fibrosis via various mechanisms, including cell death, oxidative stress, endoplasmic reticulum (ER) stress and mitochondrial disorders [46] . BL, baseline; CCR2/5, C-C chemokine receptors type 2 and type 5; FXR, farnesoid X receptor; HbA 1c , glycated haemoglobin; LXR, Liver X receptor; MPC, mitochondrial pyruvate carrier; NA, data not available; NAFLD, non-alcoholic fatty liver disease; NFS, NAFLD fibrosis score; PPAR, peroxisome proliferator-activated receptor; NASH, non-alcoholic steatohepatitis; SCD, stearoyl-CoA desaturase; SGLT, sodium-glucose cotransporter; THR, thyroid hormone receptor; T2DM, type 2 diabetes. Potential Nexus of Non-alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Insulin Resistance Between Hepatic and Peripheral Tissues
cord-318755-fip8wj6y	2020	Management of immunosuppressive therapy and drug-drug interactions in liver transplant recipients infected with COVID-19 should be cautiously practiced to prevent rejection and effectively treat the underlying infection. Although healthcare facilities are overwhelmed with management of COVID-19 patients & health resources are being rapidly consumed, the American Association for the Study of Liver Diseases (AASLD), recommended against postponing transplantation. Patients with advanced liver disease and those after LTX represent vulnerable patient cohorts with an increased risk of infection and/or a severe course of COVID-19 Because of the immunosuppressed state they have [59] . Available data on coronavirus before and during outbreaks suggest that immunosuppressed patients are not at increased risk of severe pulmonary disease compared to the general population; however, immunosuppression may prolong viral shedding in post-transplant patients with COVID-19 if they are already infected [36, 60] .
cord-323736-zup9cp6s	2020	This study tested the hypothesis that (31)P‐magnetic resonance spectroscopy ((31)P‐MRS) findings could provide reliable living images to accurately identify the degree of acute liver IRI and melatonin‐pretreated mitochondria was an innovative treatment for protecting the liver from IRI in rat. [1] [2] [3] Studies have further displayed that several key factors contribute to the hepatic injury at the initiation and during the progression of liver IRI, including those of elevation of anaerobic metabolism, dysfunction of mitochondria, insult of oxidative stress, overload of intracellular calcium, activation of liver Kupffer cells, infiltration of immune cells and release of inflammatory cytokines. Additionally, this study further tested whether the 31 P-MRS examination could provide reliable living images to accurately identify the degree of ATP consumption/depletion in hepatocytes, that is an indicator of acute liver ischaemia-reperfusion in rodent. Melatonin-pretreated mitochondria effectively protected liver against IRI and 31 P-MRS was a reliable tool for measuring the mitochondrial/ATP consumption in living animals. Hepatic 31 P-magnetic resonance spectroscopy identified the impact of melatonin-pretreated mitochondria in acute liver ischaemia-reperfusion injury
cord-324509-5c6fzdjm	2020	7 Some studies have reported the clinical characteristics of patients with coronavirus disease 2019 (COVID19) , including some factors that may lead to COVID-19-related liver damage and the relationship between liver function damage and disease prognosis. Therefore, we retrospectively analysed the clinical characteristics and dynamic changes in liver function based on different liver function levels at admission and different prognosis, in the purpose of finding out risk factors related to liver injury, and associations between markers of liver injury and clinical outcomes in COVID-19, including mortality and mechanical ventilation. 13, 17 One study had suggested that the dynamic changes in liver enzyme levels in severe patients were more significant, and AST was the parameter most correlated with mortality. In our study, the dynamic changes of ALT and AST levels were more significant in patients with liver injury and in the fatal group.
cord-324529-xbrdtxnz	2020	title: Clinical characteristics and risk factors of liver injury in COVID-19: a retrospective cohort study from Wuhan, China This study was designed to evaluate the clinical characteristics and risk factors of COVID-19-associated liver injury. extracted the currently largest cohort regarding 1099 mainly moderate SARS-CoV-2 infected patients and showed 39.4% with severe disease had elevated AST and 28.1% had elevated ALT, and the proportion was 18.2% and 19.8% in patients with non-severe disease [6] .Given that the number of patients in these studies is relatively small, information about the clinical characteristics of liver injury in these patients is scarce. The present study showed that liver injury was more prevalent in male, severe or critically ill patients with percutaneous oxygen saturation ≤ 93% or peak temperature ≥ 38.5 °C on admission, and comprehensively delineated the risk factors for COVID-19-associated liver injury.
cord-327601-4uqgwlnx	2020	1 Their study shows SARS-CoV-2 positive patients with ≥1 week history of increased aminotransferases have worse acute pulmonary disease (radiological and physiological) than those without. Considering that Interleukin (IL)-6 and C-reactive protein (CRP) are similar between patients with normal and prolonged abnormal liver aminotransferases, the authors speculate that liver injury is a direct effect of SARS-CoV-2 viral hepatitis rather than an indirect immune mediated injury. The fact that increases in liver aminotransferases occur and tend to parallel the severity of pulmonary disease remains unquestioned 2 , however, whether the liver injury is a true viral hepatitis rather than a bystander to the multi-organ pathophysiology of critical illness requires further discussion. Based on the above perspectives, we feel that raised liver aminotransferases associated with SARS-CoV-2 positivity are more likely attributable to illness severity, in which host response and iatrogenic harm (i.e. drugs, ventilation) drive bystander liver injury, thus explaining its association with mortality and in an analogous fashion to patterns seen in sepsis.
cord-328147-61gtx2h2	2020	In Mexico, 72.5% of the adult population is overweight and 9.4% have T2DM(4) Additionally, the prevalence of hepatic steatosis in Mexico ranges from 14 .4% to 62.9%, (5) and he prevalence of liver fibrosis has been reported in 8.1% (noninvasive assessment).(6) Currently, Mexico City is one of the most affected regions in the world with rising numbers of cases and deaths caused by COVID-19, and we have very few data regarding GI symptoms and LFT abnormalities and their prognostic value in Mexican patients. They also represent a challenge for therapeutic maneuvers such as imaging diagnosis, intubation, mechanical ventilation, and pronation, among others.(11) A meta-analysis including 3,207 patients with COVID-19 described that underlying chronic conditions such as hypertension, diabetes, and cardiovascular and respiratory diseases were higher in critical/non-surviving patients; clinical manifestations such as fever and dyspnea were also associated with the progression of the disease.(12) We found similar results in our study, with dyspnea as the most important associated symptom for ICU admission with OR 4.07 (CI95% 1.6-9.86).
cord-332827-gll4nqdd	2020	In published series, liver disease was not identified as a risk factor for SARS-Cov2 infection [11] [12] [13] [14] [15] . The authors state that NAFLD patients also had a higher risk of progression to severe COVID-19 and present an increased viral clearance time. Immune-mediated liver diseases, particularly autoimmune hepatitis, have not been mentioned as risk factors for COVID-19, but the immunosuppressive treatment required has triggered fears about the risk of infection in patients. Extensive records and targeted studies are needed to explore multiple open-ended questions such as the severity and mortality of COVID-19 and episodes of acute-on-chronic or decompensation associated with the presence of this disease (ascites, hepatic encephalopathy, digestive bleeding, kidney dysfunction, and the risk of infection) or the response to treatment [25, 26] . However, it is not yet possible to say whether transplantation-associated immunosuppression can alter the predisposition for the acquisition of SARS-Cov2 infection or how COVID-19 evolves in these patients.
cord-339786-elrzlbsg	2020	
cord-340325-0oh40b6r	2020	
cord-340576-dabcs3w5	2020	In individuals with chronic liver diseases (CLDs), metabolic or nutritional dysfunctions including protein-energy malnutrition (PEM) or muscle abnormalities are frequently found, which can be related to disabilities, poor quality of life, or mortality [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] . LC-related complications themselves such as hepatocellular carcinoma (HCC), ascites, spontaneous bacterial peritonitis (SBP), varices, hepatic encephalopathy (HE), and acute or chronic liver failure (ACLF) can cause sarcopenia [22, 40] . LC-related complications themselves such as hepatocellular carcinoma (HCC), ascites, spontaneous bacterial peritonitis (SBP), varices, hepatic encephalopathy (HE), and acute or chronic liver failure (ACLF) can cause sarcopenia [22, 40] . Cumulative evidence has highlighted the relevance of increase in intestinal permeability (i.e., leaky gut syndrome) and consequent bacterial translocation in the development of CLDs. Particularly, in recent hypotheses regarding patients with non-alcoholic fatty liver disease (NAFLD), intestinal permeability impairment, dietary habits, and gut dysbiosis are considered to be the main pathogenic triggers [85] [86] [87] .
cord-340710-dmow5p7k	2020	title: Hepatic pathology in patients dying of COVID-19: a series of 40 cases including clinical, histologic, and virologic data Here we report the clinical and histologic findings related to the liver in 40 patients who died of complications of COVID-19. In conclusion, we found patients dying of COVID-19 had biochemical evidence of hepatitis (of variable severity) and demonstrated histologic findings of macrovesicular steatosis and mild acute hepatitis (lobular necroinflammation) and mild portal inflammation. A more recent study performed core needle biopsies on the livers of four patients and reported nonspecific findings, attributed to preexisting disease or perimortem injury [4] . Histologically, the most frequently encountered findings were macrovesicular steatosis, mild acute hepatitis, and minimal-to-mild portal inflammation. Nonetheless, based on the pattern of injury observed and the results of the PCR analysis, SARS-CoV-2 seems to involve the liver, and is associated with, possibly causal of, macrovesicular steatosis and acute hepatitis.
cord-342808-yonbowkb	2020	
cord-342930-f7cw2ca6	2020	Although the most frequent and critical clinical 15 presentation is secondary to the involvement of the lung (fever, cough), the infection by SARS16 CoV-2 virus may lead to a systemic and multi-organ disease [10] , also involving the gastrointestinal 17 tract (nausea/vomiting, or diarrhea) [11, 12] . Although the level of serum transaminases could be already elevated before the onset of COVID-14 19, results from clinical reports and autopsy studies [26, 49, 50] suggest that liver dysfunction can 15 be an expression of a worse disease evolution, and that an isolated elevation of transaminases alone 16 is likely to be the indirect expression of a systemic inflammation. In one study, patients 17 developing abnormal liver tests had higher risks of progressing to severe disease [51] , and the 18 finding is associated with longer hospital stay [62] . Non-alcoholic fatty liver diseases in patients with 19 COVID-19: A retrospective study
cord-348024-n8wn4och	2020	
cord-353633-a4pu6rlu	2020	Non-alcoholic fatty liver disease (NAFLD) is a multifaceted metabolic disorder, whose spectrum covers clinical, histological and pathophysiological developments ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and liver fibrosis, potentially evolving into cirrhosis, hepatocellular carcinoma and liver failure. The disease is characterized initially by hepatic lipid accumulation (nonalcoholic fatty liver; NAFL), that can often progress to non-alcoholic steatohepatitis (NASH), liver fibrosis or cirrhosis, as outlined in detail elsewhere in this special issue [1] . Several studies have assessed the impact of epigenetic modifications in the development and progress of NAFLD ( Figure 2 ) as well as in the association of NAFLD with other metabolic diseases by focusing on DNA methylation, histone modifications and miRNA expression profiles that can significantly affect transcriptional activity. Proteomic analysis to identify differentially expressed proteins between subjects with metabolic healthy obesity and non-alcoholic fatty liver disease
cord-355395-rckzi8vz	2020