SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Hepatology

170

BACKGROUND: Cichorium glandulosum Boiss. et Huet is used for treatment of liver disorders, and its effects are attributed to sesquiterpenes. This study aims to investigate the hepatoprotective effects of a sesquiterpene-rich fraction (SRF) from the aerial part of C. glandulosum on carbon tetrachloride (CCl4)-induced acute hepatotoxicity in mice, and on priming with Bacillus Calmette–Guerin (BCG) followed by lipopolysaccharide (LPS)-induced immunological liver injury in mice. METHODS: SRF was suspended in water and administered to mice at 0.05, 0.10 and 0.20 g/kg body weight for 7 consecutive days. An active control drug (bifendate pills) was suspended in distilled water and administered to mice at 0.40 g/kg body weight for 7 consecutive days. Hepatotoxicity was induced by intraperitoneal injection of 0.1% CCl4 (0.2 mL/mouse) at 13 h before the last drug administration, or by tail intravenous injection of BCG (0.2 mL/mouse) before the first drug administration and LPS (0.2 mL/mouse; 8 mug) at 15 h before the last drug administration. Blood samples and the livers were collected for evaluation of the biochemical parameters of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (TBIL). RESULTS: SRF significantly reduced the impact of CCl4 toxicity. The highest dose of SRF (0.20 g/kg) was the most effective, reflected by significant reductions in the levels of AST (P = 0.001), ALT (P = 0.000) and TBIL (P = 0.009). The serum enzymatic levels induced by BCG and subsequent LPS injection were significantly and dose-dependently restored by SRF, reflected by significant reductions in the levels of AST (P = 0.003), ALT (P = 0.003) and TBIL (P = 0.007) for the highest dose of SRF (0.20 g/kg). CONCLUSION: SRF is hepatoprotective in animal models of chemical and immunological acute liver injury.

Concepts: Liver, Liver function tests, Aspartate transaminase, Alanine transaminase, Hepatology, Bilirubin, Hepatotoxicity, Chemical pathology

170

Transcatheter arterial chemoembolization (TACE) is the most widely used treatment option for unresectable hepatocellular carcinoma (HCC). Elevated serum YKL-40 level has been shown to predict poor prognosis in HCC patients undergoing resection. This study was designed to validate the prognostic significance of serum YKL-40 in patients with HCC undergoing TACE treatment.

Concepts: Lung cancer, Medical terms, Hepatocellular carcinoma, Hepatology, Radiology, Prognosis, Thought experiment, Transcatheter arterial chemoembolization

168

Portal hypertension is a common complication of chronic liver diseases and is responsible for most clinical consequences of cirrhosis, which represent the more frequent causes of death and liver transplantation in these patients. This review is aimed at clarifying the state-of-the art assessment of portal hypertension and at discussing recent developments in this field. Particular attention is paid to new noninvasive techniques that will be soon available for potential routine use.

Concepts: Medicine, Death, Medical terms, Cirrhosis, Liver, Hepatology, Hepatic portal vein, Liver transplantation

168

BACKGROUND: Situs inversus totalis represents an unusual anomaly characterized by a mirror-image transposition of the abdominal and thoracic viscera. It often occurs concomitantly with other disorders that make difficult diagnosis and management of abdominal pathology. The relationship between situs inversus totalis and cancer remains unclear. CASE PRESENTATION: We describe a 33-year old Guinean man with situs inversus totalis who presented with obstructive jaundice. Imaging and endoscopic modalities demonstrated a mass of distal common bile duct which biopsy identified an adenocarcinoma. The patient was successfully treated by cephalic pancreaticoduodenectomy followed by adjuvant chemoradiation and he is doing well without recurrence 8 months after surgery. CONCLUSION: The occurrence of bile duct adenocarcinoma in patient with situs inversus totalis accounts as a rare coincidence. In this setting, when the tumor is resectable, surgical management should be considered without contraindication and must be preceded by a careful preoperative staging.

Concepts: Cancer, Digestive system, Liver, Hepatology, Abdomen, Thorax, Situs inversus, Gallstone

168

Alagille syndrome (AS) is a multisystemic disease autosomal dominant, with variable expression. The major clinical manifestations are: chronic cholestasis, congenital heart disease, posterior embryotoxon in the eye, characteristic facial phenotype, and butterfy vertebrae. AS is caused by mutations in JAGGED1 (more than 90%) and in NOTCH2. Differential diagnosis include: infections, genetic-metabolic diseases, biliary atresia, idiopathic cholestasis. Cholestasis, pruritus and xanthomas have been successfully treated with choleretic agents (ursodeoxycholic acid) and other medications (cholestyramine, rifampin, naltrexone). In certain cases, partial external biliary diversion has also proved successful. Liver transplantation is indicated in children with cirrhosis and liver failure.

Concepts: Medicine, Cancer, Medical terms, Liver, Gastroenterology, Hepatology, Progressive familial intrahepatic cholestasis, Alagille syndrome

168

Steatotic grafts are excluded for use in partial liver transplantation (LT) due to increased risk of primary non-function. This study investigated the effects of suramin, a polysulfonated naphthylurea, on the outcome of steatotic partial LT. Rat livers were harvested after acute ethanol treatment (6 g/kg, i.g.), reduced in size to ~1/3, and transplanted. Serum alanine aminotransferase (ALT) and total bilirubin, and hepatic necrosis and apoptosis were significantly higher after transplantation of fatty partial grafts (FPG) than lean partial grafts (LPG). Suramin (5 mg/kg, i.p.) decreased ALT by ~60%, hyperbilirubinemia by 75%, necrosis by 83%, and apoptosis by 70% after FPG transplantation. Hepatic cellular 5-bromo-2'-deoxyuridine (BrdU) incorporation increased to 28% in LPG but was only 2% in FPG at 48 h and mitotic index increased to 7% in LPG but was only 0.2% in FPG, indicating suppressed regeneration in FPG. Suramin increased BrdU incorporation and mitotic index to 43% and 9%, respectively, in FPG. All FPG recipients died within 5 days. Suramin recovered survival of FPG to 62%. TNFα mRNA was 2.2-fold higher in FPG than in LPG and was associated with activation of caspase-8 and -3 in FPG. Suramin decreased TNFα and caspase activation in FPG. TGF-β, phospho-Smad2/3 and p21Cip1 were significantly higher in FPG than in LPG and suramin blocked TGF-β formation and its down-stream signaling pathway. Taken together, suramin improves the outcome of FPG transplantation, most likely by inhibition of TNFα and TGF-β formation.

Concepts: Apoptosis, Cirrhosis, Liver, Liver function tests, Alanine transaminase, Hepatology, Bilirubin, Jaundice

165

Trimethoprim-sulfamethoxazole (TMP-SMZ) is a commonly used antibiotic that has been associated with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. DRESS syndrome is characterised by fever, rash, lymphadenopathy, eosinophilia and one or more major organ involvement. Although rare, TMP-SMZ is a recognised cause of fulminant hepatic failure. We report a case of a 17-year-old Chinese, male adolescent who presented with fever, myalgia, generalised maculopapular rash and lymphadenopathy after taking TMPSMZ for acne vulgaris. He subsequently developed hepatic encephalopathy and was worked up for urgent liver transplantation. He responded well to extracorporeal liver dialysis (originally intended as a bridging therapy) and subsequently recovered without the need for liver transplantation. This case report highlights the importance of early recognition of TMPSMZ-induced DRESS syndrome and the need for early discontinuation of the drug in the affected patient. Extracorporeal liver dialysis and transplantation should be considered in the management of TMP-SMZ-induced fulminant hepatic failure.

Concepts: Medical terms, Cirrhosis, Liver, Hepatology, Liver transplantation, Hepatic encephalopathy, Liver dialysis, Acute liver failure

164

To assess the technical safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with immediate radiofrequency ablation (RFA) for large hepatocellular carcinomas (HCC) (maximum diameter ≥ 5 cm).

Concepts: Hepatocellular carcinoma, Hepatology, Radiology, Transcatheter arterial chemoembolization, Radiofrequency ablation

141

The liver plays a crucial role in coagulation cascade. Global hemostatic process is profoundly influenced by the presence of liver disease and its complications. Patients with cirrhosis have impaired synthesis of most of the factors involved in coagulation and fibrinolysis process due to a reduced liver function and altered platelet count secondary to portal hypertension. Altered routine tests and thrombocytopenia were considered in the past as associated with increased risk of bleeding. These concepts explain both the routine use of plasma and/or platelets transfusion in patients with liver cirrhosis, especially before invasive procedures, and why these patients were considered “auto-anticoagulated”. New recent evidences show that patients with liver cirrhosis have a more complex hemostatic alteration. Despite the presence of altered levels of factors involved in primary hemostasis, coagulation and fibrinolysis, patients with stable cirrhosis have a rebalanced hemostatic, which however can easily be altered by decompensation or infection, both in hemorrhagic or thrombotic direction. Patients with cirrhosis have an increased risk of venous thrombotic events (namely portal vein thrombosis) while bleeding seems to be related to the grade of portal hypertension rather than to a hemostatic imbalance. The use of anticoagulants both as treatment or prophylaxis is safe, reduces the rate of portal vein thrombosis and decompensation, and improves survival. Standard laboratory coagulation tests are unable to predict bleeding and are inadequate for the assessment of hemostatic status in these patients, hence more comprehensive tests are required to guide the management of thrombotic and bleeding complications.

Concepts: Blood, Thrombosis, Coagulation, Liver, Platelet, Hemostasis, Hepatology, Hepatic portal vein

139

Cholangiocarcinoma (CCA) is an aggressive cancer arising from epithelial cells of the bile duct. Most patients with CCA have an unresectable tumor at the time of diagnosis. In Western countries, the risk of CCA increases in patients with primary sclerosing cholangitis, whereas liver fluke infection appears to be the major risk factor for CCA in Asian countries. A diagnosis of liver fluke infection often relies on stool samples, including microscopic examination, polymerase chain reaction-based assays, and fluke antigen detection. Tests of serum, saliva and urine samples are also potentially diagnostic. The presence of liver fluke along with exogenous carcinogens magnifies the risk of CCA in people living in endemic areas. The “liver fluke-cholangiocarcinoma” carcinogenesis pathways consist of mechanical damage to the bile duct epithelium, immunopathologic and cellular reactions to the liver fluke’s antigens and excretory/secretory products, liver fluke-induced changes in the biliary tract microbiome and the effects of repeated treatment for liver fluke. A vaccine and novel biomarkers are needed for the primary and secondary prevention of CCA in endemic areas. Importantly, climate change exerts an effect on vector-borne parasitic diseases, and awareness of liver fluke should be enhanced in potentially migrated habitat areas.

Concepts: Immune system, Digestive system, Liver, Hepatology, Bile duct, Gallbladder, Cholangiocarcinoma, Primary sclerosing cholangitis