Cholestatic hepatocellular carcinoma diagnosed by deposits of Lipiodol and treated by combination of endoscopic retrograde biliary drainage and transcatheter arterial embolization

Cholestatic hepatocellular carcinoma, which grows into the bile duct and causes obstructive jaundice, is rare and difficult to diagnose. A case is presented in which cholestatic hepatocellular carcinoma was detected by deposit of Lipiodol. This is also the first case that was successfully treated by endoscopic retrograde biliary drainage and transcatheter arterial embolization.     

The biliary excretion and pharmacokinetics of mezlocillin in jaundiced patients with external bile drainage

ABSTRACT— The biliary excretion and pharmacokinetics of mezlocillin have been studied in jaundiced patients with total external bile drainage through a percutaneous transhepatic catheter. In 10 of 11 studies, 2 g mezlocillin intravenously resulted in biliary concentrations sufficient to exceed the minimum inhibitory concentrations of most common biliary pathogenic organisms. In 6 h, 0.2–6.2% of the dose given was recovered in bile. The biliary clearance was 0.21–7.82 ml/min and increased with the duration of biliary decompression. The serum half-life of mezlocillin was prolonged (1.81 ± 0.23 h, mean ± SD), and was due to reduced biliary and renal clearance.     

CASE REPORT: Light Chain Deposition Disease of the Liver Without Renal Involvement in a Patient with Multiple Myeloma Related to Liver Failure and Rapid Fatal Outcome

We describe a 36-year-old man with advanced multiple myeloma (Salmon and Durie stage III) who developed jaundice and severe cholestasis after a first cure with systemic chemotherapy of vincristine, doxorubicin, and oral dexamethasone (VAD). Serology for hepatitis A, B, and C and for CMV was negative. A liver ultrasound and CT scan showed mild hepatomegaly without evidence of extrahepatic or intrahepatic biliary tree dilatation. A percutaneous liver biopsy revealed perisinusoidal deposits of an abundant slightly eosinophilic, PAS-positive amorphous substance. Immunohistochemistry showed positivity for kappa-light chains and was negative for lambda-light chains, for IgA, IgG, IgM, and IgD immunoglobulins as well as for AA and AL proteins and for amyloid P component. A diagnosis of light chain deposition disease (LCDD) of the liver was made. The patient developed rapid deterioration of liver function, leading to a multisystem dysfunction and death. The occurrence of LCDD in multiple myeloma is close to 5% and myeloma is the underlying disease in two thirds of patients with LCDD. The kidneys are involved in almost all cases of LCDD and renal dysfunction usually reveals the disease. Only three patients with LCDD of the liver without overt renal involvement have been reported so far. This is the first observation of LCDD presenting with jaundice and severe cholestasis shortly after the diagnosis of high tumor mass myeloma, without overt renal involvement, leading rapidly to the patient's death.     

Biliary diversion for progressive familial intrahepatic cholestasis: improved liver morphology and bile acid profile

BACKGROUND AND AIMS: Progressive familial intrahepatic cholestasis (PFIC) is characterized by pruritus, intrahepatic cholestasis, low serum gamma-glutamyltransferase levels, and characteristic "Byler bile" on electron microscopy. Many patients require liver transplantation, but partial external biliary diversion (PEBD) has shown therapeutic promise. However, the effect of PEBD on liver morphology and bile composition has not been evaluated. METHODS: We reviewed liver biopsy specimens from 3 children with low gamma-glutamyltransferase PFIC before and after PEBD. Follow-up liver biopsies were performed 9-60 months after PEBD. Light and electron microscopic features were scored blindly. Biliary bile acid composition was analyzed by gas chromatography-mass spectrometry before and after PEBD in 1 patient and after PEBD in 2 patients. RESULTS: Following PEBD, all patients improved clinically. Preoperative biopsy specimens showed characteristic features of PFIC, including portal fibrosis, chronic inflammation, cholestasis, giant cell transformation, and central venous mural sclerosis. Ultrastructural findings included coarse, granular canalicular Byler bile, effaced canalicular microvilli, and proliferative pericanalicular microfilaments. Following diversion, histology showed almost complete resolution of cholestasis, portal fibrosis, and inflammation with resolution of ultrastructural abnormalities. Biliary bile acids before PEBD consisted predominantly of cholic acid. After PEBD, the proportion of chenodeoxycholic acid increased significantly in 1 patient and was above the PFIC range in a second patient. CONCLUSIONS: The resolution of hepatic morphologic abnormalities following PEBD supports PEBD as an effective therapy for PFIC. The improved biliary bile acid composition suggests enhanced bile acid secretion after PEBD, perhaps by induction of alternative canalicular transport proteins.     

老年人肝内胆汁郁积16例临床分析

总结16例老年人肝内胆汁郁积患者的临床资料,并与26例中青年患者进行比较.结果表明,药物和病毒性肝炎是引起老年人肝内胆汁郁积的常见原因,尤以药物所致者显著增多.老年患者中男性占绝大多数.两年龄组胆汁郁积型肝炎患者的临床表现、病程经过和预后等并无明显差别,但由于老年患者常伴随多种疾病,特别是胆囊结石,使病情趋于复杂,极易误诊为胆石引起的肝外阻塞性黄疸.因此,对老年黄疸患者应尽早超声探查肝胆系统.以确立肝内胆汁郁积的诊断.     

Improvement of cyclosporin A-induced cholestasis by tauroursodeoxycholate in a long-term study in the rat

Cyclosporin A is an essential immunosuppressive drug, but it is potentially toxic to the kidney and liver. Ursodeoxycholic acid, a hydrophilic bile acid, has been reported to improve cholestasis in liver disease in man. The purpose of this work was to examine whether tauroursodeoxycholate could reduce cyclosporin A-induced hepatic or renal injuries in the rat. After randomization into three groups (N=8), rats received daily for 17 days: cyclosporin A intraperitoneally alone (30 mg/kg) or cyclosporin A intraperitoneally and tauroursodeoxycholate (60 mg/kg) by gavage; controls received the cyclosporin A excipient. Under tauroursodeoxycholate, cholestastic parameters (bile flow, bile salt secretion, serum bile salts, serum bilirubin) improved significantly without affecting cyclosporin A blood levels, and excretion of the drug and its metabolites in bile increased by 47%. Serum creatinine levels were better preserved, although not significantly. These results show that tauroursodeoxycholate prevents cyclosporin A-induced cholestasis in long-term treatment in rats, possibly by facilitating the drug elimination in bile.This work was supported by grants from the Caisse Régionale d'Assurance Maladie du Sud-Est and Houdé Laboratories.     

Parenteral nutrition with fish oil-based lipid emulsion reduces the risk of cholestasis in preterm infants

ObjectivePreterm infants receive long-term parenteral nutrition (PN) for gastrointestinal immaturity. This study aimed to determine if mixed lipid emulsions containing fish oil decrease the incidence of PN-associated cholestasis by reducing oxidative stress and providing an anti-inflammatory effect.MethodsThis retrospective cohort study enrolled 399 very low birth weight premature infants (gestational age ≤32 weeks) between January 2009 and November 2017 at a single neonatal intensive care unit. Preterm infants received total PN with either mixed lipid emulsion including fish oil (SMOFlipid®, n = 195) or soybean oil-based lipid emulsion (Lipovenoes®, n = 204) for at least 7 days. We compared the outcomes of PN-associated cholestasis, comorbidities, and mortality between the groups.ResultsThe incidence of PN-associated cholestasis was significantly lower in the SMOFlipid group than in the Lipovenoes group. The duration to full feeding days was significantly shorter in the SMOFlipid group compared with the Lipovenoes group. Relevant complications, such as severe retinopathy of prematurity and bronchopulmonary dysplasia, were also significantly reduced in the SMOFlipid group compared with the Lipovenoes group.ConclusionIn premature infants, PN with fish oil-based lipid emulsions is associated with a lower incidence of PN-associated cholestasis compared with soybean oil-based lipid emulsions.     

Beneficial Effect of Caffeic Acid Phenethyl Ester (CAPE) on Hepatocyte Damage Induced by Bile Duct Ligation: An Electron Microscopic Examination

Recently the authors have reported the potent beneficial effect of caffeic acid phenethyl ester (CAPE) on cholestatic oxidative liver injury induced by acute bile ligation in Swiss albino rats. Herein, they report the ultrastructural hepatocellular alterations induced by acute bile duct ligation and the effect of CAPE administration on these alterations. Bile duct ligation resulted in many degenerative changes, such as vacuolization, mitochondrial degeneration, endoplasmic reticulum dilatation, and lysosome accumulation within the cytoplasm of hepatocytes. Mitochondrial degeneration was also observed within the cytoplasm of the cells of biliary ductular epithelium. CAPE potentially protected the hepatocytes from the cholestasis-induced cellular injury.     

Clinical Significance of Serum Soluble Fas,Fas Ligand and Fas in Intrahepatic Lymphocytes in Chronic Hepatitis C

Hepatitis C Virus (HCV) is a major etiological agent of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Fas-mediated apoptosis is the major cause of hepatocyte damage during liver disease. The present work was performed to study the fas system (Fas-FasL and soluble Fas) in chronic hepatitis C infection. Also, to correlate the degree of liver cell damage with the Fas system. The study was carried out on 45 patients positive for HCV RNA by nested RT-PCR in addition to 13 HCV negative control subjects. Wedge liver biopsies samples were obtained from patients and controls during abdominal operations for determination of cellular expression of Fas and Fas-L on hepatocytes and infiltrating lymphocytes respectively by flow cytometry. Histological activity index (HAI) was determined in chronic HCV patients. Also blood samples were taken from patients and controls for determination of sFas. There was statistically insignificant difference in Fas expression in hepatocytes of patients (P?=?0.34) in comparison to control. Meanwhile, there was a statistically significant decrease in FasL expression in patients compared to control (P< 0.001) and statistically significant increase in soluble Fas in patients compared to control (P < 0.001). The HAI of liver fibrosis for all patients were within mild score with mean ± SD 4 ± 0.5. From this study, we could conclude that Fas system is one of the important pathways regulating the response to HCV infection. Increased serum sFas in HCV patients is accompanied by down-regulation of Fas/Fas-L expression resulting in inhibition of apoptosis in liver cells as a process for elimination of virus infected cells and this may ultimately leads to chronicity of the disease.     

MMP-2和MMP-9在肝内胆管细胞癌组织中的表达及意义

目的:探讨基质金属蛋白酶2(MMP-2)与基质金属蛋白酶9(MMP-9)在肝内胆管细胞癌(ICC)组织中的表达及其与ICC患者临床病理特征及预后的关系。方法:收集2011年1月—2014年12月收治的50例ICC患者的癌组织与癌旁组织手术标本,采用免疫组织化学方法及RT-PCR方法检测MMP-2和MMP-9在以上组织中的表达,分析MMP-2和MMP-9表达与ICC患者临床病理参数以及术后生存率的关系。结果:免疫组织化学结果显示,ICC组织中MMP-2和MMP-9蛋白阳性表达率分别为34.0%和32.0%,而两者在癌旁组织中无阳性表达;RT-PCR结果显示,ICC组织中MMP-2和MMP-9的相对表达均明显高于癌旁组织(均P0.05)。MMP-2和MMP-9表达与ICC患者是否存在淋巴结转移和肿瘤分化程度有关(均P0.05),而与患者性别、年龄和肿瘤分期无关(均P0.05);MMP-2和MMP-9阳性患者生存率明显低于各自阴性者,而两者均阳性患者的生存率最低(均P0.05)。结论:ICC组织中MMP-2和MMP-9表达明显上调,且两者的表达与ICC患者恶性临床病理特征及不良预后密切相关。