肝硬化合并自发性细菌性腹膜炎病原菌及前列腺素E2、D二聚体、中性粒细胞明胶酶相关脂质运载蛋白检测的临床意义

目的探讨肝硬化合并自发性细菌性腹膜炎(SBP)病原菌及前列腺素E2(PGE2)、D二聚体(D-D)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的临床意义。方法以60例肝硬化合并SBP患者为对象,以同期60例肝硬化无SBP患者为对照组。检测患者PGE2、D-D、NGAL水平,分析其诊断肝硬化合并SBP的效能。结果观察组PGE2、NGAL水平高于对照组,D-D水平低于对照组(P<0.05)。PGE2诊断肝硬化合并SBP的AUC、敏感度、特异度、最佳截断点分别为0.876(95%CI:0.803~0.929)、86.67%、81.67%、43.08 pg/mL;D-D诊断肝硬化合并SBP的AUC、敏感度、特异度、最佳截断点分别为0.907(95%CI:0.840~0.952)、100.00%、81.67%、0.93 mg/L;NAGL诊断肝硬化合并SBP的AUC、敏感度、特异度、最佳截断点分别为0.814(95%CI:0.733~0.880)、83.33%、85.00%、24.44 ng/mL;联合检测诊断肝硬化合并SBP的AUC、敏感度、特异度、最佳截断点分别为0.976(95%CI:0.931~0.995)、100.00%、91.67%、0.35。PGE2、D-D、NGAL联合监测诊断肝硬化合并SBP的AUC高于PGE2、D-D、NGAL单独诊断(P<0.05)。结论肝硬化合并SBP患者PEG2、NGAL水平降低,D-D水平升高,检测三者水平有助于准确诊断该病。

肝硬化合并上消化道出血患者抑郁状况调查及护理干预

目的:观察护理干预用于肝硬化合并上消化道出血患者的临床治疗效果。方法观察和记录患者的性别、年龄、病程、文化程度及肝功能 Child-Pugh分级情况。所有患者于入院前填写Zung抑郁自评量表,患者在接受2个月的护理干预后再次填写评量表。结果不同性别、病程和肝功能分级的患者在抑郁的发生率具有显著差异,患者在行护理干预前SDS评分为(65.32±7.28)分,经护理干预后为(50.97±7.31)分,护理干预前后对比显著,差异均具有统计学意义(P<0.05)。结论患者经基础护理、急救护理和心理护理等相关护理干预后,抑郁状态得到显著改善。

Clinical features of acute hepatitis E super-infections on chronic hepatitis B

AIM To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B(CHB) superimposed with hepatitis E virus(HEV).METHODS This retrospective cohort study included 228 patients with acute HEV infection(showing clinical acute hepatitis symptomology and positivity for anti-HEV immunoglobulin M) with underlying CHB(confirmed by positivity for hepatitis B surface antigen and/or hepatitis B virus(HBV) DNA over 6 mo) who had been admitted to the Shanghai Public Health Clinical Center, which represents the regional tertiary hospital for infectious diseases in Shanghai city, China. Data for adverse outcomes were collected, and included severe liver diseases(defined as liver failure and/or acute liver decompensation) and liver-related mortality. Logistic regression modeling was performed to determine the risk factors for adverse outcomes.RESULTS The symptoms caused by superimposed acute hepatitis E(AHE) were much more severe in cirrhotic patients(n = 94) than in non-cirrhotic patients(n = 134), as evidenced by significantly higher liver complications(77.7% vs 28.4%, P < 0.001) and mortality rate(21.3% vs 7.5%, P = 0.002). Most of the cirrhotic patients(n = 85, 90.4%) had no prior decompensation. Among the non-cirrhotic patients, superimposed AHE caused progressively more severe diseases that corresponded with the CHB disease stages, from immune tolerant to immune reactivation phases. Few risk factors were identified in the cirrhotic patients, but risk factors for non-cirrhotic patients were found to be intermediate HBV DNA levels(OR: 5.1, P = 0.012), alcohol consumption(OR: 6.4, P = 0.020), and underlying diabetes(OR: 7.5, P = 0.003) and kidney diseases(OR: 12.7, P = 0.005). Only 28.7% of the cirrhotic patients and 9.0% of the non-cirrhotic patients had received anti-HBV therapy previously and, in all cases, the efficacy had been suboptimal. CONCLUSION CHB-related cirrhosis and intermediate HBV DNA level were associated with severe disease in superinfected patients, and successful antiviral treatment might counter this outcome.

Hepatitis B virus genotypes in southwest Iran: Molecular, serological and clinical outcomes

AIM: To investigate the associations of hepatitis B virus (HBV) genotype with HBeAg and anti-HBe status, alanine aminotransferase (ALT) levels and HBV-DNA detection in different groups of HBV-infected patients in southwest Iran. METHODS: A total of 89 HBsAg-positive serum samples were collected from the same number of patients. All sera were then investigated to determine HBV DNA and serological markers. For all the polymerase chain reaction (PCR)-positive samples, biochemical, histopathological assays and genotyping were also performed. RESULTS: Genotype D was the only type of HBV foundin different clinical forms of acute and chronic infections. There was a high prevalence of HBeAg-negative HBV- infected patients with chronic hepatitis (52.7%). Out of 55 patients with chronic hepatitis, seven (12.7%) were diagnosed with cirrhosis. A significant association between the presence of anti-HBe antibody and an increase in ALT level, among either HBeAg-negative (P = 0.01) or HBeAg-positive (P = 0.026) patients, was demonstrated. No significant differences were observed between the clinical outcomes of HBeAg-positive and -negative individuals (P = 0.24). CONCLUSION: Genotype D has been recognized as the only type of HBV found in different clinical forms of HBV infections, including cirrhosis, among the residents of southwest Iran. Anti-HBe possibly plays a role in disease progression in some patients with chronic hepatitis, at least for a period of disease.

Temporal expression of hepatic inducible nitric oxide synthase in liver cirrhosis

AIM: Nitric oxide (NO) has been implicated in the pathogenesis of liver cirrhosis. We have found inducible nitric oxide synthase (iNOS) can be induced in hepatocytes of cirrhotic liver. This study further investigated the temporal expression and activity of hepatic iNOS in cirrhosis development. METHODS: Cirrhosis was induced in rats by chronic bile duet ligatjon (BDL). At different time points after the operation, samples were collected to examine NO concentration, liver function, and morphological changes. Hepatocytes were isolated for determination of iNOS mRNA, protein and enzymatic activity. RESULTS: Histological examination showed early cirrhosis 1-2 wk after BDL, with advanced cirrhosis at 3-4 wk. Bilirubin increased dramatically 3 d after BDL, but decreased by 47% on d 14. Three weeks after BDL, it elevated again. Systemic NO concentration did not increase significantly until 4 wk after BDL, when ascites developed. Hepatocyte iNOS mRNA expression was identified 3 d after BDL, and enhanced with time to 3 wk, but reduced thereafter. iNOS protein showed a similar pattern to mRNA expression. iNOS activity decreased from d 3 to d 7, but increased again thereafter till d 21. CONCLUSION: Hepatic iNOS can be induced in the early stage, which increases with time as cirrhosis develops. lts enzymatic activity is significantly correlated with protein expression and histological alterations of the liver, but not with systemic NO levels, nor with absolute values of liver function markers.

Prevalence of metabolic syndrome, obesity and diabetes type 2 in cryptogenic cirrhosis

AIM: To evaluate the prevalence of metabolic syndrome (MS), obesity and type 2 diabetes mellitus (T2DM) in a group of Mexican Mestizo patients with cryptogenic cirrhosis (CC) and to compare this group with patients with cirrhosis secondary to other causes (disease controls). METHODS: Patients with CC, diagnosed between January, 1990 and April, 2005, were included in a retrospective study. Patients with cirrhosis caused by chronic hepatitis C, alcohol abuse or autoimmune hepatitis (AIH) served as disease controls. RESULTS: A total of 134 patients with CC were analyzed. Disease controls consisted of 81 patients with chronic hepatitis C, 33 with alcohol abuse and 20 with AIH. The median age of patients with CC was 57 years (range, 16-87); 83 (61.9%) patients were female; 53 (39.6%) were Child A, 65 (48.5%) Child B, and 16 (11.9%) were Child C cirrhosis. The prevalence of MS (29.1% vs 6%; P < 0.001), obesity (16.4% vs 8.2%; P = 0.04) and T2DM (40% vs 22.4%; P = 0.013) was higher in CC patients than in disease controls. There were no differences in sex, age or liver function tests between the two groups. CONCLUSION: The prevalence of MS, obesityand T2DM were higher in patients with CC than in patients with cirrhosis secondary to others causes. Our findings support the hypothesis that non-alcoholic steatohepatitis (NASH) plays an under-recognized role in CC.

Association of liver cirrhosis related IgA nephropathy with portal hypertension

A high incidence of IgA nephropathy has been reported in patients with liver cirrhosis, though, clinically evident nephrotic syndrome is very uncommon. Impaired hepatic clearance of circulating IgA immune complexes and subsequent deposition in renal glomeruli has been considered principally in the pathogenesis of liver cirrhosis associated IgA nephropathy. Here we report on a patient with cryptogenic liver cirrhosis and splenic vein thrombosis, who presented with nephrotic syndrome. Renal biopsy showed findings consistent with IgA nephropathy. Lower endoscopy showed features of portal hypertensive colopathy. Following initiation of propranolol and anticoagulant treatment to reduce portal pressure, a gradual decrease of proteinuria and hematuria to normal range was noted. The potential pathogenetic role of portal hypertension in the development of IgA nephropathy in cirrhotic patients is discussed.

Diagnosis and therapy of ascites in liver cirrhosis

Ascites is one of the major complications of liver cirrhosis and is associated with a poor prognosis. It is important to distinguish noncirrhotic from cirrhotic causes of ascites to guide therapy in patients with noncirrhotic ascites. Mild to moderate ascites is treated by salt restriction and diuretic therapy. The diuretic of choice is spironolactone. A combination treatment with furosemide might be necessary in patients who do not respond to spironolactone alone. Tense ascites is treated by paracentesis, followed by albumin infusion and diuretic therapy. Treatment options for refractory ascites include repeated paracentesis and transjugular intrahepatic portosystemic shunt placement in patients with a preserved liver function. Potential complications of ascites are spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). SBP is diagnosed by an ascitic neutrophil count > 250 cells/mm3 and is treated with antibiotics. Patients who survive a first episode of SBP or with a low protein concentration in the ascitic fluid require an antibiotic prophylaxis. The prognosis of untreated HRS type 1 is grave. Treatment consists of a combination of terlipressin and albumin. Hemodialysis might serve in selected patients as a bridging therapy to liver transplantation. Liver transplantation should be considered in all patients with ascites and liver cirrhosis.

Reversion of severe hepatopulmonary syndrome in a non cirrhotic patient after corticosteroid treatment for granulomatous hepatitis:A case report and review of the literature

Hepatopulmonary syndrome （HPS） is defined as a clinical triad including liver disease, abnormal pulmonary gas exchange and evidence of intrapulmonary vascular dilatations. We report a 61-year-old male presented with fatigue, long-lasting fever, loss of weight, signs of portal hypertension, hepatosplenomegaly, cholestasis and progressive dyspnoea over the last year. Clinical, laboratory and histological findings confirmed the diagnosis of granulomatous hepatitis. HPS due to hepatic granulomainduced portal hypertension was proved to be the cause of severe hypoxemia of the patient as confirmed by contrast-enhanced echocardiography. Reversion of HPS after corticosteroid therapy was confirmed by a new contrastenhanced echocardiography along with the normalization of cholestatic enzymes and improvement of the patient＇ s conditions. This is the first case of complete reversion of HPS in a non-cirrhotic patient with hepatic granuloma, indicating that intrapulmonary shunt in liver diseases is a functional phenomenon and HPS can be developed even in miscellaneous liver involvement as in this case.

How albumin administration for cirrhosis impacts on hospital albumin consumption and expenditure

AIM:To assess the impact of guidelines for albumin prescription in an academic hospital,which is a referral center for liver diseases.METHODS:Although randomized trials and guidelines support albumin administration for some complications of cirrhosis,the high cost of albumin greatly limits its use in clinical practice.In 2003,a multidisciplinary panel at Sant'Orsola-Malpighi University Hospital(Bologna,Italy)used a literature-based consensus method to list all the acute and chronic conditions for which albumin is indicated as first-or second-line treatment.Indications in hepatology included prevention of post-paracentesis circulatory dysfunction and renal failure induced by spontaneous bacterial peritonitis,and treatment of hepatorenal syndrome and refractory ascites.Although still debated,albumin administration in refractory ascites is accepted by the Italian health care system.We analyzedalbumin prescription and related costs before and after implementation of the new guidelines.RESULTS:While albumin consumption and costs doubled from 1998 to 2002,they dropped 20%after 2003,and remained stable for the following 6 years.Complications of cirrhosis,namely refractory ascites and paracentesis,represented the predominant indications,followed by major surgery,shock,enteric diseases,and plasmapheresis.Albumin consumption increased significantly after guideline implementation in the liver units,whereas it declined elsewhere in the hospital.Lastly,extra-protocol albumin prescription was estimated as<10%.CONCLUSION:Albumin administration in cirrhosis according to international guidelines does not increase total hospital albumin consumption if its use in settings without evidence of efficacy is avoided.

Clinical features of hepatopulmonary syndrome in cirrhotic patients

AIM： To evaluate the frequency, clinical and paraclinical features of hepatopulmonary syndrome （HPS） and to determine their predictive values in diagnosis of this syndrome in patients in Iran. METHODS： Fifty four cirrhotic patients underwent contrast enhanced echocardiography to detect intrapulmonary and intracardiac shunts by two cardiologists. Arterial blood oxygen, 02 gradient （A-a） and orthodoxy were measured by arterial blood gas （ABG） test. The patients positive for diagnostic criteria of HPS were defined as clinical HPS cases and those manifesting the intrapulmonary arterial dilation but no other criteria （arterial blood hypoxemia） were defined as IHPS cases. HPS frequency, sensitivity, positive and negative predictive values of clinical and paraclinical features were studied. RESULTS： Ten （18.5%） and seven （13%） cases had clinical and subclinical HPS, respectively. The most common etiology was hepatitis B. Dyspnea （100%） and cyanosis （90%） were the most prevalent clinical features. Dyspnea and clubbing were the/host sensitive and specific clinical features respectively. No significant relationship was found between HPS and splenomegaly, ascites, edema, jaundice, oliguria, and collateral veins. HPS was more prevalent in hepatitis B. PaO2〈 70 and arterial-alveolar gradient had the highest sensitivity in HPS patients. Orthodoxy specificity was 100%. CONCLUSION： Clubbing with positive predictive value （PPV） of 75% and dyspnea with negative predictive value （NPV） of 75% are the best clinical factors in diagnosis of HPS syndrome. PaO2〈70 and P （A-a） 02〉 30 and their sum, are the most valuable negative and positive predictive values in HPS patients.

Effect of heme oxygenase-1 on renal function in rats with liver cirrhosis

AIM: To investigate the role of heme oxygenase-1 (HO-1) in pathogenesis of experimental hepatorenal syndrome (HRS). METHODS: Rats were divided into liver cirrhotic group, zinc protoporphyrin IX (ZnPP) treatment group, cobalt protoporphyrin (CoPP) treatment group and sham group. Biliary cirrhosis was established by bile duct ligation in the first three groups. Rats in the ZnPP and CoPP treatment groups received intraperitoneal injection of ZnPP and CoPP, respectively, 24 h before sample collection. Expression of HO-1 mRNA in kidney was detected by reverse-transcription polymerase chain reaction, while protein expression was determined by immunohis-tochemical analysis. Hematoxylin and eosin staining was performed to observe liver cirrhosis and renal structure. Renal artery blood flow, mean arterial pressure and portal vein pressure, 24 h total urinary volume, serum and urine sodium concentrations, and creatinine clearance rate (Ccr) were also measured.RESULTS: The HO-1 mRNA and protein expression levels in kidney, 24 h total urinary volume, renal artery blood flow, serum and urine sodium concentration and Ccr were lower in cirrhotic group than in sham group (P < 0.05). However, they were significantly lower in ZnPP treatment group than in cirrhotic group and significantly higher in CoPP treatment group than in cirrhotic group (P < 0.05). CONCLUSION: Low HO-1 expression level in kidney is an important factor for experimental HRS.

Pseudocirrhosis after the Use of Taxanes and Bevacizumab in Metastatic Breast Cancer： Case Reports

Currently, multiple lines of cytotoxic chemotherapy for treatment of metastatic breast cancer are available, and Taxanes, used as monotherapy or in combination with anti-angiogenic drugs, such as Bevacizumab, are one of the most used schemes in clinical practice. These drugs have different side effects and the liver is one of the most affected organs. The objective of this paper is to report three cases of metastatic breast cancer with positive expression of hormone receptors and without amplification of HER-2 protein that were treated with Taxane and Bevacizumab, developed pseudocirrosis probably caused by these drugs and died due to liver failure. It can be drawn from the study that liver failure, as a pseudocirrhosis evolution, is an unusual but lethal event that may occur during the treatment of metastatic breast cancer with Taxanes and Bevacizumab. This warns the importance of diagnostic suspicion of this pathology.

Renal dysfunction in cirrhosis: acute kidney injury and the hepatorenal syndrome

Renal dysfunction is a common complication of liver cirrhosis and of utmost clinical and prognostic relevance.Patients with cirrhosis are more prone to developing acute kidney injury(AKI)than the non-cirrhotic population.Pre-renal AKI,the hepatorenal syndrome type of AKI(HRS-AKI,formerly known as‘type 1’)and acute tubular necrosis represent the most common causes of AKI in cirrhosis.Correct differentiation is imperative,as treatment differs substantially.While pre-renal AKI usually responds well to plasma volume expansion,HRS-AKI and ATN require different specific approaches and are associated with substantial mortality.Several paradigms,such as the threshold of 2.5 mg/dL for diagnosis of HRS-AKI,have recently been abolished and novel urinary biomarkers are being investigated in order to facilitate early and correct diagnosis and treatment of HRS-AKI and other forms of AKI in patients with cirrhosis.This review summarizes the current diagnostic criteria,as well as pathophysiologic and therapeutic concepts for AKI and HRS-AKI in cirrhosis.

Effect of allogeneic umbilical cord mesenchymal stem cell transplantation in a rat model of hepatic cirrhosis

OBJECTIVE：To determine the effects of human umbilical cord mesenchymal stem cell （UCMSC） transplantation, alone or in combination with tanshi- none IIA （Tan ⅡA） on hepatic cirrhosis in rats. METHODS： A rat model of cirrhosis was established. Rats were divided into control, UCMSC, and UCSMC plus Tan IIA groups. Rats in the UCMSC group were injected via the tail vein with 0.2 mL Dil-labeled UCMSC suspension. Intraperitoneal Tan ⅡA injections （20 mg/kg） were started on the day of UCMSC transplantation in the UCMSC plus Tan IIA group, and continued for 7 consecutive days thereafter. Rats were sacrificed 1 day, 3 days, 1 month, and 3 months after transplantation and the numbers of Dil-labeled UCMSCs colonizing the liver were determined. Albumin （ALB） and alanine aminotransferase （ALT） levels were measured in venous blood, and mRNA and protein expression lev- els of human ALB and cytokeratin （CK）-18 in liver tissues were determined by reverse transcrip- tion-polymerase chain reaction and western blotting, respectively.RESULTS： Serum ALT levels were significantly lower and serum ALB levels significantly higher in rats in the UCMSC group compared with the control group （P 〈 0.05）. Hepatic CK-18 and ALB mRNA and protein expression levels increased after transplantation, and were significantly higher in the UCMSC plus Tan ⅡA group compared with the UCMSC group （P 〈 0.05）.CONCLUSION： Human UCMSCs transplanted into rats with liver cirrhosis can grow and differentiate into hepatocyte-like cells resulting in improved liver function in vivo. Tan ⅡA further influenced transplantation outcomes.