食管胃底静脉曲张破裂大出血的内镜下硬化治疗

目的食管胃底静脉曲张破裂大出血内镜下硬化剂治疗的疗效.方法全组共82例,男50例,女32例,年龄18岁～74岁,均为住院患者,经内镜检查确诊为食管静脉重度曲张78例,中度曲张4例,肝功能按Child分级,A级20例,B级46例,C级16例.其中80例为上消化道出血急诊入院,2例为主动申请预防性硬化治疗.按住院先后随机分组,硬化剂选用5%鱼肝油酸钠,1%乙氧硬化醇,82例患者304次内镜下硬化治疗.内镜下单纯静脉内多点、大剂量、快速的注射方法和内镜先端部压迫靶静脉,序贯三点静脉穿刺技巧,与传统的内镜下硬化治疗操作方法进行比较,并经3a随访.结果止血76例(止血率95%),食管静脉曲张消失68例(食管静脉曲张消失率82.9%),54例随访3a,存活率88.9%,与传统方法比较,止血P值>0.5,食管静脉消失P值<0.01,治疗次数3.36次,P值<0.001,平均住院天数56d,P值<0.001.结论内镜下硬化治疗的新方法优于传统的内镜下硬化治疗.

Clinicopathologic characteristics of intrahepatic cholangiocarcinoma in patients with positive serum a-fetoprotein

AIM:To explore clinicopathologic characteristics of intrahepatic cholangiocarcinoma (ICC) in patients with positive serum a-fetoprotein (AFP). METHODS:One hundred and thirty one patients who underwent surgical dissection for pathologically confirmed ICC were divided into a positive AFP (> 20 ng/mL) group (n = 32) and a negative AFP group (n = 99), whose clinicopathologic features were analyzed and compared. RESULTS:The positive rate of HBsAg and liver cirrhosis of the positive AFP group was higher than that of the negative AFP group, while the positive rate of CA19-9 (> 37 U/mL) and the lymph node metastasis rate was lower. CONCLUSION:ICC patients with positive AFP share many clinicopathologic similarities with hepatocellular carcinoma.

Transient elastography for the assessment of chronic liver disease: Ready for the clinic?

Transient elastography is a recently developed non- invasive technique for the assessment of hepatic fi brosis. The technique has been subject to rigorous evaluation in a number of studies in patients with chronic liver disease of varying aetiology. Transient elastography has been compared with histological assessment of percutaneous liver biopsy, with high sensitivity and specificity for the diagnosis of cirrhosis, and has also been used to assess pre-cirrhotic disease. However, the cut-off values between different histological stages vary substantially in different studies, patient groups and aetiology of liver disease. More recent studies have examined the possible place of transient elastography in clinical practice, including risk stratifi cation for the development of complications of cirrhosis. This review describes the technique of transient elastography and discusses the interpretation of recent studies, emphasizing its applicability in the clinical setting.

Histological abnormalities of the small bowel mucosa in cirrhosis and portal hypertension

AIM: To study the small bowel (SB) mucosa on biopsy in cirrhotic patients with portal hypertension and in non-cirrhotic controls and grade fi ndings according to the Marsh criteria. METHODS: We prospectively enrolled 51 consecutive patients undergoing an upper endoscopy for their routine medical care. Twenty f ive patients with cirrhosis and portal hypertension were compared to 26 controls. We obtained coeliac serology and multiple upper small bowel biopsies on all 51 patients. A GI pathologist interpreted biopsies and graded fi ndings according to the Marsh criteria. We assessed equivalence in Marsh grade between cirrhotic and non-cirrhotic controls using the Mann-Whitney test for equivalence. RESULTS: Gender, ethnicity and age were similar between both groups. Marsh grades were equivalent between the groups. Grade of 0 was present in 96% and grade of 1 was present in 4% of both groups and there was no villus atrophy or decrease in villus/crypt ratio in patients with portal hypertension. CONCLUSION: This study provides evidence for the lack of villus atrophy in patients with cirrhosis and portal hypertension, and supports the continuous reliance on the Marsh criteria when the diagnosis of coeliac disease is to be made in the presence of cirrhosis.

Hepatic encephalopathy in patients with liver cirrhosis:Is there a role of malnutrition?

Hepatic encephalopathy(HE) is a common complica-tion in patients with liver cirrhosis but its pathogenesis remains incompletely understood.Malnutrition is com-monly encountered in patients with liver cirrhosis and it has been reported to affect the quality of life of this group of patients.Experimental studies suggest that low energy intake and poor nutritional status may facil-itate the development of HE but there are scarce data on the potential role of malnutrition in HE in patients with liver cirrhosis.Two recently published studies have evaluated the potential role of malnutrition in the development of HE in cirrhotic patients with conflicting results.In this letter to the editor we briefly present the results of the two studies as well as potential rea-sons for the conflicting results reported.

Immunohistochemical expression of intrarenal renin angiotensin system components in response to tempol in rats fed a high salt diet

AIM To determine the effect of tempol in normal rats fed high salt on arterial pressure and the balance between antagonist components of the renal renin-angiotensin system.METHODS Sprague-Dawley rats were fed with 8% NaCl high-salt （HS） or 0.4% NaCl （normal-salt, NS） diet for 3 wk, with or without tempol （T） （1 mmol/L, administered in drinking water）. Mean arterial pressure （MAP）, glomerular fltration rate （GFR）, and urinary sodium excretion （UVNa） were measured. We evaluated angiotensin Ⅱ （Ang Ⅱ）, angiotensin 1-7 （Ang 1-7）, angiotensin converting enzyme 2 （ACE2）, mas receptor （MasR）, angiotensin type 1 receptor （AT1R） and angiotensin type 2 receptor （AT2R） in renal tissues by immunohistochemistry.RESULTSThe intake of high sodium produced a slight but signifcant increase in MAP and differentially regulated components of the renal renin-angiotensin system （RAS）. This included an increase in Ang Ⅱ and AT1R, and decrease in ACE-2 staining intensity using immunohistochemistry. Antioxidant supplementation with tempol increased natriuresis and GFR, prevented changes in blood pressure and reversed the imbalance of renal RAS components. This includes a decrease in Ang Ⅱ and AT1R, as increase in AT2, ACE2, Ang （1-7） and MasR staining intensity using immunohistochemistry. In addition, the natriuretic effects of tempol were observed in NS-T group, which showed an increased staining intensity of AT2, ACE2, Ang （1-7） and MasR.CONCLUSION These findings suggest that a high salt diet leads to changes in the homeostasis and balance between opposing components of the renal RAS in hypertension to favour an increase in Ang Ⅱ. Chronic antioxidant supplementation can modulate the balance between the natriuretic and antinatriuretic components of the renal RAS.

Clinical features and management of primary biliary cirrhosis

Primary biliary cirrhosis(PBC),which is characterised by progressive destruction of intrahepatic bile ducts,is not a rare disease since both prevalence and incidence are increasing during the last years mainly due to the improvement of case finding strategies.The prognosis of the disease has improved due to both the recognition of earlier and indolent cases,and to the wide use of ursodeoxycholic acid(UDCA).New indicators of prog-nosis are available that will be useful especially for the growing number of patients with less severe disease.Most patients are asymptomatic at presentation.Pruri-tus may represent the most distressing symptom and,when UDCA is ineffective,cholestyramine represents the mainstay of treatment.Complications of long-standing cholestasis may be clinically relevant only in very ad-vanced stages.Available data on the effects of UDCA on clinically relevant end points clearly indicate that the drug is able to slow but not to halt the progression of the disease while,in advanced stages,the only thera-peutic option remains liver transplantation.

Antiviral therapy in hepatitis C virus cirrhotic patients in compensated and decompensated condition

The main goals of treating cirrhotic patients with antiviral therapy are to attain sustained viral clearance(SVR),halt disease progression,and prevent re-infection of the liver graft.However,while the medical need is great,the use of interferon and ribavirin might expose these patients to severe treated-related side effects as a large proportion of them have pre-existing hematological cytopenias.We have reviewed potential benefits and risks associated with antiviral drugs in patients with liver cirrhosis,due to hepatitis C virus(HCV) infection.In cases presenting with bridging fibrosis or cirrhosis,current regimens of antiviral therapy have attained a 44%-48% rate of SVR.In cirrhotic patients with portal hypertension,the SVR rate was 22% overall,12.5% in patients with genotype 1,and 66.7% in those with genotypes 2 and 3 following therapy with low doses of either Peg-IFN alpha-2b and of ribavirin.In patients with decompensated cirrhosis,full dosages of Peg-IFN alpha-2b and of ribavirin produced a SVR rate of 35% overall,16% in patients with genotype 1 and 4,and 59% in those with genotype 2 and 3.Use of hematological cytokines will either ensure full course of treatment to be accomplished with and prevent development of treatment-associated side effects.Major benefits after HCV eradication were partial recovery of liver metabolic activity,prevention of hepatitis C recurrence after transplantation,and removal of some patients from the waiting list for liver transplant.Several observations highlighted that therapy is inadvisable for individuals with poor hepatic reserve(Child-Pugh-Turcotte score ≥ 10).Although SVR rates are low indecompensated cirrhotics due to hepatitis C,these patients have the most to gain as successful antiviral therapy is potentially lifesaving.

Liver cirrhosis induced by long-term administration of a daily low dose of amiodarone: A case report

The anti-arrhythmic agent amiodarone （AD） is associated with numerous adverse effects, but serious liver disease is rare. The improved safety of administration of daily low doses of AD has already been established and this regimen is used for long-term medication. Nevertheless, asymptomatic continuous liver injury by AD may increase the risk of step-wise progression of non-alcoholic fatty liver disease. We present an autopsy case of AD-induced liver cirrhosis in a patient who had been treated with a low dose of AD （200 rag/d） daily for 84 too. The patient was a 85-year-old male with a history of ischemic heart disease. Seven years after initiation of treatment with AD, he was admitted with cardiac congestion. The total dose of AD was 528 g. Mild elevation of serum aminotransferase and hepatomegaly were present. Liver biopsy specimens revealed cirrhosis, and under electron microscopy numerous lysosomes with electron-dense, whorled, lamellar inclusions characteristic of a secondary phospholipidosis were observed. Initially, withdrawal of AD led to a slight improvement of serum aminotransferase levels, but unfortunately his general condition deteriorated and he died from complications of pneumonia and renal failure. Long-term administration of daily low doses of AD carries the risk of progression to irreversible liver injury. Therefore, periodic examination of liver function and/or liver biopsy is required for the management of patients receiving long-term treatment with AD.

Differences in viral kinetics between genotypes 1 and 3 of hepatitis C virus and between cirrhotic and non-cirrhotic patients during antiviral therapy

AIM： TO evaluate the impact of hepatitis C virus （HCV） infection with genotype 1 or 3 and the presence or absence of liver cirrhosis （LC） in the early viral kinetics response to treatment. METHODS： Naive patients （n = 46） treated with interferon-α （IFN-α） and ribavirin and followed up with frequent early HCV-RNA determinations were analysed. Patients were infected with genotype 1 （n = 28, 7 with LC） or 3 （n = 18, 5 with LC）. RESULTS： The first phase decline was larger in genotype 3 patients than in genotype 1 patients （1.72 vs 0.95 log IU/mL, P 〈 0.001）. The second phase slope decline was also larger in genotype 3 patients than in genotype 1 patients （0.87 vs 0.15 log/wk, P 〈 0.001）. Differences were found in both cirrhotic and non-cirrhotic patients. Genotype 1 cirrhotic patients had a slower 2^nd phase slope than non-cirrhotic patients （0.06 vs 0.18 log/wk, P 〈 0,02）. None of genotype 1 cirrhotic patients had a 1^st phase decline larger than 1 log （non-cirrhotic patients： 55%, P 〈 0.02）. A similar trend toward a slower 2nd phase slope was observed in genotype 3 cirrhotic patients but the 1^st phase slope decline was not different. Sustained viral response was higher in genotype 3 patients than in genotype 1 patients ,（72% vs 14%, P 〈 0.001） and in genotype 1 non-cirrhotic patients than in genotype 1 cirrhotic patients （19% vs 0%）. A second phase decline slower than 0.3 log per week was predictive of non-response in all groups. CONCLUSION： Genotype 3 has faster early viral decline than genotype 1. Cirrhosis correlates with a slower 2nd phase decline and possibly with a lower 1^st phase slope decline in genotype 1 patients.

Collapsing focal segmental glomerulosclerosis: Current concepts

Collapsing focal segmental glomerulosclerosis （cFSGS）, also known as collapsing glomerulopathy is currently classified under the rubric of FSGS. However, its de-fining morphological features are in stark contrast to those observed in most other variants of FSGS. During the early stage of the disease, the lesion is character-ized pathologically by an implosive segmental and/or global collapse of the glomerular capillary tufts, marked hypertrophy and hyperplasia of podocytes, and severe tubulointerstitial disease. With advancement of the disease, segmental and/or global glomerulosclerosis is also observed in association with the collapsing le-sions. The etiology of this enigmatic disorder is still elusive, but a growing list of diseases/conditions is being reported in association with this morphological pattern of renal parenchymal injury. The pathogenesis of cFSGS involves discreet epithelial cell injury leadingto cell cycle dysregulation and a proliferative cellularphenotype. From the clinical perspective, cFSGS is no-torious for its propensity to affect black people, a highincidence and severity of nephrotic syndrome, markedresistance to empirical therapy, and rapid progressionto end-stage renal disease. The lesion has also beenreported in transplanted kidneys either as recurrent orde novo disease, frequently leading to graft loss. Mostcases have been reported in western countries, but the lesion is also being increasingly recognized in the tropi-cal regions. The recent increase in reporting of cFSGS partly refects a true increase in the incidence and part-ly a detection bias. There is no specifc treatment for the disorder at present. Newer insights into the patho-genesis may lead to the development of targeted and specifc therapy in near future. There is an urgent need to increase awareness of the lesion among pathologists and nephrologists, especially those from developing countries, to ensure accurate diagnosis and appropriate managment. With the accumulation of more and more data, it is hoped that the prevailing confusion about the nosological identity of the lesion will also be resolved in a more logical way.

Evaluation and management of patients with refractory ascites

Some patients with ascites due to liver cirrhosis become no longer responsive to diuretics. Once other causes of ascites such as portal vein thrombosis, malignancy or infection and non-compliance with medications and low sodium diet have been excluded, the diagnosis of refractory ascites can be made based on strict criteria. Patients with refractory ascites have very poor prognosis and therefore referral for consideration for liver transplantation should be initiated. Search for reversible components of the underlying liver pathology should be undertaken and targeted therapy, when available, should be considered. Currently, serial large volume paracentesis （LVP） and transjugular intrahepatic portasystemic stent-shunt （TIPS） are the two mainstay treatment options for refractory ascites. Other treatment options are available but not widely used either because they carry high morlJidity and mortality （most surgical options） rates, or are new interventions that have shown promise but still need further evaluation. In this comprehensive review, we describe the evaluation and management of patients with refractory ascites from the prospective of the practicing physician.

Non-selective beta-blockers in cirrhosis:Current concepts and controversies

Non-selective beta-blockers(NSBBs) have been at the forefront in the management of portal hypertension in liver cirrhosis for the last three decades, a trusty component in the armamentarium of the Hepatologist. The role of beta-blockers has been cemented for years in cardiac disease including angina, hypertension and in heart failure, however NSBBs with their non-selective effects on β1 and β2 receptors have led to them fondly being termed "the hepatologist's aspirin". NSBBs' role in reduction of portal pressure in the setting of primary and secondary prophylaxis for variceal haemorrhage has been well established. NSBBs include propranolol, nadolol and carvedilol- with the latter having been shown to be effective in patients who often fail to demonstrate a haemodynamic response to propranolol. Recent observational studies however have served for the Hepatology community to question the beneficial role of NSBBs in portal hypertension, especially in advanced cases with refractory ascites. The deleterious effect in patients with refractory ascites in a few studies led to a U-turn in clinical practice, with some in the Hepatology community withdrawing their usage in patients with advanced cirrhosis. This also led to the "window hypothesis" suggesting there may be only be a finite time frame when NSBBs have a beneficial effect in portal hypertension. The window hypothesis proposed the window for the benefits of NSBBs is closed in early portal hypertension, opening as portal hypertension progresses with it closing in advanced liver disease. The window was proposed to close in conditions such as refractory ascites or spontaneous bacterial peritonitis when patients may not necessarily mount a compensatory haemodynamic response when on NSBBs. Some centres however have continued the practice of NSBBs in advanced cirrhosis with published data challenging the scepticisms of other groups who stop NSBBs. Thus the debate, like the window hypothesis has opened, with more questions to be answered about NSBB's mechanism of action not only in reducing portal hypertension but also their effects on systemic haemodynamics and on the pro-inflammatory pathways often activated in cirrhosis especially in advanced disease. This article serves to review the role of NSBBs in the management of portal hypertension/cirrhosis and concentrate on current concepts and controversies in this field.

Single low shear stress results in atherosclerosis in vivo

Objective: Whether single low shear stress can result in atherosclerosis without hyperliposis-diet in vivo or not is unknown. Methods: Based on an electromagnetic blood flow meter and a method to determine the pulsatile shear stress from blood flow rate waveform and its software,we developed an in vivo pulsatile blood flow rate-shear stress determining system.The left external carotid arteries of 20 adult New Zealand white rabbits were ligated and the rabbits were fed with a standard chow for 2,4,8 or 12 weeks,then the common carotid arteries of 2 sides in each rabbit were harvested for morphologic test. Results: The ligation reduced pulsatile shear stress of left common carotid significantly,for example,τ_ mean changed from(21.16±7.17) dynes/cm 2 to(3.13±2.28) dynes/cm 2(p=2.176E-21),meanwhile,the pulsatile shear stress of right common carotid did not change significantly,which lasted more than 12 weeks.Atherosclerotic plaques were found after 8 and 12 weeks in pulsatile-low-shear-stress left(not normal-shear-stress right) common carotid arteries.Conclusion:Single pulsatile low shear stress can result in atherosclerosis.It supports the pulsatile low shear stress(not hypolipidemia) is the key risk factor for atherosclerosis.

Lowering vascular calcification burden in chronic kidney disease:Is it possible?

High prevalence of atherosclerosis and arterial calcifca-tion in chronic kidney disease is far beyond the explana-tion by common cardiovascular risk factors such as aging diabetes, hypertension and dyslipidemia. The magnitude of coronary artery calcification is independently and inversely associated with renal function. In addition to cardiovascular risk factors, other chronic kidney disease-related risks such as phosphate retention, excess of calcium and prolonged dialysis vintage also contribute to the development of vascular calcifcation. Strategies to lower vascular calcifcation burden in chronic kidney dis-ease population should include minimizing chronic kidney disease and atherosclerotic risk factors. Current therapies available are non-calcium containing phosphate bind-ers, low dose active vitamin D and calcimimetic agent. The role of bisphosphonates in vascular calcification in chronic kidney disease population remains unclear. Preliminary data on sodium thiosulfate are promising, however, larger studies on effcacy and patient outcomes are necessary. Several large randomized controlled trials have confrmed the lack of beneft of statin in attenuat-ing the progression of vascular calcifcation.

Does protracted antiviral therapy impact on HCV-related liver cirrhosis progression?

AIM: To study the outcomes of patients with compensated hepatitis C virus-related cirrhosis. METHODS: Twenty-four grade A5 and 11 grade A6 of Child-Pugh classification cirrhotic patients with active virus replication, treated for a mean period of 31.3 ± 5.1 mo with moderate doses of interferon-alpha and ribavirin, were compared to a cohort of 36 patients with similar characteristics, without antiviral treatment. Salivary caffeine concentration, a liver test of microsomal function, was determined at the starting and thrice in course of therapy after a mean period of 11 ± 1.6 mo, meanwhile the resistive index of splenic artery at ultra sound Doppler, an indirect index of portal hypertension, was only measured at the beginning and the end of study. RESULTS: Eight out of the 24 A5- (33.3%) and 5 out of the 11 A6- (45.45%) treated-cirrhotic patients showed a significant improvement in the total overnight salivary caffeine assessment. A reduction up to 20% of the resistive index of splenic artery was obtained in 3 out of the 8 A5- (37.5%) and in 2 out of the 5 A6- (40%) cirrhotic patients with an improved liver function, which showed a clear tendency to decrease at the end of therapy. The hepatitis C virus clearance was achieved in 3 out of the 24 (12.5%) A5- and 1 out of the 11 (0.091%) A6-patients after a median period of 8.5 mo combined therapy. In the cohort of non-treated cirrhotic patients, not only the considered parameters remained unchanged, but 3 patients (8.3%) had a worsening ofthe Child-Pugh score (P = 0.001).CONCLUSION: A prolonged antiviral therapy with moderate dosages of interferon-alpha and ribavirin shows a trend to stable liver function or to ameliorate the residual liver function, the entity of portal hypertension and the compensation status at acceptable costs.

A review on function of the Naoxintong Capsule in anti atherosclerosis and protection of vascular endothelium

Atherosclerosis(As) is the common pathological basis of cardiovascular and cerebrovascular diseases, it starts with the injury of vascular endothelial. The Naoxintong Capsule, a modern patent traditional Chinese medicine, is composed of Huangqi, Danshen, Quanxie, Shuizhi and other sixteen herbs. It is extensively used to treat coronary heart disease, stroke and other cardiovascular and cerebrovascular diseases, with the activity of anti-coagulation, anti-inflammatory, protecting endothelial cells, anti-atherogenic and plaque stabilization.