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 dissect...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.展开更多
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 liv...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.展开更多
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 ...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.展开更多
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 patien...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.展开更多
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 ...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.展开更多
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 a...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.展开更多
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 ro...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.展开更多
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 ...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.展开更多
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,...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.展开更多
文摘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.
基金a Centenary Fellowship from the Hammersmith Hospital Trustees Research Committee, London, United KingdomThe British Medical Research Council (G99000178)+1 种基金The United Kingdom Engineering Physics and Science Research Council, Pfi zer Global Research Ltd, Sandwich, United KingdomThe United Kingdom Department of Health Research and Development Fund
文摘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.
文摘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.
基金Supported by the Alves de Queiroz Family Fund for Research
文摘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.
文摘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.
基金Supported by Grants-in-Aid No. 16590289,16790211 and 16790212, and "Open Research Center" Project for Private Universities: Matching fund Subsidy (2004-2008), from Ministry of Education, Culture, Sports, Science and Technology, Japan
文摘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.
文摘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.
文摘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.
文摘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.