13C-methacetin and 13C-galactose breath tests can assess restricted liver function even in early stages of primary biliary cirrhosis

OBJECTIVE: The 13C-methacetin breath test quantitatively evaluates cytochrome P450-dependent liver function. The 13C-galactose breath test non-invasively measures the galactose oxidation capacity of the liver. The aim of this study was to find out whether these breath tests are sensitive parameters also in non-cirrhotic patients with primary biliary cirrhosis. MATERIAL AND METHODS: Nineteen patients with early-stage primary biliary cirrhosis (no cirrhotic alterations in the liver biopsy, Ludwig stage I-III) and 20 healthy controls underwent the 13C-methacetin and 13C-galactose breath tests. RESULTS: Patients with primary biliary cirrhosis metabolized less 13C-methacetin than controls (cumulative recovery within 30 min 7.5+/-2.4% versus 14.0+/-2.6%; p < 0.001). When a cut-off > 9.8% was used for the cumulative recovery after 30 min, the methacetin breath test reached 84.2% sensitivity and 95.0 specificity. In the 13C-galactose breath test, the percentage recovery at 60 min in patients was 3.1+/-1.3%/h, and 6.3+/-1.1%/h in controls (p < 0.001). Using a cut-off > 4.7%/h, the galactose breath test reached 89.5% sensitivity and 95.0 specificity. CONCLUSIONS: In non-cirrhotic, early-stage, primary biliary cirrhosis the 13C-methacetin breath test and the 13C-galactose breath test reliably indicate decreased liver function. The 13C-galactose breath test can also predict the histological score.     

13C-methacetin breath test shortened: 2-point-measurements after 15 minutes reliably indicate the presence of liver cirrhosis

BACKGROUND AND GOALS: The 13C-methacetin breath test (MBT) measures the activity of the cytochrome P450 dependent enzyme system and has been developed to assess the functional hepatic mass. We evaluated simple modifications of the 13C-MBT to further increase its practicability and therefore clinical acceptance. STUDY: One hundred and four patients with different chronic liver diseases (including 35 patients with histologically proven cirrhosis) and 65 healthy controls underwent the 13C-MBT. Breath test results of 2-point measurements were compared with conventional breath test results (cumulative recovery after 30 min) and liver histology. RESULTS: The 2-point-measurement at 0 and 15 minutes (with a cut-off <14.6 per thousand delta over baseline) had 92.6% sensitivity and 94.1% specificity in identifying the presence of cirrhosis compared with liver histology. The 2-point-measurements at 5 and 10 minutes also provided good discrimination between cirrhotic and noncirrhotic patients. CONCLUSIONS: The 13C-MBT using 2-point-measurement of breath samples at baseline and after 15 minutes reliably indicates decreased liver function in liver cirrhosis. This simplification of the 13C-MBT will increase practicability and cost efficiency, thus facilitating its clinical acceptability.     

Measurement of hepatic functional mass by means of ^13C-methacetin and 13C-phenylalanine breath tests in chronic liver disease： Comparison with Child-Pugh score and serum bile acid levels

AIM: To evaluate and compare the clinical usefulness of ~(13)C-phenylalanine and ~(13)C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels. METHODS: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated. RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids. Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test. CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.     

IRIS13 C-美沙西汀呼气试验在肝硬化患者中的应用及评价

目的 探讨13 C-美沙西汀呼气试验在评估肝硬化患者肝功能状况中的临床应用价值.方法 42例肝硬化患者,根据传统child-Pugh分级分为A、B、C三组.均做常规肝功能生化检测及3C-美沙西汀呼气试验.结果 随着Child-Pugh分级的加重,呼气试验参数值MVmax40(40分钟前代谢速率峰值与正常值(27)的比值)、CUM40(40分钟CO2累积呼出丰度与正常值(12)的比值)和CUM120(120分钟C02累积呼出丰度与正常值(28)的比值)显著降低,组间差异有显著性(P＜0.05).三参数值与Child-Pugh分级计分及一些临床肝功能检测结果显著相关(P＜0.05).结论 IRIS13C(红外线同位素12C)-美沙西汀呼气试验能准确反应肝脏储备和代偿功能,是传统Child-Pugh分级及临床肝功能生化检测评估肝功能的有益补充,具有即时、安全、有效、定量、无创的特点.     

IRIS13C-美沙西汀呼气试验对肝功能检测临床价值与预后评估

目的探讨红外线同位素能谱分析仪(IRIS)13C-美沙西汀呼气试验在肝硬化肝功能分级及预后评估应用中的价值.方法选取肝硬化患者59例作为研究对象,健康志愿者12例作为正常对照组,进行13C-美沙西汀呼气试验肝功能检测并与Child-pugh肝功能分级进行比较,随访半年观察病情预后.结果①13C-美沙西汀呼气试验mvmax40值、cum40值及cum120值在对照组、Child-pugh A、B、C组间依次降低,组间差异均有显著性(P＜0.01),且与Child-pugh肝功能分级具有显著负相关性(r值分别为-0.562,-0.614和-0.716,P＜0.001).②13C-美沙西汀呼气试验与Child-pugh肝功能分级判定肝硬化患者肝功能状况具有一致性(Kappa=0.69,P＜0.05).③预后:13C-分级为一级(包括亚病理性肝损害3例)22例均预后良好;13C-分级为二级的14例中,2例死于上消化道大出血;13C-分级为三级的11例中5例分别先后死于肝昏迷、肝肾综合征及感染性休克.结论13C-美沙西汀呼气试验作为一种灵敏、定量的肝功能试验可用于肝硬化患者的肝功能状况分级并有助于本病手术选择与预后评估.     

IRIS13C-美沙西汀呼气试验与Child-Pugh分级、MELD评分评估肝硬化患者肝功能的比较

目的通过比较肝硬化患者13C-美沙西汀呼气试验、Child-Pugh分级及MELD评分,结合腹部CT测量肝脾体积以探讨13C-美沙西汀呼气试验评价肝脏储备和代偿功能的临床应用价值。方法 139例肝硬化患者行13C-美沙西汀呼气试验、Child-Pugh分级及MELD评分,分析各组13C-美沙西汀呼气试验的呼气参数值之间的相互关系,比较乙型肝炎肝硬化患者肝脏、脾脏体积变化以进一步评估13C-美沙西汀呼气试验反映肝细胞储备和代偿功能的作用。结果13C-美沙西汀呼气试验肝脏功能分级与肝硬化患者传统的Child-Pugh分级判定肝功能状况具有良好一致性(κ=0.55,P<0.05),与MELD评分比较具有一致性(κ=0.41,P<0.05);肝脏病变程度越重,13C-美沙西汀呼气试验量化值越小,肝硬化患者呼气参数值显著下降(P<0.05),肝细胞储备和代偿功能越差;呼气试验参数与Child-Pugh分级计分、MELD评分、血清总胆红素、国际标准化比值(INR)呈明显负相关(P<0.01),与血清白蛋白、前白蛋白、凝血酶原活动度、胆碱酯酶呈正相关(P<0.01),与肝硬化患者脾脏体积呈负相关(P<0.05),与血肌酐、ALT、肝脏体积无显著相关性(P>0.05)。68例乙型肝炎肝硬化患者中Child-Pugh分级、MELD评分越高,肝脏体积越小;13C-美沙西汀呼气试验量化值与乙型肝炎肝硬化患者肝脏体积呈正相关(P<0.05)。结论 IRIS13C(红外线同位素13C)-美沙西汀呼气试验可准确反应肝硬化患者肝脏储备及代偿功能。     

Relationship between thrombopoietin serum levels and liver function in patients with chronic liver disease related to hepatitis C virus infection

OBJECTIVES: Thrombopoietin (Tpo) is an important regulator of megakaryocyte maturation and platelet production, and is mainly produced by the liver. A decrease in Tpo production is partly responsible for the thrombocytopenia observed in patients with chronic liver disease (CLD). The aim of this study was to evaluate the relationship between Tpo serum levels and liver function in patients with CLD related to hepatitis C virus (HCV) infection. METHODS: We studied 37 patients with various degrees of HCV-related CLD. Of the patients, 17 had chronic hepatitis and 20 liver cirrhosis. Liver function was evaluated in all patients by the following hepatic blood flow dependent and independent tests that explore various hepatic metabolic functions: carbon-13 (13C)-aminopyrine breath test (13C-ABT), 13C-galactose breath test (13C-GBT), and monoethylglycinexylidide (MEGX) test. Liver function tests results were correlated with Tpo serum levels. RESULTS: Tpo serum levels were significantly lower in patients with liver cirrhosis (88 +/- 23 pg/ml) as compared to those in patients with chronic hepatitis (128 +/- 55 pg/ml, p=0.0031). However, they did not correlate with serum albumin, bilirubin, or prothrombin activity. Tpo serum levels showed a significant positive correlation with 13C-ABT results (hourly dose at 30 min, rs=0.489, p=0.002; cumulative dose at 120 min, rs=0.425, p=0.008). Moreover, they showed a fair, positive correlation with 13C-GBT hourly dose at 30 min (rs=0.366, p=0.028), and a trend toward a positive correlation with the various MEGX test sampling times (MEGX15, rs=0.314, p=0.059; MEGX30, rs=0.284, p=0.088; and MEGX60, rs=0.320, p=0.059). CONCLUSIONS: In this study we have shown that a progressive decline in liver function in patients with HCV-related CLD is paralleled by a decrease in Tpo production. The different correlations observed between Tpo and the various liver function tests suggests that this finding is mainly the result of a decrease in hepatic functional mass rather than dependent on alteration in splanchnic hemodynamic.     

Probability of liver cancer and survival in HCV-related or alcoholic-decompensated cirrhosis. A study of 377 patients.

BACKGROUND: Although chronic alcohol intake and chronic hepatitis C may progress to cirrhosis and hepatocellular carcinoma (HCC), few data are available about survival and probability of developing HCC in decompensated cirrhosis of both aetiologies. METHODS: This study identified factors related with probability of developing HCC and survival in a cohort of 377 consecutive patients with decompensated HCV-related cirrhosis (200 cases) or alcoholic cirrhosis (177 cases) without known HCC, hospitalized for their first hepatic decompensation, as well as to evaluate differences between both aetiologies. Patients were followed for a mean period of 39 +/- 2 months. RESULTS: During follow-up, 42 patients (11.1%) developed HCC (16.5% vs 5.1%) in groups HCV and alcohol, respectively; p = 0.0008), and 131 patients (34.7%) died (42% vs 26.6% in groups HCV and alcohol, respectively; p = 0.002). Age and HCV-cirrhosis were independently related to HCC development, while baseline age and Child-Turcotte-Pugh score were independently correlated with survival. CONCLUSION: Survival in decompensated HCV-related or alcoholic cirrhosis is influenced by age and baseline Child-Turcotte-Pugh score, without differences in cirrhosis aetiology. The risk of developing HCC is greater in HCV-related cirrhosis than in alcoholic cirrhosis.     

Alpha-SMA expression in hepatic stellate cells and quantitative analysis of hepatic fibrosis in cirrhosis and in recurrent chronic hepatitis after liver transplantation

BACKGROUND: The alpha isotype of actin expressed by hepatic stellate cells reflects their activation to myofibroblast-like cell and has been directly related to experimental liver fibrogenesis, and indirectly to human fibrosis in chronic liver disease. AIMS: To evaluate the changes in distribution and percentage of alpha-smooth muscle actin-positive hepatic stellate cells and the correlation with the degree of the fibrosis in cirrhotic livers, as well as in patients with recurrent HCV chronic hepatitis after liver transplantation. METHODS: Human liver biopsies were divided in four groups: (1) normal livers obtained from cadaveric liver donors (n=35), (2) cirrhosis post-HBV hepatitis (n=11), (3) cirrhosis post-HCV hepatitis (n=10), and (4) post-transplant recurrent HCV chronic hepatitis (n=13). Samples were stained with anti-alpha-smooth muscle actin antibody by immunoperoxidase method and semi-quantitatively evaluated. Liver fibrosis was assessed from specimens stained with Masson's trichrome and quantified by computer image analysis. RESULTS: The percentage of alpha-smooth muscle actin-positive hepatic stellate cells was significantly higher in the HBV cirrhosis, HCV cirrhosis and post-transplant HCV recurrent hepatitis groups (36.1+/-15.2, 23.8+/-19.7 and 27.8+/-16.4%, respectively) compared to the liver donor group (2.9+/-4.0%). The alpha-smooth muscle actin-positive hepatic stellate cells to fibrous tissue ratio were significantly higher in the post-transplant recurrent HCV hepatitis group (2.36+/-1.12) compared to both the donor livers and the HCV cirrhosis groups (0.74+/-1.09 and 1.03+/-0.91, respectively). The alpha-smooth muscle actin-positive hepatic stellate cell percentage and fibrosis correlated positively in the post-transplant recurrent HCV hepatitis group and negatively in the HCV cirrhosis group. No difference in the immunohistochemical and morphometrical variables was found between the HCV cirrhosis and HBV cirrhosis groups. CONCLUSIONS: These results indirectly confirm that, in vivo, alpha-smooth muscle actin expression is a reliable marker of hepatic stellate cells activation which precedes fibrous tissue deposition even in the setting of recurrent HCV chronic hepatitis after liver transplantation, and it could be useful to identify the earliest stages of hepatic fibrosis and monitoring the efficacy of the therapy. In the presence of advanced cirrhosis other factors, rather than alpha-smooth muscle actin-positive hepatic stellate cells, may sustain fibrosis deposition.     

Quantitative testing of liver function in relation to fibrosis in patients with chronic hepatitis B and C.

BACKGROUND/AIM: Quantitative tests of liver function may be superior to conventional tests to assess the prognosis of patients with liver diseases. There are insufficient data from quantitative testing of liver function (QTLF) for patients with chronic hepatitis B and C, particularly with regard to fibrosis. Therefore, we applied a broad panel of QTLF to these patients. METHODS: Three hundred and sixty-seven consecutive patients with chronic hepatitis B or C underwent liver biopsy and QTLF, which included tests for hepatic metabolism (aminopyrine breath test, galactose elimination capacity) and for hepatic perfusion (sorbitol clearance, indocyanine green clearance). QTLF values were correlated with liver histology (grading and staging for inflammation and fibrosis) and Child-Pugh classification for liver cirrhosis. RESULTS: In patients with no and moderate fibrosis, metabolic liver function was significantly decreased, whereas hepatic perfusion remained normal. Severe fibrosis and cirrhosis showed a significant decline in all QTLFs. Hepatic inflammation only reduced metabolic liver function, irrespective of the inflammatory grade. Viral etiology and HCV genotypes did not change QTLF. CONCLUSIONS: In summary, viral damage compromises hepatic metabolism before perfusion. Therefore, tests of metabolic liver function (aminopyrine breath test, galactose elimination capacity) should be useful to search for drugs that restore liver function in viral hepatitis irrespective of the fibrosis stage.     

13CO2 excretion in breath of normal subjects and cirrhotic patients after 13C-aminopyrine oral load. Comparison with MEGX test in functional differentiation between chronic hepatitis and liver cirrhosis

BACKGROUND/AIMS: Liver function can be evaluated using 13C breath tests that explore liver Cytochrome P450 activity. Aminopyrine is one of the first compounds used in liver function testing. Lidocaine metabolism to monoethylglycinexylidide is also a valid tool to assess liver function. Although liver Cytochrome P450 metabolizes both compounds, lidocaine metabolism is flow-dependent while aminopyrine metabolism does not depend on liver blood flow. METHODOLOGY: The 1st part of the study evaluated the appearance and disappearance rate of 13CO2 in the breath of both normal subjects and in cirrhotic patients, so as to establish optimal sampling times and to evaluate the amount of time needed before performing a subsequent breath test. The 2nd part of the study compared the aminopyrine breath test with the monoethylglycinexylidide test in patients with chronic hepatitis or cirrhosis. RESULTS: Complete 13CO2 disappearance was recorded 24 hours after the test in normal subjects, while it took 3 days to disappear from the breath of cirrhotic patients. Breath sampling at 60, 120 and 180 min were equally valid in differentiating chronic hepatitis from cirrhosis. The aminopyrine breath test and monoethylglycinexylidide test showed a good yet not close correlation. CONCLUSIONS: This study showed that in cirrhotic patients a 13C breath test can be performed 3 days after the previous one. In chronic hepatitis and cirrhotic patients, the aminopyrine breath test and the monoethylglycinexylidide test evaluated similar, but not identical, hepatic subfunctions, suggesting that multiple 13C breath test using different substrates could explore liver function better.     

13C-methacetin and 13C-galactose breath tests can assess restricted liver function even in early stages of primary biliary cirrhosis

Objective. The ¹³C-methacetin breath test quantitatively evaluates cytochrome P450-dependent liver function. The ¹³C-galactose breath test non-invasively measures the galactose oxidation capacity of the liver. The aim of this study was to find out whether these breath tests are sensitive parameters also in non-cirrhotic patients with primary biliary cirrhosis.

Material and methods. Nineteen patients with early-stage primary biliary cirrhosis (no cirrhotic alterations in the liver biopsy, Ludwig stage I–III) and 20 healthy controls underwent the ¹³C-methacetin and ¹³C-galactose breath tests.

Results. Patients with primary biliary cirrhosis metabolized less ¹³C-methacetin than controls (cumulative recovery within 30 min 7.5±2.4% versus 14.0±2.6%; p<0.001). When a cut-off?>?9.8% was used for the cumulative recovery after 30 min, the methacetin breath test reached 84.2% sensitivity and 95.0 specificity. In the ¹³C-galactose breath test, the percentage recovery at 60 min in patients was 3.1±1.3%/h, and 6.3±1.1%/h in controls (p<0.001). Using a cut-off?>?4.7%/h, the galactose breath test reached 89.5% sensitivity and 95.0 specificity.

Conclusions. In non-cirrhotic, early-stage, primary biliary cirrhosis the ¹³C-methacetin breath test and the ¹³C-galactose breath test reliably indicate decreased liver function. The ¹³C-galactose breath test can also predict the histological score.     

Goals of treatment, indication, and treatment for chronic hepatitis C

Hepatitis C virus (HCV) is a major cause of chronic hepatitis and hepatic fibrosis worldwide. Up to 85% of individuals infected with HCV develop chronic infection, which can progress to cirrhosis and hepatocellular carcinoma. The primary goal in the treatment of HCV infection is to reduce the mortality by preventing liver-related deaths associated with the development of hepatocellular carcinoma and decompensated cirrhosis. Pegylated interferons together with ribavirin are currently the standard of care for patients with chronic hepatitis. Here, I discuss the goals of treatment, indication and treatment of chronic hepatitis C.     

13C-galactose breath test and 13C-aminopyrine breath test for the study of liver function in chronic liver disease.

BACKGROUND AND AIMS: Liver biopsy examination is the gold standard to diagnose the presence of cirrhosis. The aim of this study was to evaluate the accuracy of both 13 C-aminopyrine breath test ( 13 C-ABT) and 13 C-galactose breath test ( 13 C-GBT) in the noninvasive assessment of the presence of cirrhosis in patients with chronic liver disease. METHODS: We evaluated 61 patients with chronic liver disease of diverse etiologies (21 compensated cirrhosis). All patients underwent 13 C-GBT and 13 C-ABT, and the results were expressed as a percentage of the administered dose of 13 C recovered per hour (%dose/h) and as the cumulative percentage of administered dose of 13 C recovered over time (%dose cumulative). Results were analyzed according to absence vs presence of cirrhosis. RESULTS: On average, 13 C-GBT %dose/h and %dose cumulative were decreased significantly in patients with compensated cirrhosis, and the same finding was observed for 13 C-ABT results from 30 to 120 minutes. 13 C-GBT %dose/h at 120 minutes had 71.4% sensitivity, 85.0% specificity, and 83.7% accuracy, whereas 13 C-ABT %dose cumulative at 30 minutes had 85.7% sensitivity, 67.5% specificity, and 77.1% accuracy for distinguishing between the 2 subgroups of patients. Combined assessment of 13 C-GBT and 13 C-ABT increased the diagnostic accuracy (80% positive predictive value) of either test alone and reached 92.5% specificity and 100% sensitivity for the diagnosis of cirrhosis. CONCLUSIONS: In patients with chronic liver disease, both 13 C-GBT and 13 C-ABT are useful for the diagnosis of cirrhosis. Combination of the tests increases the diagnostic yield of each test alone.     

Assessment of liver function in acute or chronic liver disease by the methacetin breath test: a tool for decision making in clinical hepatology

Patients suffering from acute or chronic liver disease require on-going assessment of disease progression in terms of the degree of hepatic fibrosis and overall liver impairment. This assessment is pivotal for determining the prognosis and for making decisions about medical treatment and liver transplantation. Currently available methods are either invasive, lack diagnostic accuracy or are limited by technical difficulties such as obesity or biochemical confounders. The metabolic breath test relies on the measurement of tagged metabolites of an organ-specific substrate in the exhaled breath. (13)C-methacetin is metabolized uniquely by the liver, and (13)CO(2) is measured continuously in the exhaled breath. Measuring this liver-specific substrate using molecular correlation spectroscopy provides a rapid, point-of-care, non-invasive method to assess liver function. The use of the (13)C-methacetin breath test (MBT) may provide a powerful tool for clinical hepatologists in decision making at the bedside. This paper reviews recent findings regarding the ability of the point-of-care (13)C-MBT to assess fibrosis, cirrhosis and hepatic functional reserve in patients with acute and chronic liver disease.     

Total effective vascular compliance in patients with cirrhosis: a study of the response to acute blood volume expansion.

Although arterial vasodilation is a well-known feature in patients with cirrhosis, the venous system remains unexplored. To measure total effective vascular compliance, a reflection of the properties of the venous system, rapid volume expansion (300 ml of a gelatin solution in 3 min) was performed in 23 patients. Eleven patients had compensated cirrhosis (Child-Pugh grade A or B), and eight had decompensated cirrhosis (Child-Pugh grade C). Four control patients had mild chronic hepatitis, normal hepatic venous pressure and normal liver architecture. Cardiac index, hepatic venous pressures, hepatic and azygos blood flow and renal plasma flow were measured before and immediately after volume expansion. Right atrial pressure was recorded during volume expansion. This allowed the calculation of total effective vascular compliance, which was higher in patients with decompensated cirrhosis than in those with compensated cirrhosis (4.65 +/- 4.21 vs. 1.34 +/- 0.63 ml.mm Hg-1.kg-1; p less than 0.05). In response to volume expansion, renal vascular resistance decreased significantly in patients with compensated cirrhosis, but not in those with decompensated cirrhosis (-30% +/- 33% vs. +2% +/- 23%; p less than 0.05). No change was seen in glomerular filtration rate. Systemic oxygen consumption increased in patients with compensated cirrhosis, but not in those patients with decompensated cirrhosis (25% +/- 33% vs. -4% +/- 9%; p less than 0.05). Although in all patients with cirrhosis volume expansion increased central venous pressures, azygos blood flow and the hepatic venous pressure gradient did not change.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical, virological and histopathological features: long-term follow-up in patients with chronic hepatitis C co-infected with S. mansoni

BACKGROUND/AIMS: Infection with Schistosoma mansoni is endemic in Egypt leading to hepatic schistosomiasis and eventually portal hypertension. The prevalence of antibodies against hepatitis virus C among Egyptians is 14-51%. The aim of the present study was to investigate the influence of schistosomiasis on chronic hepatitis C with respect to the natural course of the disease, immunology, virology and histology. PATIENTS AND METHODS: One hundred and twenty-six Egyptian patients classified into three groups: group A: chronic hepatitis C (n=33); group B: chronic schistosomiasis (n=30) and group C: chronic hepatitis C and chronic schistosomiasis (n=63) were enrolled and prospectively followed for 62.7 +/- 22 months. Patients infected with other hepatic viruses and/or parasites were excluded. Detailed history, clinical examination, CD4+ and CD8+ lymphocyte counts in blood, hematological and blood chemical values, abdominal ultrasonography, upper endoscopy, HCV RNA titer by RT/PCR, genotype and histological activity index in the liver biopsy were determined. RESULTS: Thirty patients (48%) with HCV and schistosomiasis had liver cirrhosis and Child-Pugh class C vs. five (15%) in HCV patients and none in the schistosomal group. HCV RNA levels ranged between 0.07 and 13 x 10(5) copies/ml in group A, and between 1 and 25 x 10(5) copies/ml in group C. HCV genotype 4 was detected in 58 patients with co-infection (92%) and 21 patients with HCV alone (64%). Patients with coinfection showed higher grading and staging scores in their liver biopsies. Hepatocellular carcinoma was detected only in patients with coinfection. During follow-up, the mortality rate was 12%, 3% and 48% in group A, B and C, respectively. CONCLUSIONS: Patients with concomitant HCV and schistosomiasis infection were characterized by more advanced liver disease, higher HCV RNA titers, predominance of HCV genotype 4, higher histologic activity, higher incidence of cirrhosis and hepatocellular carcinoma as well as a much higher mortality rate.     

13C-美沙西丁呼气试验联合血清胰岛素样生长因子及其结合蛋白测定对肝硬化患者肝功能状况的评估

目的 探讨13C-美沙西丁呼气试验联合血清胰岛素样生长因子-1(insulin like growth factor-1,IGF-1)、胰岛素样生长因子结合蛋白.3(insulin-like growth factor binding protein-3,IGFBP-3)测定对肝硬化患者肝功能状况评估的临床意义.方法随机选取肝炎后肝硬化14例,隔夜空腹,服用13C-美沙西丁75 mg后,通过13C红外线能谱分析仪检测10个时间段呼出碳13的含量,得出Mvmax40(40分钟前13C代谢速率峰值与正常值的比值)、CUM 40(40分钟13CO2累积呼出丰度与正常值的比值)及CUM 120(120分钟13CO2累积呼出丰度与正常值的比值),并同步采用免疫放射法定量测定血清IGF-1、IGFBP-3水平.结果肝硬化患者Mvmax 40、CUM 40、CUM 120值,在Child A、B、C各组间,除A组与B组的CUM 120值外,差异有显著性(P＜0.05).IGF-1,IGFBP-3值在Child A、B、C组间除Child A组与B组间外,差异有显著性(P＜0.05).13C Mvmax 40、CUM40、CUM 120及IGF-1、IGFBP-3值与Child pugh积分呈明显负相关(r-0.881,-0.878,-0.833,-0.700,-0.815),13C Mvmax 40、CUM 40、CUM 120值与IGF-1、IGFBP-3值呈明显正相关.结论13C美沙西丁肝功能呼气试验能对即时的肝细胞贮备功能及代偿功能进行量化评估,结合IGF-1、IGFBP-3检测,是对临床传统方法肝功能判断的有益补充.     

Quantitative testing of liver function in relation to fibrosis in patients with chronic hepatitis B and C

Abstract: Background/Aim: Quantitative tests of liver function may be superior to conventional tests to assess the prognosis of patients with liver diseases. There are insufficient data from quantitative testing of liver function (QTLF) for patients with chronic hepatitis B and C, particularly with regard to fibrosis. Therefore, we applied a broad panel of QTLF to these patients. Methods: Three hundred and sixty‐seven consecutive patients with chronic hepatitis B or C underwent liver biopsy and QTLF, which included tests for hepatic metabolism (aminopyrine breath test, galactose elimination capacity) and for hepatic perfusion (sorbitol clearance, indocyanine green clearance). QTLF values were correlated with liver histology (grading and staging for inflammation and fibrosis) and Child–Pugh classification for liver cirrhosis. Results: In patients with no and moderate fibrosis, metabolic liver function was significantly decreased, whereas hepatic perfusion remained normal. Severe fibrosis and cirrhosis showed a significant decline in all QTLFs. Hepatic inflammation only reduced metabolic liver function, irrespective of the inflammatory grade. Viral etiology and HCV genotypes did not change QTLF. Conclusions: In summary, viral damage compromises hepatic metabolism before perfusion. Therefore, tests of metabolic liver function (aminopyrine breath test, galactose elimination capacity) should be useful to search for drugs that restore liver function in viral hepatitis irrespective of the fibrosis stage.     

The aminopyrine breath test does not correlate with histologic disease severity in patients with cholestasis

To determine whether the aminopyrine breath test can be used to document the presence of cirrhosis in patients with cholestatic liver disease, 19 patients (13 primary biliary cirrhosis, 4 sclerosing cholangitis and 2 chronic extrahepatic bile duct obstruction) underwent clinical and biochemical evaluations, liver biopsies and an aminopyrine breath test. Results were compared with those in 10 patients with biopsy-proven chronic active hepatitis with bridging and/or cirrhosis and in 22 healthy subjects. The aminopyrine breath test results in the 10 cholestatic patients with cirrhosis were not significantly different from the results in precirrhotic cholestatic patients (mean +/- S.D., 11.2 +/- 5.0 vs. 11.6 +/- 2.8% dose per 2 hr, p greater than 0.05) or healthy subjects (11.5 +/- 2.9% dose per 2 hr). In contrast, the results in the patients with chronic hepatitis were markedly depressed (3.2 +/- 1.9% dose per 2 hr, p less than 0.05). The aminopyrine breath test results did not correlate with results of conventional liver function tests in the cholestatic patients. These results demonstrate that the aminopyrine breath test is not clinically useful in identifying the presence of cirrhosis in patients with cholestatic liver disease, and provide further evidence that decreased microsomal enzyme function is a late feature of cholestatic liver disease.