慢性乙型肝炎患者幽门螺杆菌感染的调查分析

目的探讨慢性乙型肝炎患者幽门螺杆菌(H.pylori)的感染情况及其临床意义。方法将167例慢性乙型肝炎患者分为肝炎组、肝硬化组、肝癌组,研究H.pylori感染状况与76例健康对照者的关系,并进一步分析H.pylori感染与肝功能、临床并发症的关系。结果慢性乙型肝炎患者H.pylori感染率为64.1%,明显高于健康对照组34.2%(P<0.01)。其中肝硬化组71.8%和肝癌组75.0%又高于肝炎组51.5%(P<0.05)。H.pylori阳性患者肝性脑病、上消化道出血及ALT水平高于H.pylori阴性患者(P<0.05),H.pylori阳性和H.pylori阴性患者的腹水并发症及TBIL差异无统计学意义(P>0.05)。结论慢性乙型肝炎患者H.pylori感染率显著增加,且H.pylori感染可能加重肝病病程。     

Clinical significance of the trimethadione tolerance test in chronic hepatitis: A useful indicator of hepatic drug metabolizing capacity

Trimethadione (TMO) was chosen as an indicator of quantitative hepatic microsomal function, and its pharmacokinetics were studied in 52 patients with chronic hepatitis. Findings in these patients were compared with those for 26 healthy subjects and 13 patients with renal failure. Patients with chronic hepatitis, but not those with renal failure, showed significant reduction in clearance (CL) and prolongation of half-life (t_1/2), and the extent of abnormalities was found to reflect the severity of histologic changes in liver tissue. The serum dimethadione (DMO)/TMO ratio 4h after the administration of TMO altered in parallel with the CL and t_1/2 of TMO, and abnormalities in this simple ratio were also related to the histologic severity of changes in the liver tissue. A low DMO/TMO ratio (<0.4) was associated with advanced histologic changes (chronic active hepatitis with bridging or chronic active hepatitis with cirrhosis), whereas a high DMO/TMO ratio (>0.4) was associated with mild histologic changes (chronic persistent hepatitis or chronic active hepatitis) (sensitivity, 0.81; specificity, 0.86). These results indicate that the DMO/TMO ratio, which can be obtained from a single blood sampling, reflects the histologic severity of changes in tissue liver, and that the TMO tolerance test is a useful indicator of quantitative liver function.     

Drug disposition in patients with HBsAg-positive chronic liver disease

Chronic infection with hepatitis B virus (HBV) results in a spectrum of hepatic abnormalities ranging from minimal liver dysfunction to severe liver failure. These patients provide an opportunity to examine the relationship between the evolution of the liver disease and the ability to metabolize drugs. We have examined hepatic drug disposition in patients with chronic persistent hepatitis, chronic active hepatitis, and cirrhosis due to HBV infection. Four model drugs were used: two low-extraction capacity-limited drugs (antipyrine and aminopyrine) and two high-extraction flow-limited drugs (ICG and lidocaine). The disposition of the four drugs tested was comparable to that of healthy controls in patients with chronic persistent hepatitis, chronic active hepatitis, and mild cirrhosis. In patients with severe cirrhosis (as defined by the presence of ascites, encephalopathy, or large esophageal varices), there was a significant impairment in the aminopyrine breath test (–31%) and in the clearance of antipyrine (–53%), lidocaine (–49%), and ICG (–54%). These results indicate that impairment of drug clearance occurs only late in the evolution of HBV-related chronic liver disease. This is in keeping with the known slow and insidious progression of the disease.Supported by grants from the Medical Research Council of Canada, The Canadian Liver Foundation and the Fonds de Recherche en Santé du Québec     

Kinetics and dynamics of calcium entry antagonists in systemic hypertension

The calcium-entry antagonists verapamil, diltiazem and nifedipine (and their analogs) are all eliminated by hepatic metabolism and the rate of disposition is dependent on the rate of liver blood flow. During long-term administration, the profound hemodynamic effects of these agents result in changes in hepatic blood flow in association with decreases in arterial pressure, and either increases or decreases in measured cardiac output. This alters the drug's rate of delivery to the site of elimination, with concomitant changes in systemic clearance and a prolongation in elimination half-life. The pharmacokinetic data determined after initial single doses, therefore, only suggest the kinetic characteristics during long-term administration, because this profile depends on the drugs' sustained effects on liver blood flow. The elimination half-life of all 3 prototypical calcium antagonists is probably significantly prolonged during long-term dosing with clinically effective regimens. Patients with hepatic disorders in which liver blood flow is altered, such as cirrhosis, have profound changes in pharmacokinetics with both short- and long-term administration of verapamil and are likely to have similar changes with other calcium antagonists. During short-term administration, the plasma concentrations of verapamil and other calcium antagonists relate closely to the observed hemodynamic (and electrophysiologic) effects. With long-term administration, however, these correlations are much less impressive. When given in tablet form, nifedipine lowers blood pressure roughly in proportion to plasma levels between 20 and 200 ng/ml; verapamil plasma levels between 80 and 800 ng/ml are associated with antihypertensive efficacy. Plasma level measurements, therefore, are not of clinical importance as guides to antihypertensive therapy, except to identify noncompliance or abnormal patterns of drug handling.     

Significance of plasma glutathione determination in patients with alcoholic and non-alcoholic liver disease

Plasma glutathione levels were determined in 79 patients with various types of liver disease and 18 healthy controls in order to study their significance in the course of liver disease. Plasma was taken at the time of needle liver biopsy. A positive linear correlation was found between plasma and hepatic glutathione concentrations, as has been suggested in experimental animals. In patients with acute viral hepatitis, chronic hepatitis, non-alcoholic liver cirrhosis and alcoholic liver disease, plasma glutathione levels were significantly decreased compared with those in controls. Of importance is the fact that the plasma levels increased after recovery in patients with acute viral hepatitis and after abstinence from alcohol intake in patients with alcoholic liver disease. Determination of plasma glutathione may be valuable in the evaluation of liver disease, particularly in acute viral hepatitis and alcoholic liver disease in which the hepatic content of glutathione is suggested to be decreased. Such patients may be susceptible to oxidative stress and radical-related hepatic injury.     

Pharmacokinetics of Famotidine after Intravenous Administration in Liver Disease

The pharmacokinetics of famotidine were studied after the administration of a single intravenous dose of 20-mg to seven normal volunteers, six patients with chronic hepatitis, 14 patients with compensated cirrhosis, and seven patients with decompensated cirrhosis. The plasma terminal elimination half-life of famotidine was significantly prolonged and famotidine total body clearance was significantly reduced in patients with decompensated cirrhosis, whose creatinine clearance was 57.2 +/- 6.7 ml/min/1.48 m2, but these changes were not significant in patients with chronic hepatitis (creatinine clearance: 109.2 +/- 10.5 ml/min/1.48 m2) or in patients with compensated cirrhosis (creatinine clearance: 72.2 +/- 26.5 ml/min/1.48 m2 in comparison with normal volunteers. The total volume of distribution at steady state was not significantly different between the normal volunteers and the three groups of patients. Famotidine total body clearance showed a weak but significant correlation with the creatinine clearance (r = 0.66, p less than 0.001), serum albumin level (r = 0.51, p less than 0.01), and serum total bilirubin level (r = 0.36, p less than 0.05), which suggested that the reduction in clearance was due in part to the concomitant renal impairment, as well as hepatic dysfunction in these patients. In conclusion, famotidine total body clearance was reduced in decompensated cirrhosis, indicating that the dose schedule requires modification in patients with this condition.     

Serum tenascin levels in chronic liver disease

To evaluate the diagnostic significance of tenascin, the extracellular matrix glycoprotein in chronic liver disease, serum tenascin levels were measured by a newly developed ELISA in 21 patients with chronic persistent hepatitis, in 55 with chronic active hepatitis, in 59 with liver cirrhosis, in 31 with hepatocellular carcinoma, in 26 with acute hepatitis and in 66 healthy subjects. The serum tenascin level was significantly elevated in the patients with chronic active hepatitis, liver cirrhosis, hepatocellular carcinoma, and acute hepatitis when compared with the healthy subjects (P<0.001). The serum tenascin level also increased with increasing severity of chronic liver diseases. A significant correlation was observed between the serum tenascin levels and serum levels of various extracellular matrix proteins such as type III procollagen N-aminoterminal peptide (PIIIP), laminin and the 7S domain of type IV collagen (P<0.001). A strong positive correlation was observed between the serum tenascin levels and histologic findings, particularly in the degree of hepatic fibrosis. This is the first report documenting serum tenascin level increases in patients with various chronic liver diseases. The measurement of the serum tenascin levels may provide additional information relevant to the study of connective tissue.     

Prevalence and clinical implications of HFE gene mutations (C282Y and H63D) in patients with chronic hepatitis B and C in Taiwan.

BACKGROUND/AIMS: The implication of hemochromatosis (HFE) gene mutations in chronic viral hepatitis remains controversial. We therefore studied the prevalence of HFE mutations and their impact on the progression of chronic viral hepatitis in Taiwan. PATIENTS & METHODS: H63D and C282Y mutations were screened by using polymerase chain reaction followed by restriction fragment length polymorphism in 152 chronic hepatitis B patients with various stages of liver disease, 87 chronic hepatitis C patients with various stages of liver disease, and 49 healthy controls. The distribution of each allele frequency was then compared among different groups of patients and in various stages of liver disease. RESULTS: All three groups of patients were C282Y wild type and the majority of H63D mutations were heterozygotes. Although statistically not significant, allele frequencies of H63D mutation in hepatitis B-related liver cirrhosis (6%) and hepatitis C-related liver cirrhosis (9.1%) were higher than those in healthy control (2%). After adjustment for age and sex, hepatitis B patients with H63D heterozygosity had a higher likelihood of cirrhosis than those with H63D wild type (odds ratios (OR): 3.2, confidence interval (CI): 0.49-20.5, P = 0.22). Similarly, hepatitis C patients with H63D homozygosity had a higher likelihood of cirrhosis compared with those with H63D wild type (OR: 2.35, CI : 0.19-28.5, P = 0.52). CONCLUSIONS: Almost all Taiwanese are C282Y wild type. H63D heterozygote and homozygote, occurring in less than 5% of the subjects, tended to be associated with the development of liver cirrhosis, irrespective of viral etiology. Screening for H63D mutation might be considered in patients with chronic viral hepatitis in Taiwan.     

Natural history of chronic hepatitis B virus infection in adults with emphasis on the occurrence of cirrhosis and hepatocellular carcinoma

The natural course of perinatally acquired hepatitis B virus (HBV) infection has three phases. In the first ‘immune tolerance phase’, patients are HBeAg positive and have high serum levels of HBV DNA, but have no symptoms, normal ALT levels and minimal histological activity. The second ‘immune clearance phase’ usually occurs between 15 and 35 years of age, during which HBV replication declines, accompanied by increased serum ALT levels and inflammatory activity in the liver; HBeAg to anti‐HBe seroconversion is then observed, frequently preceded by a flare of the ALT level. The average rate of spontaneous HBeAg seroconversion is 10% per year. In the third ‘low‐replicative phase’, serum HBsAg persists, but HBeAg is no longer detectable and HBV DNA can only be detected by PCR assay. During this phase, patients are usually asymptomatic and liver disease is inactive; some patients, however, may progress to cirrhosis and hepatocellular carcinoma (HCC). The ultimate outcome of chronic HBV infection appears to depend on the duration and severity of liver injury during the immune clearance phase. About 2.1% of patients with chronic type B hepatitis develop cirrhosis each year. Patients who have a severe acute exacerbation complicated by subacute hepatic failure or who have recurrent episodes of acute exacerbations with bridging hepatic necrosis are more likely to develop cirrhosis. A significant proportion of those with HBsAg eventually develop HCC; they have a 100‐fold increased risk of HCC relative to those without. The development of HCC, however, is closely related to the severity of the underlying liver disease. The annual incidence of HCC is only 0.1% in asymptomatic HBsAg individual, 1% in patients with chronic hepatitis B, but increases to 3–10% in patients with cirrhosis. Some anti‐HBe‐positive patients continue to have active liver disease and they should be tested for HBV DNA by hybridization assay to determine whether the disease results from replicative precore mutant HBV infection or other causes of liver disease, such as superinfection with HCV and HDV. A substantial number of apparently healthy HBV‐infected individuals are first recognized when they present with episodes of acute hepatitis. About 30% of these cases could be attributed to other hepatotropic virus superinfection. Acute viral hepatitis in patients with concurrent HBV infection is associated with an increased risk of fulminant hepatic failure. Finally, HBsAg disappears from serum in about 1% of patients each year. HCV superinfection can enhance the termination of HBsAg positivity. HCV, however, replaces HBV as the dominant cause of chronic viral hepatitis. The outcome of HBV‐infected persons with ‘spontaneous’ seroclearance of HBsAg is usually favourable, though progress to cirrhosis and HCC is still possible.     

Osteodystrophy in patients with chronic hepatitis and liver cirrhosis

Bone mineral density (BMD) of the lumber vertebrae and factors related to bone metabolism were determined in patients with chronic viral hepatitis and patients with liver cirrhosis to clarify correlations between hepatic dysfunction, considered to be one of the causes of hepatic osteodystrophy, and decrease in bone mass. BMD of the second to fourth lumbar vertebrae was determined with a Lunar (Madison, WI, USA) DPX, a dual-energy X-ray absorptiometry diagnostic system. BMD was significantly lowest in patients with liver cirrhosis, followed by patients with chronic hepatitis, and healthy subjects, in this order. There was a significantly positive but weak correlation between albumin and BMD. Levels of 25(OH)D and 1,25(OH)₂D were significantly lower in patients with liver cirrhosis than in those with chronic hepatitis. BMD and vitamin D were decreased in all patients whose cholinesterase (ChE) was below 0.3ΔpH. Urinary pyridinoline(Upyr) was significantly higher in the patients with liver cirrhosis, in whom bone mass was decreased, than in the patients with chronic hepatitis, whereas serum osteocalcin levels were distributed in the upper normal range in patients with chronic hepatitis and those with liver cirrhosis. There was a positive correlation between 25(OH)D and serum osteocalcin levels in patients with liver cirrhosis. These results indicate that osteogenesis is decreased and suggest that the decrease in BMD which occurs in viral liver cirrhosis, probably related to decreased, bone formation and slight promotion of bone resorption, reflects deranged hepatic function. This is the first report of Upyr and urinary deoxypyridinoline (UDpyr) determination in patients with liver cirrhosis and patients with chronic hepatitis. The negative correlation of Upyr and UDpyr with ChE is a novel finding.     

Quantitative testing of liver function in patients with cirrhosis due to chronic hepatitis C to assess disease severity

BACKGROUND/AIMS: Quantitative testing of liver function (QTLF) may allow a prognostic assessment of patients with various liver diseases. However, there are insufficient data about patients with liver cirrhosis due to hepatitis C. PATIENTS/METHODS: 86 consecutive patients (58 males, 28 females, age: 48.3 +/- 11.7 years) with chronic hepatitis C (HCV RNA pos.) underwent sonographically guided liver biopsy to confirm the diagnosis of cirrhosis. QTLF included aminopyrine breath test (microsomal liver function), galactose elimination capacity (cytosolic liver function), sorbitol clearance (liver plasma flow) and indocyanine green clearance (liver perfusion). Values were correlated with the Child-Pugh classification. RESULTS: 55% of the patients (n=47) had cirrhosis of Child-Pugh grade A, 28% of grade B (n=24) and 17% of grade C (n=15). QTLF showed a steady decrease from Child-Pugh grade A to grade B and to grade C. Contrary to markedly reduced tests of metabolic liver function in Child-Pugh grade patients, surrogate tests of hepatic perfusion were at the lower normal limit. All QTLF were significantly reduced in Child-Pugh grade B and C patients compared to healthy controls. Differences between the three Child grades were significant. CONCLUSION: In patients with cirrhosis due to hepatitis C, QTLF correlated inversely with Child-Pugh grades. Since in cirrhosis of grade A, surrogate tests of hepatic perfusion remained at the lower normal limit, whereas those of metabolic function were decreased, QTLF may be a tool to predict prognosis or complications in early cirrhosis due to chronic hepatitis C.     

Environmental Triggers for Inflammatory Bowel Disease

Infections are common in patients with chronic liver disease, especially those with cirrhosis. Patients with advanced liver disease, who develop bacterial infections, are at a substantially higher risk of death. As liver disease progresses, most immunizations lose their effectiveness. Overall, it is important to address immunization needs in patients with chronic liver disease early on, when immunizations are most effective. Inactivated or killed-type vaccinations rather than live, attenuated vaccinations are always preferable in patients with cirrhosis. The influenza vaccination is less effective in patients with cirrhosis and in the early post-liver transplant setting as compared to healthy individuals. The influenza vaccination may prevent hepatic decompensation, but further data are needed to confirm this. Yearly inactivated influenza vaccinations should be provided to those with chronic liver disease. The pneumonia vaccination is less effective in patients with cirrhosis, with a further decline in protective serologies after liver transplantation. Standard guidelines for the administration of Pneumovax23 for immunocompromised hosts apply to patients with chronic liver disease. Chronic liver disease also leads to higher non-response rates to the hepatitis B vaccination. Early-stage chronic liver disease patients should receive conventional hepatitis B series. Cirrhotics benefit from a double-dose hepatitis B vaccination at standard intervals. Hepatitis A superimposed on chronic viral hepatitis or chronic liver disease increases risk of mortality. Hepatitis A vaccination effectiveness wanes in cirrhosis, and should if possible be given before the development of cirrhosis. More data are needed for routine use of herpes zoster and human papillomavirus in chronic liver disease.     

乙型肝炎肝静脉彩色多普勒超声特点

目的探讨慢性肝炎肝静脉频谱波形的变化特点及其对肝纤维化、肝硬化病变程度估计的临床意义。方法应用彩色多普勒超声诊断仪,共检测了143例患者,25例健康正常人。将健康正常人肝静脉频谱与慢性肝病组的肝静脉频谱改变进行对照分析,并依据肝功能及临床诊断进行分析。结果肝右静脉频谱波形中,HV1、HV2型可能与临床诊断中肝硬化相关;另加分的HV0亚型及HV1亚型与临床诊断中肝纤维化程度密切相关。结论利用彩色多普勒超声观察慢性肝病患者的频谱波形改变特点,特别是利用HV0亚型及HV1亚型两型,可以及早提示肝纤维化,对病变程度进行估计,指导临床治疗。     

Serum leptin levels in patients with nonalcoholic chronic liver disease

BACKGROUND/AIMS: The elevated serum leptin level of patients with alcoholic cirrhosis has been reported, however, the precise mechanism is still unknown. Leptin expression and protein synthesis have also been detected in activated hepatic stellate cells in cell cultures, which play a major role in hepatic fibrosis. We evaluated the serum leptin levels of patients with nonalcoholic liver diseases including cirrhosis and chronic hepatitis. We also investigated the hepatic clearance of leptin by determining the serum leptin level in blood samples obtained from the portal and hepatic veins. METHODOLOGY: The serum leptin level of 44 patients with nonalcoholic chronic liver disease (male/female = 21/23, cirrhosis/chronic hepatitis = 30/14) and 40 control subjects (male/female = 20/20) was determined in blood samples obtained from the antecubital vein by enzyme-linked immunosorbent assay. We also assessed the relationship between the leptin level and various biochemical tests of liver function. Additionally, we determined the leptin levels in the portal and the hepatic venous blood (nonalcoholic cirrhosis = 10, nonhepatic disease = 4). RESULTS: There were positive correlations between the serum leptin level and body mass index among males and among females in the liver disease group and in the control group. However, the serum leptin level of the liver disease group and control group did not differ significantly. Among the 44 liver disease patients, only the serum cholesterol level was significantly correlated with the serum leptin level after adjusting for sex and body mass index by multiple regression analysis. Furthermore, the leptin level in hepatic venous blood was significantly lower than that in portal venous blood. However, the ratio of [leptin level in hepatic venous blood]/[leptin level in portal venous blood] in the cirrhosis group, and that in the nonhepatic disease group, did not significantly differ. CONCLUSIONS: The serum leptin level of patients with nonalcoholic liver diseases is not elevated. On the other hand, the serum leptin level of patients with alcoholic cirrhosis has been reported to be elevated. The difference in the serum leptin level of patients with nonalcoholic liver disease and that of patients with alcoholic cirrhosis may be due to a difference in factors such as the levels of cytokines or sex steroids, and/or nutrition. Furthermore, it is likely that leptin is cleared in part by the portosystemic circulation through the liver.     

Evaluation of the diagnostic value of serum and tissue apoptotic cytokeratin-18 in patients with chronic hepatitis C

Background and study aimsHepatitis C virus (HCV) is considered the most common aetiology of chronic liver disease (CLD) in Egypt. The disease severity ranges from mild illness to cirrhosis and hepatocellular carcinoma. A role for apoptosis in liver damage caused by HCV chronic infection has been suggested. Cytokeratin 18 (CK-18) is the major intermediate filament protein in the liver and is a known caspase substrate in hepatocyte apoptosis. Therefore, we analysed the serum and tissue levels of CK-18 in patients with chronic HCV infection to evaluate its role in hepatocyte apoptosis. We also correlated CK-18 expression with the severity of hepatic pathology.Patients and methodsThis study examined 80 Egyptian patients with liver disease. There were 69 patients with chronic hepatitis C and 11 patients with hepatitis C-induced cirrhotic changes. Fifteen healthy controls were also included in the study. The levels of CK-18 fragment were quantified in paired serum and liver biopsy samples.ResultsThe serum and tissue CK-18 levels were reduced in chronic HCV patients compared to early cirrhosis patients. This result indicates that serum levels of CK-18 and the hepatic expression of CK-18 might play an important role in disease progression. The serum and tissue levels of CK-18 were significantly increased and directly correlated with inflammation severity, stage of fibrosis, and ALT levels in the chronic HCV group and the cirrhotic liver group. There was no significant difference in viral load between patient cohorts.ConclusionThe serum level and the hepatic expression of CK-18 are related to disease activity and are directly correlated with METAVIR scoring. This result suggests that serum CK-18 levels may be useful for monitoring disease activity in chronic HCV and liver cirrhosis patients.     

Long-term histologic follow-up study of alcoholic liver disease.

Forty Japanese patients with alcoholic liver disease (nonspecific change, 9; fatty liver, 5; hepatic fibrosis, 4; chronic hepatitis, 12; alcoholic hepatitis, 5; liver cirrhosis, 5) were followed for 3-17 yr (average 8 yr) with repeated liver biopsies (2-5 times; average 2.5 times) at intervals of more than 3 yr. All of the patients continued to consume alcohol during this observation period. Five out of 12 patients with chronic hepatitis and 2 of 5 patients with alcoholic hepatitis eventually progressed to cirrhosis, while none of the 4 patients with hepatic fibrosis became cirrhotic. Anti-hepatitis C virus antibody was positive in 2 patients with liver cirrhosis among 12 patients whose sera were available. Two patients with cirrhosis died of hepatic failure and one patient died of hepatocellular carcinoma. These data suggest that the long-term prognosis of alcoholic liver disease is not necessarily poor, but patients with chronic hepatitis or alcoholic hepatitis can be at risk of progression to cirrhosis.     

Anti-smooth muscle antibodies in a hospital population

A total of 139 sera being 60 patients with liver disease were tested for auto-antibodies. Twenty six of the 60 patients had active chronic hepatitis, 19 acute hepatitis, 3 cirrhosis, 3 hepatosplenic schistosomiasis mansoni, and 9 miscelaneous liver pathology. We found positivity for smooth muscle antibody in 26 cases: smooth muscle antibody-V in 15 cases, for smooth muscle antibody-T in 9, and for smooth muscle antibody-G in 10 other patients. Nine out of 10 patients with positive smooth muscle antibody-G had chronic active hepatitis and the remaining had cirrhosis. The other kinds of smooth muscle antibodies were irregularly distributed among the different hepatic disease studied. The higher levels of auto-antibodies were found mostly in chronic hepatic disease.     

Pharmacokinetics of ciprofloxacin in patients with liver cirrhosis.

BACKGROUND: Bacterial infections are common in patients with cirrhosis of liver and are frequently treated with ciprofloxacin. Literature on pharmacokinetics of ciprofloxacin in patients with cirrhosis of the liver is scanty. The present study compared the pharmacokinetics of ciprofloxacin in cirrhotic patients with that in healthy volunteers. METHODS: In 20 patients with cirrhosis of liver (all Child-Pugh class B) and 10 healthy volunteers, plasma levels of ciprofloxacin were measured using high-performance liquid chromatography at several time points after a 500-mg oral dose. Various pharmacokinetic parameters were calculated. RESULTS: No significant differences were observed in maximum plasma levels reached (mean [SD] 2.6 [0.6] vs 2.6 [1.3] microg/ml), time taken for maximum plasma levels to be reached (1.3 [0.6] vs 1.5 [0.9] h), t1/2a (0.7 [0.3] vs 0.4 [0.9] h), elimination half-life (3.6 [1.2] vs 3.2 [1.8] h), and area under the curve (19.3 [3.8] vs 21.9 [4.5] microg/mL x h) in healthy volunteers and cirrhotic patients, respectively. CONCLUSIONS: Pharmacokinetics of ciprofloxacin is unaltered in patients with liver cirrhosis. Ciprofloxacin can be safely administered in the usual doses in such patients.     

Detection of male DNA in the liver of female patients with primary biliary cirrhosis

BACKGROUND/AIMS: Primary biliary cirrhosis is a chronic cholestatic liver disease characterized by progressive inflammatory destruction of bile ducts, with eventual hepatic fibrosis and cirrhosis. Since primary biliary cirrhosis affects predominantly middle-aged women and has pathological similarities to hepatic graft-versus-host-disease, we investigated whether fetal cell microchimerism might be involved in the development of this disease. METHODS: The presence of Y-chromosome-specific sequences was analyzed by polymerase chain reaction using peripheral blood mononuclear cells from women with primary biliary cirrhosis (n=18) and healthy (control) women (n=18), and by in situ hybridization of liver biopsy sections from women with primary biliary cirrhosis (n=19) and women with chronic hepatitis C or alcoholic liver disease (n=20). RESULTS: Male cells were detected in liver biopsy specimens of 8 of 19 patients (42%) with primary biliary cirrhosis. Y-chromosome-containing cells were not seen in any of the liver biopsy specimens from women with chronic hepatitis C or alcoholic liver disease. Male cells were detected in peripheral blood mononuclear cells from one healthy control at a level of 1 male cell per 10(6) female cells, but were not detected in peripheral blood mononuclear cells of women with primary biliary cirrhosis. CONCLUSIONS: The presence of male cells in the liver of women with primary biliary cirrhosis raises the possibility that fetal cell microchimerism may be involved in the pathogenesis of this chronic liver disease.