Serum total bile acid level as a sensitive indicator of hepatic histological improvement in chronic hepatitis C patients responding to interferon treatment

Shima, Toshihide; Tada, Hisashi; Morimoto, Michio; Nakagawa, Yoshihiro; Obata, Hirozumi; Sasaki, Toshiyuki; Park, Hyohun; Nakajo, Shinobu; Nakashima, Tomoki; Okanoue, Takeshi; Kashima, Kei

doi:10.1046/j.1440-1746.2000.02126.x

Cited by 21 publications

(16 citation statements)

References 20 publications

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“…Altered bile cholesterol levels have been implicated in gallstone related problems, including gallbladder cancer. Increased levels of bile acids in serum have also been reported in liver disease, indicating the altered physiology of biliary metabolites in patients with liver related problems [15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Visualization of Bile Homeostasis Using ¹H‐NMR Spectroscopy as a Route for Assessing Liver Cancer

Gowda

Shanaiah

Cooper

et al. 2008

Lipids

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Changes in bile synthesis by the liver or alterations in the enterohepatic circulation due to a variety of etiological conditions may represent a novel source of liver disease-specific biomarkers. Bile from patients with liver diseases exhibited significant changes in the levels of glycine- and taurine-conjugated bile acids, phospholipids, cholesterol and urea relative to non-liver disease controls. Cholangiocarcinoma and non-malignant liver diseases (NMLD) showed the most significant alterations. Further, hepatocellular carcinoma (HCC) could be differentiated from NMLD (p = 0.02), as well as non-liver disease controls (p = 0.02) based on the amounts of bile acids, phospholipids and/or cholesterol. HCC also differed with cholangiocarcinoma although not significantly. Urea increases somewhat in non-malignant liver disease relative to non-liver disease controls, while the bile acids, phospholipids and cholesterol all decrease significantly. The ratio between some major bile metabolites also distinguished NMLD (p = 0.004–0.01) from non-liver disease controls. This snapshot view of bile homeostasis, is obtainable from a simple nuclear magnetic resonance (NMR) approach and demonstrates the enormous opportunity to assess liver status, explore biomarkers for high risk diseases such as cancers and improve the understanding of normal and abnormal cellular functions.

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Section: Introductionmentioning

confidence: 99%

Visualization of Bile Homeostasis Using ¹H‐NMR Spectroscopy as a Route for Assessing Liver Cancer

Gowda

Shanaiah

Cooper

et al. 2008

Lipids

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“…5 Hepatotoxicity implicated from occupational and drug exposure has also been associated with elevations in total bile acid concentrations. [9][10][11][12][13] Recently, we published the results of a clinical investigation conducted in 11 human immunodeficiency virus (HIV)-infected patients on the pharmacokinetics, safety, and efficacy of an antiretroviral regimen that included three protease inhibitors: amprenavir, ritonavir, and saquinavir. 14 During that study, drug-induced hepatotoxicity was diagnosed in one of the 11 patients.…”

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confidence: 99%

Plasma Bile Acid Concentrations in Patients with Human Immunodeficiency Virus Infection Receiving Protease Inhibitor Therapy: Possible Implications for Hepatotoxicity

et al. 2010

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Study Objectives-To evaluate whether patients with human immunodeficiency virus (HIV) infection who were receiving protease inhibitor therapy had altered bile acid concentrations compared with noninfected control subjects, and whether bile acid concentrations could predict the onset of hepatotoxicity caused by protease inhibitors.Design-Retrospective sample analysis from a prospectively conducted clinical trial. Setting-Academic research center.Patients-Eleven adults with advanced HIV disease who were taking protease inhibitor-based antiretroviral therapy, one of whom had developed protease inhibitor-induced hepatotoxicity. Measurements and MainResults-Plasma concentrations of cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), and taurocholic acid (TC) were analyzed by using a novel highperformance liquid chromatography with tandem mass spectrometry detection method. Comparisons of the relative contribution of each bile acid to the total bile acid pool were made with previously published values and with bile acid concentrations contained in two pooled plasma samples from healthy, non-HIV-infected volunteers analyzed in our laboratory. Each pooled plasma sample used for this analysis contained contributions from three non-HIV-infected volunteers. The LCA and TC concentrations in HIV-infected patients were 3-4-fold higher than those previously reported for non-HIV-infected subjects; concentrations of other bile acids were similar to those of previous reports. The relative contribution of CDCA to the total bile acid pool was 9% in HIV-infected patients compared with 30-50% in noninfected subjects. Total and individual bile acid concentrations in the HIV-infected patient who developed hepatotoxicity were similar to the bile acid concentrations from the other study patients who did not develop hepatotoxicity.Conclusion-These data suggest that bile acid concentrations may be altered by HIV infection and/or protease inhibitor therapy. However, further investigations should be performed to assess whether antiretroviral-associated hepatotoxicity can be predicted by alterations in individual bile acid concentrations. Recently, we published the results of a clinical investigation conducted in 11 human immunodeficiency virus (HIV)-infected patients on the pharmacokinetics, safety, and efficacy of an antiretroviral regimen that included three protease inhibitors: amprenavir, ritonavir, and saquinavir. 14 During that study, drug-induced hepatotoxicity was diagnosed in one of the 11 patients. In this current study, we used blood samples obtained from that study to determine whether the average plasma concentrations of individual bile acids of HIVinfected patients differ compared with a population of non-HIV-infected individuals, whether protease inhibitor therapy influences bile acid concentrations during a dosing interval, and whether elevations in total or individual plasma bile acid concentrations might be an early signal of drug-induced hepat...

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“…In contrast, TNF-␣ was associated with hepatic inflammation, but not with fibrosis. Other tests were investigated, including glutathione, 60 ␣ fetoprotein, 69,73,80 prothrombin time, 70,71,76 pseudocholinesterase, 70 manganese superoxide dismutase, 70 ␤-N-galactosidase, 70 ␣-2-macroglobin, 70 ␤-globulin, 70 albumin, 70,76 ␥ glutamyl transpeptidase, 70,71,76,81 bilirubin, 61,71,76 lactate dehydrogenase, 76 AST, 71,76 alkaline phosphatase, 76 white blood cell count, 76 creatinine, 71 total bile acids, 81 and immunoglobulin G. 51 Similar to the cytokines, these tests frequently were associated with fibrosis. However, these markers were less useful as a group than the markers discussed above, and only limited data were available on these markers.…”

Section: Results Of Studies On Other Testsmentioning

confidence: 99%

Role of liver biopsy in management of chronic hepatitis C: A systematic review

et al. 2002

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This systematic review addresses 2 questions pertinent to the need for pretreatment liver biopsy in patients with chronic hepatitis C: how well do liver biopsy results predict treatment outcomes for chronic hepatitis C? How well do biochemical blood tests and serologic measures of fibrosis predict the biopsy findings in chronic hepatitis C? Medline and other electronic databases were searched from January 1985 to March 2002. Additional articles were sought in references of pertinent articles and recent journals and by querying experts. Articles were eligible for review if they reported original human data from a study that used virological, histological, pathologic, or clinical outcome measures. Paired reviewers assessed the quality of each eligible study and abstracted data. Studies suggested that advanced fibrosis or cirrhosis on initial liver biopsy is associated with a modestly decreased likelihood of a sustained virological response (SVR) to treatment. Also, studies relatively consistently showed that serum aminotransferases have modest value in predicting fibrosis on biopsy; that extracellular matrix tests hyaluronic acid and laminin may have value in predicting fibrosis, and that panels of tests may have the greatest value in predicting fibrosis or cirrhosis. Biochemical and serologic tests were best at predicting no or minimal fibrosis, or at predicting advanced fibrosis/cirrhosis, and were poor at predicting intermediate levels of fibrosis. Thus, evidence suggests that liver biopsy may have some usefulness in predicting efficacy of treatment in patients with chronic hepatitis C, and biochemical blood tests and serologic tests currently have only modest value in predicting fibrosis on liver biopsy.

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Serum total bile acid level as a sensitive indicator of hepatic histological improvement in chronic hepatitis C patients responding to interferon treatment

Abstract: A decrease in serum TBA level reflected histological improvement in the liver more precisely than did changes in the other liver function test values following IFN therapy.

Cited by 21 publications

References 20 publications

Visualization of Bile Homeostasis Using ¹H‐NMR Spectroscopy as a Route for Assessing Liver Cancer

Visualization of Bile Homeostasis Using ¹H‐NMR Spectroscopy as a Route for Assessing Liver Cancer

Plasma Bile Acid Concentrations in Patients with Human Immunodeficiency Virus Infection Receiving Protease Inhibitor Therapy: Possible Implications for Hepatotoxicity

Role of liver biopsy in management of chronic hepatitis C: A systematic review

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Serum total bile acid level as a sensitive indicator of hepatic histological improvement in chronic hepatitis C patients responding to interferon treatment

Abstract: A decrease in serum TBA level reflected histological improvement in the liver more precisely than did changes in the other liver function test values following IFN therapy.

Cited by 21 publications

References 20 publications

Visualization of Bile Homeostasis Using 1H‐NMR Spectroscopy as a Route for Assessing Liver Cancer

Visualization of Bile Homeostasis Using 1H‐NMR Spectroscopy as a Route for Assessing Liver Cancer

Plasma Bile Acid Concentrations in Patients with Human Immunodeficiency Virus Infection Receiving Protease Inhibitor Therapy: Possible Implications for Hepatotoxicity

Role of liver biopsy in management of chronic hepatitis C: A systematic review

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Visualization of Bile Homeostasis Using ¹H‐NMR Spectroscopy as a Route for Assessing Liver Cancer

Visualization of Bile Homeostasis Using ¹H‐NMR Spectroscopy as a Route for Assessing Liver Cancer