Serum Carnitine Levels in Chronic Hepatitis C Patients Before and After Lymphoblastoid Interferon-?? Treatment

Malaguarnera, Mariano; Restuccia, Salvatore; Fazio, Ignazio Di; Zoccolo, Anna Maria; Ferlito, L.; Bentivegna, Prospera

doi:10.2165/00063030-199912010-00007

Cited by 17 publications

(14 citation statements)

References 13 publications

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“…Similar to the findings of other groups, this study illustrates that cytokines, or factors derived from immune cells/reactions, play an important role in determining how the liver responds to acute injury. However, IL-6 levels are also typically elevated in several ''chronic fibro-inflammatory disorders,'' 35 including chronic viral hepatitis type C, 36 and recent studies by Ezure et al 32 in our laboratories show that IL-6 plays an even more important role in the hepatic response to chronic injury. It will also be interesting to determine whether IL-6 plays a role in the susceptibility to tumors, via its ability to simultaneously affect the number of cells undergoing DNA synthesis and apoptosis.…”

Section: Discussionmentioning

confidence: 69%

Mitosis and apoptosis in the liver of interleukin-6-deficient mice after partial hepatectomy

Sakamoto¹,

Liu²,

Murase³

et al. 1999

Hepatology

249

161

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Recently, it was shown that hepatocyte DNA synthesis after partial hepatectomy (PH) is impaired in interleukin-6-deficient (IL-6 ؊/؊ ) mice, which results in significantly delayed, but eventual, recovery of normal liver weight, compared with the IL-6 ؉/؉ controls. Four possible compensatory mechanisms might explain this phenomenon: 1) hepatocyte hypertrophy; 2) activation of the oval cell compartment and subsequent maturation to hepatocytes; 3) non-oval biliary epithelial cell (BEC) proliferation; and/or 4) differential rates of apoptotic cell death in the regenerating liver. These hypotheses were tested by subjecting IL-6 ؊/؊ and IL-6 ؉/؉ mice to PH and determining sequential liver weight, histology, hepatocyte and BEC 5Ј-bromo-2Ј-deoxyuridine (BrdU) labeling, liver DNA content, ␣-fetoprotein (AFP) mRNA production, and apoptosis at several time points after PH. Consistent with previous studies, we show that the absence of IL-6 significantly impairs hepatocyte DNA synthesis and delays liver weight recovery after PH, but the defect observed in this study is less severe than that previously reported, and no excess mortality, massive necrosis on histology, nor differences in liver injury test are seen. Interestingly, the IL-6 ؊/؊ mice show more hepatocyte BrdU pulse labeling than the IL-6 ؉/؉ controls at 24 hours, but less at 36, 48, and 60 hours. Continuous BrdU infusion up to 60 hours after PH showed a cumulative hepatocyte labeling index of 79.5% in IL-6 ؉/؉ mice and 70.8% in IL-6 ؊/؊ mice, respectively (P F .03). However, despite a lower labeling index and significantly delayed weight recovery, hepatic mass was equally restored in the two groups by 96 hours. There was no evidence of oval cell proliferation in the IL-6 ؊/؊ mice, as determined by routine histology and AFP mRNA analysis, and non-oval BEC proliferation was also slightly impaired in the IL-6 ؊/؊ mice compared with the IL-6 ؉/؉ mice. In addition, liver DNA content per gram of liver showed an increase compared with normal at 60 hours in both groups, but by 96 hours, there was no difference between the two groups. Thus, neither oval cell nor BEC proliferation, nor hepatocyte hypertrophy, could account for the eventual equivalent weight recovery. There was, however, a difference between the two groups in the rate of apoptosis. In normal livers of both IL-6 ؊/؊ and IL-6 ؉/؉ mice, apoptotic cells were uncommon, and even fewer such cells were detected at 24, 36, and 48 hours after PH. Between 60 and 96 hours after PH, a wave of apoptosis spread through the livers of both groups. The number of apoptotic cells was directly proportional to the magnitude of hepatocyte BrdU labeling and liver DNA content after PH, and the difference between the nadir of apoptosis at 24 hours and the peak at 96 hours was greater for the IL-6 ؉/؉ mice. In addition, a direct comparison between the two groups at 96 hours showed that hepatocyte apoptosis was significantly lower in the IL-6 ؊/؊ versus the IL-6 ؉/؉ mice (P F .02). Treatment of the IL-6 ؊/؊ mice with rIL-6 completely r...

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Section: Discussionmentioning

confidence: 69%

Mitosis and apoptosis in the liver of interleukin-6-deficient mice after partial hepatectomy

Sakamoto¹,

Liu²,

Murase³

et al. 1999

Hepatology

249

161

View full text Add to dashboard Cite

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“…Figure 4b shows the MS/MS spectrum of the ion at m/z 520 in positive ion mode. Because the fragment ion at m/z 184 as a characteristic choline moiety from lysophosphati-dylcholine (LysoPC) [24,25] was detected, the ion at m/z 520 was identified to be LysoPC (18:2). Similarly, other LysoPCs as well as phosphatidylcholine (PC) and pho-phatidylethanolamine (PE) were tentatively identified in positive ion mode.…”

Section: Identification Of Differentiating Metabolitesmentioning

confidence: 99%

Metabolomics Analysis of the Responses to Partial Hepatectomy in Hepatocellular Carcinoma Patients

Chan¹,

Lin²,

Sun³

et al. 2011

AJAC

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In this study, liquid chromatography/quadrupole time of flight mass spectrometry (LC/QTOFMS) was employed for investigating the metabolome of the sera collected from hepatocellular carcinoma (HCC) patients before and 3 to 5 months after partial hepatectomy. To investigate the changes in metabolic phenotypes after the hepatic resection, principal components analysis (PCA) and support vector machine (SVM) were performed for the data grouping and classification. Based on the obtained SVM model, mass spectrometry spectra, database searching as well as the confirmation from authentic standards, several differentiating metabolites were tentatively identified. To improve visualization, z-score plot and heat map display were performed, which exhibited the changes in concentration of the metabolites. As a result, depletion of circulating carnitine, reduced amino acid biosynthesis and increased rate of lipid peroxidation were observed. Meanwhile, up-regulation of hypoxanthine indicated that purine metabolism might serve as the salvage pathway. Collectively, the results reflected metabolic responses to surgical operation in HCC patients, suggesting perturbation of energy metabolism may occur in 3 to 5 months after the partial hepatectomy.

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“…It exerts its actions by binding to its cell-surface receptor. Serum levels of IL6 were found to be significantly increased in patients with chronic hepatitis B (Malaguarnera et al, 1997;Song et al, 2000) and in patients with chronic hepatitis C patients (Wang et al, 1999). However, the association between polymorphisms of IL6 gene and chronic hepatitis B progression has not been studied, nonetheless the importance of IL6 in conjunction with progression of chronic hepatitis disease remains.…”

Section: Introductionmentioning

confidence: 99%

Association between interleukin 6 promoter variants and chronic hepatitis B progression

Park

Lee²,

Kim³

et al. 2003

Exp Mol Med

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Interleukin 6 (IL6) plays an essential role in the regulation of immune response to chronic disease. In this study, the three known single nucleotide polymorphisms (SNPs) in the IL6 promoter region were genotyped in a large chronic hepatitis B cohort to evaluate the effects of IL6 promoter variants. The single base extension method was used for this genotyping. Haplotypes were constructed by the three SNPs in IL6. Allele frequencies were compared for; i) patients with chronic hepatitis (CH) and chronic carriers vs. chronic hepatis patients with clinical evidence of liver cirrhosis (LC) (i.e., portal hypertension), ii) cirrhotic patients with hepatocellular carcinoma (HCC) vs. without HCC by logistic regression, and iii) with respect to the time intervals from the onset of infection to HCC. Results were analyzed by Cox relative hazard analysis on the assumption that all the patients were infected during early infancy. The frequencies of each SNP were 0.002 (IL6-597 G A), 0.25 (IL6-572 C G) and 0.002 (IL6-174 G C), respectively, in the Korean population (n = 1,046). No significant associations were detected between IL6-572 C G and chronic hepatitis B outcome in this study; i.e., LC occurrence on CH (OR = 0.16-1.27, P = 0.13-0.71) and HCC occurrence on LC (OR = 1.04-1.23, P = 0.89-0.60) of heterozygotes and homozygotes for G allele in referent comparison to homozygotes for common allele (C/C genotype), and time interval to HCC (RH = 0.67-1.00; P = 0.14-0.99). In conclusion, there appeared to be no significant associations between IL6 promoter variants and disease outcome in chronic hepatitis B.

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Serum Carnitine Levels in Chronic Hepatitis C Patients Before and After Lymphoblastoid Interferon-?? Treatment

Cited by 17 publications

References 13 publications

Mitosis and apoptosis in the liver of interleukin-6-deficient mice after partial hepatectomy

Mitosis and apoptosis in the liver of interleukin-6-deficient mice after partial hepatectomy

Metabolomics Analysis of the Responses to Partial Hepatectomy in Hepatocellular Carcinoma Patients

Association between interleukin 6 promoter variants and chronic hepatitis B progression

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