Gut. 2010 Oct 6. [Epub ahead of print]
Bokemeyer M, Ding XQ, Goldbecker A, Raab P, Heeren M, Arvanitis D, Tillmann HL, Lanfermann H, Weissenborn K.
Hannover Medical School, Hannover, Germany.
Objective Fatigue, mood disturbances and cognitive dysfunction are frequent in patients infected with hepatitis C virus (HCV) who have mild liver disease. The reason is still unclear. The present study aims to gain more insight into the pathomechanism by combining an extensive neuropsychological examination with magnetic resonance spectroscopy in four different brain regions in a patient group covering the whole spectrum of neuropsychiatric findings in patients afflicted with HCV who have only mild liver disease. Methods 53 HCV-positive patients with only mild liver disease and differing degrees of neuropsychiatric symptoms were studied with single-voxel MRS of the parietal white matter, occipital grey matter, basal ganglia and pons. Brain metabolite concentrations were quantitatively analysed by using LCmodel. MRS data were compared to those of 23 healthy controls adjusted for age, and analysed for relationships with the extent of neuropsychiatric symptoms. Results Choline (p=0.02), creatine (p=0.047) and N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (NN, p=0.02) concentrations in the basal ganglia and choline concentrations in the white matter (p=0.045) were significantly higher in the patients than in controls. Interestingly, the difference was most evident for the patients with low fatigue scores (eg, white matter: choline: p=0.001, creatine: p=0.003, NN: p=0.031). Myo-inositol differed significantly between groups in the white (p=0.001) and grey matter (p=0.003). Fatigue correlated negatively with white matter NN, choline and creatine and myo-inositol levels in white and grey matter and basal ganglia (p<0.01). Conclusion As the increase of choline, creatine and myo-inositol are usually interpreted to indicate glial activation and macrophage infiltration in chronic inflammation and slow virus infections of the brain the present data endorse the hypothesis, that HCV infection may induce neuroinflammation and brain dysfunction. The concomitant increase of NN and the negative correlation to the extent of fatigue suggest a cerebral compensatory process after HCV infection.
PMID: 20926642 [PubMed - as supplied by publisher]
So far, several non-invasive fibrosis indices such as the APRI, the Forns index, the FibroIndex, and the FibroTest have been developed. The Fibro-Stiffness index showed its superior correlation with fibrosis stage compared with the APRI, the Forns index and the FibroIndex. The Fibro-Stiffness index and LS showed a significant difference between neighboring fibrosis stages except between F0 and F1 in the estimation group. The AUC of the Fibro-Stiffness index was the highest among the 5 examined methods for F ≥ 2, F ≥ 3 and F = 4 in the estimation group, and for F ≥ 3 and F = 4 in the validation group. The AUCs of the APRI, the Forns index and the FibroIndex for predicting F4 in the present study were similar to the values reported in their respective original manuscripts (APRI, 0.88; Forns index, 0.81; FibroIndex, 0.86)[6,11]. Therefore, the results of the present study can be considered to be appropriate. The superiority of the Fibro-Stiffness index was further demonstrated by the accuracy values. The accuracy of the Fibro-Stiffness index was highest for F ≥ 2, F ≥ 3 and F = 4 in both the estimation group and validation group.
Although the Fibro-Stiffness index was shown to be a highly accurate index, the positive predictive value was rather low for F4. A combination of the Fibro-Stiffness index and hyaluronic acid was shown to improve the diagnostic performance. Serum hyaluronic acid has been reported to be useful for diagnosis of liver fibrosis and cirrhosis[8,30]. In the estimation group and in the validation group, both the accuracy and positive predictive value of the combination of the Fibro-Stiffness index and hyaluronic acid were higher than those of the Fibro-Stiffness index alone, and were the highest among all the 6 examined methods. The fact that a combination of the Fibro-Stiffness index and hyaluronic acid enables us to diagnose F4 with a sensitivity of 91%-100% and positive predictive value of 48%-57% is important, because the risk of hepatocellar carcinoma or bleeding from esophageal varices is high in patients with F4[2,3].
For predicting F ≥ 1, the Fibro-Stiffness index was inferior to the other fibrosis indices in terms of sensitivity, accuracy and negative predictive value. The combination of Fibro-Stiffness index with AST improved sensitivity, accuracy and negative predictive value in both the estimation group and the validation group. However, the combination of Fibro-Stiffness index with AST was still inferior to the APRI in the estimation group, and inferior to the FibroIndex and the APRI in the validation group. Further investigation is necessary to improve the diagnostic efficacy of the Fibro-Stiffness index for F ≥ 1.
In chronic viral hepatitis, the presence of significant fibrosis (F ≥ 2) indicates the need for antiviral therapies. The Fibro-Stiffness index showed a highly accurate diagnostic performance for F ≥ 2 in both the estimation group and validation group. Thus the patients with a Fibro-Stiffness index of ≥ 10.12 which indicate F ≥ 2 will be candidates for liver biopsy or interferon treatment.
In conclusion, a new fibrosis index for non-invasive assessment of liver fibrosis, the Fibro-Stiffness index, was constructed using LS measured by FibroScan, platelet count and prothrombin time and was validated. The Fibro-Stiffness index demonstrated superior diagnostic performance to LS alone, the APRI, the Forns index and the FibroIndex for F ≥ 2, F ≥ 3 and F = 4. The diagnostic performance of the Fibro-Stiffness index for F4 was further improved by combination with hyaluronic acid levels.
The stage of liver fibrosis is important for clinical management of chronic hepatitis C, since the treatment and prognosis of chronic hepatitis depend on the fibrosis stage. Liver biopsy is the gold standard for the assessment of fibrosis stage. However, it is an invasive and expensive procedure, and its accuracy is sometimes questionable.
A number of non-invasive fibrosis indices, such as the aminotransferase-to-platelet ratio index (APRI), the Forns index and the FibroIndex have been proposed for assessment of liver fibrosis. Transient elastography with the use of a new apparatus, FibroScan, for measurement of liver stiffness (LS) was developed. LS has been reported to correlate with liver fibrosis in various liver diseases. So far no fibrosis indices incorporating LS have been reported. In the present study, we developed a new non-invasive fibrosis index, the Fibro-Stiffness index, which incorporated LS.
Innovations and breakthroughs
The Fibro-Stiffness index consists of LS, platelet count and prothrombin time. In the present study, its usefulness was compared with LS, the APRI, the Forns index and the FibroIndex. The diagnostic performance of the Fibro-Stiffness index was superior to other indices. Furthermore, the diagnostic performance of the Fibro-Stiffness index for F4 was further improved by combination with hyaluronic acid.
Using the Fibro-Stiffness index, it is possible to assess the stage of liver fibrosis of patients with chronic hepatitis C non-invasively, accurately and quantitatively. Therefore, the Fibro-Stiffness index is useful not only for the diagnosis of stage of liver fibrosis but also for the assessment of regression of liver fibrosis by interferon treatment in patients with chronic hepatitis C.
Fibro-Stiffness index: a new non-invasive fibrosis index which we developed in the present study and consists of LS, platelet count and prothrombin time. Its diagnostic performance is superior to other indices.
The authors proposed a novel index for non-invasive assessment of hepatic fibrosis. Its reliability was validated on another group of patients. I think the index is clinically useful and significant.
Peer reviewers: Dr. Assy Nimer, MD, Assistant Professor, Liver Unit, Ziv Medical Centre, Box 1008, Safed 13100, Israel; Munechika Enjoji, MD, PhD, Department of Clinical Pharmacology, Fukuoka University, 8-17-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan
S- Editor Tian L L- Editor Cant MR E- Editor Lin YP
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