Liver stiffness was measured by transient elastography (FibroScan) in 228 consecutive patients with chronic viral hepatitis, with (115) or without cirrhosis (113), to study its correlations with serum transaminases [alanine aminotransferase (ALT)], fibrosis stage and surrogate noninvasive markers of fibrosis (APRI, FORNS, FibroTest and hyaluronic acid). The dynamic profiles of serum transaminases and liver stiffness were compared by multiple testing in 31 patients during a 6-month follow-up. We identified 8.3 and 14 kPa as the fibrosis >/=F2 and cirrhosis cut-offs, respectively: their sensitivities were 85.2%/78.3%; specificities 90.7%/98.2%; positive predictive values 93.9%/97.8%; negative predictive values 78.8%/81.6%; diagnostic accuracies 87.3%/88.2%. FibroScan performed better than the other surrogate markers of fibrosis (P < 0.001). Other than fibrosis, other factors independently associated with liver stiffness were ALT for all patients and chronic hepatitis patients (P < 0.001), and 12-month persistently normal ALT (biochemical remission, P < 0.001) in cirrhotics. In patients with biochemical remission either spontaneous or after antiviral therapy (48 of 228, 21%), liver stiffness was lower than in patients with identical fibrosis stage, but elevated ALT (P < 0.001). The liver stiffness dynamic profiles paralleled those of ALT, increasing 1.3- to 3-fold during ALT flares in 10 patients with hepatitis exacerbations. Liver stiffness remained unchanged in 21 with stable biochemical activity (P = 0.001). In conclusion, transient elastography is a new liver parameter that behaves as a reliable surrogate marker of fibrosis in chronic viral hepatitis patients, provided that its relationship with major changes of biochemical activity is taken into account.

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AIM:To investigate the usefulness of transient elastography by Fibroscan (FS), a rapid non-invasive technique to evaluate liver fibrosis, in the management of chronic hepatitis B virus (HBV) carriers. METHODS: In 297 consecutive HBV carriers, we studied the correlation between liver stiffness (LS), stage of liver disease and other factors potentially influencing FS measurements. In 87 chronic hepatitis B (CHB) patients, we monitored the FS variations according to the spontaneous or treatment-induced variations of biochemical activity during follow-up. RESULTS: FS values were 12.3 ± 3.3 kPa in acute hepatitis, 10.3 ± 8.8 kPa in chronic hepatitis, 4.3 ± 1.0 kPa in inactive carriers and 4.6 ± 1.2 kPa in blood donors. We identified the cut-offs of 7.5 and 11.8 kPa for the diagnosis of fibrosis ≥ S3 and cirrhosis respectively, showing 93.9% and 86.5% sensitivity, 88.5% and 96.3% specificity, 76.7% and 86.7% positive predictive value (PPV), 97.3% and 96.3% negative predictive value (NPV) and 90.1% and 94.2% diagnostic accuracy. At multivariate analysis in 171 untreated carriers, fibrosis stage (t = 13.187, P < 0.001), active vs inactive HBV infection (t = 6.437, P < 0.001), alanine aminotransferase (ALT) (t = 4.740, P < 0.001) and HBV-DNA levels (t = -2.046, P = 0.042) were independently associated with FS. Necroinflammation score (t = 2.158, > 10/18 vs ≤ 10/18, P = 0.035) and ALT levels (t = 3.566, P = 0.001) were independently associated with LS in 83 untreated patients without cirrhosis and long-term biochemical remission (t = 4.662, P < 0.001) in 80 treated patients. During FS monitoring (mean followup 19.9 ± 7.1 mo) FS values paralleled those of ALT in patients with hepatitis exacerbation (with 1.2 to 4.4-fold increases in CHB patients) and showed a progressive decrease during antiviral therapy. CONCLUSION: FS is a non-invasive tool to monitor liver disease in chronic HBV carriers, provided that the pattern of biochemical activity is taken into account. In the inactive carrier, it identifies non-HBV-related causes of liver damage and transient reactivations. In CHB patients, it may warrant a more appropriate timing of control liver biopsies.

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Hepatitis C virus (HCV) exists in vivo as a highly variable mixture of closely related genomes (quasispecies), but the pathogenetic significance of such heterogeneity is still largely unknown. To investigate this issue, we compared the composition of HCV quasispecies found in the liver, peripheral blood mononuclear cells (PBMC) and plasma of ten patients by single-strand conformation polymorphism analysis of the E2/NS1 region and sequencing of the variants detected. We found considerable quasispecies differences between the liver and PBMC in all the patients, involving variant numbers, relative quantities and relative electrophoretic mobilities, but no apparent tissue-specific trend. Genome variants present in the liver and/or PBMC were not detected in the corresponding plasma samples, while certain HCV variants were present only in plasma. No dominant amino acids or amino acid pattern characteristic of variants present solely in the PBMC were detected in the E2/NS1 region sequenced.Hepatitis C virus (HCV) exists within infected hosts as a variably complex system of related genomes (quasispecies) generated by the limited fidelity of RNA replication. Recent evidence has shown that quasispecies composition exhibits extensive variation within individual isolates (Okada et al., 1992) and can vary spontaneously both over time (Kao et al., 1995) and with liver disease progression . In addition, the extent of HCV quasispecies diversity has been reported to be predictive of responsiveness to interferon treatment (Moribe et al., 1995) and to decrease markedly

The pathogenic potential of the newly discovered TT virus (TTV) is currently a matter of conjecture. Its presence was investigated in the serum of 660 patients, by polymerase chain reaction. TTV was detected in 50% of 221 patients with unselected pathologies, and no significant differences related to age, sex, or organ disease were noted. TTV was present at a significantly higher rate in hemophiliacs (73%) and at lower rates in patients with cirrhosis (30%) and rheumatoid arthritis (28%). Patients with other liver diseases, systemic lupus erythematosus, or psoriasis or receiving hemodialysis had rates of infection similar to those in unselected patients. TTV-positive patients treated with interferon-alpha for underlying type C hepatitis showed no appreciable changes of TTV viremia levels. Type 1b was by far the most frequent viral genotype (92%), followed by types 2c (5%) and 1a (3%).

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