Apoptosis plays an important role in the progression of alcohol-induced liver disease to cirrhosis. Oxidative stress is an early event in the development of apoptosis. The major aim of this study was to study the conditions in which oxidative stress occurs in chronic alcoholism and its relationship with apoptosis of hepatocytes. We have found that oxidative stress is associated with chronic ethanol consumption in humans and in rats, in the former independently of the existence of alcohol-induced liver disease. Ethanol or acetaldehyde induces apoptosis in hepatocytes isolated from alcoholic rats, but not in those from control rats.

High-resolution magic angle spinning (HR-MAS) 1H NMR spectroscopy of intact human liver needle biopsies has not been previously reported. HR-MAS NMR spectra collected on 17 specimens with tissue amounts between approximately 0.5 and 12 mg showed very good spectral resolution and signal-to-noise ratios. One-dimensional 1H spectra revealed many intense signals corresponding to cellular metabolites. In addition, some high molecular weight metabolites, such as glycogen and mobile fatty acids, could be observed in some spectra. Resonance assignments for 22 metabolites were obtained by combining the analysis of three different types of 1D 1H spectral editing, such as T2 filtering or the nuclear Overhauser effect and 2D TOCSY and 13C-HSQC spectra. Biochemical stability of the liver tissue during up to 16 h of magic angle spinning at 277 K was studied. Biochemical trends corresponding to the different pathologies were observed, involving free fragments of lipids among other metabolites. NMR signal intensity ratios can be useful for discrimination among non-pathological, hepatitis C affected and cirrhotic liver tissues. Overall, this work demonstrates the applicability of HR-MAS NMR spectroscopy to the biochemical characterization of needle biopsies of the human liver.

Hepatitis C virus (HCV) is a major health problem worldwide, infecting an estimated 170 million people. The high genetic variability of HCV contributes to the chronicity of hepatitis C. Here, we report results from a large-scale sequence analysis of 67 patients infected with HCV genotype 1, 23 with subtype 1a and 44 with subtype 1b. Two regions of the HCV genome were analysed in samples prior to combined therapy with alpha interferon plus ribavirin, one compressing the hypervariable regions (HVR1, HVR2 and HVR3) of the E2 glycoprotein and another one including the interferon-sensitive determining region (ISDR) and the V3 domain of the NS5A protein. Genetic diversity measures showed a clear tendency to higher genetic variability levels in nonresponder patients to antiviral treatment than in responder patients, although highly disperse values were present within each response group for both subtypes. A more detailed analysis of amino acid composition revealed the presence of several subtype-specific variants in a few positions, but no discriminating positions between responder and nonresponder patients were detected. Our results also revealed that most amino acid positions were highly conserved, especially for subtype 1a. We conclude that the outcome of the antiviral treatment might depend not only on the nature of one or a few independent positions, but more likely on the combination of several positions along the HCV genome. Moreover, the own host's ability to generate an appropriate systemic response, in combination with the action of antivirals, is also likely to be essential for treatment outcome.

To characterize the relationship between findings on magnetic resonance (MR) images and histologic changes in chronic liver disease, a prospective study was performed in 100 patients with chronic hepatitis and cirrhosis and 28 healthy subjects. Biopsy specimens, obtained in all patients before MR imaging, were evaluated with the histologic activity (HA) index; MR images were obtained with short inversion time inversion-recovery (STIR) and spin-echo sequences. On STIR images, normal livers were iso-intense to fat. Significant differences (P < .001) existed between signal intensity of normal livers and that of diseased livers, which were brighter than normal livers on STIR images. The ratio of signal intensity of liver to that of fat on STIR images was associated with an HA index grouped by severity (P < .05): Patients with higher HA scores had a brighter liver. Signal intensity ratios on MR images were statistically significantly associated with periportal and lobular necrosis and portal inflammation. The signal intensity of liver on STIR images is associated with the degree of histologic severity in patients with chronic liver disease.