Biomedical subjects

Antonia D'Errico

Publications and source records attributed to Antonia D'Errico.

17 recordsLinked to original sources

PubMed2006

Systemic lupus erythematosus following virological response to peginterferon alfa-2b in a transplanted patient with chronic hepatitis C recurrence.

Autoimmune manifestations are common both in patients chronically infected by hepatitis C virus, and in patients transplanted for non-autoimmune diseases. A correlation between interferon based treatment and autoimmune diseases or the development of autoantibodies is well established in non-transplanted patients, but few data are available about transplanted patients. It is unclear whether interferon may increase the incidence of acute cellular rejection and there are few reports on the development of atypical autoimmune manifestations during post-liver transplantation interferon or pegylated interferon treatment. We describe a case of systemic lupus erythematosus following treatment with pegylated interferon alfa-2b in a transplanted patient with recurrence of chronic hepatitis C. Our experience suggest that pegylated interferon may induce autoimmune diseases in the immunosuppressed host, different from acute cellular rejection and call for a great attention to possible autoimmune disorders development during interferon based treatments in liver transplanted patients.

Antiviral Agents↗

PubMed2006

Aspartyl-(asparaginyl)-beta-hydroxylase regulates hepatocellular carcinoma invasiveness.

BACKGROUND/AIMS: We measured aspartyl (asparaginyl)-beta-hydroxylase (AAH) gene expression in human hepatocelluar carcinoma and surrounding uninvolved liver at both the mRNA and protein level and examined the regulation and function of this enzyme. METHODS: Since growth of HCC is mediated by signaling through the insulin-receptor substrate, type 1 (IRS-1), we examined-if AAH is a downstream gene regulated by insulin and IGF-1 in HCC cells. In addition, IRS-1 regulation of AAH was examined in a transgenic (Tg) mouse model in which the human (h) IRS-1 gene was over-expressed in the liver, and an in vitro model in which a C-terminus truncated dominant-negative hIRS-1 cDNA (hIRS-DeltaC) was over-expressed in FOCUS HCC cells. The direct effects of AAH on motility and invasiveness were examined in AAH-transfected HepG2 cells. RESULTS: Insulin and IGF-1 stimulation increased AAH mRNA and protein expression and motility in FOCUS and Hep-G2 cells. These effects were mediated by signaling through the Erk MAPK and PI3 kinase-Akt pathways. Over-expression of hIRS-1 resulted in high levels of AAH in Tg mouse livers, while over-expression of hIRS-DeltaC reduced AAH expression, motility, and invasiveness in FOCUS cells. Finally, over-expression of AAH significantly increased motility and invasiveness in HepG2 cells, whereas siRNA inhibition of AAH expression significantly reduced directional motility in FOCUS cells. CONCLUSIONS: The results suggest that enhanced AAH gene activity is a common feature of human HCC and growth factor signaling through IRS-1 regulates AAH expression and increases motility and invasion of HCC cells. Therefore, AAH may represent an important target for regulating tumor growth in vivo.

Animals↗

PubMed2006

Aspartyl-asparagyl beta hydroxylase over-expression in human hepatoma is linked to activation of insulin-like growth factor and notch signaling mechanisms.

Aspartyl-(asparagyl)-beta-hydroxylase (AAH) is overexpressed in various malignant neoplasms, including hepatocellular carcinomas (HCCs). The upstream regulation of AAH and its functional role in Notch-mediated signaling and motility in HCC cells was accessed. The mRNA transcript levels of AAH, insulin receptor substrate (IRS), insulin and insulin-like growth factor (IGF) receptors and polypeptides, Notch, Jagged, and HES were measured in 15 paired samples of HCC and adjacent HCC-free human liver biopsy specimens using real-time quantitative RT-PCR and Western blot analysis. Overexpression of AAH was detected in 87% of the HCC relative to the paired HCC-free liver tissue. IRS-1, IRS-2, and IRS-4 were each overexpressed in 80% of the HCC samples, and IGF-I and IGF-2 receptors were overexpressed in 40% and 100% of the HCCs, respectively. All HCC samples had relatively increased levels of Notch-1 and HES-1 gene expression. Overexpression of AAH led to increased levels of Notch, and co-immunoprecipitation experiments demonstrated a direct interaction between AAH and Notch as well as its ligand Jagged. In conclusion, contributions to the malignant phenotype of HCC is due to activation of IGF-I and IGF-II signaling that results in over-expression of both AAH and Notch. The functional role of AAH in relation to cell motility has been linked to increased activation of the Notch signaling pathway.

Aged↗

PubMed2006

Detection of HCV antigens in liver graft: relevance to the management of recurrent post-liver transplant hepatitis C.

The aim of this study was to evaluate how the immunohistochemical detection of liver hepatitis C virus (HCV) antigens (HCV-Ag) could support the histologic diagnosis and influence the clinical management of post-liver transplantation (LT) liver disease. A total of 215 liver specimens from 152 HCV-positive patients with post-LT liver disease were studied. Histologic coding was: hepatitis (126), rejection (34), undefined (24; coexisting rejection grade I and hepatitis), or other (31). The percentage of HCV-Ag infected hepatocytes were evaluated, on frozen sections, by an immunoperoxidase technique. HCV-Ag were detectable early in 57% of cases within 30 days post-LT, 92% of cases between 31 and 180 days, and 74% of cases after more than 180 days. Overall, HCV-Ag were detected more frequently in histologic hepatitis as compared to rejection (P < 0.0001) with a higher percentage of positive hepatocytes (P < 0.00001). In 16 patients with a high number of HCV-Ag-positive hepatocytes (65%; range 40-90%) a clinical diagnosis of recurrent hepatitis (RHC) was made despite inconclusive histopathologic diagnosis. Multivariate analysis identified the percentage of HCV-Ag-positive hepatocytes and the time post-LT as independent predictors for RHC (P = 0.008 and P = 0.041, respectively) and the number of HCV-Ag-positive hepatocytes >/=50% as the only independent predictor for nonresponse (P < 0.001) in 26 patients treated with alpha-interferon plus ribavirin. In conclusion, HCV reinfection occurs early post-LT, reaching its peak within 6 months. Immunohistochemical detection of post-LT HCV reinfection support the diagnosis of hepatitis when the histologic features are not conclusive. A high number of infected cells, independently from the genotype, represents a negative predictive factor of response to antiviral treatment.

Adult↗

PubMed2004

Liver transplantation for hepatocellular carcinoma: further considerations on selection criteria.

The selection criteria in liver transplantation for HCC are a matter of debate. We reviewed our series, comparing two periods: before and after 1996, when we started to apply the Milan criteria. The study population was composed of patients with a preoperative diagnosis of HCC, confirmed by the pathological report and with a survival of >1 year. Preoperative staging as revealed by radiological imagining was distinguished from postoperative data, including the variable of tumor volume. After 1996 tumor recurrences significantly decreased (6 out of 15 cases, 40% vs. 3 out of 48, 6.3%, P < .005) and 5-year patient survival improved (42% vs. 83%, P < .005). Not meeting the Milan criteria was significantly related to higher recurrence rate (37.5% vs. 12.7%, P < .05) and to lower 5-year patient survival (38% vs. 78%, P < .005%) in the preoperative analysis, but not in the postoperative one. The alfa-fetoprotein level of more than 30 ng/dL and the preoperative tumor volume of more than 28 cm3 predicted HCC recurrences in the univariate and mutivariate analysis (P < .005 and P < .05, respectively). The ROC curve showed a linear correlation between preoperative tumor volume and HCC recurrence. Milan criteria significantly reduced tumor recurrences after liver transplantation, improving long-term survival. In conclusion, the efficacy of tumor selection criteria must be analyzed with the use of preoperative data, to avoid bias of the postoperative evaluation. Tumor volume and alfa-fetoprotein level may improve the selection of patients.

Adult↗

PubMed2004

Detection of recipient's cells in liver graft using antibodies to mismatched HLA class I antigens.

Engraftment by recipient's (R) cells has been already demonstrated in gender mismatched liver grafts using fluorescence in situ hybridization (FISH), with contrasting results concerning epithelial cells. Mismatch for human leukocyte antigen (HLA) class I (HLA-I) is quite common in patients with orthotopic liver transplantation (OLT). We thus aimed to assess whether monoclonal antibodies (MoAbs), currently employed in the HLA typing process, could be used to study the dynamics of R cells in liver grafts. A total of 50 frozen liver biopsies from 37 patients receiving a HLA mismatch liver were tested. Biopsies were obtained from 3 days to more than 360 days after OLT. Frozen sections of graft biopsies were stained using an immunoperoxidase technique with the proper MoAbs. In selected cases, a double immunofluorescence was also performed. Circulating R blood cells and sinusoidal cells were occasionally observed in liver biopsies obtained within 10 days after OLT and were commonly detected after 1 month. The number of sinusoidal cells continued to increase up to 6 months, as shown on serial biopsies. On the whole, R blood cells and R sinusoidal cells were detected in 86% and 82% of the biopsies, respectively. R hepatocytes and biliary cells were detected after 40 and 60 days after OLT, respectively, in 14% (hepatocytes), 8% (bile ducts), and 12% (proliferating bile ducts) of the biopsies. R hepatocytes presented as single cells or groups of few cells; their number was lower than 1% and apparently did not increase with time after OLT. In conclusion, it is possible to detect R cells in liver graft using MoAbs to specific mismatched HLA-I alleles. R sinusoidal cells start to appear after 10 days and are commonly observed after 1 month; bile duct cells and hepatocytes appear later and their number does not increase with time. Engraftment by R epithelial cells seems to be less important than previously reported.

Antibodies, Monoclonal↗

PubMed2004

Thorough intraoperative analysis of breast sentinel lymph node biopsies: histologic and immunohistochemical findings.

BACKGROUND: We report the use of a thorough intraoperative sentinel lymph node (SLN) biopsy screening procedure for patients with small N0 breast tumors. METHODS: Sixty-eight consecutive female patients with monofocal stage I or "small" stage II (ie, 2.1-3.0 cm) N0 tumors received intraoperative SLN screening according to a procedure on the basis of comprehensive histologic analysis and cytokeratin immunohistochemical determination (CkID) of adjacent frozen sections of the SLN taken at 50-microm cutting levels. RESULTS: The maximum duration of intraoperative analysis including CkID was 40 minutes. Positive SLN were found in 15/68 (22%) patients (always in a single node); they included 5 instances of micrometastasis and 3 of carcinomatous lymphangitis. In the 14 patients who underwent axillary lymph node dissection, no further metastasis was found at histologic analysis or CkID. SLN positivity correlated with histologic type (P=.044), intratumoral or peritumoral vascular invasion (P<.001) and Mib1 score (P=.042). CONCLUSIONS: It is possible for an experienced team to perform intraoperative SLN screening for T1 or small T2 N0 breast tumors with frozen sections taken at 50-microm cutting levels. This procedure facilitates identification of micrometastasis, as well as of carcinomatous lymphangitis to help understand the biologic implications of these small lesions in the long term. SLN positivity appears to correlate with histologic type, intratumoral/peritumoral vascular invasion and Mib1 score.

Adult↗

PubMed2004

Detection of the M30 neoepitope as a new tool to quantify liver apoptosis: timing and patterns of positivity on frozen and paraffin-embedded sections.

One of the first stages of apoptosis is cytokeratin cleavage mediated by caspases, which is associated with the expression of a neoepitope, the cleavage site of cytokeratin 18, identifiable by the M30 monoclonal antibody. The aim of this study was to evaluate the timing of neoantigen expression and its modifications in the various morphologic stages of apoptosis on frozen and paraffin-embedded sections from liver biopsies of patients with chronic hepatitis or transplanted liver. The appearance of this neoepitope coincides with the gradual disappearance of cytokeratins, with the appearance of nuclear DNA fragmentation, and with the presence of Councilman bodies. The staining patterns on paraffin-embedded sections of liver specimens were similar to those found in frozen sections, with a reduced sensitivity. The M30 antibody is correlated with apoptosis, and its specificity for epithelial cells makes this method the first choice for routine evaluation of apoptosis in liver epithelial cells.

Antibodies, Monoclonal↗

PubMed2003

A multiorgan donor cancer screening protocol: the Italian Emilia-Romagna region experience.

BACKGROUND: We describe the Emilia-Romagna screening protocol for all multiorgan donors within this region of Italy and report on the first 2 years of implementation. SETTING: Setting is a 24-hour multidisciplinary call service covering the 16 intensive care units in Emilia-Romagna (3,969,000 inhabitants) and a centralised pathology center, directed by a transplant coordination center. STUDY POPULATION AND PERIOD: All 271 effective donor candidates presenting in Emilia-Romagna in 2001-2002. PROTOCOL: Anamnesis, external examination, and thorough laboratory and instrumental screening is followed by sampling of internal effusions and evaluation of all internal organs. All suspect findings are then investigated by extemporary pathologic evaluation. To fit national legal requirements, candidates are classified as standard risk (no transmissible risk); nonstandard risk (low-risk of transmission, eligibility restricted to certified clinical emergencies pending informed consent); and unacceptable risk (unconditional exclusion because of high-risk pathologies). RESULTS: The protocol was successfully implemented for all 271 candidates. In addition to 14 independent exclusions, clinical suspicion of cancer was raised for 61 donors presenting with 82 lesions or effusions. Along with one case of lymph-node tuberculosis (unacceptable risk), histocytologic screening revealed eight cases of malignancy (5 prostate, 1 papillary-thyroid, 1 follicular-thyroid, and 1 renal cell, all nonstandard risk); the remainder were benign (standard risk). Protocol implementation led to exclusion of 8 (3.0%) candidates (1 nonstandard risk transplantation was performed). CONCLUSIONS: This stringent protocol-now adopted with some modifications at a national level-provides an initial example of a feasible intervention aimed at maximising donation safety while rationalizing use of marginal donors.

Adolescent↗

PubMed2003

Expression of beta-galactoside alpha2,6 sialyltransferase and of alpha2,6-sialylated glycoconjugates in normal human liver, hepatocarcinoma, and cirrhosis.

beta-Galactoside alpha2,6-sialyltransferase (ST6Gal.I) mediates the addition of alpha2,6-linked sialic acid to glycoproteins. ST6Gal.I is strongly expressed by the liver and is up-regulated in several cancers, but little is known of its regulation in human liver diseases. We have investigated the expression of ST6Gal.I and its product, the alpha2,6-sialylated lactosamine, in normal human liver, hepatocarcinoma (HCC), and cirrhosis. We found that both ST6Gal.I activity and mRNA can undergo up- or down-regulation in different HCC patients. At the mRNA level, the groups of specimens showing the highest expression were HCC of grade 2, HCC developed without preexisting cirrhosis, and HCC of male patients. The lectin from Sambucus nigra (SNA) reveals a significative overexpression of alpha2,6-sialylated glycoconjugates in HCC tissue homogenates and their intracellular accumulation in HCC histological sections, even though in a few cases the extent of alpha2,6-sialylation dramatically decreases. Transcription of the gene occurs through at least two different promoters, resulting in two differentially expressed mRNA species. RNA in situ hybridization reveals that the ST6Gal.I mRNA can be expressed at a quantitatively heterogeneous level among the neoplastic cells. Neither ST6Gal.I expression nor alpha2,6-sialylation are altered in cirrhosis. These data indicate that neoplastic transformation but not cirrhosis can alter the process of alpha2,6-sialylation of liver glycoproteins.

Aged↗

PubMed2003

Increased expression of p21 (WAF1/CIP1) cyclin-dependent kinase (CDK) inhibitor gene in chronic allograft nephropathy correlates with the number of acute rejection episodes.

The p21 (WAF1/CIP1) cyclin-dependent kinase (CDK) inhibitor gene is considered to be the senescence marker in some recent publications. Expression of the gene was evaluated in 14 normal human kidney tissues of different ages and in nine chronically rejected renal allografts. All normal kidneys were negative for p21 expression. Glomerular, tubular and interstitial expression of the marker was detected in 88.9% ( P<0.0001) and vascular expression in 66.7% of chronically rejected grafts ( P<0.001). No correlation was found between the intensity of p21 expression and recipient age, donor age or number of human leukocyte antigen (HLA) mismatches. The marker was expressed more in grade 3 of chronic allograft nephropathy (CAN) than in grade 2 ( P=0.059 for glomerular score). Tubular expression of p21 was correlated with the number of acute rejections: P<0.05 for three vs one and two, and P=0.0046 for three vs no previous acute rejection episodes.

Acute Disease↗

PubMed2003

Increased expression of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor genes in aging human kidney and chronic allograft nephropathy.

BACKGROUND: The goal of the current study was to examine the potential value of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor (CDKI) genes in the process of human kidney aging in vivo, and in the development of chronic allograft nephropathy (CAN). METHODS: Expression of p16(INK4a) and p27(Kip1) CDKI genes was evaluated and compared in 20 normal human kidney tissues of different ages (range, 21 to 80 years) and in 9 chronically rejected kidney grafts. Age dependency of marker expression was analyzed by the Pearson correlation and linear regression. RESULTS: Expression of p16 in cortical tubular (CTS) and interstitial (CIS) cells of normal kidney was age dependent (correlation coefficients: 0.608 and 0.726, 95% confidence interval [CI]: 0.227 to 0.828 and 0.417 to 0.884, respectively). Cortical tubular expression of p27 was also correlated with increasing age (0.672, 95% CI: 0.327 to 0.859). Linear regression analyses confirmed the linearity of marker relationship with age (coefficient of determination R(2):0.370, 0.452, and 0.527 for CIS p16, CTS p27, and CTS p16, respectively). The mean chronological and predicted graft ages (53 +/- 21 and 76 +/- 8.9 years, respectively) were significantly different (P = 0.0126). The glomeruli, tubules, and interstitial cells of rejected grafts expressed significantly higher levels of p16 and p27 than normal kidneys. Expression of p16 in glomerular and cortical interstitial cells was higher in grade 3 of CAN than in grade 2 (P = 0.013 and 0.004, respectively). CONCLUSION: The results of the current study show that expression of p16(INK4a) and p27(Kip1) CDKI genes is increased in cortical cells of the aging human kidney and in chronic allograft rejection, supporting the senescence theory of CAN.

Adolescent↗

PubMed2003

Primary diffuse meningeal melanomatosis: radiologic-pathologic correlation.

We report a case of primary diffuse meningeal melanomatosis, a rare variant of primary malignant melanoma of the CNS, in a 68-year-old woman. The disease mimicked intracranial hypotension syndrome and was diagnosed only at autopsy (CSF cytologic results were negative). CT revealed hydrocephalus with effacement of the cerebral convexity sulci and abnormal contrast enhancement in the right sylvian and frontoparietal fissures, whereas MR imaging showed diffuse marked dural and leptomeningeal contrast enhancement. In retrospect, these nonspecific findings correlated with the extensive leptomeningeal invasion in the cerebral hemispheres, brain stem and spinal cord. The clinical, radiologic, and pathologic features of diffuse meningeal melanomatosis are reviewed.

Aged↗

PubMed2002

Relevance of biologic markers in colorectal carcinoma: a comparative study of a broad panel.

BACKGROUND: Although pathologic stage is currently the main prognostic indicator for patients with colorectal carcinoma (CRC), mounting evidence suggests that, in its current form, it is insufficient to predict clinical outcome. To assess biologic markers of primary CRC that may improve clinical staging and provide useful information for the application of novel therapeutic strategies, the authors investigated a panel of markers that included transforming growth factor alpha (TGF alpha), epithelial growth factor receptor (EGF-R; the protein product of the c-erb B2/HER-2 oncogene), matrix metalloproteinase 2 (MMP-2), insulin-like growth factor II (IGF-II), vascular endothelial growth factor (VEGF), and angiogenesis, as evaluated by microvessel density (MVD). METHODS: Two groups of CRC were studied: 1) surgical samples from patients who achieved a disease free survival of at least 6 years (CRC-M0) and 2) surgical specimens of both primary tumors and synchronous or metachronous liver metastases (CRC-M1). RESULTS: Chi-square analysis revealed that expression levels of TGF-alpha, c-erb B2/HER-2, MMP-2, IGF-II, VEGF, and MVD (but not EGF-R) were significantly higher in CRC-M1 samples compared with CRC-M0 samples (P < 0.001, P < 0.05, P < 0.001, P < 0.001, P < 0.01, and P < 0.001, respectively). Logistic regression analysis showed that TGF-alpha, IGF-II, and MMP-2 had significantly greater expression in CRC-M1 samples independent of the other variables (including tumor classification, histologic grade, and patient age). If all three markers had > or = 25% expression, then the probability of developing liver metastasis was 99.5%. CONCLUSIONS: Based on the evidence of this study, TGF-alpha MMP-2, and IGF-II seem suitable candidates for a selective panel of markers designed to provide significant additional information with respect to the current pathologic staging system for patients with colorectal carcinoma.

Adult↗

PubMed2002

Slowly tapering off steroids protects the graft against hepatitis C recurrence after liver transplantation.

Chronic hepatitis C represents a major clinical problem after liver transplantation, but factors influencing the recurrent disease have not been well characterized. We analyzed the clinical records of all the patients transplanted for hepatitis C virus (HCV)-related liver disease in our Center between 1991 and 1997. Eighty consecutive HCV-positive (+) patients (60 men, ages 28 to 64) survived more than 1 month after transplantation and were followed for a median of 45 months. Diagnosis of recurrent chronic hepatitis C was made in 38 patients (47.5%), of whom 22 had moderate/severe chronic hepatitis. Decompensated cirrhosis occurred in six patients (7.5%). No difference in patient survival was found between patients with and without hepatitis C recurrence. No association was found between recurrent hepatitis C and presumed risk factors. The method of tapering off corticosteroids was significantly associated with both hepatitis C recurrence and the severity of hepatitis. In patients receiving a higher daily prednisone dose, 12 months after transplantation, the proportion of recurrent hepatitis C was 35.7% versus 66.6% (P = .02; odds ratio [OR], 3.6; 95% confidence interval (CI): 1.25 to 10.36), and among patients receiving a higher daily prednisone dose, 6 months after transplantation, the proportion of moderate/severe chronic hepatitis C was 40% versus 89% (P = .03; OR: 0.08, 95% CI: 0.008 to 0.84). Finally, prednisone dose at month six was significantly associated with disease-free survival of the liver graft. In conclusion, our results seem to indicate that in HCV-infected liver transplant recipients, a long-term treatment with corticosteroids, slowly tapered off over time, may prevent the more aggressive forms of recurrent liver disease.

Adult↗

PubMed2002

Primary paraganglioma strictly confined to the liver and mimicking hepatocellular carcinoma: an immunohistochemical and in situ hybridization study.

We describe a case of primary nonfunctioning paraganglioma that, unlike any other previously reported case, was strictly confined to the liver and must therefore have arisen on liver parenchyma. An asymptomatic 46-year-old man was referred to us for laparotomy and a right hemihepatectomy after a preoperative diagnosis of fibrolamellar hepatocellular carcinoma, based on a fine-needle biopsy. An 8-cm resiliently firm, pale gray nodule with a large central area of fibrosis and a thin fibrous capsule was resected. The polygonal eosinophilic tumor cells containing round nuclei lacking nucleoli were arranged in small nests set in a vascularly rich stroma. At immunohistochemistry neoplastic cells were strongly positive for chromogranin A, neuron-specific enolase, synaptophysin, and IGF-II protein; they were negative for keratin, S-100 protein, CD10, vimentin, and smooth muscle actin. In situ hybridization confirmed that, as in other sites, liver paraganglioma can express IGF-II gene. Conversely (and unlike hepatocellular carcinomas), the neoplastic cells did not express albumin mRNA, which was detected only in surrounding hepatocytes. The clinical course was benign and the patient is well and free of neoplastic disease 9 years after surgery. Knowledge of the entity should avoid possible confusion with hepatocellular carcinoma, especially of the fibrolamellar variety.

Carcinoma, Hepatocellular↗

PubMedDate not supplied

Hepatocyte proliferation and apoptosis in relation to oxidative damage in alcohol-related liver disease.

In alcohol-related liver disease, free radicals play a part in the pathogenesis of liver damage and may influence cell turnover. The aims of this study were to correlate lipid peroxidation, antioxidant defence and iron metabolism with cell proliferation and apoptosis in alcoholic liver injury, and also in comparison with virus-related liver disease. In 45 patients [10 with chronic alcoholic liver damage (CALD), 24 with HCV-related (HCV) and 11 with HBV-related chronic hepatitis (HBV)], and 10 control subjects, we investigated serum ferritin, liver tissue iron, cysteine, reduced/oxidized glutathione, malondialdehyde, histology with hepatocyte proliferation and the apoptotic index. Ferritin, iron levels and malondialdehyde were significantly higher in HCV and CALD than in HBV, and malondialdehyde correlated with both iron and ferritin. Glutathione levels were significantly lower in CALD than in HCV, HBV and control subjects, whereas cysteine levels were significantly higher. The apoptotic index was slightly lower in CALD, with apoptosis occurring more frequently in the centrilobular area, while CALD had fewer proliferating hepatocytes, both overall and in the periportal and centrilobular areas. This study confirms that chronic alcohol intake: (1) induces more peroxidative damage, which correlates with iron loading; (2) reduces antioxidant defence, lowering reduced glutathione liver availability; (3) induces an accumulation of cysteine, a glutathione precursor/metabolite in the liver, probably due to gamma-glutamyltransferase induction; (4) correlates with a lesser extent and different distribution of hepatocyte proliferation and apoptosis than in viral liver damage. This last finding may explain the different types of liver cirrhosis deriving from alcoholic liver damage and the lower cancer risk.

Adult↗