Hepatitis: Codes L

Codes L, Matos L, Paraná R. · Medicine School of Bahia, Federal University of Bahia, Salvador, BA, Brazil. · Braz J Infect Dis. · Pubmed #17684642 links to  free full text

Abstract: The main injury caused by hepatitis C virus is the hepatic fibrosis, as a result of a chronic inflammatory process in the liver characterized by the deposit of components from the extracellular matrix. The fibrosis development leads to the modification of the hepatic architecture, of the hepatocellular function and to irregularities in the microcirculation. The tissue remodeling process observed in fibrosis has stellate cells, located at the space of Disse, as main acting agents. These cells, in response to a harmful stimulus, undergo phenotypic changes from non-proliferating cells to proliferating cells that express a- smooth-muscle actin (alpha-SMA), a process called as transdifferentiation. There are evidences that the oxidative stress is involved in the chronic liver disease and serves as bond between the injury and the hepatic fibrosis. A number of studies suggest that the estrogen, at physiological levels, presents an antifibrogenic action probably through an antioxidant effect, decreasing the levels of lipid peroxidation products in the liver and blood, thus inhibiting the myofibroblastic transformation of stellate cells and contributing for gender-associated differences in relation to the fibrosis development. The aim of this paper was to describe data from literature concerning the interaction between chronic hepatitis C and estrogens, pregnancy, use of oral contraceptives, menopause and hormone reposition therapy.

Paraná R, Schinoni MI, de Freitas LA, Codes L, Cruz M, Andrade Z, Trepo C. · Gastro-Hepatology Unit, Faculty of Medicine, University Hospital of Bahia, Bahia, Brazil. · Liver Int. · Pubmed #17032416 No free full text.

Abstract: BACKGROUND/AIM: Pegylated interferon (Peg-IFN) plus ribavirin is the standard therapy for hepatitis C. Peg-IFN has several antiviral mechanisms, but its role in hepatitis C treatment seems to be related to its immunomodulatory effect. Ribavirin, an antiviral agent, potentiates IFN activity when added to it. Both drugs are associated with adverse reactions of different magnitudes. Autoimmune phenomena have been reported with this treatment. In this paper, we describe cases of ALT/GGT flares during Peg-IFN plus ribavirin treatment, which related to the appearance of anti-Golgi antibody and disease progress. METHODS: We investigated three patients with hepatitis C and severe ALT/GGT flares during Peg-IFN and ribavirin treatment coinciding with anti-Golgi complex antibody as the only marker of autoimmunity. We then reviewed the medical files and tested anti-Golgi antibody in stored sera from 25 patients treated with conventional IFN and in 14 patients treated with Peg-IFN. RESULTS: The three patients were male, over 45 years of age; all were relapsers and non-responders. Anti-Golgi antibody was positive during treatment coinciding with ALT/GGT flares but with hepatitis C virus (HCV)-RNA negativity, disappearing after stopping treatment, with normalization of ALT/AST levels. One patient had progression of fibrosis from F2 to F3 despite negativity of HCV-RNA. In the last group, only two patients treated with Peg-IFN experienced ALT/GGT flares but without anti-Golgi antibody CONCLUSIONS: The presence of anti-Golgi complex antibody could be a marker of a temporary autoimmune phenomenon and progressive disease.

Codes L, Asselah T, Cazals-Hatem D, Tubach F, Vidaud D, Paraná R, Bedossa P, Valla D, Marcellin P. · Service d'Hépatologie, University of Paris VII, AP-HP Hôpital Beaujon, Clichy, France. · Gut. · Pubmed #17005762 No free full text.

Abstract: BACKGROUND AND AIMS: The rates of fibrosis progression in chronic hepatitis C are significantly different between males and females. The antifibrogenic effect of oestrogen has been proposed, possibly via inhibition of stellate cells. The aim of this study was to evaluate the severity of chronic hepatitis C in women, in relation to the menopause, steatosis and hormone replacement therapy (HRT). METHODS: From November 2003 to October 2004, women with chronic hepatitis C were enrolled prospectively. A questionnaire was completed prospectively and a blood sample was obtained on the day of biopsy. We identified characteristics associated with moderate/severe fibrosis using univariate and multivariate analysis. RESULTS: 251 women were included in the study. 122 women (52%) were menopausal and 65 were receiving HRT. 61 (24%) women with moderate/severe fibrosis (F2-F4, Metavir score) had a longer known duration of infection (>15 years), a higher body mass index and presented with steatosis more frequently than 190 (76%) women with mild fibrosis (F0-F1). Women with F2-F4 were more often menopausal (67% v 47%). The probability of fibrosis F2-F4 was lower for menopausal women receiving HRT (p = 0.012). Steatosis was more frequent and more severe in menopausal women. CONCLUSIONS: Severity of fibrosis was associated with a longer duration of infection (>15 years), a higher body mass index, advanced steatosis and the menopause. Menopausal women receiving HRT presented with a lower stage fibrosis. These results reinforce the hypothesis of a protective role of oestrogens in the progression of fibrosis. Steatosis may be implicated in the progression of fibrosis after the menopause.

Rocca P, Codes L, Chevallier M, Trépo C, Zoulim F. · Service d'Hépatologie et de Gastro-Entérologie, Hôpital de l'Hôtel-Dieu, Lyon. · Gastroenterol Clin Biol. · Pubmed #15657545 No free full text.

Abstract: We report the case of a 56 year-old woman with post-transfusion chronic hepatitis C who presented with a severe ALT flare up associated with a rapid progression of liver fibrosis during interferon alpha 2b therapy. Several hypotheses were considered to explain the etiology of this ALT flare: there was no viral super infection by other hepatotropic viruses, no toxic hepatitis, no metabolic disease, and no other specific liver diseases could be identified. HLA typing showed a specific profile A1 B8 DR3 (risk factor of auto-immunization during interferon alpha therapy) with antinuclear antibodies and anti smooth muscle antibodies. This case suggests that auto-immunization induced by interferon alpha should be investigated in case of ALT flare that is not followed by an HCV breakthrough.

Codes L, de Freitas LA, Santos-Jesus R, Vivitski L, Silva LK, Trepo C, Reis MG, Paraná R. · Federal University of Bahia, Salvador, BA, Brazil. · Braz J Infect Dis. · Pubmed #14636481 links to  free full text

Abstract: Hepatitis C virus displays a high degree of genetic mutation, with considerable heterogeneity, motivating clinical and biomolecular investigations. It is necessary to understand the effects of genotypes on the course of the disease, as well as their peculiarities at the regional level. OBJECTIVE: The study objective was to compare epidemiological, biochemical and histological aspects of hepatitis C virus genotypes 1 and 3 in Salvador, Bahia. Study DESIGN: Data were collected retrospectively from outpatient medical records. MATERIALS AND METHODS: 127 patients with positive anti-HCV results were selected, based on detectable RNA-HCV (RT-PCR) of genotypes 1a, 1b and 3a. RESULTS: Thirty-nine (30.7%) individuals were infected by subtype 1a, 45 (35.4%) by subtype 1b and 43 (33.9%) by subtype 3a. Most (73.2%) patients were male, with an average age of 47.8 years. The subtype 1b-infected patients had the highest average age (512 +/-11.17; P=0.09). The use of illicit injected drugs was more frequent among subtype 3a infected individuals when compared with genotype 1 (6/43; 14% and 3/84; 3.6%, respectively; P=0,06). No significant differences were found for other epidemiological characteristics. Average values for GT, AST, ALT and ferritin did not differ between the groups (64, 78, 109, 276, respectively). Thyroid dysfunction occurred in 7/30 (23.3%) of those infected by genotype 3 (P=0.05). Cryoglobulinemia was also more frequent in this group (5/13, 38%, P=0.02). Most patients presented limited necro-inflammatory activity, stages 2 and 3 by the METAVIR Classification. In some cases, dissociation was noticed between inflammatory activity and fibrosis. No significant differences were found in the histopathological findings of the various genotypes. Younger patients had a significantly smaller degree of necrosis in stomatocytosis (P=0.032) and fibrosis (P=0.012). Intense parenchymatous activity and lymphoid follicles were more frequent among alcohol consumers (P=0.06 and P=0.04, respectively). CONCLUSIONS: In Bahia, genotype 3 dissemination seems to be associated with illicit drug use. The disease evolution depends on a function of complex interactions between virus and host. Age and alcohol consumption stand out as important variables in the development of cirrhosis.

Paraná R, Codes L, Andrade Z, Freitas LA, Santos-Jesus R, Reis M, Cotrim H, Cunha S, Trepo C. · Gastro-Hepatology Unit, University Hospital of Bahia, Bahia, Brazil,CPgMS-UFBA, Bahia-Salvador, Brazil. · Int J Infect Dis. · Pubmed #14563227 No free full text.

Abstract: Non-A-E hepatitis and acute cryptogenic hepatitis are the names given to the disease of patients with clinical hepatitis, but in whom serologic evidence of A-E hepatitis has not been found. Over a period of 8 years, we evaluated in Brazil 32 patients who fulfilled the criteria for this diagnosis in order to determine patterns of the clinical illness, laboratory parameters, or histologic features. Each patient was subjected to virologic tests to exclude A-E hepatitis and cytomegalovirus/Epstein-Barr virus infection. Drug-induced hepatitis and autoimmune disease were also excluded. Wilson's disease was excluded in young patients. The course of the disease was clinical/biochemical recovery in 3 months in 25 patients and persistent alanine aminotransferase (ALT) elevation in 7 patients. Three of these had chronic hepatitis, and one had severe fibrosis on liver biopsy. During the acute illness, mean peak ALT was 1267 IU/L, bilirubin was 4.0 mg/dL, and ferritin was 1393 IU/mL. GB virus type C (GBV-C) was found in six patients, and TT virus (TTV) in five patients. We conclude that, in Brazil, non-A-E hepatitis probably originates from still unidentified viruses. The course of the disease and the histologic patterns are similar to those recorded for known viruses. Continuous survey for the specific etiologic agents is needed.

Codes L, de Jesus RS, Cunha S, Cruz M, Paraná R. · Universidade Federal da Bahia. · Rev Soc Bras Med Trop. · Pubmed #12621665 No free full text.

Abstract: There are interactions between hepatotropic viruses and the host immune system, which could contribute to liver damage in viral hepatitis. The aim of this study was to investigate the frequency of autoantibodies in patients with acute viral hepatitis and their relationship with biochemical activity, severity of acute illness and chronicity rate. From 1992 to 2000, 156 patients with acute viral hepatitis were enrolled in a prospective study. Among these, hepatitis A was detected in 32%, hepatitis B in 31%, hepatitis C in 8%, hepatitis E in 3% and 24% were considered non A-E hepatitis. During the acute phase, 20.5% of patients presented ANA and 14.8% anti-smooth muscle antibody positive. During convalescence, 6.4% of patients showed ANA and 3.9% anti-smooth muscle positive. Comparison between autoantibodies-positive and negative groups showed no differences regarding ALT and bilirubin levels. In conclusion, autoantibodies can occur in acute viral hepatitis but there are no prognostic consequences.

Paraná R, Cruz M, Santos-Jesus R, Ferreira K, Codes L, Cruz T. · Division of Endocrinology--Federal University of Bahia, Brazil. · Braz J Infect Dis. · Pubmed #11136525 No free full text.

Abstract: High prevalence of thyroid autoantibodies, with or without overt thyroiditis, has been described in hepatitis C patients, particularly in those undergoing alpha-interferon treatment. The aim of this study was to describe the frequency and clinical outcome of thyroid disease in a cohort of HCV carriers before and during combination therapy with interferon plus ribavirin. Between May, 1997, and May, 1999, 111 previously untreated (naive) patients were treated with a-interferon plus ribavirin for 6 or 12 months. Of those, 67 (60%) patients were male and 44 (40%) female. Thyroid function was evaluated in all patients by testing free T4, TSH and antiTPO within 30 days prior to treatment, 90 days after treatment was initiated, and 6 months after treatment was concluded. Abnormal thyroid tests were observed in 4 (3.6%) patients--1 male and 3 female--before the onset of antiviral treatment. Three patients were already undergoing T4 replacement due to Hashimoto thyroiditis and 1 patient had positive antiTPO with normal free T4 and TSH. All 4 patients completed the treatment regime for HCV, but required hormone replacement. Among the patients with a normal thyroid function test prior to treatment (107 cases), 5 (4.6%) developed thyroid test abnormalities; 2 patients had hypothyroidism due to autoimmune thyroiditis; 1 patient became positive for antiTPO antibodies but thyroid function remained normal, and 2 patients had subacute thyroiditis. Four of these patients (80%) were female and 1 was male (20%). A family history of thyroid disease was strongly predictive of thyroid abnormalities during antiviral treatment. In conclusion, there is a low prevalence of thyroid function abnormalities in HCV carriers with no prior antiviral treatment. Family history of thyroid disease reinforces the special attention to thyroid abnormality development before considering antiviral therapy. Subacute thyroiditis during combination therapy was observed, but its pathogenesis is still unknown. Evaluation of thyroid function during and after antiviral treatment is strongly recommended because thyroid related symptoms can be easily misinterpreted as medication side effects.

Paraná R, Codes L, Andrade Z. · No affiliation provided · Hepatology. · Pubmed #11343268 No free full text.

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