Liana Codes

Comparative study of Hepatitis C virus genotypes 1 and 3 in Salvador, Bahia

UNLABELLED 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.

Chronic hepatitis C and fibrosis: evidences for possible estrogen benefits

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.

Anti-Golgi complex antibodies during pegylated-interferon therapy for hepatitis C.

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.

Freqüência e implicações dos auto-anticorpos em hepatites agudas virais

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.

Clinical, histologic and serologic evaluation of patients with acute non-A-E hepatitis in north-eastern Brazil: is it an infectious disease?

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. Wilsons 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.

Auto-immunisation induite par l’interféron alpha dans un contexte d’hépatite virale C chronique

Resume Nous rapportons le cas d’une femme de 56 ans, presentant une hepatite C chronique post-transfusionnelle, qui a presente sous traitement antiviral par interferon alpha-2b, une poussee cytolytique associee a une evolution rapidement fibrosante de la maladie hepatique. Plusieurs hypotheses ont ete evoquees pour expliquer cette cytolyse. Une surinfection virale par les autres virus hepatotropes, une hepatite medicamenteuse, une hepatopathie metabolique, de surcharge ou genetique ont ete eliminees. Le typage HLA a montre la presence d’un haplotype A1 B8 DR3, facteur de risque a l’auto-immunisation sous interferon alpha. Le malade presentait des d’anticorps anti-nucleaires et des anticorps anti muscles-lisses tres fortement positifs. Cette observation suggere qu’en dehors de l’echappement virologique, l’auto-immunisation doit etre evoquee devant toute cytolyse survenant chez un malade traite par interferon alpha dans le cadre d’une hepatite C chronique.

New Onset Diabetes and Non-Alcoholic Fatty Liver Disease after Liver Transplantation

BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is an emerging cause of graft dysfunction after liver transplantation (LT) frequently related to the development of new onset diabetes after LT (NODAT). This study was undertaken to evaluate the frequencies of NODAT and NAFLD after LT, to investigate their major risk factors and the impact of de novo or recurrent NAFLD in graft function. MATERIAL AND METHODS 119 patients submitted to LT were prospectively evaluated. RESULTS After 4 ± 1 years, NODAT, recurrent and de novo NAFLD were observed in 31%, 56% and 43% of the subjects, respectively. Only 3 patients had non-alcoholic steatohepatitis (NASH) without fibrosis. Other risk factors for NAFLD such as arterial hypertension (AHT), metabolic syndrome (MS), hypertriglyceridemia and obesity were seen in 51%, 50%, 35% and 24% of the subjects, respectively. In addition, insulin resistance (IR), assessed by HOMA-IR and β-cell dysfunction, determined by HOMA-β, were observed in 16% and 94% of the patients, respectively. Occurrence of NODAT was associated with male gender, higher waist circumference, higher HOMA-IR and lower HOMA-β values. No correlation was found between NAFLD and NODAT, MS, hypertriglyceridemia, obesity and HOMA-IR and HOMA-β levels. CONCLUSIONS NODAT, recurrent and de novo NAFLD are common after LT but are not associated with signs of graft dysfunction, possibly due to the low frequency of IR and NASH. No correlation is observed between NAFLD and NODAT, MS, hypertriglyceridemia, obesity and IR. β-cell dysfunction and diabetes, however, are seen in most of the patients, possibly due to calcineurin inhibitor toxicity.BACKGROUND & AIMS Non-alcoholic fatty liver disease (NAFLD) is an emerging cause of graft dysfunction after liver transplantation (LT) frequently related to the development of new onset diabetes after LT (NODAT). This study was undertaken to evaluate the frequencies of NODAT and NAFLD after LT, to investigate their major risk factors and the impact of de novo or recurrent NAFLD in graft function. MATERIAL AND METHODS 119 patients submitted to LT were prospectively evaluated. RESULTS After 4 ± 1 years, NODAT, recurrent and de novo NAFLD were observed in 31%, 56% and 43% of the subjects, respectively. Only 3 patients had non-alcoholic steatohepatitis (NASH) without fibrosis. Other risk factors for NAFLD such as arterial hypertension (AHT), metabolic syndrome (MS), hypertriglyceridemia and obesity were seen in 51%, 50%, 35% and 24% of the subjects, respectively. In addition, insulin resistance (IR), assessed by HOMA-IR and β-cell dysfunction, determined by HOMA-β, were observed in 16% and 94% of the patients, respectively. Occurrence of NODAT was associated with male gender, higher waist circumference, higher HOMA-IR and lower HOMA-β values. No correlation was found between NAFLD and NODAT, MS, hypertriglyceridemia, obesity and HOMAIR and HOMA-β levels. CONCLUSIONS NODAT, recurrent and de novo NAFLD are common after LT but are not associated with signs of graft dysfunction, possibly due to the low frequency of IR and NASH. No correlation is observed between NAFLD and NODAT, MS, hypertriglyceridemia, obesity and IR. β-cell dysfunction and diabetes, however, are seen in most of the patients, possibly due to calcineurin inhibitor toxicity.

Hepatoportal sclerosis related to the use of herbals and nutritional supplements. Causality or coincidence

INTRODUCTION AND AIM Non-cirrhotic idiopathic portal hypertension (NCIPH), also known as hepatoportal sclerosis (HPS) is a disease of uncertain etiology. However, many pathophysiological mechanisms has been postulated, including thrombophilia, chronic recurrent infections and exposure to drugs or toxins. In this context, it appears to be of multifactorial etiology or resulting from a portal vascular endothelium aggression. It is important to consider whether the use of dietary supplements and herbs can trigger or contribute to the occurance of HPS. We report a possible association of HPS with the consumption of herbal and / or dietary supplements. MATERIAL AND METHODS We describe two cases of HPS in patients without known etiology causes associated with this disease. RESULTS Both patients were females who were diagnosed with HPS following the consumption of Herbalife® products and putative anorexigenic agents in the herbal infusions. Image-based analysis and the assessment of the histopathological alterations found in the livers confirmed the diagnosis. The histopatological analysis of liver samples from both patients showed portal tracts enlarged by fibrosis with disappearance or reduction in the diameter of the portal vein branches. In many portal tracts, portal veins branches were replaced by aberrant thin-walled fendiforme vessels. The bile ducts and branches of the hepatic artery show normal aspects. CONCLUSION After the exclusion of other etiologic factors and a comprehensive analysis of clinical history, consumption of Herbalife® products and anorexigenic agents was pointed-out as a puttative predisposing factor for the development of the disease.

Hepatite aguda criptogênica: uma entidade heterogênea com possibilidades de complicações

Acute or chronic hepatitis with no defined causes constitute a problem for clinical and gastroenterologists. In spite of sophisticated tests, a substantial proportion of hepatitis remains with no certain cause. They are cryptogenic hepatitis or hepatitis no A-E. Possible aetiologies are suggested: unknown virus, metabolic diseases or auto-immune hepatitis with atypical presentation. Recently, our group demonstrated that, in a reference center for hepatic diseases in Brazil, 17% of cases of acute hepatitis are cryptogenic, with some aspects suggesting viral aetiology. We described four clinical cases of acute cryptogenic hepatitis, demonstrating the heterogeneity of this condition that may be associated with possible complications. This justifies a careful epidemiological and laboratorial investigation, as well as a follow-up of those patients

Cumulative positive fluid balance is a risk factor for acute kidney injury and requirement for renal replacement therapy after liver transplantation

AIM To analyze whether fluid overload is an independent risk factor of adverse outcomes after liver transplantation (LT). METHODS One hundred and twenty-one patients submitted to LT were retrospectively evaluated. Data regarding perioperative and postoperative variables previously associated with adverse outcomes after LT were reviewed. Cumulative fluid balance (FB) in the first 12 h and 4 d after surgery were compared with major adverse outcomes after LT. RESULTS Most of the patients were submitted to a liberal approach of fluid administration with a mean cumulative FB over 5 L and 10 L, respectively, in the first 12 h and 4 d after LT. Cumulative FB in 4 d was independently associated with occurrence of both AKI and requirement for renal replacement therapy (RRT) (OR = 2.3; 95%CI: 1.37-3.86, P = 0.02 and OR = 2.89; 95%CI: 1.52-5.49, P = 0.001 respectively). Other variables on multivariate analysis associated with AKI and RRT were, respectively, male sex and Acute Physiology and Chronic Health Disease Classification System (APACHE II) levels and sepsis or septic shock. Mortality was shown to be independently related to AST and APACHE II levels (OR = 2.35; 95%CI: 1.1-5.05, P = 0.02 and 2.63; 95%CI: 1.0-6.87, P = 0.04 respectively), probably reflecting the degree of graft dysfunction and severity of early postoperative course of LT. No effect of FB on mortality after LT was disclosed. CONCLUSION Cumulative positive FB over 4 d after LT is independently associated with the development of AKI and the requirement of RRT. Survival was not independently related to FB, but to surrogate markers of graft dysfunction and severity of postoperative course of LT.