Rechallenge in idiosyncratic drug-induced liver injury: An analysis of cases in two large prospective registries according to existing definitions.

INTRODUCTION: Data on positive rechallenge in idiosyncratic drug-induced liver injury (DILI) are scarce. We aim to analyse the clinical presentation, outcome and drugs associated with positive rechallenge in two DILI registries. METHODS: Cases from the Spanish and Latin American DILI registries were included. Demographics, clinical characteristics and outcome of cases with positive rechallenge according to CIOMS/RUCAM and current definitions were analysed. RESULTS: Of 1418 patients with idiosyncratic DILI, 58 cases had positive rechallenge (4.1%). Patients with positive rechallenge had shorter duration of therapy (p=0.001) and latency (p=0.003). In patients with rechallenge, aspartate transaminase levels were increased (p=0.026) and showed a prolonged time to recovery (p=0.020), albeit no differences were seen in terms of fatal outcomes. The main drug implicated in rechallenge was amoxicillin-clavulanate (17%). The majority of re-exposure events were unintentional (71%). Using both existing definitions of positive rechallenge, there were four cases which exclusively fulfilled the current criteria and five which only meet the historical definition. All cases of positive rechallenge, irrespective of the pattern of damage, fulfilled the criteria of either alanine transaminase (ALT) ≥3 times the upper limit of normal (ULN) and/or alkaline phosphatase (ALP) ≥2 times ULN. CONCLUSIONS: Episodes of rechallenge were characterised by shorter duration of therapy and latency, and longer time to resolution, but did not show an increased incidence of fatal outcome. Based on our findings, ALT ≥3 times ULN and/or ALP ≥2 times ULN, regardless of the pattern of damage, is proposed as a new definition of rechallenge in DILI.

Quality of life, work ability and oral health among patients with chronic liver diseases.

BACKGROUND: This study aimed to explore the associations between health-related quality of life and work ability with the oral health status of patients with chronic liver disease. MATERIAL AND METHODS: A cross-sectional study included 150 patients with chronic liver disease, consecutively seen at University Hospital, Salvador, Brazil. Oral health was evaluated by the Decayed, Missing, and Filled Teeth (DMFT) index and by the presence of gingivitis and periodontitis. Salivary flow was "reduced" when <1.0 mL/min. Health-related quality of life was evaluated by using the 36-Item Short Form Health Survey questionnaire (SF-36); work ability was evaluated by the Work Ability Index questionnaire. RESULTS: All health-related quality of life indicators were systematically lower among the 99 patients with reduced salivary flow than among the 51 patients with normal salivary flow. Physical Functioning, Role-Physical, and Physical Component Summary scores were strongly correlated (P < 0.005 or less) with the number of Missing Teeth and with DMFT index. Reduced salivary flow was associated (P < 0.05) with poor work ability. Patients with poor or moderate work ability presented higher (P < 0.001) means of the DMFT index than those with good or excellent work ability. CONCLUSIONS: Patients with chronic liver disease who present poor oral health presented low health-related quality of life and poor work ability. These findings reinforce the need of these patients for specialized stomatological care.

Oral Health and Quality of Life in Candidates for Liver Transplantation.

BACKGROUND: There is a gap in the scientific literature about the association between oral health and the health-related quality of life of patients on the liver transplantation waiting list. The aim of this work was to describe aspects of oral health and quality of life of patients on a liver transplantation waiting list. METHODS: This was a cross-sectional study among 116 patients with chronic hepatic disease: 29 on a liver transplantation waiting list (Model for End-Stage Liver Disease score ≥15) and 87 under monitoring in a gastroenterology service in a Brazilian university hospital. Oral health was evaluated according to criteria recommended by the World Health Organization and by the European Association of Dental Public Health. Health-related quality of life was evaluated by means of the 36-Item Short-Form Health Survey (SF-36). RESULTS: Patients on the liver transplantation waiting list presented poorer health-related quality of life than those who were not on the list in the domains physical functioning, role physical, bodily pain, general health perceptions, and social functioning and in the physical component summary. Periodontitis affected 72.4% of the patients on the liver transplantation waiting list, but only 27.6% of the patients not on that list. Reduced salivary flow was associated with poorer mental health component summary in hepatitis C patients. CONCLUSIONS: Patients on the liver transplantation waiting list presented poorer health-related quality of life than those who were not on the list, mainly in the indicators concerning physical health, as well as higher frequencies of decayed teeth and periodontitis. The mental health component summary was associated with reduced salivary flow in hepatitis C patients.

Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids.

BACKGROUND: We have observed an increase in hepatotoxicity (DILI) reporting related to the use of anabolic androgenic steroids (AAS) for bodybuilding. AIM: To characterise phenotype presentation, outcome and severity of AAS DILI. METHODS: Data on 25 cases of AAS DILI reported to the Spanish (20) and Latin-American (5) DILI Registries were collated and compared with previously published cases. RESULTS: AAS DILI increased from representing less than 1% of the total cases in the Spanish DILI Registry in the period 2001-2009 to 8% in 2010-2013. Young men (mean age 32 years), requiring hospitalisation, hepatocellular injury and jaundice were predominating features among the AAS cases. AAS DILI caused significantly higher bilirubin values independent of type of damage when compared to other drug classes (P = 0.001). Furthermore, the cholestatic AAS cases presented significantly higher mean peak bilirubin (P = 0.029) and serum creatinine values (P = 0.0002), compared to the hepatocellular cases. In a logistic regression model, the interaction between peak bilirubin values and cholestatic damage was associated with the development of AAS-induced acute kidney impairment (AKI) [OR 1.26 (95% CI: 1.035-1.526); P = 0.021], with 21.5 ×ULN being the best bilirubin cut-off point for predicting AKI risk (AUCROC 0.92). No fatalities occurred. CONCLUSIONS: Illicit recreational AAS use is a growing cause of reported DILI that can lead to severe hepatic and renal injury. AAS DILI is associated with a distinct phenotype, characterised by considerable bilirubin elevations independent of type of damage. Although hepatocellular injury predominates, acute kidney injury develops in cholestatic cases with pronounced jaundice.

HBV/HDV co-infection in the Western Brazilian Amazonia: an intriguing mutation among HDV genotype 3 carriers.

HDV infection still remains a serious public health problem in Amazonia. There are few data regarding the biomolecular aspects of HBV/HDV co-infection in this region. We studied 92 patients HBsAg(+) /anti-HDV IgG(+) followed at the Hepatitis Referral Centers of Porto Velho (RO), Rio Branco and Cruzeiro do Sul (AC), Brazil, from March 2006 to March 2007 for whom the HDV and/or the HBV genotype could be determined. The HDV genotype could be determined in 90 patients, while the HBV genotypes could be positively determined in 74. HBV subgenotype F2 is the most prevalent (40.2%), followed by the subgenotypes A1 (15.2%) and D3 (8.7%), while 16.4% were other subgenotypes or genotypes, 4.3% were discordant and 15.2% were unamplifiable. Surprisingly, HDV genotype 3 (HDV-3) was found in all of the HBV/HDV-infected patients that could be genotyped for HDV, confirming that HDV-3 can associate with non-F HBV genotypes. However, a HDV-3 mutant was found in 29.3% of patients and was more frequently associated with non-F HBV genotypes (P < 0.001) than were nonmutant strains, suggesting that the mutation may facilitate association of HDV-3 with non-F HBV genotypes.

Antiviral efficacy of entecavir in nucleos(t)ide-naïve patients of Black/African descent with chronic hepatitis B.

This single-arm, open-label, descriptive study assessed the efficacy and safety of entecavir (ETV) in nucleos(t)ide-naïve Black/African American patients with chronic hepatitis B (CHB), a patient population underrepresented in ETV registration trials. Forty patients with HBeAg(+) or HBeAg(-) compensated CHB of self-described Black/African American race received ETV 0.5 mg daily for 52 weeks; 37 patients completed 52 weeks of treatment. At Week 48, 29/40 (72.5%, noncompleter = failure) patients achieved the primary endpoint of HBV DNA <50 IU/mL. Rates for HBeAg loss (11/22; 50%) and HBeAg seroconversion (9/22; 41%) were high, possibly due to the high HBV genotype A prevalence (70%). No patient experienced virological breakthrough. Samples for resistance testing were available in 6/8 patients with HBV DNA >50 IU/mL at Week 48 or last on-treatment visit. No ETV resistance was detected. The safety profile of ETV was consistent with that observed in ETV registration trials. This study shows that in Black/African American patients with CHB, ETV was well tolerated and demonstrated comparable antiviral efficacy to that observed in White and Asian patients in ETV Phase III studies.

Oral health profile of cirrhotic patients awaiting liver transplantation in the Brazilian Northeast.

BACKGROUND: Infections are a frequent cause of morbidity and mortality among postoperative liver transplant (OLT) patients and a leading cause of decompensated chronic liver disease (CLD) among patients awaiting the procedure. Oral lesions that are frequently observed in subjects with CLD may represent foci for systemic infections before and after OLT. AIMS: To evaluate the oral health profile of patients with CLD awaiting OLT. METHODS: One hundred thirty one patients including 100 males of overall mean age 49.5 ± 10.8 years with CLD were listed for OLT and examined for oral health status according to a established protocol. RESULTS: One hundred thirty (99%) patients were partially edentulous; 66 (51%) had chewing difficulties; and 63 (48%) experienced reduced salivary flow. With respect to periodontal disease and oral infections, 68 (25%) had periodontitis, 63 (48%) had periapical lesion, 64 (49%) had abscesses, and 59 (45%) had root fragments. Loss of follow-up was observed in 21 subjects. Among the 110 other patients, 63 (57%) underwent dental treatments with complications in only two cases. Interestingly, mortality was significantly lower among treated (31%) versus nontreated patient (79%; P<.001). CONCLUSIONS: Poor oral health status observed in most CLD patients may represent a source of systemic infections before and after OLT. Treatment of such lesions was feasible in the majority of the patients and seemed to be associated with a reduction in mortality.

Antiphospholipid antibodies in Brazilian hepatitis C virus carriers.

Hepatitis C, a worldwide viral infection, is an important health problem in Brazil. The virus causes chronic infection, provoking B lymphocyte dysfunction, as represented by cryoglobulinemia, non-organ-specific autoantibody production, and non-Hodgkin's lymphoma. The aim of this research was to screen for the presence of antiphospholipid autoantibodies in 109 Brazilian hepatitis C virus carriers without clinical history of antiphospholipid syndrome. Forty healthy individuals were used as the control group. IgA, IgG, and IgM antibodies against cardiolipin and ss2-glycoprotein I were measured with an enzyme-linked immunosorbent assay, using a cut-off point of either 20 UPL or 20 SBU. While 24 (22.0%) hepatitis C carriers had moderate titers of IgM anticardiolipin antibodies (median, 22.5 MPL; 95%CI: 21.5-25.4 MPL), only three carriers (<3%) had IgG anticardiolipin antibodies (median, 23 GPL; 95%CI: 20.5-25.5 GPL). Furthermore, IgA anticardiolipin antibodies were not detected in these individuals. Male gender and IgM anticardiolipin seropositivity were associated in the hepatitis C group (P = 0.0004). IgA anti-ss2-glycoprotein-I antibodies were detected in 29 of 109 (27.0%) hepatitis C carriers (median, 41 SAU; 95%CI: 52.7-103.9 SAU). Twenty patients (18.0%) had IgM anti-ss2-glycoprotein I antibodies (median, 27.6 SMU; 95%CI: 23.3-70.3 SMU), while two patients had IgG antibodies against this protein (titers, 33 and 78 SGU). Antiphospholipid antibodies were detected in only one healthy individual, who was seropositive for IgM anticardiolipin. We concluded that Brazilian individuals chronically infected with hepatitis C virus present a significant production of antiphospholipid antibodies, mainly IgA anti-ss2-glycoprotein I antibodies, which are not associated with clinical manifestations of antiphospholipid syndrome.

Antiphospholipid antibodies in Brazilian hepatitis C virus carriers

Hepatitis C, a worldwide viral infection, is an important health problem in Brazil. The virus causes chronic infection, provoking B lymphocyte dysfunction, as represented by cryoglobulinemia, non-organ-specific autoantibody production, and non-Hodgkin's lymphoma. The aim of this research was to screen for the presence of antiphospholipid autoantibodies in 109 Brazilian hepatitis C virus carriers without clinical history of antiphospholipid syndrome. Forty healthy individuals were used as the control group. IgA, IgG, and IgM antibodies against cardiolipin and ß2-glycoprotein I were measured with an enzyme-linked immunosorbent assay, using a cut-off point of either 20 UPL or 20 SBU. While 24 (22.0 percent) hepatitis C carriers had moderate titers of IgM anticardiolipin antibodies (median, 22.5 MPL; 95 percentCI: 21.5-25.4 MPL), only three carriers (<3 percent) had IgG anticardiolipin antibodies (median, 23 GPL; 95 percentCI: 20.5-25.5 GPL). Furthermore, IgA anticardiolipin antibodies were not detected in these individuals. Male gender and IgM anticardiolipin seropositivity were associated in the hepatitis C group (P = 0.0004). IgA anti-ß2-glycoprotein-I antibodies were detected in 29 of 109 (27.0 percent) hepatitis C carriers (median, 41 SAU; 95 percentCI: 52.7-103.9 SAU). Twenty patients (18.0 percent) had IgM anti-ß2-glycoprotein I antibodies (median, 27.6 SMU; 95 percentCI: 23.3-70.3 SMU), while two patients had IgG antibodies against this protein (titers, 33 and 78 SGU). Antiphospholipid antibodies were detected in only one healthy individual, who was seropositive for IgM anticardiolipin. We concluded that Brazilian individuals chronically infected with hepatitis C virus present a significant production of antiphospholipid antibodies, mainly IgA anti-ß2-glycoprotein I antibodies, which are not associated with clinical manifestations of antiphospholipid syndrome.

Peginterferon alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy.

Peginterferon alfa plus ribavirin is currently the treatment of choice for chronic hepatitis C. Peginterferon alfa-2a (40KD) plus ribavirin has given an overall sustained virological response of 18% in F3/F4 previous nonresponder US patients. We evaluated the effectiveness of peginterferon alfa-2a (40KD) plus ribavirin in Brazilian patients who were relapsers or nonresponders to previous interferon-based therapy. One-hundred-thirty-four patients with biopsy-proven chronic hepatitis C, HCV RNA positive, elevated ALT and who were either relapsers (n=37) or nonresponders (n=97) to at least 24 weeks of conventional interferon/ribavirin therapy were retreated with peginterferon alfa-2a (40KD) 180mg/qw and ribavirin 800 mg bid for 48 weeks. Efficacy was assessed as virological response (defined as undetectable HCV RNA) at the end of treatment (EoT) and at the end of follow-up (SVR - Sustained Virological Response). Safety assessments consisted of clinical and laboratory evaluations. In the patient sample, 72% were genotype 1 and 34% were cirrhotic. In an intention-to-treat analysis, relapser patients showed 78% EoT response and 51% SVR. Nonresponders showed 57% EoT response and 26% SVR. Positive predictive factors of SVR were non-1 genotype and relapser state. Six percent of the patients interrupted treatment because of adverse events and 45% had dose reduction (mainly associated with leucopenia and anemia). Brazilian patient relapsers and nonresponders to conventional interferon and ribavirin treatment can achieve a sustained virological response when retreated with peginterferon alfa-2a (40KD) and ribavirin. The safety profile is similar to that of naive patients.

Peginterferon alfa-2a (40KD) (PEGASYS®) plus ribavirin (COPEGUS®) in retreatment of chronic hepatitis C patients, nonresponders and relapsers to previous conventional interferon plus ribavirin therapy

Peginterferon alfa plus ribavirin is currently the treatment of choice for chronic hepatitis C. Peginterferon alfa-2a (40KD) plus ribavirin has given an overall sustained virological response of 18 percent in F3/F4 previous nonresponder US patients. We evaluated the effectiveness of peginterferon alfa-2a (40KD) plus ribavirin in Brazilian patients who were relapsers or nonresponders to previous interferon-based therapy. One-hundred-thirty-four patients with biopsy-proven chronic hepatitis C, HCV RNA positive, elevated ALT and who were either relapsers (n=37) or nonresponders (n=97) to at least 24 weeks of conventional interferon/ribavirin therapy were retreated with peginterferon alfa-2a (40KD) 180mg/qw and ribavirin 800mg bid for 48 weeks. Efficacy was assessed as virological response (defined as undetectable HCV RNA) at the end of treatment (EoT) and at the end of follow-up (SVR - Sustained Virological Response). Safety assessments consisted of clinical and laboratory evaluations. In the patient sample, 72 percent were genotype 1 and 34 percent were cirrhotic. In an intention-to-treat analysis, relapser patients showed 78 percent EoT response and 51 percent SVR. Nonresponders showed 57 percent EoT response and 26 percent SVR. Positive predictive factors of SVR were non-1 genotype and relapser state. Six percent of the patients interrupted treatment because of adverse events and 45 percent had dose reduction (mainly associated with leucopenia and anemia). Brazilian patient relapsers and nonresponders to conventional interferon and ribavirin treatment can achieve a sustained virological response when retreated with peginterferon alfa-2a (40KD) and ribavirin. The safety profile is similar to that of naive patients.

Seroprevalence of hepatitis B and C in the Western Brazilian Amazon region (Rio Branco, Acre): a pilot study carried out during a hepatitis B vaccination program.

In 1999, on the occasion of the application of the first vaccine dose during the state vaccination campaign against hepatitis B virus (HBV), 390 individuals from the town of Rio Branco, Acre, aged two or more years were selected for the determination of the seroprevalence of HBV and HCV. HBV markers (HBsAg, anti-HBs, and anti-HBc IgG) were determined on this occasion and anti-HBs antibodies were also assessed 30 days after the third vaccine dose. At the time of vaccination, 39% of the individuals were still susceptible to HBV, while 61% presented serologic evidence of previous HBV contact or previous vaccination. The individuals with previous HBV contact were significantly older (p<0.001) than those without HBV markers. Of the 192 individuals who returned for reexamination, 30 days after the third dose, 158 (82.3%) had received three vaccine doses, and only 60 (31.2%) belonged to the group without HBV markers. In these individuals, the seroconversion rate after the third dose was 92% (55/60). In conclusion, we found considerable HBV in this population, indicating the need for pursuing the immunization programs. We also found high rates of vaccination coverage in the Western Brazilian Amazon region.

Seroprevalence of hepatitis B and C in the Western Brazilian Amazon region (Rio Branco, Acre): a pilot study carried out during a hepatitis B vaccination program

In 1999, on the occasion of the application of the first vaccine dose during the state vaccination campaign against hepatitis B virus (HBV), 390 individuals from the town of Rio Branco, Acre, aged two or more years were selected for the determination of the seroprevalence of HBV and HCV. HBV markers (HBsAg, anti-HBs, and anti-HBc IgG) were determined on this occasion and anti-HBs antibodies were also assessed 30 days after the third vaccine dose. At the time of vaccination, 39 percent of the individuals were still susceptible to HBV, while 61 percent presented serologic evidence of previous HBV contact or previous vaccination. The individuals with previous HBV contact were significantly older (p<0.001) than those without HBV markers. Of the 192 individuals who returned for reexamination, 30 days after the third dose, 158 (82.3 percent) had received three vaccine doses, and only 60 (31.2 percent) belonged to the group without HBV markers. In these individuals, the seroconversion rate after the third dose was 92 percent (55/60). In conclusion, we found considerable HBV in this population, indicating the need for pursuing the immunization programs. We also found high rates of vaccination coverage in the Western Brazilian Amazon region.

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

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 percent) individuals were infected by subtype 1a, 45 (35.4 percent) by subtype 1b and 43 (33.9 percent) by subtype 3a. Most (73.2 percent) 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 percent and 3/84; 3.6 percent, 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 percent) of those infected by genotype 3 (P=0.05). Cryoglobulinemia was also more frequent in this group (5/13, 38 percent, 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.

Comparative study of hepatitis C virus genotypes 1 and 3 in Salvador, Bahia Brazil.

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.

[Antibodies to hepatitis C virus in patients undergoing hemodialysis in Salvador, BA, Brazil]. / Anticorpo contra o vírus C da hepatite em pacientes sob programa de hemodiálise em Salvador, BA, Brasil.

BACKGROUND: Hepatitis C infection in hemodialysis units has been evaluated in different geographic regions. AIMS: The prevalence of anti-HCV in patients undergoing hemodialysis program in the city of Salvador, State of Bahia, Brazil, was studied and its association with transfusions, duration of hemodialysis and ALT elevation. METHOD: During a period of 17 months, all patients undergoing dialytic treatment, were evaluated. The total number of patients was 395, all of whom completed a questionnaire and provided serum samples for laboratory analysis. Serological levels were measured for ALT and the samples were tested for anti-HCV using ELISA II with a further confirmation using RIBA III. RESULTS: Anti-HCV was positive in 23.8% (94/395). The presence of transfusions was associated with anti-HCV and as the number of transfusions used increased, so did the frequency of anti-HCV. Of the patients who never received transfusions, 12.5% (6/48) were anti-HCV positive. The duration of dialytic treatment lasted from 53.44 +/- 36.45 months in the anti-HCV positive group and 22.10 +/- 22.75 months for the group testing negative. ALT elevation was more frequent in the anti-HCV positive group. Positivity for the RIBA III fractions was 79.8%, 100%, 80.9% and 52.1%, for c100-3, c33, c22 and NS5, respectively. The anti-NS5 was even less frequent in the group with elevated ALT. CONCLUSIONS: The prevalence of anti-HCV in patients undergoing chronic hemodialysis in Salvador, Bahia, is elevated and it is associated with transfusions, a longer duration of dialytic treatment and ALT elevation.

Comparative study of bacterial infection prevalence between cirrhotic patients with and without upper gastrointestinal bleeding.

Bacterial infection is a frequent complication in patients with chronic liver disease, mainly during the advanced stages. There is evidence that the main factors that contribute to a predisposition to infection in cirrhotic patients are related to hepatic failure with consequent immunodeficiency. Invasive procedures (diagnostic or therapeutic) can predispose to bacterial infections, and upper gastrointestinal bleeding (UGB) is considered a potentially important risk factor. A group of cirrhotic patients (child B and C Pugh groups) were evaluated retrospectively by chart reviews regarding the prevalence of bacterial infection during hospitalization to determine whether UGB was a risk factor. An infection was considered present if a specific organ system was identified or if fever (> 38(o)C) persisted for more than 24 hours with associated leukocytosis. Spontaneous bacterial peritonitis was based on classical criteria. Eighty-nine patients were evaluated. Fourty-six patients presented with UGB, and 43 patients had no UGB (control). There were infections recorded in 25/46 (54%) patients with UGB, and 15/43 (35%) in those without UGB (p=0.065). The ratio of the number of infections/admitted patients, was significantly larger in the group with UGB (0.78 +/- 0.89 vs. 0.39 +/- 0.62; p=0.028) since patients had more than one infection. In the UGB group compared to non UGB group, ascites was more frequent (67% vs. 42%; p=0.027); they were more likely to have undergone endoscopic procedures (p<0.001) and the mean +/- SD for platelets count was smaller (96,114 +/- 57,563 vs 145,674 +/- 104,083; p=0.007). The results show that UGB is an important contribution to bacterial infection among Child B and C cirrhotic patients.

Effect of interferon-alpha on experimental septal fibrosis of the liver - study with a new model.

Interferon-alpha is used in antiviral therapy in humans, mainly for viral hepatitis B and C. An anti-fibrotic effect of interferon has been postulated even in the absence of anti-viral response, which suggests that interferon directly inhibits fibrogenesis. Rats infected with the helminth Capillaria hepatica regularly develop diffuse septal fibrosis of the liver, which terminates in cirrhosis 40 days after inoculation. The aim of this study was to test the anti-fibrotic effect of interferon in this experimental model. Evaluation of fibrosis was made by three separate methods: semi-quantitative histology, computerized morphometry and hydroxyproline measurements. Treatment with interferon-alpha proved to inhibit the development of fibrosis in this model, especially when doses of 500,000 and 800,000 IU were used for 60 days. Besides confirming the anti-fibrotic potential of interferon-alpha on a non-viral new experimental model of hepatic fibrosis, a clear-cut dose-dependent effect was observed.

Schistosomiasis mansoni and viral B hepatitis in woodchucks.

BACKGROUND/AIMS: An interaction between human schistosomiasis and viral hepatitis B has often been suggested, but never established. The experimental investigation has been hampered by the lack of a suitable model. Only woodchucks are susceptible to both Schistosoma mansoni and a B-like hepatitis virus (WHV) infections. This study explores the relevance of this unique model regarding hepatitis/schistosomiasis interactions. METHODS: Woodchucks (Marmota monax and Marmota marmota) were infected with: (a), S. mansoni; (b), WHV; or (c), both S. mansoni and WHV. RESULTS: Following the experimental parasitic infection of woodchucks, with or without WHV, schistosomiasis presented a peculiar and severe course in early infection, involving mostly the intestines. Subsequently, the intestinal and hepatic lesions underwent considerable modulation and the periovular granulomas decreased in size and number, while the parasitic infection tended to self-cure within the 9 months following infection. Nine woodchucks inoculated with the hepatitis virus alone presented with several degrees of acute and chronic hepatitis, with one of them dying of hepatocarcinoma 1 year after inoculation. Four woodchucks with concomitant viral and schistosome infections presented with a simple additive pattern of lesions, without any evidence of modification or aggravation of either one of the two infections. Similarly, no significant impact of schistosomiasis on WHV serum markers could be seen. CONCLUSIONS: Schistosomiasis and viral hepatitis in woodchucks run parallel courses, with neither apparent special histological features derived from the association of the two conditions, nor modulation of WHV replication. Schistosomiasis itself, however, was observed to run a peculiar course in the woodchuck. The present data are important for consideration in further experiments exploring the interplay between schistosomiasis and viral hepatitis induced liver damage in this unique experimental host.