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.

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.

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.

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.

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.

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.

Short report: further evidence for hepatitis E in the Brazilian Amazon.

During an investigation of a hepatitis outbreak occurring in a small village in the Brazilian Amazon, serum samples from 16 recent hepatitis cases and 66 of their asymptomatic relatives were tested for the presence of hepatitis A, B, C, and E markers. Sanitation is poor and organized disposal of sewage is absent in the village. Two of the 16 hepatitis cases were non-A, non-B and non-C hepatitis, but their sera reacted to hepatitis E antibodies of the IgG class (anti-HEV). Likewise, sera from seven of the 66 asymptomatic relatives were positive for anti-HEV. Four of the nine anti-HEV positive sera had their reactivity confirmed by a neutralization test using synthetic peptides based on the nucleotide sequences of open reading frames 2 (ORF2) and 3 (ORF3) encoded in the HEV genome. To our knowledge, this is the first report suggesting the occurrence of acute E hepatitis cases in the Brazilian Amazon.

Prevalence of hepatitis E virus IgG antibodies in patients from a referral unit of liver diseases in Salvador, Bahia, Brazil.

Hepatitis E virus (HEV) is prevalent in Asia and Africa. Recently, it was also described in Mexico, but epidemiologic data from other Latin American countries are scarce. The seroprevalence of anti-HEV in a referral hepatology unit in northern Brazil was determined by testing for anti-HEV IgG in 701 serum samples from our serum bank. Specimens analyzed were from 200 blood donors, 79 patients with acute viral hepatitis (AVH), 392 hemodialyzed patients, and 30 carriers of schistosomiasis. Duplicate test results for anti-HEV were positive in four (2%) of 200 of the blood donors, three (10%) of the 30 carriers of schistosomiasis, and in none of the 392 hemodialyzed patients. Fourteen (17.7%) of the AVH patients were positive, as were six (25%) of 24 with hepatitis A virus, three (11%) of 26 with hepatitis B virus, 0 (0%) of 12 with hepatitis C virus, and five (29%) of 17 with non-A, non-B, non-C hepatitis viruses. Among AVH cases, those with hepatitis A virus had a higher frequency of anti-HEV positivity compared with all other hepatotropic viruses (P < 0.0003). We conclude that HEV is prevalent in northern Brazil. The higher prevalence in patients compared with blood donors could be explained by the lower social condition of patients who sought public health service in this area, in contrast with the heterogeneous socioeconomic distribution of blood donors. Patients with AVH due to hepatitis A had a greater frequency of anti-HEV, probably because of similar routes of transmission for both hepatitis A and E viruses. Finally, the absence of anti-HEV in the hemodialyzed group could be explained by a lower immunologic response found in patients with chronic renal failure.

Hepatitis C virus genotypes in a northeastern area of Brazil.

We used a reverse transcription-polymerase chain reaction (RT-PCR) to obtain the genotypes of circulating hepatitis C virus (HCV) in patients from a Gastro-Hepatology Unit in the city of Salvador (Bahia State) in northeastern Brazil. Viral RNA was detected in 83 (65.4%) of 127 anti-HCV seropositive serum samples. Positivity was significantly associated with alterations in levels of aspartate aminotransferase and alanine aminotransferase (P < 0.05). Genotyping of HCV was performed by RT-PCR using genotype-specific primers from the core region: 24.1% were infected with subtype 1a, 38.6% with 1b, 3.6% with 2, 21.7% with 3a, and 12.0% with a mixed genotype. There was no difference in genotype distribution when compared with results from other Brazilian locations. Surprisingly, the high frequency of genotype 3 in Brazilian samples continues to be different from that reported around the world and warrants further investigation.

Severe strongyloidiasis during interferon plus ribavirin therapy for chronic HCV infection.

Ribavirin is a nucleoside analogue, recently introduced in hepatitis C virus (HCV) therapy, that has postulated immunomodulatory and immunosuppressive action. Strongyloidiasis is an helmintic infection caused by Strongyloides stercoralis, endemic in tropical countries. Severe strongyloidiasis has been demonstrated after immunosuppression by corticosteroids evolving some fatal cases. Here, we describe two cases of severe strongyloidiasis coincident with ribavirin plus interferon therapy for treating HCV infection. The review of our monotherapy protocol with interferon did not disclose any case of symptomatic strongyloidiasis pointing to a possible role of ribavirin in modifying immune response to S. stercoralis. We propose a careful screening for S. stercoralis before initiating ribavirin therapy or even empiric antihelmintic treatment.

Hepatic capillariasis in rats: a new model for testing antifibrotic drugs.

Rats infected with the helminth Capillaria hepatica regularly develop septal hepatic fibrosis that may progress to cirrhosis in a relatively short time. Because of such characteristics, this experimental model was selected for testing drugs exhibiting antifibrosis potential, such as pentoxifylline, gadolinium chloride and vitamin A. Hepatic fibrosis was qualitatively and quantitatively evaluated in liver samples obtained by partial hepatectomy and at autopsy. The material was submitted to histological, biochemical and morphometric methods. A statistically significant reduction of fibrosis was obtained with pentoxifylline when administered intraperitoneally rather than intravenously. Gadolinium chloride showed moderate activity when administered prophylactically (before fibrosis had started), but showed a poor effect when fibrosis was well advanced. No modification of fibrosis was seen after vitamin A administration. Hydroxyproline content was correlated with morphometric measurements. The model appears to be adequate, since few animals die of the infection, fibrosis develops regularly in all animals, and the effects of different antifibrotic drugs and administration protocols can be easily detected.

New hepatitis viruses.

Three new hepatitis viruses are reviewed; Hepatitis E Virus (HEV), Hepatitis G Virus (HGV), and Transfusion Transmitted Virus (TTV). Only HEV has been clearly associated with liver damage. It is transmitted by the fecal-oral route and tends to occur in poor socio-economic conditions. Acute disease is diagnosed by the presence of anti-HEV IgM antibodies in the serum. Hepatitis G virus and TTV are transmitted parenterally. HGV is the same agent as GBV-C. Although it is hepatotropic, and high levels of viremia may occur, pathogenicity to the liver has not been proven. TTV may also be transmitted by the fecal-oral route. It is abundant in liver tissue but, like HGV, pathogenicity has not been proven.

Thyroid disease in HCV carriers undergoing antiviral therapy with interferon plus ribavirin.

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.

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.

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.

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.

Fulminant hepatitis with microvesicular steatosis (a histologic comparison of cases occurring in Brazil--Labrea hepatitis--and in central Africa--Bangui hepatitis).

A similar histopathologic picture of fatal hepatitis associated with widespread acute fatty changes in hepatocytes and single-cell necrosis was seen in epidemic cases occurring in two distinct equatorial areas having high prevalences of HBV and HDV infections. The cases were previously considered to be two different entities; Labrea hepatitis in Brazil, and Bangui hepatitis in the Central African Republic. However, the histopathologic findings suggest that they are pathogenetically and etiologically related to HBV and HDV infections, probably modified by some as yet unknown factor(s) present in equatorial forest zones.

[Paracentesis associated to dextran-70 in the treatment of ascites in patients with chronic liver diseases: a randomized therapeutic study]. / Paracentese associada a Dextran-70 no tratamento da ascite de hepatopatas crônicos: ensaio terapêutico randomizado.

The treatment of ascites of large volume in chronic liver disease patients was evaluated in the present study. We compared diuretics with paracentesis and an infusion of Dextran-70. Therapeutic efficacy, complications and length of hospital stay were the variables studied. Of the 38 patients, 20 were selected randomly. They were evaluated using clinical, laboratory and/or histological criteria: 10 patients in the paracentesis group with Dextran-70 and 10 in the diuretic group. The groups were similar with respect to age, diagnosis and Child-Pugh classification. However, there was a greater number of males in the paracentesis group with Dextran-70. In each paracentesis, an average of 9.41 liters (4.5 to 14.1) of ascitic fluid was collected. The average hospitalization period in the paracentesis group with Dextran-70 was 10.5 days (8-14), significantly less when compared to the diuretic group: 24.4 days (14-48). In the diuretic group one patient presented complications such as hyperkalemia, increased urea and creatinine levels, while in the paracentesis group with Dextran-70 one patient presented a temperature above 38 degrees C during treatment. The results suggest that paracentesis associated with Dextran-70 could be a therapeutic alternative for chronic liver disease patients with ascites in our population. It was effective; it had no significant side effects; it reduced the length of hospital stay and therefore should decrease the cost and the risk of complications in patients requiring prolonged hospitalization periods.

[Hepatitis B virus markers in peripheral blood mononuclear cells]. / Marcadores do vírus da hepatite B em células mononucleares do sangue periférico.

Recent studies have shown tropism of the hepatitis B virus (HBV) by peripheral blood mononuclear cells (PBMC). The consequences of this phenomenon and their clinical use are not yet clear, however. Seventy-nine patients were studied between March 1989 and October 1990. Sixty-nine patients had chronic liver disease with histological evaluations, and 10 were vaccinated for HBV. The following markers were determined: serum: HBsAg, HBeAg, anti-HBe, antitotal-HBc, anti-HBs, anti-HCV, HBV-DNA; lysated PMBC cells: HBsAg, HBeAg. Hepatic tissue: HBsAg, HBcAg. Four groups were formed according to serology. Group I--positive HBsAg patients (n = 25) HBsAg was observed in the lysated of PBMC in 19 (76%) of the patients. HBeAg in PBMC was detected in 8 (32%), all of them showed evidence of viral replication (presence of HBcAg and/or HBV-DNA in the serum HBcAg in the tissue). Group II--antitotal HBc/anti-HBs positive (n = 14), HBsAg in PBMC was found in 5 (36%) and HBeAg in 1 (7.0%). In this patient replication markers in the serum and in the tissue (HBV-DNA, HBcAg) was also present. Three patients out of 9 anti-HBs positive had HBsAg in PBMC. Group III--seronegative patients for HBV. HBsAg was present in PBMC in 2 (6.6%) of the patients, but was absent in all of them. There was concomitant presence of HBsAg in MN and the hepatic tissue in 1 patient. Replication markers were not observed in the group. Group IV--10 asymptomatic individuals vaccinated for HBV. Except anti-HBs in serum, no other HBV marker could be identified in serum or in PBMC.(ABSTRACT TRUNCATED AT 250 WORDS)