Plasma hydroxy-metronidazole/ metronidazole ratio in hepatitis C virus-induced liver disease

It has been suggested that the measurement of metronidazole clearance is a sensitive method for evaluating liver function. The aim of this study was to evaluate the usefulness of plasma hydroxy-metronidazole/metronidazole ratios as indicators of dynamic liver function to detect changes resulting from the various forms of chronic hepatitis C virus (HCV) infection. A total of 139 individuals were studied: 14 healthy volunteers, 22 healthy, asymptomatic, consecutive anti-HCV-positive HCV-RNA negative subjects, 81 patients with chronic hepatitis C (49 with moderate/severe chronic hepatitis and 34 with mild hepatitis), and 20 patients with cirrhosis of the liver. HCV status was determined by the polymerase chain reaction. Plasma concentrations of metronidazole and its hydroxy-metabolite were measured by reverse-phase high-performance liquid chromatography with ultraviolet detection in a blood sample collected 10 min after the end of a metronidazole infusion. Anti-HCV-positive HCV-RNA-negative individuals demonstrated a significantly reduced capacity to metabolize intravenously infused metronidazole compared to healthy individuals (0.0478 ± 0.0044 vs 0.0742 ± 0.0232). Liver cirrhosis patients also had a reduced plasma hydroxy-metronidazole/metronidazole ratio when compared to the other groups of anti-HCV-positive individuals (0.0300 ± 0.0032 vs 0.0438 ± 0.0027 (moderate/severe chronic hepatitis) vs 0.0455 ± 0.0026 (mild chronic hepatitis) and vs 0.0478 ± 0.0044 (anti-HCV-positive, HCV-RNA-negative individuals)). These results suggest an impairment of the metronidazole metabolizing system induced by HCV infection that lasts after viral clearance. In those patients with chronic hepatitis C, this impairment is paralleled by progression of the disease to liver cirrhosis.

Hepatitis C virus infection, cryoglobulinemia, and peripheral neuropathy: a case report

Hepatitis C virus (HCV) is essentially hepatotropic but its manifestations can extend beyond the liver. It can be associated with autoimmune diseases, such as mixed cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroiditis, and lymphoproliferative disorders. The mechanisms that trigger these manifestations are not completely understood. We describe a 48-year-old man with chronic HCV infection (circulating HCV RNA and moderate hepatitis as indicated by liver biopsy), cryoglobulinemia, and sensory and motor peripheral neuropathy. The diagnosis of multineuropathy was confirmed by clinical examination and electromyographic tests. A nerve biopsy revealed an inflammatory infiltrate in the perineurial space and signs of demyelination and axonal degeneration. The patient had no improvement of neurological symptoms with the use of analgesics and neuro-modulators. He was then treated with interferon-alpha (3 million units subcutaneously, 3 times per week) and ribavirin (500 mg orally, twice a day) for 48 weeks. Six months after the end of therapy, the patient had sustained viral response (negative HCV RNA) and remission of neurological symptoms, but cryoglobulins remained positive. A review of the literature on the pathogenesis and treatment of neurological manifestations associated with HCV infection is presented. This report underscores the need for a thorough evaluation of HCV-infected patients because of the possibility of extrahepatic manifestations. Antiviral treatment with interferon and ribavirin can be effective and should be considered in patients with neurological complications associated with HCV infection.

Co-circulation of genotypes IA and IB of hepatitis A virus in Northeast Brazil

The Northeast region is the location of most cases of acute hepatitis A virus (HAV) in Brazil. In the present study, the genotypes of HAV strains from Pernambuco State, one of most populous states in the Northeast region, were characterized. Blood samples positive for anti-HAV IgM from 145 individuals (mean age = 29.1 years), collected during 2002 and 2003, were submitted to nested RT-PCR for amplification of the 5'non-translated region (5'NTR) and VP1/2A regions of the HAV genome. The VP1/2A and 5'NTR regions were amplified in 39 and 21% of the samples, respectively. Nucleotide sequencing was carried out in 46% of VP1/2A and in 53% of 5'NTR isolates. The identity in nucleotide sequence of the VP1/2A region ranged from 93.6 to 100.0%. Phylogenetic analysis of the VP1/2A sequences showed that 65% belong to sub-genotype IA and 35% to sub-genotype IB. Co-circulation of both sub-genotypes was observed in the two years studied. Distinct clusters of highly related sequences were observed in both sub-genotypes, suggesting endemic circulation of HAV strains in this area. In the 5'NTR isolates, 92.7-99.2% identity was observed and two isolates presented one deletion at position 413. Phylogenetic analysis showed that genotype IA strains cluster in the tree in the same way as genotype IB strains, but one IIIA isolate from Spain clusters with genotype IB strains. These results do not allow us to state that 5'NTR could be used to genotype HAV sequences. This is the first report of co-circulation of sub-genotypes IA and IB in this region, providing additional information about the molecular epidemiology of HAV strains in Brazil.

There is no difference in hepatic fibrosis rates of patients infected with hepatitis C virus and those co-infected with HIV

Some studies have suggested that human immunodeficiency virus (HIV) infection modifies the natural history of hepatitis C virus (HCV) infection, accelerating the progression of fibrosis and the development of cirrhosis. Our objective was to evaluate the fibrosis progression rate (FPR) in HCV/HIV-co-infected patients, and to identify factors that may influence it. HCV-mono-infected and HCV/HIV-co-infected patients with a known date of HCV infection (transfusion or injection drug use) and a liver biopsy were included. The FPR was defined as the ratio between the fibrosis stage (Metavir score) and the estimated length of infection in years and the result was reported as fibrosis units per year. The factors studied were gender, age at infection, consumption of alcohol, aminotransferase levels, histological activity grade, HCV genotype and viral load, CD4 cell count, HIV viral load, and the use of antiretroviral therapy. Sixty-five HCV-infected (group 1) and 53 HCV/HIV-co-infected (group 2) patients were evaluated over a period of 19 months. The mean FPR of groups 1 and 2 was 0.086 ± 0.074 and 0.109 ± 0.098 fibrosis units per year, respectively (P = 0.276). There was a correlation between length of HCV infection and stage of fibrosis in both groups. The age at infection, the aspartate aminotransferase level (r = 0.36) and the inflammatory activity grade were correlated with the FPR (P < 0.001). No difference in FPR was found between HCV-mono-infected and HCV/HIV-co-infected patients.

Role of p53 codon 72 polymorphism in chromosomal aberrations and mitotic index in patients with chronic hepatitis B

Polymorphisms of the p53 gene, which participates in DNA repair, can affect the functioning of the p53 protein. The Arg and Pro variants in p53 codon 72 were shown to have different regulation properties of p53-dependent DNA repair target genes that can affect various levels of cytogenetic aberrations in chronic hepatitis B patients. The present study aimed to examine the frequency of chromosomal aberrations and the mitotic index in patients with chronic hepatitis B and their possible association with p53 gene exon 4 codon 72 Arg72Pro (Ex4+119 G>C; rs1042522) polymorphism. Fifty-eight patients with chronic hepatitis B and 30 healthy individuals were genotyped in terms of the p53 gene codon 72 Arg72Pro polymorphism by PCR-RFLP. A 72-h cell culture was performed on the same individuals and evaluated in terms of chromosomal aberrations and mitotic index. A high frequency of chromosomal aberrations and low mitotic index were detected in the patient group compared to the control group. A higher frequency of chromosomal aberrations was detected in both the patient and the control groups with a homozygous proline genotype (13 patients, 3 control subjects) compared to patients and controls with other genotypes [Arg/Pro (38 patients, 20 control subjects) and Arg/Arg (7 patients, 7 control subjects)]. We observed an increased frequency of cytogenetic aberrations in patients with chronic hepatitis B. In addition, a higher frequency of cytogenetic aberrations was observed in p53 variants having the homozygous proline genotype compared to variants having other genotypes both in patients and healthy individuals.

Hepatitis B vaccination in hemodialysis patients: different points of view for conclusion

The present letter to the editor shows the other aspect of Hepatitis B vaccination in hemodialysis patients.

HIV infection and related risk behaviors in a community of recyclable waste collectors of Santos, Brazil

OBJECTIVE: To estimate the seroprevalence of HIV, hepatitis B and C and syphilis and to describe risk behaviors associated to their transmission among recyclable waste collectors. METHODS: A seroepidemiological survey was carried out in the city of Santos, Southeastern Brazil, in 2005. A total of 315 individuals were enrolled in the survey, of which 253 subjects underwent serological testing HIV, hepatitis B and C and syphilis. Statistical analysis consisted of univariate and bivariate analyses (cross-tabulation and odds ratio) and multivariate analysis (by logistic regression), relating HIV infection with established risk behaviors and seropositivity. RESULTS: Overall seroprevalences were: HIV, 8.9%; hepatitis B, 34.4%; hepatitis C, 12.4%; and syphilis, 18.4%. Subjects were characterized by a predominance of males with low educational and economic levels, subjected to parenteral and sexual exposures to HIV and other sexually transmitted infections. Multivariate analysis results indicated that risk factors for both sexually and parenterally related exposure were significantly associated with HIV in this community. CONCLUSIONS: Seroprevalences found in the study were approximately 10 to 12 times higher than the national average. These communities are socially marginalized and generally not recognized by national programs as potentially endangered populations.

RESEARCH OF ANTIGEN AND ANTIBODIES FROM RETROVIRUSES, CMV AND HBV AMONG PRISONERS OF THE PENITENTIARY COMPLEX OF THE REGION OF CAMPINAS, SP, BRAZIL

Some viruses of the families Retroviridae, such as Human T Lymphotropic Virus (HTLV); Herpesviridae as the Cytomegalovirus (CMV) and Hepadnaviridae such as the Hepatitis B Virus (HBV) are liable to be co-transmitted with the Human Immunodeficiency Virus (HIV). Since prisoners are exposed to several and important risk factors involved in the transmission of HIV and the above mentioned viruses, male inmates from the penitentiary complex of Campinas, SP, Brazil, including HIV + and HIV - ones, were examined for the presence of HTLV-I and/or II antibodies; IgG and IgM anti-CMV antibodies, and the research of the superficial hepatitis B antigen (HBsAg). The presence of anti-HTLV-I and/or II was determined by the Western Blot (WB) technique, whereas IgG and IgM anti-CMV and the search of HBsAg were carried out by the Microparticle Enzyme Immunoassay (MEIA-Abbott Lab).With regard to anti-HTLV-I and/or II, 58.3% (14/24-Number of positive reactions/number of sera examined) were reactive among the anti-HIV positive sera. Conversely, only 12.5% (3/24) among the HIV- negative sera showed positive reactions to HTLV-I and/or II antibodies. When looking for IgG anti-CMV percentages of 97.7% (43/44) and 95% (38/40) were obtained for anti-HIV positive and negative sera, respectively. As to IgM anti-CMV antibodies 11.36% (5/44) and 2.5% (1/40) of reactive sera were found for anti-HIV positive and negative, respectively. The HBsAg was found in 12.8% (5/39) of the sera which were anti-HIV positive.

HTLV-1/2 seroprevalence and coinfection rate in Brazilian first-time blood donors: an 11-year follow-up

The seroprevalence and geographic distribution of HTLV-1/2 among blood donors are extremely important to transfusion services. We evaluated the seroprevalence of HTLV-1/2 infection among first-time blood donor candidates in Ribeirão Preto city and region. From January 2000 to December 2010, 1,038,489 blood donations were obtained and 301,470 were first-time blood donations. All samples were screened with serological tests for HTLV-1/2 using enzyme immunoassay (EIA). In addition, the frequency of coinfection with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), Chagas disease (CD) and syphilis was also determined. In-house PCR was used as confirmatory test for HTLV-1/2. A total of 296 (0.1%) first-time donors were serologically reactive for HTLV-1/2. Confirmatory PCR of 63 samples showed that 28 were HTLV-1 positive, 13 HTLV-2 positive, 19 negative and three indeterminate. Regarding HTLV coinfection rates, the most prevalent was with HBV (51.3%) and HCV (35.9%), but coinfection with HIV, CD and syphilis was also detected. The real number of HTLV-infected individual and coinfection rate in the population is underestimated and epidemiological studies like ours are very informative.

SEROLOGICAL MARKERS OF VIRAL, SYPHILITIC AND TOXOPLASMIC INFECTION IN CHILDREN AND TEENAGERS WITH NEPHROTIC SYNDROME: CASE SERIES FROM MATO GROSSO STATE, BRAZIL

Some infections can be the cause of secondary nephrotic syndrome. The aim of this study was to describe the experience of a Renal Disease Reference Clinic from Central Brazil, in which serological markers of some infectious agents are systematically screened in children with nephrotic syndrome. Data were obtained from the assessment of medical files of all children under fifteen years of age, who matched nephrotic syndrome criteria. Subjects were tested for IgG and IgM antibodies against T. gondii and cytomegalovirus; antibodies against Herpes simplex, hepatitis C virus and HIV; and surface antigen (HBsAg) of hepatitis B virus. The VDRL test was also performed. 169 cases were studied. The median age on the first visit was 44 months and 103 (60.9%) patients were male. Anti-CMV IgG and IgM were found in 70.4% and 4.1%, respectively. IgG and IgM against Toxoplasma gondii were present in 32.5% and 5.3%, respectively. Two patients were positive for HBsAg, but none showed markers for HIV, hepatitis C, or Treponema pallidum. IgG and IgM against herpes simplex virus were performed on 54 patients, of which 48.1% and 22.2% were positive. IgM antibodies in some children with clinical signs of recent infection suggest that these diseases may play a role in the genesis of nephrotic syndrome.

Lues maligna in an HIV-infected patient

We report such a case of malignant syphilis in a 42-year-old HIV-infected man, co-infected with hepatitis B virus, who presented neurolues and the classical skin lesions of lues maligna. The serum VDRL titer, which was 1:64 at presentation, increased to 1:2,048 three months after successful therapy with penicillin, decreasing 15 months later to 1:8.

Clinical and laboratory characteristics associated with dyslipidemia and liver steatosis in chronic HBV carriers

Introduction Chronic hepatitis B virus (HBV) infection and liver steatosis (LS) are the most common causes of chronic liver disease, and their coexistence is frequently observed in clinical practice. Although metabolic syndrome is the main cause of LS, it has not been associated with HBV infection. The aims of this study were to describe the lipid profile and prevalence of LS among HBV carriers and to identify the characteristics associated with LS in this group. Methods This retrospective cross-sectional study included hepatitis B surface antigen (HBsAg)-positive patients evaluated during 2011 and 2012. Results Of the 83 patients included, the mean age was 46.4±12.5 years, 53% were men, and 9.1% were hepatitis B e antigen (HBeAg) -positive. These patients exhibited the following lipid profile: total cholesterol = 175.4±38.8mg/dL, low-density lipoprotein (LDL) = 113.0±32.7mg/dL, and triglycerides = 91.1±45.2mg/dL. Their fasting glucose was 95.3±14.5g/dL, and fasting insulin was 6.1±5.9µIU/mL. Liver steatosis was observed on abdominal ultrasound in 11.3% of individuals. Factors associated with the presence of LS included higher levels of total cholesterol, prothrombin activity, fasting insulin, and body mass index (BMI) as well as lower levels of aspartate aminotransferase (AST). Conclusions These findings suggest that LS in patients with chronic HBV appears to be a consequence of metabolic alterations and insulin action rather than of viral factors.

Opportunistic infections among individuals with HIV-1/AIDS in the highly active antiretroviral therapy era at a Quaternary Level Care Teaching Hospital

INTRODUCTION : In this study, clinical-laboratory and epidemiological characteristics are described for a group of 700 individuals with HIV (human immunodeficiency virus)/AIDS (acquired immunodeficiency syndrome) in the ART (antiretroviral therapy) era at a teaching hospital that provides a quaternary level of care, with an emphasis on opportunistic infections (OIs), co-infections and immune profile. METHODS : A retrospective cross-sectional study of AIDS cases was conducted from 1998 to 2008 by reviewing medical records from the Base Hospital/FUNFARME (Fundação Faculdade Regional de Medicina), São José do Rio Preto, São Paulo, Brazil. RESULTS: The individuals were 14 to 75 years of age, and 458 were males. Heterosexuals accounted for 31.1% of all patients. Eighty-three percent were on ART, and 33.8% of those presented difficulties with treatment adherence. OIs were analyzed from medical records, and Pneumocystis jiroveci pneumonia was the most prevalent, regardless of the LTCD4+ (TCD4+ Lymphocytes) levels. Individuals whose viral loads were ≥10,000 showed a 90% greater chance of neurotoxoplasmosis. For P. jiroveci pneumonia, neurotoxoplasmosis, esophageal candidiasis, pulmonary tuberculosis and neurocryptococcosis, the chances of infection were higher among patients with LTCD4+ levels below 200 cells/mm3. HIV/hepatitis C virus (HCV) and HIV/hepatitis B virus (HBV) co-infections were significantly associated with death. CONCLUSIONS : OIs remain frequent in the ART era even in populations where the access to medical care is considered satisfactory.

Portal hypertension in schistosomiasis: pathophysiology and treatment

In heavily infected young patients, there is a "non-congestive" phase of the disease with splenomegaly which can improve after chemoterapy. A strong correlation between hepatosplenic form and worm burden in young patients has been repeatedly shown. The pattern of vascular intrhepatic lesions seems to depend on two mechanisms: (a) egg embolization, with a partial blocking of the portal vasculature; (b) the appearance of small portal collaterals along the intrahepatic portal sistem. The role played by hepatitis B virus (HBV) and C virus infections in the pathogenesis of liver lesions is variably considered. Selective arteriography shows a reduced diameter of hepatic artery with thin and arched branches outlining vascular gaps. A rich arterial network , as described in autopsy cases, is usually not seen in vivo, except after splenectomy or shunt surgery. An augmented hepatic arterial flow was demonstrated in infected animals. These facts suggest that the poor intrahepatic arterial vascularization demonstrated by selective arteriography in humans is due to a "functional deviation"of arterial blood to the splenic territory. The best results obtained in treatment of portal hypertension were: esophagogastric desvascularization and splenectomy (EGDS), although risk of rebleeding persists; classical (proximal) splenorenal shunt (SRS) should be abandoned; distal splenorenal shunt may complicate with hepatic encephalopaty, although later and in a lower percentage than in SRS. Propranolol is currently under investigation. In our Department, schistosomotic patients with esophageal varices bleeding are treated by EGDS and, if rebleeding occurs, by sclerosis of the varices.

Interrelationship between Schistosomiasis and concomitant diseases

The biological literature contains many examples of mutual influences between different species of parasites, especially with respect to concomitant helminth infections. Several situations are known in wich the association of infection by Shistosoma mansoni with other pathogens in the same host results in a type of disease wich differs from the simple summation of the individual effects of each infection. The present study concerns concomitant infections involving S. mansoni and enterobacteriaceae; S. mansoni and other helmints such as Ascaris lumbricoides, Ancylostomids, Toxocara canis and species of the genus Hymenolepis; S. mansoni and different protozoa such as Trypanosoma cruzi, T. brucei, Toxoplasma gondii and Plasmodium berghei. The interaction between hepatitis B virus and S. mansoni, leading to prolonged viremia and worsening of liver damage, is also discussed. The paper also treats the simultaneous occurrence of schistosomiasis and other aggravating factors such as malnutrition and neoplasias wich may alter the host's response to the trematode.