Prevalence of hepatitis B in people living with HIV/AIDS in Latin America and the Caribbean: a systematic review and meta-analysis.

BACKGROUND: Hepatitis B virus (HBV) infection is a major cause of chronic liver disease worldwide. In immunocompromised patients, the chronicity rates of HBV infection are higher, but the rates of hepatitis Be antigen (HBeAg) and HBsAg loss and seroconversion to anti-HBe and anti-HBs are lower than those in immunocompetent subjects. This study aimed to evaluate articles on the prevalence of HBsAg in people living with human immunodeficiency virus (HIV) /AIDS (PLWHA) in Latin America and the Caribbean (LAC). METHODS: We searched the PubMed, Latin American and Caribbean Health Sciences, and Embase databases for studies up to November 2016 on infection with HIV and HBV in LAC without period or language restrictions. We did not include case reports, case series, review articles, comments, or studies with a sample size smaller than 100. We also evaluated the quality of the articles using a list of criteria totaling 21 items. RESULTS: Of the 28 selected articles (n = 18,457) published from 1999 to 2016, 18 studies (64.3%) were from Brazil, 3 (10.7%) were from Argentina, 2 (7.1%) were from Chile, 2 (7.1%) were from Cuba, 1 (3.6%) was from Colombia, 1 (3.6%) was from Venezuela, and 1 (3.6%) was from Jamaica. The mean score for the assessment of the study quality was 11.6 (range: 8-16). The estimated pooled prevalence of HBsAg among PLWHA in the selected studies was 7.0% (95% CI 7.0-7.0%). The pooled prevalence of HBsAg was 8.0% (95% CI 8.0-9.0%) in the studies published from 1999 to 2006 and 6.0% (95% CI 5.0-6.0%) in the studies published during the later timeframe. CONCLUSIONS: The results of this review indicate the need to increase the investment in preventive measures against hepatitis B, particularly when the impact of adequate vaccination in this population is considered. Future studies with larger sample sizes are needed in LAC to determine the true prevalence of hepatitis B throughout the region and to clarify and address the risk factors associated with the acquisition of infection.

The rs738409 polymorphism of the PNPLA3 gene is associated with hepatic steatosis and fibrosis in Brazilian patients with chronic hepatitis C.

BACKGROUND: Prospective studies have shown that 80% of acute hepatitis C virus (HCV) cases progress to chronic infection; approximately 10-20% of patients with these conditions will develop liver cirrhosis within 2 to 3 decades, and 1-5% will develop liver cancer. Some studies have indicated that the rs738409 polymorphism of the PNPLA3 gene is associated with steatosis and the progression of advanced fibrosis. This study assessed the contribution of the PNPLA3 rs738409 polymorphism with regard to the steatosis and degree of liver fibrosis in Brazilian patients diagnosed with chronic hepatitis C. METHODS: A total of 290 patients were evaluated at the Clinics Hospital of the School of Medicine, University of São Paulo, between 2010 and 2015. The inclusion criteria were age ≥ 18 years and positive anti-HCV antibody and HCV RNA tests. The participants were evaluated based on medical consultation, blood tests, and liver biopsies conducted before specific antiviral therapies were applied. The associations between the rs738409 PNPLA3 gene polymorphism and steatosis and advanced fibrosis were tested under a recessive inheritance model using logistic regression analysis, including age, gender, BMI, ethnicity/color, HOMA-IR, alcohol intake, HCV genotype 3, and the rs58542926 TM6SF2 gene polymorphism as covariates. RESULTS: The mean age of the patients was 54.9 years old (range, 28 to 82 years), and 124 (42.8%) patients were male; 226 (77.9%) were white, 43 (14.8%) were pardo, and 21 (7.2%) were black Brazilians. Of the patients included in this study, 133 (45.9%) presented with the CC genotype, 63 (21.7%) with the CG genotype, and 94 (32.4%) with the GG genotype of the PNPLA3 gene I148M variant. We observed that the associations between PNPLA3 rs738409 GG genotype and steatosis was significant (OR: 2.16; 95% CI 1.26-3.72). The same genotype was associated to advanced fibrosis too (OR:2.64; 95% CI 1.26-5.53). CONCLUSIONS: Associations between the rs738409 polymorphism of the PNPLA3 gene genotype GG and hepatic steatosis and advanced fibrosis were observed. Studies are still needed to clarify the influence of these polymorphisms on hepatic steatosis and degree of fibrosis among individuals diagnosed with chronic hepatitis C.

Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation.

Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.

Chronic hepatitis C: hepatic fibrosis evolution after ineffective specific treatment.

BACKGROUND/AIMS: Specific treatment of chronic hepatitis C is effective in 50% of patients, improving the liver's fibrosis, necroinflammatory changes and steatosis. However, in patients still viremic after treatment the extension of these benefits remains doubtful. The evolution of the disease in this group and its relationship to demographic data, biometric indices and time lapse between biopsies was evaluated. METHODOLOGY: In 141 patients, paired biopsies were classified and compared according to fibrosis grading. Necroinflammation, steatosis, demographic data (age and gender), body mass index (BMI) and time lapse between biopsies were compared with fibrosis grading. RESULTS: The grade of fibrosis of the patients, after approximately 3.5 years time lapse between biopsies, could be classified into 4 groups; Improved: 29 (20.0%), Unaltered: 64 (45.0%), Worsened: 48 (34%) and Cirrhotic: 14 (9.93%). For necroinflammation, the Improved/Unaltered groups were statistically similar but different from the Worsened and Cirrhotic. The mean age, BMI and time lapse between biopsies were statistically similar in all groups. Steatosis occurred in 35 (24.82%) between biopsies and its incidence was reduced in the Worsened and Cirrhotic groups. CONCLUSIONS: Fibrosis turned into cirrhosis in a significant number of patients, after a short time lapse. The reverse correlation of steatosis to fibrosis and its occurrence during the time lapse between biopsies suggests it might induce hepatic necrosis and contribute to fibrogenesis.

Clinical and histological characteristics of HIV and hepatitis C virus-co-infected patients in Brazil: a case series study.

UNLABELLED: Hepatitis C virus (HCV) is an important factor contributing to morbidity and mortality in patients co-infected with HIV and HCV. In addition, liver biopsy is an important tool in the clinical management of these patients. Although liver biopsy is controversial, it is recommended for all patients. Data regarding the clinical and histological characteristics of these patients are scarce not only in Brazil but in Latin America as a whole. With the goal of better understanding these characteristics and the benefit of liver biopsy indications in this disease setting, data collected from 234 patients followed from 1996 to 2004 at Casa da AIDS, São Paulo, were analyzed. The following variables were extracted from the patients' medical files at the time of liver biopsy: sex, age, hepatitis C infection risk factors, hepatitis C infection duration, ALT levels, CD4+ T cell counts, history of alcohol abuse, history of antiretroviral therapy, HCV genotype, and liver histological alterations. CONCLUSIONS: 1 - Hepatitis C virus 1 and 3 were the most frequently identified genotypes and were diagnosed in 72% and 25.5% of cases respectively; 2 - Structural liver alterations were found to be mild or absent in 48.2% (113/234) of the analyzed patients; 3 - Fifty-three patients (23%) had normal ALT levels and 4 - Significant liver architectural changes (F2-F3) were evident in 22.5% of the patients with normal ALT levels.

Hepatitis C treatment: shorter and better?

Herein, we present a synthesis of two publications that evaluate an abbreviated therapeutic approach to treating chronic hepatitis C virus (HCV) infection. Based on those publications, we discuss the use of the early virologic response (EVR) as a tool for the optimized management of patients under treatment, as well as reviewing concepts of HCV viral kinetics. The fourth-week EVR, characterized by HCV RNA dropping to undetectable levels, allows individuals infected with HCV genotype 1 and presenting low baseline viral loads to be treated with the combination of pegylated interferon and ribavirin for 24 weeks, whereas individuals infected with HCV genotypes 2 or 3 can be treated for only 12 weeks. Therefore, by adopting abbreviated treatment regimens optimized through early prediction of sustained viral response, it is possible to increase the number of patients treated without incurring the excess costs related to high rates of treatment failure and management of adverse outcomes, as well as avoiding the risks of unnecessarily exposing patients to drugs that have the potential to be highly toxic.

I consensus for the management and treatment of hepatitis B carried out by the Brazilian society of infectious diseases.

This paper reports on the conclusions reached by the Hepatitis Committee of the Brazilian Society of Infectious Diseases in their I Consensus for the Management and Treatment of Hepatitis B. The subjects considered most relevant or controversial among those discussed by the Consensus Group, which met in the city of São Roque on July 21-23, 2006, are summarized in this report. A systematic review on topics related to hepatitis B was carried out and published in the Brazilian Journal of Infectious Diseases. We strongly recommend that readers consult the Proceedings of the Consensus Meeting in which a full, detailed report on the topics discussed is published, whereas in the Consensus, these topics are concisely and objectively summarized.

Detection of HCV by PCR in serum and PBMC of patients with hepatitis C after treatment.

Although hepatitis C is mainly hepatotropic, some studies suggest that hepatitis C virus (HCV) infects peripheral blood mononuclear cells (PBMC), using them as a reservoir, which might contribute to the development of resistance to treatment. Fifty-four hepatitis-C patients, who had been submitted to treatment, were selected. Blood samples were collected on the same day for the detection of HCV RNA in serum and PBMC by PCR, using the Amplicor HCV 2.0 assay (Roche Diagnostics). HCV genotyping was performed using the INNO-LiPA HCV kit (Versant, Bayer Diagnostics). HCV RNA was detected in both serum and PBMC in 35 (64%) patients and no RNA in 16 (29.6%). Disagreement between the serum and PBMC results was observed for three patients (5.6%), with HCV RNA being detected in PBMC but not in serum. Four months later, new serum and PBMC samples were collected from one of these patients and HCV RNA was detected in both samples, showing that PBMC can reveal signs of a lack of response to treatment. We conclude that the absence of HCV in the serum of patients with chronic hepatitis C by the end of treatment does not mean that there is no circulating virus. HCV in mononuclear cells may be an indicator of the persisting infection.

Portal CD4+ and CD8+ T lymphocyte correlate to intensity of interface hepatitis in chronic hepatitis C.

BACKGROUND: The pathogenesis of chronic hepatitis C is still a matter of debate. CD4+ and CD8+ T lymphocytes (TL) are typically observed within the portal and periportal spaces of affected livers, but their functional role in hepatitis C progression has not been fully elucidated. METHODS: CD4+ and CD8+ TL were quantified by immunohistochemistry in portal and periportal spaces of 39 liver biopsies from patients with chronic hepatitis C. They were associated to demographic data, histological parameters, laboratory findings of patients and hepatitis C genotypes. RESULTS: There was high numbers of CD4+ and CD8+ TL from which the density of CD4+ T was higher than CD8+ TL in portal and periportal spaces. CD4+ and CD8+ TL were directly correlated to intensity of interface hepatitis. CD8+ TL correlated to serum enzyme levels. CONCLUSION: The high numbers of CD4+ and CD8+ TL in portal and periportal spaces and their correlation to interface hepatitis suggest that hepatitis C evolution depends on the action of intrahepatic T lymphocytes, lending support to the notion of an immune-mediated mechanism in the pathogenesis of chronic hepatitis C.

Weight-based combination therapy with peginterferon alpha-2b and ribavirin for naïve, relapser and non-responder patients with chronic hepatitis C.

Combination therapy with pegylated interferon and ribavirin is considered the new standard therapy for naïve patients with chronic hepatitis C. We evaluated the efficacy and safety of treatment with weight-based peginterferon alpha-2b (1.5 mg/kg per week) plus ribavirin (800-1,200 mg/day) for 48 weeks in naïve, relapser and non-responder (to previous treatment with interferon plus ribavirin) patients with chronic hepatitis C. Sixty-seven naïve, 26 relapser and 40 non-responder patients were enrolled. The overall sustained virological response (SVR) for the intention-to-treat population was 54% for naïve, 62% for relapser and 38% for non-responder patients. In the naïve subgroup, SVR was significantly higher in patients with the non-1 genotype (67%) compared to those with genotype 1 (45%). In relapsers and non-responders, SVR was, respectively, 69% and 24% in patients with genotype 1 and 43% and 73% in those with genotype non-1. There were no significant differences in SVR rates among the three body weight ranges (<65 kg, 65-85 kg and >85 kg) in any of the subgroups. Early virological response (EVR) was reached by 78%, 81% and 58% of naïve, relapser and non-responder patients, respectively, and among those with EVR, 63%, 67% and 61%, respectively, subsequently achieved SVR. All of the non-responder patients who did not have EVR reached SVR. Treatment was discontinued in 13% of the patients, due to loss to follow-up, hematological abnormalities or depression.

[Factors associated with severe evolutive forms of chronic infection with hepatitis C virus]. / Fatores associados às formas evolutivas graves da infecção crônica pelo vírus da hepatite C.

To assess the factors associated with the development of moderate and severe fibrosis, the medical records of 426 patients with chronic hepatitis C virus infection attended at the Infectious and Parasitic Diseases Clinic of the University of São Paulo Faculty of Medicine from January 1 to December 31, 2000 were reviewed. Of the patients included in the study, 56.3% were male and 43.7%, female. Patient age ranged from 18 to 69 years. Blood transfusion was the most frequent form of hepatitis C virus transmission, detected in 128 (30%) cases, and no risk factor was detected in 187 (43.9%) patients. Patient distribution regarding architectural changes observed in a liver biopsy was: grade 0 (14.1%); grade 1 (51.2%); grade 2 (20.6%); grade 3 (8%); grade 4 (6.1%). Multivariate analysis revealed a positive correlation between fibrosis severity and age greater than 40 years at the time of the liver biopsy, serum albumin levels below normal lower limits, gamma-glutamyltransferase levels equal to or higher than twice upper normal limits, platelet numbers less than 150,000/mm(3) and high necroinflammatory activity. The data obtained were inconclusive regarding a possible correlation between severity of fibrosis and alcoholism.

[Risk factors for HIV infection among patients infected with hepatitis C virus]. / Fatores de risco para infecção pelo HIV em pacientes com o vírus da hepatite C.

OBJECTIVE: Human immunodeficiency virus and hepatitis C virus share the same routes of transmission. Currently, there is a high frequency of co-infection worldwide, especially among users of injectable drugs and in subjects with history of blood transfusions. The aim of the present study was to evaluate risk factors associated to human immunodeficiency virus infection in patients infected with hepatitis C virus. METHODS: We carried out an epidemiological case-control study, including 118 patients (cases) infected by both viruses and 233 patients (controls) infected only by the hepatitis C virus. Between January 1999 and November 2001, patients responded to a questionnaire assessing sociodemographic and professional characteristics, and major risk factors for virus infection. After description and initial comparison, variables were evaluated by univariate analysis and then by multivariate logistic regression for variables selected through the maximum likelihood test. RESULTS: Co-infection was associated with female sex (OR = 2.89; 95% CI: 1.16-7.08), being divorced/widow (OR = 3.91; 95% CI: 1.34-11.35), past or current use of illegal drugs (OR = 3.96; 95% CI: 1.55-10.13) and to the habit of sharing pipes or needles (OR = 10.28; 95% CI: 4.00-6.42). CONCLUSIONS: Among patients infected with hepatitis C virus, female sex is a risk factor for HIV infection after adjustment for the habit of sharing pipes and needles. Being divorced/widow, use of illegal drugs, and the habit of sharing pipes and syringes were associated to co-infection.

Risk factors associated with hepatitis C among patients co-infected with human immunodeficiency virus: a case-control study.

A case-control study was carried out to assess the risk factors associated with hepatitis C in patients infected with human immunodeficiency virus. One hundred eighteen patients tested positive for hepatitis C virus (HCV) and were included as cases, and 117 tested negative for HCV and were included as controls. Information was collected through a questionnaire. The risk factors that showed a significant association with co-infection by multivariate analysis were an age of 30-39 years (odds ratio [OR] = 4.65, 95% confidence interval [CI] = 1.31-16.43), an age of 40-49 years (OR = 6.48, 95% CI = 1.70-24.78), an age > 50 years (OR = 7.50, 95% CI = 1.54-36.68), use of intravenous drugs (OR = 25.46, 95% CI = 4.91-131.88), use of inhaled illicit drugs (OR = 3.56, 95% CI = 1.22-10.44), anal intercourse (OR = 3.93, 95% CI = 1.27-12.13), a sexual partner with a history of liver disease (OR = 5.45, 95% CI = 1.33-22.32), a sexual partner with a history of blood transfusions (OR = 4.79, 95% CI = 0.95-24.19), and sexual partner with a history of intravenous drug use (OR = 3.46, 95% CI = 1.24-9.65).

Hepatitis C in patients co-infected with human immunodeficiency virus. A review and experience of a Brazilian ambulatory.

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) share the same transmission mechanisms. The prevalence of HCV in the HIV-infected population varies from region to region, throughout the world, depending on different exposure factors to both viruses. Co-infection with HIV accelerates the progression of the disease caused by HCV, appears to worsen the progression of the HIV infection and increases HCV transmission. Therefore, clinical management and treatment of HCV is a priority in medical facilities that receive HIV-infected patients. Clinical management of these patients involves specific diagnostic procedures and appropriately trained medical staff. The indication of treatment should meet specific clinical and laboratory criteria. There are a number of drugs currently available to treat hepatitis C in co-infected patients.

Clinical laboratory assessment of hepatitis C and HIV coinfected patients according to the antiretroviral therapy received.

During the year of 2001, a retrospective, descriptive study in order to determine the influence of the antiretroviral therapy received by 111 HIV-HCV coinfected patients who had undergone at least one liver biopsy was conducted, 74 of them were treated with a protease inhibitor regimen (WPI), and 37 with a non-protease inhibitor regimen (NPI). The main characteristics found were: a young patient population (mean age 41 years old in both groups), composed in most part of male individuals (74.3% WPI and 51.4% NPI) with previous risk factors for both infections (WPI 93.2% and NPI 89.2%). The most significant findings included AIDS-defining disease (WPI 18.9% and NPI 13.5% of the cases), elevated hepatic enzyme levels (WPI: SGOT 52.1 and NPI 53.2), absence of liver disease-related symptoms (16.2% for both groups), average CD4 count > 350 for both groups (WPI 362.2 and NPI 378.1), predominantly low-grade fibrosis in both populations (0-2 in 63.6% of WPI patients and in 80% of NPI patients), with necro-inflammatory activity ranging from 5-7 in 51.3% and 42.9% of WPI patients and NPI patients, respectively. It is suggested a sequential biopsy to better evaluate the evolution of the hepatic disease, according to the HAART regimen received.

Patients with chronic hepatitis C and normal transaminases.

Hepatitis C virus infection evolves progressively persisting in the majority of patients (85%). Most patients have high ALT (alanine aminotransferase) levels and approximately 25% normal ALT. The latter are usually female and there is no association between genotype and severity of hepatic lesion. Histologic analysis usually shows small lesion and absence or low amount of fibrosis, despite cirrhosis having been reported. Aiming at assessing prevalence, demographic, genotypical and anatomopathological characteristics in patients with normal ALT levels, we have carried out a study of 68 chronic hepatitis C patients between January 1997 and April 2000. There was a prevalence of 13.8% chronic hepatitis C patients with normal ALT levels, 45.6% of which were male and 54.4% female, the mean age being 38 +/- 13 years. We found a predominance of genotype 1 in 84.7% of the patients, genotype 2 in 6.8% and genotype 3 in 10.7%. In 52.9% of the cases liver biopsies revealed liver reaction, periportal activity score 0-1 was observed in 85.3% of the patients and score 2-4 was seen in 14.7%. Structural activity score 0-1 was seen in 73.5% of the patients and score 2-4 in 26.5% of them. Periportal activity > or = 2 and structural activity > 1 was seen in 29%, but steatosis was not seen in 73.5%. Our results suggest the need to revisit for liver biopsy practice in patients with chronic hepatitis C and normal transaminases.

HCV serotypes in Brazilian patients.

OBJECTIVE: To investigate the prevalence of the different types of hepatitis C virus (HCV) in a population of chronic HCV carriers using the Murex HCV serotyping 1-6 assay. METHODS: All serum samples from these patients had a positive nested PCR HCV reaction. The sera were submitted to ELISA, modified, for the identification of antibodies against HCV serotypes 1, 2, 3, 4, 5 and 6 (Murex HCV serotyping 1-6 assay). RESULTS: The viral serotype was identified in 166 (75.8%) of the 219 patients, 108 (65.11%) males and 58 (34.9%) females. Patient age ranged from 12 to 73 years, with a mean of 41.1 years. The form of acquisition of the disease most frequently reported was blood transfusion. The results showed a predominance of type 1 (70.0%), followed by type 3 (22.3%) and type 2 (4.2%). CONCLUSION: Samples presenting low and very close optical density readings may lead to discrepant diagnoses concerning HCV serotypes and should be confirmed by genotyping. The serotyping can be useful in clinical practice and can be of help in establishing the prognosis of the disease, also favoring epidemiologic studies independently of the technology required for genotyping tests.

Are anti-interferon antibodies the cause of failure in: chronic HCV hepatitis treatment?

A follow-up study was made of 94 chronic hepatitis C patients at a hepatitis clinic in Brazil, after interferon alpha (IFN-alpha) therapy, to determine the influence of anti-interferon antibodies on treatment outcome. Patients diagnosed as having chronic hepatitis C, confirmed by PCR (HCV RNA) and liver biopsy, were treated with interferon alpha 2a or 2b for at least six months, and were followed up for 24 weeks after termination of treatment in order to assess biochemical, virological and clinical pathology responses. Only 6% of the 94 patients developed anti-IFN antibodies, 70% presented a biochemical response and 23% maintained a sustained virological response. Clinical evaluation revealed that in only 2 patients was there progression of fibrosis; the necro-inflammatory score indicated that 72% maintained the same activity, 12% had worsening necro-inflammatory activity, and the remaining 16% had decreased activity. There was no significant correlation of demographic and laboratory variables with levels of anti-interferon antibodies. Similarly, biochemical and virological responses were not influenced by anti-interferon antibodies. Multivariate analysis by logistic regression revealed that clinical pathological parameters, staging and necro-inflammatory activity did not influence the response to the virus.

Hepatitis C viral load does not predict disease outcome: going beyond numbers.

The analysis of 58 patients with chronic hepatitis C without cirrhosis and treated with interferon-alpha demonstrated that hepatitis C viral (HCV) load does not correlate with the histological evolution of the disease (p = 0.6559 for architectural alterations and p = 0.6271 for the histological activity index). Therefore, the use of viral RNA quantification as an evolutive predictor or determinant of the severity of hepatitis C is incorrect and of relative value. A review of the literature provided fundamental and interdependent HCV (genotype, heterogeneity and mutants, specific proteins), host (sex, age, weight, etc) and treatment variables (dosage, time of treatment, type of interferon) within the broader context of viral kinetics, interferon-mediated immunological response (in addition to natural immunity against HCV) and the role of interferon as a modulator of fibrogenesis. Therefore, viral load implies much more than numbers and the correct interpretation of these data should consider a broader context depending on multiple factors that are more complex than the simple value obtained upon quantification.