Adalgisa de Souza Paiva Ferreira

HBV carrying drug-resistance mutations in chronically infected treatment-naive patients.

BACKGROUND Nucleoside/nucleotide analogue (NA) treatment causes selection pressure for HBV strains carrying mutations conferring NA resistance. Drug-resistance mutations occur in the reverse transcriptase (RT) region of the HBV polymerase gene and spontaneously arise during viral replication. These mutations can also alter the hepatitis B surface (HBs) protein and in some cases reduce binding to HBs antibodies. The spread of NA-resistant HBV may impact the efficacy of antiviral treatment and hepatitis B immunization programmes. In this study, we used direct sequencing to assess the occurrence of HBV carrying known mutations that confer NA resistance in the largest cohort of treatment-naive patients with chronic hepatitis B (CHB) to date. METHODS HBV DNA samples isolated from 702 patients were sequenced and the RT region subjected to mutational analysis. RESULTS There was high genetic variability among the HBV samples analysed: A1 (63.7%), D3 (14.5%), A2 (3.3%), A3 (0.1%), B1 (0.1%), B2 (0.1%), C2 (0.9%), D1 (0.9%), D2 (4.6%), D4 (5.1%), D unclassified subgenotype (0.7%), E (0.6%), F2a (4.6%), F4 (0.4%) and G (0.4%). HBV strains harbouring mutations conferring NA resistance alone or combined with compensatory mutations were identified in 1.6% (11/702) of the patients. CONCLUSIONS HBV strains harbouring resistance mutations can comprise the major population of HBV quasispecies in treatment-naive patients. In Brazil, there is a very low frequency of untreated patients who are infected with these strains. These findings suggest that the spread and natural selection of drug-resistant HBV is an uncommon event and/or most of these strains remain unstable in the absence of NA selective pressure.

Is hepatitis C more aggressive in renal transplant patients than in patients with end-stage renal disease?

Background The eventual impact of immunosuppression on the natural history of hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD) is still unknown because of the lack of comparative data for HCV-infected patients with ESRD and renal transplant patients. The aim of this study was to compare the biochemical and histological characteristics of chronic HCV infection in renal transplants patients and ESRD patients undergoing hemodialysis. Methods Thirty-eight renal transplant patients and 38 ESRD patients undergoing hemodialysis who were chronically infected with HCV and were matched for gender, age at infection, and estimated time of infection were included in the study. The groups were compared regarding laboratory and histological variables. Results Renal transplant patients showed similar alanine aminotransferase and higher gamma-glutamyltransferase levels (P=0.05) when compared with ESRD patients. Comparative analysis of histological variables revealed a higher proportion of cases with septal fibrosis (P=0.04) and confluent necrosis (P=0.01) among transplant-recipient patients. No difference between groups was observed regarding the intensity of portal and periportal inflammatory infiltrates. Steatosis was more prevalent among transplant-recipient patients (P<0.001). There was no difference between groups regarding the prevalence of lymphoid aggregates or bile duct injury. Conclusion Renal transplant patients had a larger proportion of cases with septal fibrosis and confluent necrosis than did ESRD patients, suggesting that renal transplantation might modify the natural history of hepatitis C in ESRD patients, leading to a more aggressive liver disease.

High prevalence of hepatitis B virus subgenotypes A1 and D4 in Maranhão state, Northeast Brazil

In this study, we determined the prevalence of HBV subgenotypes in Maranhão state, located in northeastern Brazil, where the population is heterogeneous, with a high proportion of African descendants. HBV was detected in 119 of 133 (89.5%) chronic hepatitis B patients, including 103 (86.5%) who were HBeAg-negative. Using phylogenetic analysis of the S/Polymerase region of HBV DNA, subgenotype A1 was found to be the most prevalent (67%), followed by genotype D (28%; subgenotype D4 was detected in 24%, D3 in 3%, and D2 in 1%). Genotype F, clustering with subgenotype F2a, was found in six (5%) patients. The topology of the phylogenetic tree showed that HBV/A1 sequences did not cluster together, suggesting that more than one strain was introduced into Maranhão. On the other hand, HBV/D4 sequences formed a monophyletic cluster, suggesting a single entry of this strain in this population. This study showed that HBV/A1 was the only subgenotype of HBV/A present in the population from Maranhão and indicated that in this region HBV/A1 was not restricted to an Afro-descendant community where it was previously reported, but is widely distributed among general population of HBV chronic carriers. Unexpectedly, we found a high frequency of HBV subgenotype D4. Together with previously reported data on the distribution of HBV/D4 in the world, these findings suggest that this subgenotype was more prevalent in the African continent in the past and may have been introduced in Maranhão by means of the slave trade during the late XVIII century, when the largest number of African slaves arrived to this region.

Is alanine aminotransferase a good marker of histologic hepatic damage in renal transplant patients with hepatitis C virus infection

Abstract:  Introduction:  Renal transplant (RTx) patients with hepatitis C frequently show normal levels of alanine aminotransferase (ALT) and the significance of ALT in this group has not been established.

Acute hepatitis C in Brazil: Results of a national survey

The incidence of acute hepatitis C has decreased in the world. However, new cases are still reported. The objective of this study was to obtain data of acute hepatitis C in Brazil and to identify risk factors of transmission, diagnostic criteria, clinical presentation, evolution, and treatment. A questionnaire was sent to all members of the Brazilian Society of Hepatology. Sixteen centers participated with a total of 170 cases between 2000 and 2008. Among them, 37 had chronic renal failure on hemodialysis and were evaluated separately. The main diagnostic criterion in non‐uremic patients was ALT (alanine aminotransferase) elevation associated with risk factors. In patients with chronic renal failure, anti‐hepatitis C virus (HCV) seroconversion was the most frequent criterion. Among the 133 non‐uremic patients the main risk factors were hospital procedures, whereas in hemodialysis patients, dialysis was the single risk factor in 95% of the cases. Jaundice was more frequent in non‐uremic patients (82% vs. 13%; P < 0.001) and ALT levels were higher in these individuals (P < 0.001). Spontaneous clearance was more frequent in non‐uremic patients (51% vs. 3%; P < 0.001). Sixty‐five patients were treated: 39 non‐uremic patients and 26 on dialysis. Sustained virological response rates were 60% for non‐uremic and 58% for uremic patients (P = 0.98). There was no association of these rates with the study variables. These findings show that cases of acute hepatitis C are still occurring and have been related predominantly to hospital procedures. Measures to prevent nosocomial transmission should be adopted rigorously and followed to minimize this important source of infection observed in this survey. J. Med. Virol. 83:1738–1743, 2011.

Factors associated with the progression of hepatic fibrosis in end-stage kidney disease patients with hepatitis C virus infection.

Background Few studies have evaluated the histological aspects of hepatitis C virus (HCV) infection in hemodialysis patients and the factors related to the progression of hepatic fibrosis in this population have not been defined. Aim To evaluate the influence of host-related factors on the fibrosis progression in end-stage renal disease (ESRD) patients with HCV infection. Methods HCV-infected ESRD patients who submitted to liver biopsy were included. The fibrosis stages were classified according to METAVIR scoring system. For the identification of factors associated with more advanced liver fibrosis, the patients were classified into two groups: group 1, absence of septal fibrosis (F0-1) and group 2, presence of septal fibrosis (F2-4). Groups 1 and 2 were compared regarding demographic, epidemiological, and laboratory variables and logistic regression analysis was used to identify the variables that were independently associated with the presence of septal fibrosis. Results A total of 216 ESRD patients (63% men, 44±11 years) were included. In the histological analysis, the fibrosis stages were as follows: F0=36%, F1=41%, F2=12%, F3=7, and 4% had cirrhosis (F4). In the logistic regression model, the variables that were independently associated with the presence of septal fibrosis were duration of infection, estimated age at infection, coinfection with HBV and aspartate aminotransferase levels. Conclusion These findings support the importance of obtaining an adequate immune response to HBV vaccination and careful monitoring of liver disease in patients who become infected at an advanced age and/or those presenting elevated aspartate aminotransferase levels, as these are the main factors associated with the presence of septal fibrosis in ESRD patients.

Prevalence of hepatitis B among pregnant women assisted at the public maternity hospitals of São Luís, Maranhão, Brazil

INTRODUCTION Hepatitis B virus (HBV) infection is an important worldwide public health problem. In Brazil, the Ministry of Health estimates that 15% of the population has had contact with HBV, and that the mean rate of chronic carriers in Northeastern Brazil is around 0.5%. OBJECTIVE The aim of this study was to assess the prevalence of HBV markers in pregnant women receiving prenatal care at the public maternity hospitals of São Luís. METHODS Demographical and epidemiological data were collected from 541 pregnant women according to the research protocol. Blood samples were collected, and the anti-HBc test was performed first. If positive, the sample was subsequently tested for HBsAg and anti-HBs. All HBsAg and/or anti-HBc positive samples were additionally tested for HBV-DNA. RESULTS 40 (7.4%) pregnant women turned out positive for anti-HBc. Of those, five (0.9%) were HBsAg positive, four (0.7%) were anti-HBc positive with negative HBsAg and anti-HBs, and 31 (5.7%) were positive for anti-HBc and anti-HBs. Anti-HBc positivity was associated with family history of hepatitis and education level below 11 years of schooling. HBV-DNA was positive in only one HBsAg-positive sample. There was no HBV-DNA positivity among HBsAg negative samples. CONCLUSIONS The prevalence of HBsAg in pregnant women in this study confirmed that São Luís is a low endemicity area. Occult hepatitis B was not detected in these samples.

Acromegalic cardiomyopathy in an extensively admixed population: is there a role for GH/IGF‐I axis?

A specific acromegaly‐related cardiomyopathy has been described in the literature, largely in Caucasians, which is independent of other risk factors, mainly hypertension.

High incidence of tuberculosis in patients treated for hepatitis C chronic infection

Brazil is one of the 22 countries that concentrates 80% of global tuberculosis cases concomitantly to a large number of hepatitis C carriers and some epidemiological risk scenarios are coincident for both diseases. We analyzed tuberculosis cases that occurred during α-interferon-based therapy for hepatitis C in reference centers in Brazil between 2001 and 2012 and reviewed their medical records. Eighteen tuberculosis cases were observed in patients submitted to hepatitis C α-interferon-based therapy. All patients were human immunodeficiency virus-negative. Nine patients (50%) had extra-pulmonary tuberculosis; 15 (83%) showed significant liver fibrosis. Hepatitis C treatment was discontinued in 12 patients (67%) due to tuberculosis reactivation and six (33%) had sustained virological response. The majority of patients had a favorable outcome but one died. Considering the evidences of α-IFN interference over the containment of Mycobacterium tuberculosis, the immune impairment of cirrhotic patients, the increase of tuberculosis case reports during hepatitis C treatment with atypical and severe presentations and the negative impact on sustained virological response, we think these are strong arguments for latent tuberculosis infection screening before starting α-interferon-based therapy for any indication and even to consider IFN-free regimens against hepatitis C when a patient tests positive for latent tuberculosis infection.

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.