Interferon-related gene array in predicting the efficacy of interferon therapy in chronic hepatitis B / 生物医学工程学杂志

This study aims to clarify host factors of IFN treatment in the treatment of chronic hepatitis B (CHB) patients by screening the differentially expressed genes of IFN pathway CHB patients with different response to interferon (IFN) therapy. Three cases were randomly selected in IFN-responding CHB patients (Rs), non-responding CHB patients (NRs) and healthy participants, respectively. The human type I IFN response RT 2 profiler PCR array was used to detect the expression levels of IFN-related genes in peripheral blood monocytes (PBMCs) from healthy participants and CHB patients before and after Peg-IFN-α 2a treatment. The results showed that more differentially expressed genes appeared in Rs group than NRs group after IFN treatment. Comparing with healthy participants, IFNG, IL7R, IRF1, and IRF8 were downregulated in both Rs and NRs group before IFN treatment; CXCL10, IFIT1, and IFITM1 were upregulated in the Rs; IL13RA1 and IFI35 were upregulated in the NRs, while IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1, and ADAR were downregulated. The expression of IL15, IFI35 and IFI44 was downregulated by 4.09 ( t = 10.58, P < 0.001), 5.59 ( t = 3.37, P = 0.028) and 10.83 ( t = 2.8, P = 0.049) fold in the Rs group compared with the NRs group, respectively. In conclusion, IFN-response-related gene array is able to evaluate IFN treatment response by detecting IFN-related genes levels in PBMC. High expression of CXCL10, IFIT1 and IFITM1 before treatment may suggest satisfied IFN efficacy, while high expression of IL13RA1, IL15, IFI35 and IFI44 molecules and low expression of IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1 and ADAR molecules may be associated with poor IFN efficacy.

Associations between gene polymorphisms of signal transducer and activator of transcription 3 and the susceptibility to hepatitis B virus related liver cirrhosis / 中华预防医学杂志

To investigate the associations between gene polymorphisms of signal transducer and activator of transcription 3 (STAT3) and liver cirrhosis (LC) after hepatitis B virus (HBV) infection. A case-control study was conducted in 243 patients with hepatitis B cirrhosis (HBV-LC, case group) and 486 HBV-infected subjects without LC (non-LC, control group) collected from January 2018 to September 2020 at the Changsha Central Hospital Affiliated to Nanhua University. Three single nucleotide polymorphisms (SNPs) of STAT3 gene, including rs4796793C>G, rs2293152C>G, and rs1053004T>C were selected through literature and biological information database, and the genotypes were detected by real-time fluorescent quantitative PCR (RFQ-PCR). The distribution differences of STAT3 SNPs genotypes between the two groups were compared using Chi-square test and haplotype analysis was conducted by Shesis online. The proportion of HBV C genotype in HBV-LC patients was significantly higher than that in the control group (80.91% vs. 70.79%, χ2=7.109, P=0.008), while the logarithm of ALT was significantly lower than that of the control group (1.78±0.43 vs. 1.95±0.54, t=3.801, P=0.000). The genotypes distributions of rs4796793, rs2293152, and rs1053004 were not significantly different between HBV-LC and non-LC in overall analysis and stratified analysis by gender (χ²=2.610, 1.505, 0.586, 2.653, 2.685, 1.583, 0.351, 5.388, 0.339, respectively, P>0.05 for each). Among the subjects infected with HBV genotype C, rs1053004 CC (vs. TT) significantly increased the risk of HBV-LC [odds ratio (OR) = 1.40, 95% confidence interval (CI): 1.03-1.91]. Among the HBV-infected subjects with HBeAg negative, rs4796793 GG genotype (vs. CC) and G allele (vs. C) significantly increased the risks of HBV-LC (OR = 2.17, 95%CI: 1.11-4.23; OR = 1.45, 95%CI: 1.06-1.97, respectively). Haplotypes analysis showed that the frequency of haplotype C-G-T composed of rs4796793, rs2293152, and rs1053004 was significantly lower in HBV-LC than that in the control group (non-LC) (27.3% vs. 35.6%, χ²=9.949, P = 0.001). The correlation between STAT3 and HBV-LC is different in HBV-infected subjects with different infection status. The HBV-infected subjects carrying haplotype rs4796793C-rs2293152G-rs1053004T of STAT3 gene have significantly decreased risk of LC.

DNA Methylation and Transcription of HLA-F and Serum Cytokines Relate to Chinese Medicine Syndrome Classification in Patients with Chronic Hepatitis B / 中国结合医学杂志

OBJECTIVE@#To explore the molecular bases of Chinese medicine (CM) syndrome classification in chronic hepatitis B (CHB) patients in terms of DNA methylation, transcription and cytokines.@*METHODS@#Genome-wide DNA methylation and 48 serum cytokines were detected in CHB patients (DNA methylation: 15 cases; serum cytokines: 62 cases) with different CM syndromes, including dampness and heat of Gan (Liver) and gallbladder (CHB1, DNA methylation: 5 cases, serum cytokines: 15 cases), Gan stagnation and Pi (Spleen) deficiency (CHB2, DNA methylation: 5 cases, serum cytokines: 15 cases), Gan and Shen (Kidney) yin deficiency (CHB3, DNA methylation: 5 cases, serum cytokines: 16 cases), CHB with hidden symptoms (HS, serum cytokines:16 cases) and healthy controls (DNA methylation: 6 cases). DNA methylation of a critical gene was further validated and its mRNA expression was detected on enlarged samples. Genome-wide DNA methylation was detected using Human Methylation 450K Assay and furthered verified using pyrosequencing. Cytokines and mRNA expression of gene were evaluated using multiplex biometric enzyme-linked immunosorbent assay (ELISA)-based immunoassay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively.@*RESULTS@#Totally 28,667 loci, covering 18,403 genes were differently methylated among CHB1, CHB2 and CHB3 (P<0.05 and |Δβ value| > 0.17). Further validation showed that compared with HS, the hg19 CHR6: 29691140 and its closely surrounded 2 CpG loci were demethylated and its mRNA expressions were significantly up-regulated in CHB1 (P<0.05). However, they remained unaltered in CHB2 (P>0.05). Levels of Interleukin (IL)-12 were higher in CHB3 and HS than that in CHB1 and CHB2 groups (P<0.05). Levels of macrophage inflammatory protein (MIP)-1α and MIP-1β were higher in CHB3 than other groups and leukemia inhibitory factor level was higher in CHB1 and HS than CHB2 and CHB3 groups (P<0.05). IL-12, MIP-1α and MIP-1β concentrations were positively correlated with human leukocyte antigen F (HLA-F) mRNA expression (R2=0.238, P<0.05; R2=0.224, P<0.05; R=0.447, P<0.01; respectively). Furthermore, combination of HLA-F mRNA and differential cytokines greatly improved the differentiating accuracy among CHB1, CHB2 and HS.@*CONCLUSIONS@#Demethylation of CpG loci in 5' UTR of HLA-F may up-regulate its mRNA expression and HLA-F expression was associated with IL-12, MIP-1α and MIP-1β levels, indicating that HLA-F and the differential cytokines might jointly involve in the classification of CM syndromes in CHB.@*REGISTRATION NO@#ChiCTR-RCS-13004001.

Association of serum levels of C-reactive protein with CRP-717 T/C polymorphism and viremia in HCV and HBV carriers

Abstract INTRODUCTION: The present study investigated the association of the rs2794521 polymorphism in the CRP gene in individuals with chronic hepatitis B and C, correlating it with markers of hepatic inflammation, fibrosis scores, viral load, and plasma protein levels. METHODS: The study analyzed 185 blood samples obtained from patients with hepatitis B (n=74) and hepatitis C (n=111) and 300 samples from healthy donors. Genotyping was performed by real-time polymerase chain reaction, and protein levels were quantified using the automated immunoturbidimetric method. RESULTS: The TT genotype was the most frequent in all studied groups and was associated with higher plasma levels of the protein but not with the progression of liver disease. Low levels of C-reactive protein were associated with increased viremia and scores indicative of severe fibrosis and cirrhosis. CONCLUSIONS: The present results demonstrated a close relationship between the ability of the virus to replicate and cause liver damage and low serum concentrations of C-reactive protein. Future research may determine if these results can be interpreted as a possible form of escape for the virus by decreasing its action as an opsonin and decreasing phagocytosis, which are functions of C-reactive protein in the immune response.

Association between TGFß1 polymorphisms and chronic hepatitis B infection in an Iranian population

Abstract INTRODUCTION: Transforming growth factor-beta 1 (TGFβ1) is a potent suppressive cytokine that contributes to chronic hepatitis B (CHB) infection. Disparities in TGFβ1 production among individuals have been attributed to TGFβ1 genetic polymorphisms. We examined whether three putative polymorphisms in TGFβ1[-509 C/T (rs1800469), +869 C/T (rs1800470), and +11929 C/T (rs1800472)]are associated with CHB infection in a South-Eastern Iranian population. METHODS: In total, 341 subjects were recruited, including 178 patients with CHB and 163 healthy individuals as controls. Genotyping of the three TGFβ1 SNPs was performed by tetra amplification refractory mutation system-PCR. RESULTS: TheTGFβ1 +869 TT vs.CC genotype in codominant (OR=0.445, p=0.012) and TT vs. TC+CC in the recessive (OR=0.439, p=0.003) model as well as the variant allele T vs. C(OR=0.714, p=0.038) were associated with lower CHB infection risk. However, the +11929 C/T polymorphism was associated with increased CHB risk, and the CT vs. CC genotype (OR=2.77, P=0.001) and T variant allele (OR=2.53, P=0.002) were risk factors for CHB. Furthermore, TTT (+869/-509/+11929) and CCC haplotypes were risk and protective factors for CHB, respectively. We found no significant association between viral DNA load and TGFβ1 genotype or hepatic enzyme levels (p >0.05). CONCLUSIONS: Results indicated that the TGFβ1+869TT genotype and T allele were protective factors, whereas the +11929 CT genotype and T allele were risk factors for CHB infection.

Circulating microRNA as a marker for predicting liver disease progression in patients with chronic hepatitis B

Abstract INTRODUCTION Hepatitis B virus (HBV) constitutes an important risk factor for cirrhosis and hepatocellular carcinoma (HCC). The link between circulating microRNAs and HBV has been previously reported, although not as a marker of liver disease progression in chronic hepatitis B (CHB). The aim of this study was to characterize miRNA expression profiles between CHB with and without cirrhosis or HCC. METHODS: A total of 12 subjects were recruited in this study. We employed an Affymetrix Gene Chip miRNA 3.0 Array to provide universal miRNA coverage. We compared microRNA expression profiles between CHB with and without cirrhosis/HCC to discover possible prognostic markers associated with the progression of CHB. RESULTS: Our results indicated 8 differently expressed microRNAs, of which miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, and miRNA-3200 were up-regulated, whereas miRNA-182 and miRNA-4485 were down-regulated in patients with CHB who progressed to cirrhosis/HCC as compared to those without progression. CONCLUSIONS: We demonstrated the differential expression of miRNA-935, miRNA-342, miRNA-339, miRNA-4508, miRNA-3615, miRNA-3200, miRNA-182, and miRNA-4485 between patients with HBV without cirrhosis/HCC and those who had progressed to these more severe conditions. These miRNAs may serve as novel and non-invasive prognostic markers for early detection of CHB-infected patients who are at risk of progression to cirrhosis and/or HCC.

Association of PRKAA1 gene polymorphisms with chronic hepatitis B virus infection in Chinese Han population

ABSTRACT Objective: Studies have indicated that AMPK play critical roles in the regulation of innate immunity and inflammatory responses. However, the role of the polymorphisms of PRKAA1 gene in immune-response to infectious organisms remains unknown. To evaluate the potential role of PRKAA1/AMPKα1 in the immune-response to HBV, we conducted this case-control study. Methods: We recruited 276 patients (145 men and 131 women; average age, 51.6 years) with chronic HBV infection (CHB) and 303 healthy controls (166 men and 137 women; average age, 54.2 years). All the subjects were unrelated individuals of Chinese Han Population. Three SNPs of PRKAA1gene were tested. Results: Rs1002424 polymorphism showed significant difference in the allele frequencies, but no difference in the genotype frequencies (allele: p = 0.039411, OR95%CI = 0.783479 [0.621067-0.988362]; genotype: p = 0.104758); rs13361707 polymorphism showed significance in allele analysis, but not in genotype analysis (allele: p = 0.034749, OR95%CI = 1.284303 [1.017958-1.620335]; genotype: p = 0.098027); rs3792822 polymorphism was demonstrated to have significant differences in both genotype and allele frequencies between cases and controls (allele: p = 0.029286, OR95%CI= 0.741519 [0.566439-0.970716]; genotype: p = 0.034560). The haplotype results showed that CTG and TCA in the rs13361707-rs1002424-rs3792822 block were significantly associated with the happening of HBV (CTG: p = 0.036854, OR95%CI = 1.281 [1.015-1.617]; p = 0.030841, OR95%CI = 0.743 [0.568-0.973]). Conclusion: These findings suggest that PRKAA1 polymorphisms may contribute to the susceptibility of chronic HBV infection in Chinese Han origin.

Mutations in the S gene and in the overlapping reverse transcriptase region in chronic hepatitis B Chinese patients with coexistence of HBsAg and anti-HBs

Abstract Background The mechanism underlying the coexistence of hepatitis B surface antigen and antibodies to HBsAg in chronic hepatitis B patients remains unknown. Aims This research aimed to determine the clinical and virological features of the rare pattern. Methods A total of 32 chronic hepatitis B patients infected by HBV genotype C were included: 15 carrying both HBsAg and anti-HBs (group I) and 17 solely positive for HBsAg (group II). S gene and reverse transcriptase region sequences were amplified, sequenced and compared with the reference sequences. Results The amino acid variability within major hydrophilic region, especially the “a” determinant region, and within reverse transcriptase for regions overlapping the major hydrophilic region in group I is significantly higher than those in group II. Mutation sI126S/T within the “a” determinant was the most frequent change, and only patients from group I had the sQ129R, sG130N, sF134I, sG145R amino acid changes, which are known to alter immunogenicity. Conclusions In chronic patients, the concurrent HBsAg/anti-HBs serological profile is associated with an increased aa variability in several key areas of HBV genome. Additional research on these genetic mutants are needed to clarify their biological significance for viral persistence.

Cuidados em saúde entre portadores de diabetes mellitus autorreferido no Brasil, Pesquisa Nacional de Saúde, 2013 / Health care among adults with self-reported diabetes mellitus in Brazil, National Health Survey, 2013

Resumo: Objetivo: Descrever medidas do cuidado assistencial destinadas ao paciente com diabetes mellitus autorreferido no Brasil. Métodos: Foram utilizados dados da Pesquisa Nacional de Saúde(2013), estudo transversal de base populacional, referentes ao cuidado em saúde com o diabetes mellitus autorreferido, quanto ao uso de serviços de saúde e acesso a medicamentos. Resultados: A prevalência de diabetes mellitus autorreferido foi de 6,2%, e 11,5% da população nunca fez uma glicemia na vida. Dos adultos que referiram diabetes mellitus , 80,2% tomaram medicamentos nas duas semanas anteriores à entrevista, 57,4% usaram o Programa Farmácia Popular, 73,2% receberam assistência médica e 47,1% realizaram o atendimento nas Unidades Básicas de Saúde. Em 65,2%, o médico que atendeu na última consulta era o mesmo das consultas anteriores, 95,3% dos pacientes conseguiram realizar os exames complementares solicitados e 83,3% conseguiram fazer as consultas com o médico especialista. A avaliação de pés e olhos foi relatada por 35,6 e 29,1% dos portadores de diabetes mellitus , respectivamente. Relataram internação hospitalar por causa do diabetes ou de alguma complicação 13,4% dos adultos, e outros 7,0% relataram limitações nas atividades diárias. Em geral, mulheres, assim como a população mais idosa, de maior escolaridade, brancos e residentes nas regiões Sul e Sudeste, tiveram maior prevalência da doença e maior acesso aos serviços, medicamentos e consultas. Discussão: Os cuidados aos portadores de diabetes foram recebidos de forma adequada, na maioria dos casos, o que é essencial para manter a qualidade de vida dos pacientes e prevenir desfechos mais graves.

Abstract: Objective: To describe the care measurements provided to patients with self-reported diabetes mellitus in Brazil. Methods: Data from the Brazilian National Health Survey (2013) were used. This is a cross-sectional population-based study in which the subjects with self-reported diabetes mellitus answered questions concerning their use of health services and access to medicine. Results: The prevalence of self-reported diabetes mellitus was 6.2%, while 11.5% of the population had never undergone a glucose testing. From the adults with diabetes mellitus, 80.2% had taken medications two weeks before the interview, 57.4% used the Popular Pharmacy Program, 73.2% received medical care, and 47.1% were cared for in the Health Basic Units. In 65.2%, the physician who cared for them in the last appointment was the same from previous ones, 95.3% of the patients were able to perform the required complementary examinations, and 83.3% could go to the appointments with a specialist. About 35.6 and 29.1% of the subjects with diabetes mellitus reported feet and eyes examination, respectively. About 13.4% declared previous hospitalization owing to diabetes or any complications, and 7.0% mentioned limitations in their daily activities owing to the disease. In general, women and the elderly people, those with higher education levels, white, and those living in the south and southeastern regions showed a higher prevalence of the disease and greater access to services, medicine, and appointments. Discussion: The care reported by patients with diabetes, which is essential to maintain their quality of life and prevent serious outcomes, seemed, in most cases, to be adequate.

Toll-like receptor 3 gene polymorphisms are not associated with the risk of hepatitis B and hepatitis C virus infection

INTRODUCTION: The present study investigated the prevalence of two single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 3 (TLR3) gene in patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). METHODS: Samples collected from HCV (n = 74) and HBV (n = 35) carriers were subjected to quantitative real-time PCR (qPCR) to detect the presence of the SNPs rs5743305 and rs3775291 in TLR3 and to measure the following biomarkers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and prothrombin time (PT). A healthy control group was investigated and consisted of 299 HCV- and HBV-seronegative individuals. RESULTS: No significant differences in allele, genotype and haplotype frequencies were observed between the investigated groups, and no association was observed between the polymorphisms and histopathological results. Nevertheless, genotypes TA/AA (rs5743305) and GG (rs3775291) appear to be associated with higher levels of ALT (p<0.01), AST (p<0.05) and PT (p<0.05). In addition, genotypes TT (rs5743305; p<0.05) and GG (rs3775291; p<0.05) were associated with higher GGT levels. CONCLUSIONS: This genetic analysis revealed the absence of an association between the polymorphisms investigated and susceptibility to HBV and HCV infection; however, these polymorphisms might be associated with a greater degree of biliary damage during the course of HCV infection. .

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.

Genotypes of hepatitis B virus in central Anatolia, Kayseri, Turkey

To investigate the distribution of hepatitis B virus [HBV] genotypes among patients with chronic hepatitis B in Kayseri, Turkey. The study took place in the Department of Microbiology, Erciyes University, Kayseri, and Lontek Laboratory, Istanbul, Turkey, from January 2005 to October 2007. One hundred and ten patients with chronic hepatitis B were included in this study. Hepatitis B virus DNA in sera were investigated by using the real-time polymerase chain reaction. Viral DNA was extracted from 200 microL of serum using the QIA amp DNA min Elute kit [Qiagen, Hilden, Germany]. Reaction mixture was prepared by Fluorion HBV QNP 2.0 [lontek, Istanbul, Turkey]. Genotype D was detected in 107 of 110 [97.2%] patients, however, genotyping failed in 3 patients [2.7%]. No other genotypes were found. The vast majority of Turkish patients with chronic hepatitis B have genotype D

Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes

OBJECTIVES: Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection. METHODS: From 2003 to 2008, 155 myeloma patients were examined to determine their chronic hepatitis virus infection statuses using serologic tests for the hepatitis B (HBV) and C viruses (HCV). Clinical parameters and outcome variables were retrieved via a medical chart review. RESULTS: The estimated prevalences of chronic HBV and HCV infections were 11.0 percent (n = 17) and 9.0 percent (n = 14), respectively. The characteristics of patients who were hepatitis virus carriers and those who were not were similar. However, carrier patients had a higher prevalence of conventional cytogenetic abnormalities (64.3 percent vs. 25.0 percent). The cumulative incidences of grade 3-4 elevation of the level of alanine transaminase, 30.0 percent vs. 12.0 percent, and hyperbilirubinemia, 20.0 percent vs. 1.6 percent, were higher in carriers as well. In a Kaplan-Meier analysis, carrier patients had worse overall survival (median: 16.0 vs. 42.4 months). The prognostic value of carrier status was not statistically significant in the multivariate analysis, but an age of more than 65 years old, the presence of cytogenetic abnormalities, a beta-2-microglobulin level of more than 3.5 mg/L, and a serum creatinine level of more than 2 mg/ dL were independent factors associated with poor prognosis. CONCLUSION: Myeloma patients with chronic hepatitis virus infections might be a distinct subgroup, and close monitoring of hepatic adverse events should be mandatory.

Influence of Transforming Growth Factor-beta1 Gene Polymorphism at Codon 10 on the Development of Cirrhosis in Chronic Hepatitis B Virus Carriers

Transforming growth factor (TGF)-beta1 is a key cytokine producing extracellular matrix. We evaluated the effect of TGF-beta1 gene polymorphism at codon 10 on the development of cirrhosis in patients with chronic hepatitis B. One hundred seventy eight patients with chronic hepatitis (CH, n=57) or liver cirrhosis (LC, n=121), who had HBsAg and were over 50 yr old, were enrolled. The genotypes were determined by single strand conformation polymorphism. There were no significant differences in age and sex ratio between CH and LC groups. HBeAg positivity and detection rate of HBV DNA were higher in LC than in CH groups (P=0.055 and P=0.003, respectively). There were three types of TGF-beta1 gene polymorphism at codon 10: proline homozygous (P/P), proline/leucine heterozygous (P/L), and leucine homozygous (L/L) genotype. In CH group, the proportions of P/P, P/L, and L/L genotype were 32%, 51%, and 17%, respectively. In LC group, the proportions of those genotypes were 20%, 47%, and 33%, respectively. The L/L genotype was presented more frequently in LC than in CH groups (P=0.017). Multivariate logistic regression analysis confirms that detectable HBV DNA (odds ratio [OR]: 3.037, 95% confidence interval [CI]: 1.504-6.133, P=0.002) and L/L genotype (OR: 3.408, 95% CI: 1.279-9.085, P=0.014) are risk factors for cirrhosis.

Association of cytokine genetic polymorphism with hepatites B infection evolution in adult patients

The infection by the hepatitis B virus (HBV) has different forms of evolution, ranging from self-limited infection to chronic hepatic disease. The objective of this study was to evaluate the influence of cytokine genetic polymorphisms in the disease evolution. The patients were divided into two groups, one with chronic HBV (n = 30), and the other with self-limited infection (n = 41). The genotyping for TNF (-308), TGFB1 (+869, +915), IL-10 (1082, -819, and -592), IL-6 (-174), and IFNG (+874) was accomplished by the PCR-SSP (polymerase chain reaction with sequence specific primers technique using the One Lambda kit. Although no statistically significant differences were found between the groups, the combination of TNF -308GG and IFNG +874TA was found in a lower frequency in chronic patients than in individuals with self-limited infection (26.7 versus 46.3 percent; P = 0.079; OR = 0.40; IC95 percent = 0.14-1.11). In chronic patients with histological alterations it was not observed the genotype TGFB1+869 C/C, against 24.4 percent in the self limited infection group (100 versus 75.6 percent; P = 0.096; OR = 7.67; IC95 percent = 0.42-141.63). Further studies in other populations, and evaluation of a greater number of individuals could contribute for a better understanding of the cytokine genetic polymorphism influence in HBV infection evolution.

Lamivudina por tempo prolongado no tratamento da hepatite B crônica no estado de Mato Grosso / Long-term use of lamivudine for treating chronic hepatitis B in the State of Mato Grosso

Para avaliar resultados do tratamento da hepatite B crônica com lamivudina, 100mg ou 150mg diários, foram acompanhados 34 pacientes em um serviço em Cuiabá, Mato Grosso. Entre os 34, 21 (62 por cento), eram cirróticos e 24 (70 por cento) HBeAg positivos. Genótipo viral foi determinado em 18, sendo predominante o genótipo A (12). O acompanhamento teve mediana de 27 meses (7 a 64). Do total, 23 (67 por cento) apresentaram resposta bioquímica entre dois e 24 meses de tratamento. Dos 24 pacientes com positividade para o HBeAg, 13 (54 por cento) apresentaram negativação do HBeAg durante o acompanhamento. Entre os anti-HBe positivos, 70 por cento tiveram normalização das aminotransferases. Quatorze (41 por cento) não apresentaram resposta bioquímica ou sorológica de início ou apresentaram breakthrough. Em seis dos que não responderam, foram encontradas as mutações L180M e M204V. Quatro pacientes faleceram após pelo menos 21 meses de lamivudina e três cirróticos desenvolveram hepatocarcinoma após 24 meses. A partir do terceiro ano surgiram complicações, como hepatocarcinoma ou hemorragia digestiva. Os presentes achados sugerem que resposta precoce ao tratamento com lamivudina pode estar associada a um melhor controle da hepatite B crônica.

To assess the results from lamivudine treatment (100 mg or 150 mg) for chronic hepatitis B, 34 patients were followed at a clinic in Cuiabá, Mato Grosso, Central Brazil. Among them, 21 (62 percent) had liver cirrhosis and 24 (70 percent) were HBeAg-positive. The viral genotype was determined for 18 patients, among whom genotype A was the most prevalent (12). The median follow-up was 27 months (range from 7 to 64 months). Among the total, 23 (67 percent) presented a biochemical response after 2 to 24 months of treatment. Among the 24 HBeAg-positive subjects, 13 (54 percent) became HBeAg-negative during the follow-up. Among the anti-HBe-positive patients, 70 percent obtained normalization of aminotransferase levels. Fourteen (41 percent) did not present any initial biochemical or serological response or presented breakthrough. The L180M and M204V mutations were found in six of the non-responders. Four patients died after at least 21 months of lamivudine and three patients with liver cirrhosis developed liver cancer after 24 months. From the third year onwards, complications such as digestive system hemorrhage or liver cancer started to emerge. The present findings suggest that an early response to lamivudine treatment may be associated with better control over chronic hepatitis B.

Tumor necrosis factor-alpha gene promoter polymorphism in Iranian patients with chronic hepatitis B.

BACKGROUND: Clearance of hepatitis B virus (HBV) infection requires a good host immune response. Cytokines like tumor necrosis factor-alpha (TNF- alpha) may play a role in such immune response. Genetic changes in TNF-a gene promoter region are known to influence TNF- alpha expression. We therefore studied the role of one such mutation in chronic HBV infection. METHODS: Presence of -308 G/A polymorphism in the promoter region of TNF- alpha gene was looked for in 100 patients with chronic HBV infection, 91 subjects with spontaneously recovered HBV infection and 89 healthy controls, using a PCR-RFLP method. RESULTS: Variant alleles (A/A or A/G) were found in 22 of 100 (22%) patients with chronic HBV infection, 21 of 91 (23%) subjects with spontaneous HBV clearance and 14 of 89 (15.7%) control subjects (p=ns for inter-group comparisons). CONCLUSION: TNF- alpha promoter polymorphism -308A is common in Iranian population, but has no association with development of chronic HBV infection.

HLA class II genotyping in chronic hepatitis B infection.

OBJECTIVES: To analyze the role of HLA genotypes in persistence of chronic hepatitis B in Western India. METHODS: HLA genotyping for class II-DR was done in 26 subjects having chronic hepatitis B infection (HBsAg positive) and in 100 healthy controls. Statistics were done using Halden's modification of Woolf's formula. RESULT: Significant association of chronic hepatitis B infection was found for class II-DR antigens DRB1*15XX (57.6 vs. 25%) and DRB1*11XX (23 vs. 4%). DRB1*13XX (0 vs. 19%) was negatively associated with chronic hepatitis B infection. CONCLUSION: HLA phenotype, which varies with different regions, is one of the factors in persistence of hepatitis B infection. Our study supports negative association of DRB1*13XX to persistence of HBV. Also there may be role of DRB1*11XX and DRB1*15XX in persistence of HBV and development of chronic HBV hepatitis.

Association between interleukin 6 promoter variants and chronic hepatitis B progression

Interleukin 6 (IL6) plays an essential role in the regulation of immune response to chronic disease. In this study, the three known single nucleotide polymorphisms (SNPs) in the IL6 promoter region were genotyped in a large chronic hepatitis B cohort to evaluate the effects of IL6 promoter variants. The single base extension method was used for this genotyping. Haplotypes were constructed by the three SNPs in IL6. Allele frequencies were compared for; i) patients with chronic hepatitis (CH) and chronic carriers vs. chronic hepatis patients with clinical evidence of liver cirrhosis (LC) (i.e., portal hypertension), ii) cirrhotic patients with hepatocellular carcinoma (HCC) vs. without HCC by logistic regression, and iii) with respect to the time intervals from the onset of infection to HCC. Results were analyzed by Cox relative hazard analysis on the assumption that all the patients were infected during early infancy. The frequencies of each SNP were 0.002 (IL6-597 G>A), 0.25 (IL6-572 C>G) and 0.002 (IL6-174 G>C), respectively, in the Korean population (n = 1,046). No significant associations were detected between IL6-572 C>G and chronic hepatitis B outcome in this study; i.e., chronic hepatitis B outcome in this study; i.e., LC occurrence on CH (OR = 0.16-1.27, P = 0.13- 0.71) and HCC occurrence on LC (OR = 1.04-1.23, P = 0.89-0.60) of heterozygotes and homozygotes for G allele in referent comparison to homozygotes for common allele (C/C genotype), and time interval to HCC (RH = 0.67-1.00; P = 0.14-0.99). In conclusion, there appeared to be no significant associations between IL6 promoter variants and disease outcome in chronic hepatitis B.