Serum mannan-binding lectin in egyptian patients with chronic hepatitis C: its relation to disease progression and response to treatment

Background

Chronic hepatitis C virus (HCV) infection is a major worldwide public health problem. Egypt has the highest prevalence of adult HCV infection in the world, averaging 15%–25% in rural communities. Mannan-binding lectin (MBL) is a liver-derived pluripotent serum lectin that plays a role in the innate immune system of the host. It is an acute-phase protein that is involved in the activation of the classical complement pathway. MBL may play a defensive role in HCV infection.

Objectives

To investigate the relationship between MBL concentration and HCV infection in Egyptian patients suffering chronic hepatitis C.

Patients and Methods

Serum samples obtained from 35 Egyptian hepatitis C patients and 30 normal controls were assayed for MBL. MBL concentrations were correlated to disease characteristics and treatment response.

Results

Serum MBL was significantly higher in HCV patients than in controls, but no relationship was found between MBL concentration and disease progression in terms of hepatic fibrosis and inflammation. Responders to interferon (INF)-based therapy had significantly higher serum MBL than non-responders.

Conclusions

We found no association between serum MBL concentration and progression of HCV related liver disease. Responders to INF-based therapy had significantly higher serum MBL than non-responders.     

Mannose-Binding Lectin Polymorphisms in Patients with Hepatitis C Virus Infection

Background: Persistent infection with hepatitis C virus (HCV) leads to liver cirrhosis (LC) and often to liver cancer. Little is known about host factors that determine the variable natural history. Mannose-binding lectin (MBL) is an important constituent of the innate immune system. In white patients there is an association between codon 52 mutation of the MBL gene and persistent hepatitis B virus (HBV) infection. To determine whether MBL gene polymorphisms affect the course of HCV infection, we investigated the association between MBL gene polymorphisms and HCV infection in Japanese subjects. Methods: Fifty-two HCV-infected Japanese patients (8 with chronic inactive hepatitis (CIH), 31 with chronic active hepatitis (CAH), 13 with LC) and 50 normal controls were studied. MBL gene mutations were determined by means of polymerase chain reaction and restriction fragment length polymorphism analyses. Results: Codon 52 and codon 57 mutations were absent in all subjects. Homozygous mutation in codon 54 was present in one (0.9%) patient. Heterozygous codon 54 mutation was present in 17 (32%) of the 52 patients and in 21 (41%) of the controls. No significant difference in the frequency of codon 54 mutation was observed between patient and control groups. However, although no significant relationship was observed between MBL polymorphisms and the levels of HCV RNA, all patients with heterozygous or homozygous codon 54 mutations had CAH or LC. In contrast, 8 of the 34 patients without codon 54 mutation remained at CIH. (P = 0.0405). Conclusion: MBL may be one of the factors that influence the course of HCV infection.     

The Correlation of Il28B Genotype With Sustained Virologic Response In Romanian patients With Chronic Hepatitis C

Background

Multiple variables influencing the sustained virologic response (SVR) in chronic hepatitis C have been evaluated. One of them is genetic polymorphism near the IL28B gene.

Objectives

The aim of this study was to evaluate the influence of IL28B genotypes on SVR rates in a group of patients with chronic hepatitis C from the western part of Romania.

Patients and Methods

A retrospective study was performed in 107 consecutive patients, previously treated with standard-of-care medication for chronic hepatitis C, identified from the databases of 2 centers. Patient demographics, viral load before treatment and at 12, 24, and 72 weeks from the treatment start, and IL28B genotype were evaluated.

Results

Among the 107 patents in the study group, 54 patients had SVR (50.5%), and 62 (57.9%) showed a complete early virologic response (cEVR). The SVR rates according to IL28B genotype were as follows: 73.1% in patients with genotype C/C, 40.9% in those with genotype C/T, and 57.1% in those with genotype T/T (i.e., 73.1% among patients with the C/C genotype vs. 43.7% among those with non-C/C genotypes; P = 0.0126). The cEVR rates were 80.8% in patients with the C/C genotype vs. 51.2% in those with non-C/C genotypes (P = 0.011).

Conclusions

In our cohort of 107 Caucasian HCV patients, the SVR rate was 50.5% with standard-of-care treatment. The SVR rate was directly related to the IL28B genotype: 73.1% in the C/C genotype vs. 43.7% in non-C/C genotypes (P = 0.0126).     

The mannose‐binding lectin gene polymorphisms and systemic lupus erythematosus: Two case–control studies and a meta‐analysis

Objective

Mannose‐binding lectin (MBL) enhances opsonization and activates complement. Dysfunctional alleles of MBL have been associated with low plasma concentrations of MBL and increased risk of systemic lupus erythematosus (SLE), but genotyping studies have shown inconsistent results. We performed case–control studies of the MBL polymorphisms in 2 Caucasian cohorts and a meta‐analysis incorporating all published results of MBL genotyping in SLE to explore whether the MBL functional variants are associated with SLE.

Methods

MBL genotypes at 7 single‐nucleotide polymorphisms were sequenced in 96 European American patients with SLE and 96 age‐, race‐, and sex‐matched controls. MBL codons 52, 54, and 57 were genotyped in 285 German patients with SLE and 200 race‐matched controls. Allele frequencies of all known variants were tallied for meta‐analysis.

Results

Although there was a trend toward association with MBL polymorphisms in both patient cohorts evaluated, none of them was significantly associated with SLE on its own. Seventeen comparisons from 15 studies were included in the meta‐analysis. Publication bias was excluded by Egger's regression test (P = 0.14). The overall odds ratio for MBL codon 54 variant B was 1.406 (95% confidence interval 1.221–1.608; P < 0.001). Stratification by ethnicity showed significantly increased odds ratios for association of the MBL codon 54B variant with SLE in African, Asian, and Caucasian cohorts.

Conclusion

Meta‐analysis of all available studies on MBL polymorphisms and SLE shows that MBL variant alleles such as MBL exon 1 codon 54 B, promoter –550 L, and promoter –221 X are SLE risk factors. This association is robust and persists after incorporation of data from our 2 cohorts in which the association failed to reach significance.

     

Mannose-binding lectin polymorphisms in patients with hepatitis C virus infection

BACKGROUND: Persistent infection with hepatitis C virus (HCV) leads to liver cirrhosis (LC) and often to liver cancer. Little is known about host factors that determine the variable natural history. Mannose-binding lectin (MBL) is an important constituent of the innate immune system. In white patients there is an association between codon 52 mutation of the MBL gene and persistent hepatitis B virus (HBV) infection. To determine whether MBL gene polymorphisms affect the course of HCV infection, we investigated the association between MBL gene polymorphisms and HCV infection in Japanese subjects. METHODS: Fifty-two HCV-infected Japanese patients (8 with chronic inactive hepatitis (CIH), 31 with chronic active hepatitis (CAH), 13 with LC) and 50 normal controls were studied. MBL gene mutations were determined by means of polymerase chain reaction and restriction fragment length polymorphism analyses. RESULTS: Codon 52 and codon 57 mutations were absent in all subjects. Homozygous mutation in codon 54 was present in one (0.9%) patient. Heterozygous codon 54 mutation was present in 17 (32%) of the 52 patients and in 21 (41%) of the controls. No significant difference in the frequency of codon 54 mutation was observed between patient and control groups. However, although no significant relationship was observed between MBL polymorphisms and the levels of HCV RNA, all patients with heterozygous or homozygous codon 54 mutations had CAH or LC. In contrast, 8 of the 34 patients without codon 54 mutation remained at CIH. (P = 0.0405). CONCLUSION: MBL may be one of the factors that influence the course of HCV infection.     

Mannose binding lectin gene mutations are associated with progression of liver disease in chronic hepatitis B infection

Mannose-binding lectin (MBL) plays an important role in immune defense. We examined the MBL gene mutations and MBL levels in Chinese hepatitis B and hepatitis C patients with and without symptomatic cirrhosis. We recruited 190 hepatitis B and C patients, and 117 normal Chinese as controls. Serum MBL levels were measured by enzyme-linked immunosorbent assay. MBL gene mutation at codons 52, 54, and 57 was detected by polymerase chain reaction (PCR) assay. In asymptomatic hepatitis B and C patients, there was no increase in codons 52, 54, and 57 mutation, but the MBL levels were significantly lower than those in the controls. Codon 54 mutation rate was increased to 44.4% (P =.007) in symptomatic hepatitis B cirrhosis and 64.3% (P =.0026) in patients with spontaneous bacterial peritonitis (SBP). There was no increase in codon 54 mutation rate in hepatitis B-related hepatocellular carcinoma (HCC). In chronic hepatitis B infection, the odds ratio for an individual with codon 54 mutation to develop cirrhosis was 1.84 (95% CI: 1.21-2. 81) and to develop SBP was 4.58 (95% CI: 1.73-12.16). Chronic hepatitis B and hepatitis C infection lowered the MBL levels, probably by suppressing MBL production. Codon 54 mutation of MBL was associated with progression of disease in chronic hepatitis B infection.     

Investigation of Transforming Growth Factor-β1 Gene Polymorphisms Among Iranian Patients With Chronic Hepatitis C

Background

Chronic hepatitis C infection is caused by the hepatitis C virus (HCV), and its clinical complications include liver cirrhosis, liver failure, and hepatocellular carcinoma.Transforming growth factor-β1 (TGF-β1) is an important cytokine in cell growthand differentiation, angiogenesis, extracellular matrix formation, immune responseregulation, and cancer development and progression.

Objectives

The aim of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in TGF-β1 and chronic HCV infection among patients referred to the Taleghani Hospital, Tehran, Iran between 2008 and 2010.

Patients and Methods

In this case-control study, samples were collected using a convenience sampling method. We genotyped 164 HCV patients and 169 healthy controls for 3 SNPs in the TGF-β1 gene (-509 promoter, codon 10, and codon 25). We determined the SNP genotypes by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. To confirm the PCR-RFLP genotyping results, 10% of the samples were re-genotyped using a direct sequencing method.

Results

There were no significant differences in the allelic frequency distribution of SNPs at -509 C/T, +869 C/T, or +915 G/C between HCV patients and the healthy controls. Genotyping results for all three polymorphic sites were similar with no statistically significant differences between the groups.

Conclusions

Most of the Iranian patients (over 85%), both healthy controls and HCV patients, had the GG genotype at the +915 G/C position, resulting in a high level of TGF-β1 production. Therefore, we concluded that the SNPs investigated by us cannot be considered as prognostic factors for HCV infection in our population, despite being reported as prognostic markers in other populations. Moreover, there is a possibility that most of the population is susceptible to HCV infection.     

The influence of human leukocyte antigen and IL-10 gene polymorphisms on hepatitis B virus outcome

Context

The clinical outcome of hepatitis B virus (HBV) infection is variable, ranging from spontaneous recovery to an inactive carrier state, chronic hepatitis, occult HBV infection, liver cirrhosis, or hepatocellular carcinoma.

Evidence Acquisition

This variable pattern and clinical outcomes of the infection were mainly determined by virological and host genetic factors. Since the most of host genetic factors associated with HBV infection have currently focused on human leukocyte antigen (HLA) associations and interleukin (IL)-10 gene polymorphisms, this review focuses on the recent progresses in these issues to provide prognostic markers for the outcome of HBV infection.

Results

A study on serum levels of IL-10 in occult HBV infected patients reported that the higher level of IL-10 production may suppress function of the immune system against HBV in patients with occult HBV infection. IL-10 promoter polymorphism at position -592 is associated with susceptibility to occult HBV infection.

Conclusions

Findings of this study suggest that the host HLA polymorphism is an important factor in determining outcome of HBV infection but regarding IL-10 gene promoter polymorphisms, we are still have a long way to achieve a definite conclusion.     

G1896A Precore Mutation and Association With HBeAg Status,Genotype and Clinical Status in Patients With Chronic Hepatitis B

Background:

Precore stop codon (G1896A) mutation is one of the commonest mutations found in patients with chronic hepatitis B. However, over the years, this mutation was not reported much in Malaysia.

Objectives:

We therefore investigated the presence of G1896A mutation in Malaysian population and its association with HBeAg status, clinical stage, hepatitis B virus (HBV) genotype and e-seroconversion rate.

Patients and Methods:

Serum samples from 93 patients confirmed as hepatitis B carriers were collected for molecular assay. The whole genome of HBV was amplified by polymerase chain reaction and directly sequenced. The precore and basal core promoter regions were analyzed for presence of mutations.

Results:

The most commonly observed mutation in the precore region was C1858T with 64.5% prevalence. The precore mutation of interest (G1896A) was identified in 25.8% of isolates. The basal core promoter mutations detected were A1762T-G1764A (26.9%), C1653T (8.6%), A1752G (10.8%) and C1766T (2.2%). No significant association was observed between G1896A mutation and HBeAg-negativity. Nonetheless, G1896A was highly prevalent among HBV genotype B. Clinical association revealed that subjects with G1896A mutations were mainly detected in asymptomatic chronic hepatitis B (58.3%) and liver cirrhosis (41.7%). One subject was diagnosed with fulminant hepatitis (4.2%) and 8.3% had hepatocellular carcinoma (HCC).

Conclusions:

Our data suggested an intermediate prevalence of G1896A mutation among Malaysian hepatitis B carriers. The stop codon mutation has a significant association with genotype B and patients with chronic hepatitis B and liver cirrhosis.     

Lack of Association Between Transforming Growth Factor Beta 1 -509C/T and +915G/C Polymorphisms and Chronic Hepatitis B in Iranian Patients

Background:

Chronic hepatitis B is one of the world''s major health concern. The etiological agent of this infection is hepatitis B virus (HBV), which can evade the immune system response. Transforming growth factor beta 1 (TGF-β1) can act against HBV by suppressing the viral replication. The TGF-β1 also plays an important role in preventing liver damage in chronically HBV infected patients.

Objectives:

In this study, the association of TGF-β1 +915G/C and -509C/T gene polymorphisms with chronic hepatitis B was evaluated in Iranian patients.

Materials and Methods:

A population-based case–control study was conducted in Taleghani Hospital, Tehran. A number of 220 patients with chronic hepatitis B and the same number of healthy control subjects were designated the case and the control groups. The PCR-Restriction Fragment Length Polymorphism Method (PCR-RFLP) method was used for genotyping both polymorphisms. Ten percent of the control samples were sequenced to confirm the results.

Results:

No statically significant differences in genotype distribution and allele frequency were observed for both polymorphisms between healthy controls and patients with chronic hepatitis B.

Conclusions:

There was no association between TGF-β1 -509C/T and +915G/C polymorphisms with chronic hepatitis B and it seems that these changes don not play a significant role in increasing the risk of chronic infection in Iranian patients.     

Impact of the IL-10 Promoter Gene Polymorphisms in the Severity of Chronic Hepatitis B Infection

Background:

Interleukin-10 (IL-10) is an important anti-inflammatory cytokine. The polymorphisms of its promoter gene have been considered to be related with the chronicity of hepatitis B infection.

Objectives:

The aim of this study was to evaluate the polymorphisms at different positions in the IL-10 promoter gene in patients with chronic hepatitis B.

Patients and Methods:

Totally, 166 patients with chronic hepatitis B infection were enrolled. Genotypes at different positions (i.e. -819, - 592, and - 1082) in the IL-10 gene promoter were determined.

Results:

The C/A genotype at position -592, C/T genotype at position -819, and GCC/ATA haplotype of the IL-10 gene promoter were significantly more common in the patients with cirrhosis. The genotypes were significantly different between the hepatitis B e antigen (HBeAg)-negative and HBeAg-positive patients at position -592 (C/A and C/C), position -819 (C/C and C/T), and position -1082 (A/A and G/A).

Conclusions:

Some IL-10 promoter gene polymorphisms predisposed the infected hepatitis B virus cases to cirrhosis in our study population.     

Frequency of HIV and HCV Co-Infections in Chronic HBV Patients Referred to Taleghani Hospital, Tehran, Iran from 2006 to 2010

Background

Co-infection with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) in patients with chronic hepatitis B virus (HBV) infection can alter the course of the disease.

Objectives

In this study, we investigated the frequency of HIV and/or HCV co-infection in chronic HBV patients and related risk factors in acquiring the HCV and or HIV co-infectionit.

Patients and Methods

We studied 264 chronic HBV patients who visited the Gastrointestinal and Liver Ward of the Taleghani Hospital, Tehran, Iran between 2006 and 2010. Demographic information and records of possible risky behavior were obtained. Antibodies against HBV, HCV, and HIV, levels of alanine transaminase (ALT) and aspartate transaminase (AST), and conversion from hepatitis B e antigen (HBeAg) to hepatitis B e antibody (HBeAb) were evaluated.

Results

Of 264 patients with chronic HBV in this study, 184 patients (70%) were men and 78 patients (30%) were women. Only 1 patient (0.37%) was positive for anti-HIV antibody, whereas 12 patients (4.54%) were positive for anti-HCV antibody. None of the patients had co-infection with all 3 viruses (HBV, HIV, and HCV).

Conclusions

This study demonstrated that the prevalence of HCV is higher than that of HIV in chronic HBV patients. Since HCV or HIV co-infection affects the therapeutic outcome in chronic HBV patients, testing for HIV and HCV is recommended, especially for patients with a history of risky behavior.     

Distribution and risk factors of hepatitis B virus infection in the general population of Central Iran

Background

Hepatitis B is the most common chronic viral infection in humans and the most common cause of death among viral hepatitis. As 70% to 80% of chronic hepatitis cases are caused by HBV in Iran, this virus alone is considered the most important cause of liver diseases and the major cause of mortality arising from viral hepatitis cases in Iran.

Objectives

We planned this study to determine the prevalence of hepatitis B in the general population of Qom, central Iran.

Patients and Methods

The present study is a cross-sectional study. A total of 3690 samples were collected from 7 rural clusters and 116 urban clusters. Ten teams, each consisting of 2 trained members, were assigned to conduct the sampling and fill the questionnaires. The data were analyzed using SPSS.

Results

The prevalence rate of hepatitis B infection in Qom Province was 1.3%. The mean age of the patients with hepatitis B was 44.17 years. The prevalence of hepatitis B was 1.6% in men and 1.1% in women. Moreover, the prevalence of hepatitis B correlated positively with age, tattooing, and literacy level.

Conclusions

The prevalence rate of hepatitis B in Qom is 1.3%. It is possible to prevent the disease by increasing public awareness. Further investigation on clinical presentations and a determination of the genotype of the virus are suggested.     

Association of Plasminogen Activator Inhibitor-1 Gene Polymorphism with Inflammatory Bowel Disease in Iranian Azeri Turkish Patients

Background/Aim:

Previous studies have shown the association of some genetic factors, such as Plasminogen activator inhibitor type-1 (PAI-1) 4G/5G polymorphism, with the development of inflammatory bowel disease (IBD). We aimed to study this polymorphism as a risk factor in IBD patients in this cohort.

Patients and Methods:

One hundred and fifteen IBD patients and 95 healthy controls were selected from Iranian Azeri Turks and -6754G/5G polymorphism of PAI-1 gene was tested by polymerase chain reaction using allele-specific primers confirmed by sequencing.

Results:

There was no significant difference of PAI-1 polymorphism between IBD patients and the control group (P > 0.05). Furthermore, these data showed no significant difference between Crohn''s disease and ulcerative colitis patients. However, 4G/4G homozygotes have reduced probability to progression of loss of appetite, whereas 5G/5G genotypes have increased risk for development of chronic diarrhea without blood, nausea, and loss of appetite.

Conclusions:

Although our study showed no significant association of PAI-1 polymorphism between patients and control group, the carriers of 4G/4G genotype and 4G allele had reduced risk for the progression of IBD features in this cohort.     

Hepatitis B Virus Genotype B and High Expression of Interferon Alpha Receptor β Subunit are Associated With Better Response to Pegylated Interferon Alpha 2a in Chinese Patients With Chronic Hepatitis B Infection

Background

Hepatitis B virus (HBV) is one of leading causes of various hepatic diseases including acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hundreds of million people worldwide are infected by HBV, chronically.

Objectives

This study in conducted to investigate the influence of Hepatitis B virus (HBV) genotypes and type I IFN-αreceptor β subunit (IFNAR2) expression in liver on response to treatment with pegylated IFN-α-2a (Peg-IFN-α-2a) for chronic hepatitis B infection.

Patients and Methods

In this study, 65 eligible patients with chronic hepatitis B disease were enrolled. HBV genotypes of these patients were analyzed by using PCR-RFLP of the surface gene of HBV. The expression of IFNAR2 in the liver was immune histochemically investigated using anti-IFNAR2 antibody. All immune histochemical slides were read semi-quantitatively by image analysis. Chronic hepatitis B patients were treated with Peg-IFN-α2a therapy for a 48-week period and followed up for 24 weeks. Baseline characteristics and sustained viral response (SVR) to Peg-IFN-α-2a therapy were evaluated.

Results

55 % of patients exhibited HBV genotype B and 31.7 % patients exhibited HBV genotypes C infections. After treatment with Peg-IFN-α-2a, SVR was achieved in 66.7 % of patients with HBV genotype B and in 26.3 % of patients with HBV genotype C (P = 0.009). Semiquantitative and the image analysis indicated by gray level values revealed a higher IFNAR2 expression in the group with severe inflammation (P < 0.001). Patients’ high IFNAR2 protein expression had a significant impact on SVR to Peg-IFN-α-2a therapy (P = 0.028).

Conclusions

HBV genotype B and high expression of IFNAR2 in the liver of chronic hepatitis B patients are closely associated with better response to Peg-IFN-α-2a therapy in chronic hepatitis B disease.     

The Role of Interleukin-28b Gene Polymorphisms in Chinese Patients With Chronic Hepatitis C Treated With Pegylated Interferon and Ribavirin

Background:

Interleukin-28B (IL28B) single nucleotide polymorphism (SNP) rs8099917 has been described to be associated with response to treatment with pegylated interferon and ribavirin (PEG-IFN/RBV) in patients with chronic hepatitis C from the North America, Europe, Asia countries like Japan and Taiwan. Whether this holds true for Chinese patients remains unknown.

Objectives:

We aimed to study the effects of IL28B rs8099917 on antiviral therapy responses in Chinese patients with hepatitis C.

Patients and Methods:

IL28B rs8099917 was genotyped in 263 patients with hepatitis C virus (HCV) infection and 244 healthy controls in Tianjin, China using TaqMan SNP genotyping method. The roles of rs8099917 and clinical characteristics in antiviral treatment were analyzed by logistic regression.

Results:

Among 263 patients with chronic HCV infection, 223 had a TT genotype (84.8%). Frequencies of TG/GG genotypes in patients with hepatitis C were significantly different from those of healthy controls (15.2% vs. 9.0%; P = 0.033). Patients with HCV infection had a higher G allele frequency than healthy controls (7.8% vs. 4.7%; P = 0.044). Univariate analysis revealed no significant association between rs8099917 and sustained virological response (SVR) (P = 0.612). However, it was found that HCV genotypes 2a/3a, age, prothrombin time (PT), albumin (ALB) and cholesterol (CHO) were associated with SVR. In multivariate analysis, only ALB was significantly an independent predictor of SVR (OR = 1.223; 95%CI: 1.046−1.430; P = 0.011).

Conclusions:

In contrast with T, rs8099917 G is a susceptible allele to HCV in China. ALB can independently predict SVR. Rs8099917 may play a quiet role to predict treatment response of patients with hepatitis C who received PEG−IFN/RBV therapy in China.     

Distribution of IL28B Genotypes in Iranian Patients with Chronic Hepatitis C and Healthy Individuals

Background

IL28B polymorphism is recognized as one of the most prominent predictors of hepatitis C spontaneous and treatment-induced clearance. Interestingly, the favorable genotypes of IL28B are found to be more frequent in Asian ethnicity than Caucasian and African populations, respectively. A few studies reported that there is a mysterious association between the IL28B polymorphism and the hepatitis C virus (HCV) genotype in patients with chronic hepatitis C but they did not give any reason for this phenomenon.

Objectives

The foremost purpose of this study was to compare the distribution of IL28B genotypes between Iranian healthy individuals and patients with chronic hepatitis C.

Patients and Methods

In this study, 921 patients with chronic hepatitis C and 142 healthy individuals were included. The IL28B rs12979860 and rs8099917 polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results

The frequency of IL28B rs12979860 CC, CT, and TT genotypes in chronic hepatitis C patients was 38%, 48.8%, and 13.2% and in healthy individuals was 43.7%, 48.6%, and 7.7%. Also, the frequency of IL28B rs8099917 TT, GT, and GG genotypes in chronic hepatitis C patients was 58.3%, 37.1%, and 4.6% and in healthy individuals was 64.1%, 32.4% and 3.5%. The differences in the distribution of IL28B rs12979860 and rs8099917 genotypes between patients with chronic hepatitis C and healthy individuals were not statistically significant. When we compared the distribution of IL28B genotypes between the healthy group and the HCV infected patients by HCV genotype, we found 9.8% higher frequency of rs12979860 CC genotype in the healthy individuals than HCV genotype 1 infected patients (P = 0.03) however there was no significant difference in the distribution of rs12979860 genotypes between the healthy and HCV genotype 3 infected groups (P = 0.46).

Conclusions

It seems that the impact of IL28B polymorphism on the spontaneous clearance of HCV genotype 1 is more prominent than HCV genotype 3 which results in the observation of higher rs12979860 C allele frequency in chronic hepatitis C patients with HCV genotype 3 than HCV genotype 1.     

Heme oxygenase-1 mRNA expression in egyptian patients with chronic liver disease

Background

Chronic liver disease (CLD) is a global medical problem. This disease is associated with increased hepatic oxidative stress. One of the antioxidant enzymes that protect cells against this stress is heme oxygenase-1 (HO-1).

Objectives

This study aimed to investigate the mRNA expression of HO-1 in Egyptian patients with CLD and its relation to oxidative stress biomarkers.

Patients and Methods

Levels of serum ferritin, carboxyhemoglobin, malondialdehyde (MDA), and erythrocyte-reduced glutathione (GSH) were measured, and HO-1 mRNA expression was detected in 45 CLD patients (15 with nonalcoholic steatohepatitis [NASH], 15 with chronic hepatitis C, and 15 with liver cirrhosis) and 15 healthy controls.

Results

HO-1 mRNA expression was increased in patients with NASH, chronic hepatitis C, and liver cirrhosis compared to controls. The expression in cirrhotic patients was significantly higher than that in patients with NASH and chronic hepatitis C. Compared to controls, patients with NASH, chronic hepatitis C, and liver cirrhosis had higher levels of ferritin, carboxyhemoglobin, and MDA and lower levels of GSH. HO-1 mRNA expression was positively correlated with levels of carboxyhemoglobin, serum ferritin, and serum MDA and negatively correlated with levels of erythrocyte GSH in CLD patients.

Conclusions

HO-1 mRNA expression was significantly increased in CLD patients, and the increase reflected the severity of the disease. The significant relationship between the increased HO-1 expression and oxidative stress biomarkers in patients with CLD suggests that HO-1 may play an important role in protecting the liver from oxidative stress-dependent damage. Therefore, induction of HO-1 could be a novel therapeutic option for CLD.     

Prognostic Significance of Serum Galectin-3 Levels in Patients with Hepatocellular Cancer and Chronic Viral Hepatitis

Background/Aim:

Galectins affect diverse physiological and pathophysiological processes such as development, inflammation, and tumor growth. We aimed to compare serum galectin-3 levels in three patient groups with chronic hepatitis B and C virus (HBV, HCV), cirrhosis secondary to HBV or HCV, and hepatocellular carcinoma (HCC) secondary to HBV or HCV and evaluate the role of galectin-3 during HCC progression.

Patients and Methods:

Nineteen patients with hepatocellular cancer, 22 patients with cirrhosis, and 24 patients with chronic hepatitis B and C were included in this study. Serum galectin-3 levels in different liver diseases were assessed by enzyme-linked immunosorbent assay.

Results:

The mean galectin-3 levels were 4.61 ng/mL (±2.32) in HCC patients, 5.68 ng/mL (±2,2) in cirrhotic patients, 1.98 ng/mL (±1.50) in chronic viral hepatitis group. There were no statistical differences between HCC and cirrhotic patients (P = 0.5), but lower in chronic hepatitis group statistically compared with cirrhosis and HCC (P < 0.001, P = 0.002, respectively). In case of cirrhotic patients, galectin-3 levels were significantly higher in patients with cirrhosis secondary to HCV compared with HBV (P = 0.03). When we evaluated galectin-3 levels in HCC patients, it was found to be 3.92 ng/mL in HCC secondary to hepatitis B and 5.37 ng/mL in HCC secondary to hepatitis C.

Conclusion:

Serum galectin-3 levels in patients with chronic HBV or HCV may guide us about progression to cirrhosis or HCC and prognosis of the disease. Especially, galectin-3 levels may be more pronounced in case of HCV.     

Development and Validation of a Simple, Rapid and Inexpensive PCR-RFLP Method for Genotyping of Common IL28B Polymorphisms: A Useful Pharmacogenetic Tool for Prediction of Hepatitis C Treatment Response

Background

In 2009, 3 genome-wide association studies implicated IL28B single-nucleotide polymorphisms (SNPs) as the strongest genetic pretreatment predictor of sustained virological response (SVR) in hepatitis C infection. Recently, the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) included IL28B testing in their guidelines.

Objectives

The main aim of this study was to develop and validate a simple, rapid, and inexpensive polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for genotyping of common IL28B polymorphisms (rs12979860 and rs8099917).

Patients and Methods

Two methods were developed to genotype common IL28B polymorphisms: 1) PCR-sequencing as a reference method and 2) PCR-RFLP as a rapid and inexpensive method. Both polymorphisms were genotyped in 104 Iranian hepatitis C patients by both methods simultaneously. To validate the PCR-RFLP method, the PCR-RFLP genotyping results should be 100% concordant with the PCR-sequencing results.

Results

Genotyping of rs12979860 and rs8099917 by PCR-RFLP was concordant with PCR-sequencing in 104 (100%) individuals. The analytical sensitivity and specificity of the PCR-RFLP method for genotyping of both SNPs are 100%. Among these 104 patients with chronic hepatitis C, the frequency of the rs12979860 CC, CT and TT genotypes were 40.4%, 47.1% and 12.5% and the frequency of the rs8099917 TT, GT and GG genotypes were 59.6%, 35.6% and 4.8%, respectively. Also, three IL28B haplotypes (rs12979860-rs8099917) were found among our patients including C-T, T-G and T-T with 63.9%, 22.6% and 13.5% frequency, respectively. C-G haplotype was absent in all of our patients.

Conclusions

We have developed a validated, fast, and simple PCR-RFLP method for genotyping of common IL28B SNPs that is more cost-effective than sequencing.