Prospective study of BK virus infection and nephropathy during the first year after kidney transplantation.

INTRODUCTION: The aim of this study was to assess the prevalence and severity of BK virus infection, BK virus nephritis, and related risk factors among kidney transplant recipients. MATERIALS AND METHODS: BK viremia during the first year of kidney transplantation was assessed prospectively in 32 successive recipients. BK virus DNA was extracted and determined in all samples by real-time polymerase reaction assay for 1 year after kidney transplantation. RESULTS: The mean age of the patients was 33.3 ± 15.3 years. Sixteen patients (50%) received antithymocyte globulin for induction therapy. Living donor transplant consisted of 75% of the kidney donations. Maintenance immunosuppressive therapy included cyclosporine A in 27 patients (84.4%), plus tapering prednisolone and mycophenolate mofetil. BK viremia was detected in 8 patients (25%). The highest detected plasma viral load was less than 4000 copies per milliliter. BK virus was respectively positive in 5 (62.5%), 2 (25%), and 1 (12.5%) patients during the first 4, 8, and 12 months after transplantation. Biopsy-proven rejection and antirejection therapy by methylprednisolone pulses were 5 and 2.3 times more common in patients with BK virus infection (P = .01 and P = .01), respectively. CONCLUSIONS: Despite occurrence of BK virus infection in 25% of our patients, BK nephropathy did not develop in any of them. Routine screening of BK virus infection, particularly in centers with low prevalence of BK virus nephritis, may not be cost effective for predicting this disease.

Prevalence of hepatitis delta virus (HDV) infection in chronic hepatitis B patients with unusual clinical pictures.

BACKGROUND: Probably 5% of the HBV carriers have HDV super infection. The risk of fulminant hepatitis, cirrhosis and hepatocellular carcinoma is higher in superinfection than the settings when HBV is alone. OBJECTIVES: The aim of this study was to evaluate the prevalence of HDV in Iranian HBV isolates and to compare their clinical and virological pictures as well as their HDV genetic variations with other worldwide isolates. PATIENTS AND METHODS: 81 carriers with positive results for HBsAg with upper limit ranges of ALT and low or undetectable levels of HBV viral load who did not respond to HBV therapy were selected. After RT amplification of HDV Delta antigen, direct sequencing and phylogenetic study were performed to explore the genotype(s) and nucleotide/amino acid variations. RESULTS: 12 (14.8%) patients had positive results for both HDV RNA and anti-HDV. The mean ALT level was higher in HDV positive patients (75.9 U/ML) than HBV-mono-infected individuals; however, the mean HBV viral load was lower in coinfected patients than HBV-mono-infected patients. Phylogenetically, genotype I was the only detected genotype, and the most closely related isolates were of Turkish, Italian and Mongolian origin. Within the delta Ag, there were 326 nucleotide mutations, of which 111 and 215 were silent and missense, respectively. The total number of amino acid substitution was 148; most were located in known functional/epitopic domains. There was no correlation between the numbers of amino acid mutations, with clinical, virological status of the patients. CONCLUSIONS: HDV should be suspected in HBV carriers with unusual clinical and virological pictures. Relatedness of Iranian HDV isolates to Italian and Turkish sequences proposed a common Caucasian origin for the distribution of HDV genotype I in this ethnic group.

Hepatitis B virus surface antigen (HBsAg) mutations are rare but clustered in immune epitopes in chronic carriers from Sistan-Balouchestan Province, Iran.

BACKGROUND: Hepatitis B virus (HBV) gene and protein variations have frequently been observed in chronic patients. The aims of this study were to determine the genotypes as well as the patterns of HBsAg variations in chronically-infected patients from the south-eastern part of Iran. METHODS: Twenty- one chronic inactive HBV carriers from Sistan-Balouchestan Province (an area with a low prevalence of HBV complications such as cirrhosis and hepatocellular carcinoma [HCC]) were enrolled. The surface genes were amplified, sequenced, and subsequently aligned using international and national Iranian database. RESULTS: All strains belonged to genotype D, subgenotype D1, and subtype ayw2. Of all 39 mutations occurred at 31 nucleotide positions, 15 (38.5%) were missense (amino acid altering) and 24 (61.5%) were silent (no amino acid changing). At the amino acid level, 15 substitutions occurred; 10 (66.67%) were distributed in different immune epitopes, five of which (33.33%) were in B cell epitopes; four (36.27%) were distributed in T helper epitopes, and one (6.67%) occurred inside CTL epitopes. CONCLUSION: A narrowly-focused immune pressure has been on the surface proteins, especially at the B cell level, led to the emergence of escape mutants in these patients that might be related to the pathogenicity of HBV chronic infection. Also, due to the negative selection imposed on HBV genome and the uniqueness of genotype D in this ethnic group, complications (cirrhosis and HCC) are lower than other published studies.

Drug-related mutational patterns in hepatitis B virus (HBV) reverse transcriptase proteins from Iranian treatment-naïve chronic HBV patients.

BACKGROUND: Immunomodulators and Nucleotide analogues have been used globally for the dealing of chronic hepatitis B virus (HBV) infection. However, the development of drug resistance is a major limitation to their long-term effectiveness. OBJECTIVES: The aim of this study was to characterize the hepatitis B virus reverse transcriptase (RT) protein variations among Iranian chronic HBV carriers who did not receive any antiviral treatments. MATERIALS AND METHODS: Hepatitis B virus partial RT genes from 325 chronic in active carrier patients were amplified and directly sequenced. Nucleotide/amino acid substitutions were identified compared to the sequences obtained from the database. RESULTS: All strains belonging to genotype D.365 amino-acid substitutions were found. Mutations related to lamivudine, adefovir, telbivudine, and entecavir occurred in (YMDD) 4% (n = 13), (SVQ) 17.23% (n = 56), (M204I/V + L180M) 2.45% (n = 8) and (M204I) 2.76% (n = 9) of patients, respectively. CONCLUSIONS: RT mutants do occur naturally and could be found in HBV carriers who have never received antiviral therapy. However, mutations related to drug resistance in Iranian treatment-naïve chronic HBV patients were found to be higher than other studies published formerly. Chronic HBV patients should be monitored closely prior the commencement of therapy to achieve the best regimen option.

The prevalence of hepatitis B virus surface antigen (HBsAg) variations and correlation with the clinical and serologic pictures in chronic carriers from Khorasan Province, North-East of Iran.

This study was designed to determine the correlation of hepatitis B virus surface Ag (HBsAg) variations with the clinical/serological pictures among chronic HBsAg positive patients. The surface gene (S-gene) was amplified and directly sequenced in twenty-five patients. Eight samples (group I) contained at least one mutation at the amino acid level. Five showed alanine aminotransferase (ALT) levels above the normal range of which only one sample was anti-HBe positive. Group II (17 samples) did not contain any mutation, 4 were anti-HBe positive and 9 had increased ALT levels. In both groups, from a total of 18 mutations, 5 (27.5%) and 13 (72.5%) occurred in anti-HBe and HBeAg positive groups respectively. The small number of amino acid mutations might belong to either the initial phase of chronicity in our patients; or that even in anti-HBe positive phase in Iranian genotype D-infected patients, a somehow tolerant pattern due to the host genetic factors may be responsible.