Immunogenicity and safety of a quadrivalent recombinant influenza vaccine manufactured in Iran (FluGuard) in volunteers aged 18-60 years: A double-blind, non-inferiority, randomized controlled trial.

BACKGROUND: This study aimed to evaluate the non-inferiority of the FluGuard (a quadrivalent recombinant vaccine manufactured by Nivad Pharmed Salamat Company in Iran) by comparing its immunogenicity and safety with Vaxigrip Tetra (a quadrivalent inactivated vaccine manufactured by Sanofi Pasteur in France). MATERIALS AND METHODS: In this double-blind, randomized controlled trial, eligible volunteers aged 18-60 were randomized to receive either FluGuard or Vaxigrip Tetra vaccines. Immunogenicity was evaluated using the Hemagglutination Inhibition (HAI) assay and reported with the geometric mean titer (GMT), seroprotection, and seroconversion. In addition, vaccine safety was assessed by interviewing participants through phone calls. RESULTS: Out of 110 randomized volunteers, 51 and 53 were entered into the final analysis in the Vaxigrip and FluGuard groups, respectively. Vaxigrip had a higher seroprotection rate for the H1N1 strain compared with FluGuard (98 % vs. 91 %). Besides, FluGuard had higher seroprotection rates for H3N2 (74 % vs. 69 %), B-Yamagata (87 % vs. 84 %), and B-Victoria (66 % vs. 41 %) strains compared with Vaxigrip. In all four strains, FluGuard was non-inferior to Vaxigrip with the upper bounds of the 95 % CI on the ratio of the GMTs < 1.5: H1N1 (1.25), H3N2 (0.94), B-Yamagata (0.62), and B-Victoria (0.59). Furthermore, FluGuard was non-inferior to Vaxigrip with the upper bounds of the 95 % CI on the difference between the seroconversion rates < 10 %: H1N1 (2 %), H3N2 (10 %), B-Yamagata (-10 %), and B-Victoria (-29 %). The prevalence of solicited adverse drug reactions did not differ between groups. Furthermore, participants did not experience serious adverse events. CONCLUSION: Our findings support the non-inferiority of the FluGuard vaccine to the Vaxigrip vaccine regarding immunogenicity and safety. CLINICAL TRIAL REGISTRY: The study protocol was approved by the Iranian Registry of Clinical Trials (IRCT20210901052358N5).

Diagnosis of Toxoplasma Infection in Allogenic Pre HCTSP Patients Using Molecular Methods.

Background: We aimed to estimate the incidence of Toxoplasma infection in T. gondiiseropositive patients under allogeneic hematopoietic stem cell transplantation (HSCT). Methods: The present research was a prospective study on 54 whole blood samples of allogeneic HSCT recipients, who were referring to bone narrow transplantation centers affiliated to Shahid Beheshti University of Medical Sciences, Tehran, Iran in 2018. All patients were IgG positive against T. gondii. Results: Overall, 54 Toxoplasma positive pre-HCTSP patients were enrolled. 53.7% (n= 29) were male, also 1.9% (n=1) had germ-line type of the disease. The Multiple myeloma patients had higher age in comparison with other disease, but pairwise comparison showed the difference of age between Multiple myeloma patients were statistically significant with Acute lymphoblastic leukemia, Acute myeloblastic leukemia and Huntington's disease (P< 0.05). The results of PCR assay showed 5.6% (n= 3) of the patients were infected with Toxoplasma. Conclusion: PCR method has detected considerable incidence of Toxoplasma infection for monitoring HSCT recipients at risk for toxoplasmosis, and many patients who showed the incidence of toxoplasmosis had previous infections with the Toxoplasma parasite.

An investigation into the Effects of Intravenous Vitamin C on Pulmonary CT Findings and Clinical Outcomes of Patients with COVID 19 Pneumonia A Randomized Clinical Trial.

PURPOSE: In late December 2019, a series of unexplained cases of pneumonia were reported in Wuhan, China. On January 12, 2020, the World Health Organization temporarily named the virus responsible for the emerging cases of pneumonia as the 2019 coronavirus. Acute respiratory distress syndrome (ARDS) due to Covid-19 has rapidly spread around the world, and while no specific treatment or vaccine has been reported, mortality rates remain high. One of the suggested treatments for cellular damage in the pathogenesis of ARDS caused by the coronavirus is the administration of high doses of intravenous vitamin C. Considering the paucity of literature on the therapeutic effects of high doses of intravenous vitamin C in patients with ARDS resulting from the coronavirus, this study was conducted to assess this therapeutic supplement in these patients. MATERIALS AND METHODS: This study was performed as a single-center clinical trial in patients with a documented diagnosis of COVID-19 pneumonia. 54 eligible patients with moderate to severe COVID-19 symptoms, based on specific inclusion and exclusion criteria, were included in the investigation and randomly divided into two groups. The control group consisted of 26 patients who received standard treatment, whereas the treatment group was comprised of 18 patients administered intravenous vitamin C at a dose of 2 g every 6 hours for 5 days in addition to standard treatment. Demographic characteristics, underlying diseases, length of hospital stay, and mortality rates were reviewed and collected. Oxygen saturation, respiratory rates, serum C Reactive Protein (CRP) levels, lymphopenia and lung parenchymal involvement on CT were investigated at the time of admission and on the sixth day after hospitalization. Finally, all variables were analyzed with IBM SPSS Statistics 23 software and a significant statistical difference was defined for all variables, P <0.05. RESULTS: Of these variables, the amount of oxygen saturation in the vitamin C group increased significantly from 86±5% on the first day of hospitalization to 90±3% on the sixth day of hospitalization (P value=0.02). Also, the respiratory rate in the vitamin C group decreased significantly from 27±3 on the first day of hospitalization to 24±3 on the sixth day of hospitalization (P value=0.03). Lung CT scans of patients in the two groups reported by two radiologists were also compared. Based on the report of the radiologists, the rate of lung involvement in the vitamin C group was significantly lower than in the control group at the end of treatment (P value=0.02). CONCLUSION: Due to the effectiveness of high doses of intravenous vitamin C on reducing lung involvement and improving clinical symptoms, further studies with a larger sample size are recommended to demonstrate the effects of this drug supplement.

Anti-tuberculosis Induced Stevens-Johnson Syndrome Due to Misdiagnosis of Mycobacterium Abscessus Urinary Tract Infection as Tuberculosis.

Mycobacterium abscessus complex is one of the most important groups of non-tuberculosis mycobacteria, which can cause infection in several organs of the human body. In this study, we report a rare cause of urinary tract infection which was presented with the chief complaint of hematuria and dysuria. The patient was treated by a clarithromycin based approach and the result of the culture and polymerase chain reaction were negative after 3 months of treatment. Informed consent was taken from the patient for publishing the case.

Descriptive Analysis of COVID-19 among Health Care Workers in a Tertiary Center in Iran.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spread widely all around the world and has infected too many healthcare workers (HCWs) as the pioneers combating coronavirus disease 2019 (COVID-19). This study aims to evaluate the symptoms and outcome of medical staff from a tertiary hospital in Tehran, Iran. Materials and Methods: The diagnoses of 29 HCWs presenting COVID-19 symptoms were confirmed by molecular and imaging studies. Epidemiologic and disease-related data were collected via phone calls and filling a questionnaire and then analyzed descriptively. Results: Eighteen (62.1%) of the affected HCWs were males. The mean age of them was 41.86 years with a lower average (38.27) for females than males. Nurses comprised 41.4% of our population. Only 2 (6.9%) patients were admitted to the respiratory care unit (RCU) (), marked as critical patients. The most presented symptoms were fever (79.3%) and dyspnea (79.3%). Overall, 55.2% of them had a longer exposure time (more than a week), which was more frequent in men than women. Conclusion: Fever was the most prevalent symptom among the study group. Even though the clinical features of COVID-19 among HCWs cannot be copiously determined by this study, it highlights the requirement for comparative studies to illustrate differences among HCWs and the general population. There might be an association between the duration of the exposure and the risk of the infection in men.

COVID-19 and kidney transplant recipients.

BACKGROUND: The novel coronavirus has become a global threat and healthcare concern. The manifestations of COVID-19 pneumonia in transplant patients are not well understood and may have more severe symptoms, longer duration, and a worse prognosis than in immunocompetent populations. AIMS: This study proposed to evaluate the clinical characteristics of COVID-19 pneumonia in kidney transplant recipients. PATIENTS/METHODS: Clinical records, laboratory results, radiological characteristics, and clinical outcome of 24 kidney transplant patients with COVID-19 pneumonia were evaluated from March 20, 2020, to May 20, 2020. RESULTS: The most common symptom was shortness of breath (70.8%), followed by fever (62.5%) and cough (45.8%). Five patients had leukopenia, and only one patient had leukocytosis, while 75% of the patients had a white blood cell (WBC) count in the normal range, and 79% of recipients developed lymphopenia. All of the patients had an elevated concentration of C-reactive protein and an increase in blood urea levels. Chest CT images of 23 patients (95.8%) showed typical findings of patchy ground-glass shadows in the lungs. Of the 24 patients, 12 were admitted to ICU (invasive care unit), and ten of 24 patients (41.6%) died, and 14 patients were discharged after complete recovery. CONCLUSION: It seems that COVID-19 is more severe in transplant patients and has poorer outcomes. Multiple underlying diseases, low O2 saturation, and multilobar view in chest CT scan may be of prognostic value. However, many SARS-CoV-2 demonstrations are similar to those of the general population.

Comparing the Efficacy and Safety of Treating Chronic Hepatitis B Infection during Pregnancy with Lamivudine, Telbivudine, and Tenofovir: A Meta-analysis.

Background and Aims: The perinatal transmission of hepatitis B virus (HBV) remains an important global health problem. Here, a systematic review and meta-analysis were conducted to evaluate the evidence regarding the efficacy and maternal/fetal safety of treating pregnant women with lamivudine, telbivudine (LdT), and tenofovir (TDF). Methods: A PubMed and Scopus search resulted in 1,076 records, which were reduced to 36, containing 7,717 pregnant women with chronic HBV infection and 7467 infants meeting the inclusion criteria. The latest search was in August 2019. Results: Treatment with LdT, but not lamivudine and TDF, could significantly reduce the hepatitis B virus surface antigen-positive rate (odds ratio (OR) = 0.37) in infants; it also led to higher rates of hepatitis B e antigen loss (OR = 12.14), hepatitis B e antigen seroconversion (OR = 8.93), and alanine aminotransferase normalization in mothers (OR = 1.49). Each of these treatments was able to significantly reduce HBV DNA positivity at birth (total OR = 0.19) and mother-to-child-transmission of HBV (total OR = 0.15), and to cause higher rates of HBV DNA suppression in mothers (total OR = 25.53). However, nucleos(t)ide analogues might also be involved in creatine kinase elevation (total OR = 7.48). In contrast, no significant association was found between nucleos(t)ide analogue therapy and preterm/premature births, congenital malformation, low birth weight, and abortion or fetal/infant death. The results suggested LdT's high capability of preventing mother-to-child-transmission. However, TDF failed to show significant associations to a reduced risk of mother-to-child-transmission, probably due to the low number of patients included. Conclusions: Although using either lamivudine, LdT, or TDF could lead to more favorable maternal/fetal outcomes, LdT seemed to show more potential in resolving certain infant- and maternal-related outcomes. More studies on the safety profile of such treatments are required.

Phylogenetic Analysis of Hepatitis B Virus among Household Members with HBV Chronic Infection.

BACKGROUND: Intrafamilial spread of Hepatitis B virus (HBV) infection in Iran has only been investigated with serological testing without using molecular studies as the most informative and definitive type of analysis. METHODS: In the present study, intrafamilial transmission of HBV among family members of Iranian index HBsAg carriers was investigated using phylogenetic analysis of the S region of the viral genome. Nested polymerase chain reaction was used for detection of HBV DNA in serum samples from 22 index and 43 contact patients with chronic HBV infection. HBV DNA was detected in 37 samples (14 indexes, 23 contacts). The S gene region of the DNA isolates was subjected to direct sequencing and phylogenetic analysis by Bioedit, Mega and Phylip programs. RESULTS: All isolates (from 26 patients) were clustered with genotype D, of which 24 strains were of subgenotype D1, subtype ayw2, while 2 additional strains were of subgenotype D2, subtype ayw3. Evidence of intrafamilial transmission of the virus was found in 8 families studied phylogenetically. Overall, 60 changes were detected in the amino acid sequences of the surface antigen protein in 23 patients. Four premature stop codons occurred in 3 isolates at residues 69 and 182. Seven out of 8 families displayed 25-100% common amino acid substitutions among their members. CONCLUSION: Our data corroborated intrafamilial transmission of HBV, as evidenced by concordant HBV genotype among household members, viral sequence homology and close genetic relatedness of the strains on the phylogenetic tree, and horizontal transmission of S gene mutations among family members.

Nucleotide Substitutions in Hepatitis B Viruses Derived from Chronic HBV Patients.

BACKGROUND: Mutations in the S gene (HBsAg), pre-core (PC), and basic core promoter (BCP) of the hepatitis B virus (HBV) infection are correlated with disease progression. This study assessed the frequency of mutations in the S gene, PC, and BCP regions in chronic hepatitis B (CHB) patients. METHODS: 104 formerly known CHB patients who visited Tehran Hepatitis centers, were included. The viral load of samples was determined based on the TaqMan method. Regions of the S gene, PC and BCP were amplified by the nested PCR. Positive PCR products were sequenced and analyzed. RESULTS: 33 successfully sequenced S gene region revealed all the derived strains were genotype D, with the majority (90.9%) belonging to the ayw2 subtype, and the rest (9.1%) to the ayw1 subtype. The prevalence of mutations was found to be 51.0% and 18.0% in the HBsAg and the Major Hydrophilic Region, respectively. 70.0% of amino acid changes within HBsAg occurred in different immune epitopes, of which 27.0% and 72.0% were located in B cell and Th epitopes, respectively. 26 successfully sequenced PC and BCP regions showed at least one mutation in 84.6% of the HBV strains. The PC and BCP mutations were G1896A (61.0%), G1899A (23.0%), A1762T/G1764A (23.0%) and G1764T/C1766G (26.0%). None of the strains with A1762T/G1764A mutation carried the G1764T/C1766G mutant. CONCLUSIONS: Our results showed common mutations within HBsAg, occurring in immune epitopes, a high rate of G1896A mutations in the PC region, and a negative correlation between the emergence of A1762T/G1764A mutation and the G1764T/C1766G mutant in the BCP region.

Toward cure chronic hepatitis B infection and hepatocellular carcinoma prevention: Lessons learned from nucleos(t)ide analogues therapy.

Nucleos(t)ide analogues (NAs) could successfully suppress hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB). However, due to probable development of drug resistance or low/delayed response, these treatments may not be satisfactory. In addition to the HBV DNA polymerase inhibiting activity, these drugs could lead to changes in cytokines profiles. It is important to monitor these changes so that they could be used as target of treatment. Evaluating the previously reported immune responses due to NAs treatments, it was concluded that interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), and IL-12 increase after the treatment. This will be followed by the improved capacity of immune cells for eliminating HBV. In contrast, regulatory responses including IL-10 and transforming growth factor-beta (TGF-ß) significantly decreased as the result of NAs therapy. Unexpectedly, T helper (Th) 17-associated cytokines also decreased significantly. These results could be used to employ the new strategies to suppress viral replication, minimize HBV DNA levels, inducing hepatitis B e antigen (HBeAg) seroconversion or even hepatitis B surface antigen (HBsAg) seroclearance. In order to accomplish these goals, extended treatment with high dose of both IL-12 and IFN in combination with high barrier to resistance NA might significantly improve the HBsAg seroclearance rate. Considering the danger of emerging aberrant immune responses, determining the optimum dosage as well as close monitoring of patients during the treatment is strongly advised. In order to make HBV immunotherapy practical, further studies are needed to confirm these results.

Manipulation of Regulatory Cells' Responses to Treatments for Chronic Hepatitis B Virus Infection.

BACKGROUND: Identification of effective treatments in hepatitis B virus (HBV) infection remains a controversial topic. Although the currently approved drugs for HBV control the disease's progression and also limit associated outcomes, these drugs may not fully eradicate HBV infection. In addition to better managing patients with chronic hepatitis B (CHB) infection, the induction of seroclearance by these drugs has been a commonly discussed topic in recent years. OBJECTIVES: In this study, we focused on treating CHB infection via the manipulation of T cells' responses to identify possible approaches to cure CHB. MATERIALS AND METHODS: All studies relevant to the role of cellular and humoral responses in HBV infection (especially regulatory cells) were investigated via a systematic search of different databases, including PubMed, Scopus, and Google Scholar. Considering extracted data and also our unpublished data regarding the association between regulatory cytokines and CHB, we introduced a novel approach for the induction of seroclearance. RESULTS: Considering the increased levels of regulatory cytokines and also regulatory T cells (Tregs) during CHB, it seems that these cells are deeply involved in CHB infection. The inhibition of regulatory T cells may reverse the dysfunction of effector T cells in patients with CHB infection. In order to inhibit Tregs' responses, different types of approaches could be employed to restore the impaired function of effector T cells. The blockade of IL-10, IL-35, CTLA-4, PD-1, and TIM-3 were discussed throughout this study. Regardless of the efficacy of these methods, CHB patients may experience serious liver injuries due to the cytotoxic action of CD8+ T cells. Antiviral therapy and a decrease in HBV DNA to undetectable levels could also significantly reduce the risk of the hepatitis B flare. CONCLUSIONS: The inhibition of Tregs is a novel therapeutic approach to cure chronically HBV infected patients. However, further studies are needed to investigate the safety and efficacy of this approach.

Tumor Necrosis Factor-α-308 G/A Polymorphisms and Risk of Hepatocellular Carcinoma: A Meta-Analysis.

CONTEXT: Hepatocellular carcinoma (HCC) is a common disorder throughout the world that can develop due to various factors, including genetics. Tumor necrosis factor-α (TNF-α) is the most frequently studied cytokine related to the risk of developing HCC, and an association between the 308 position of the TNF-α promoter (TNF-α-308) and HCC risk has been confirmed in various reports. EVIDENCE ACQUISITION: The PubMed, Scopus, and Google Scholar databases were searched through July 12, 2015, for studies on associations between TNF-α-308 and the risk of HCC. To determine this association, odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: A total of 23 case-control studies were investigated, involving 3,389 cases and 4,235 controls. The overall conclusion was that the A allele was more frequent in case groups compared to control groups (13.4% vs. 8.4%). Thus, the A allele was significantly associated with increased HCC risk (OR = 1.77; 95% CI = [1.26-2.50]; P value < 0.002). In addition to the allelic model, the dominant model (AA + AG vs. GG) was significantly associated with HCC risk (OR = 1.80; CI = [1.29-2.51]; P value < 0.001). In the sensitivity analysis for co-dominant (AA vs. GG) and recessive models (AA vs. AG + GG), no trustworthy associations with the risk of HCC development were observed. CONCLUSIONS: This meta-analysis indicated that the TNF-α-308 G/A polymorphism is significantly associated with increased susceptibility to HCC. However, to confirm this finding, more studies are needed on TNF-α-308 G/A polymorphisms associated with HCC.

Hepatitis B Reactivation During Immunosuppressive Therapy or Cancer Chemotherapy, Management, and Prevention: A Comprehensive Review-Screened.

CONTEXT: Due to the close relationship between the immune system and the hepatitis B virus (HBV) replication, it is essential to monitor patients with current or past HBV infection under any type of immunosuppression. Cancer chemotherapy, immunosuppressive therapies in autoimmune diseases, and immunosuppression in solid organ and stem cell transplant recipients are the major reasons for hepatitis B virus reactivation (HBVr). In this review, the challenges associated with HBVr are discussed according to the latest studies and guidelines. We also discuss the role of treatments with different risks, including anti-CD20 agents, tumor necrosis factor-alpha (TNF-α) inhibitors, and other common immunosuppressive agents in various conditions. EVIDENCE ACQUISITION: Through an electronic search of the PubMed, Google Scholar, and Scopus databases, we selected the studies associated with HBVr in different conditions. The most recent recommendations were collected in order to reach a consensus on how to manage patients at risk of HBVr. RESULTS: It was found that the positive hepatitis B surface antigen (HBsAg), the high baseline HBV DNA level, the positive hepatitis B virus e antigen (HBeAg), and an absent or low hepatitis B surface antibody (HBsAb) titer prior to starting treatment are the most important viral risk factors. Furthermore, rituximab, anthracycline, and different types of TNF-α inhibitors were identified as the high-risk therapies. By analyzing the efficiency of prophylaxis on the prevention of HBVr, it was concluded that those with a high risk of antiviral resistance should not be used in long-term immunosuppressants. Receiving HBV antiviral agents at the commencement of immunosuppressant therapy or chemotherapy was demonstrated to be effective in decreasing the risk of HBVr. Prophylaxis could also be initiated before the start of therapy. For most immune suppressive regimes, antiviral therapy should be kept up for at least 6 months after the cessation of immunosuppressive drugs. However, the optimal time of prophylaxis keeping should be increased in cases associated with rituximab or hematopoietic stem cell transplants. According to the latest studies and guidelines from different bodies, recommendations regarding screening, monitoring, and management of HBVr are outlined. CONCLUSIONS: Identification of patients at the risk of HBVr before immunosuppressive therapy is an undeniable part of treatment. Starting the antiviral therapy, based on the type of immunosuppressive drugs and the underlying disease, could lead to better management of disease.

Multiple intracranial tuberculomas in a post-kidney transplant patient.

Tuberculosis (TB) is a serious public health problem worldwide, particularly in developing countries. The most common presentation of TB is the pulmonary form; however, extrapulmonary manifestations are not uncommon, particularly in the immunocompromised patients. TB of the central nervous system is the most severe extrapulmonary presentation. We report a post-kidney transplant patient who had multiple ring-like lesions on contrast-enhanced magnetic resonance imaging (MRI). Based on the results of MRI and biopsy specimen, the patient was diagnosed with multiple intracranial tuberculomas. He was treated successfully with a standard quadruple therapy of rifampicin, isoniazid, ethambutol and pyrazinamide.

Comparison of Vitamin D Levels in Naive, Treated, and Inactive Carriers with Chronic Hepatitis B Virus.

Background and Aims: During recent years, the relationship between vitamin D levels and chronic hepatitis B (CHB) infection has attracted many researchers' attention. However, the results relating to the association of vitamin D levels and HBV infection have been conflicting and there remains a lack of knowledge about the effects of antiviral treatments on vitamin D level. Methods: Eighty-four patients with CHB were assessed and divided into three groups: inactive carriers (n = 28), treated (n = 34), and new (treatment-naïve) cases (n = 22). Thirty-two healthy controls (HCs) were included to enable comparison with the CHB groups. The levels of vitamin D3 were measured and statistically compared among the various groups. Results: Male subjects had higher levels of vitamin D3 (41.25 vs 28.85, p < 0.01). No association was found among any of the groups when compared with the HC group. Despite the significant association, the HCs demonstrated a higher level of vitamin D3, which was lower in the treated group, the inactive carrier group, and the new cases group (new case [29.82] < inactive carrier [32.91] < treated [39.56] < control [44.88]). The HBV DNA levels were not associated with vitamin D3 levels in the inactive carriers (p = 0.171), the treated groups (p = 0.192), and the new cases (p = 0.369). Moreover, the alanine transaminase and aspartate transaminase levels were not associated with vitamin D3 levels for any of the HBV-infected groups. Conclusions: Vitamin D3 contributes to the clinical statues of CHB patients. There is also a possible correlation between clinically healthy CHB patients and vitamin D3 level.

Seroclearance of Hbsag in Chronic Hepatitis B Virus Patients on Lamivudine Therapy: A 10 Year Experience.

INTRODUCTION: The aim of this study was to determine hepatitis B surface antigen (HBsAg) seroclearance rate among patients treated with lamivudine at a specialized tertiary care referral hospital in Tehran, Iran. METHODS: All patients on lamivudine (biovudin®) therapy at a dose of 100 mg/day, who showed seroclearnace between March 2001 and September 2011 were recruited. The main evaluation parameters were duration of HBsAg seroclearance and duration of HBsAg seroconversion. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were evaluated using standard methods. HBsAg seroclearance was defined as two consecutive negative serums HBsAg at least 6 months apart, whereas HBsAg seroconversion was defined as the disappearance of serum HBsAg and the presence of anti-HBs for >6 months. RESULTS: A total of 203 chronic HBV patients treated with lamivudine at a dose of 100 mg/day were included in the study. HBsAg seroclearance and seroconversion were observed in 11 patients after the initiation of the lamivudine therapy. Overall, in lamivudine responder patients, the mean time to HBsAg seroclearance was 26.90±10.93 months (range: 12-48 months). Furthermore, the responders showed seroconversion after a mean time of 26.90±11.08 months from the initiation of lamivudine therapy. When comparing the characteristics of those who have responded to lamivudine and those who have not responded, baseline HBV-DNA levels was significantly lower in responder than non responder patients (p<0.001). Meantime, there was no difference in age, sex, baseline ALT, AST and liver biopsy score between lamivudine responder and lamivudine non-responder patients. CONCLUSION: Despite introduction of tenofovir and entecavir as first line treatment for chronic HBV infection, lamivudine remains to be a low cost, safe and effective drug for HBsAg seroclearnace.

Can serum level of HBsAg differentiate HBeAg-negative chronic hepatitis B from inactive carrier state?

Hepatitis B envelope antigen (HBeAg)-negative hepatitis B virus (HBV) infection exerts both inactive carrier (IC) state and chronic hepatitis B (CHB), which are sometimes difficult to be differentiated. We aimed to assess the role of hepatitis B surface antigen (HBsAg) level in differentiation of CHB and IC among a group of chronic HBeAg-negative HBV-infected patients. A total of 251 HBeAg-negative HBV-infected patients were enrolled. Serum HBV DNA and HBsAg levels were determined for each patient. HBV DNA quantification with cutoff value 2000IU/mL for diagnosis of CHB had 99.0% sensitivity and 74.1% specificity. A cutoff value of HBsAg level at 1000IU/mL was more reliable for diagnosis of CHB with 82.7% sensitivity and 66.2% specificity than other HBsAg cutoff values. There was a positive correlation between HBV DNA and HBsAg levels in both CHB (r=0.42, P<0.001) and IC (r=0.43, P<0.001) groups. Single-point HBsAg quantification did not have enough sensitivity and specificity for differentiation of HBeAg-negative CHB and IC state.

Non-invasive histologic markers of liver disease in patients with chronic hepatitis B.

BACKGROUND: An exact histologic staging of liver fibrosis is essential for identifying the best therapeutic strategy and determining the disease prognosis in patients with chronic hepatitis B (CHB). While liver biopsy has a vital role in the management of liver diseases, it also sustains some limitations hampering its widespread use. OBJECTIVES: In this study, we evaluated and compared several available indices of the severity of liver diseases in patients with hepatitis. PATIENTS AND METHODS: EXCLUSION CRITERIA WERE AS FOLLOWS: decompensated liver disease, alcoholic liver disease or alcohol intake of 40 g or more per week; co-infection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus. RESULTS: Results showed that AST to platelet ratio index (APRI) (odds ratio = 2.35, P = 0.01) and age (odds ratio = 1.04, P = 0.007) were independently predictive of the presence of significant liver necrosis and inflammation. On the other hand, AARPRI (odds ratio = 3.8, P = 0.07), age (odds ratio = 1.04, P = 0.02), and ALT levels (odds ratio = 1.01, P = 0.007) were predictive of a significant liver fibrosis. Further analysis with receiver-operating curve showed that none of these predictors had a fair diagnostic value (area under the curve < 70). CONCLUSIONS: The APRI had the highest sensitivity and specificity (64% and 71%, respectively) for prediction of the presence of liver disease. We suggest that APRI may be applicable for the detection of a severe liver disease.