Effects of Curcuminoids on Systemic Inflammation and Quality of Life in Patients with Colorectal Cancer Undergoing Chemotherapy: A Randomized Controlled Trial.

BACKGROUND: Colorectal cancer (CRC) is the third and the fourth most common cancer in Iranian men and women, respectively. Curcuminoids are known to exertprotective effects against several kinds of cancers. We aim to assess the effects of curcuminoids on serum pro- and anti-inflammatory cytokines and quality of life in patients with colorectal cancer undergoing chemotherapy. MATERIAL AND METHODS: This study was a double-blind placebo-controlled trial in patients with CRC (stage 3) aged ≥20 years, who had chemotherapy after the surgery and were referred to Baqiyatallah Oncology Clinic. Patients were randomly assigned to the treatment group receiving curcuminoids capsules (500 mg/day) (n = 36), or the control group taking placebo capsules (n = 36) for 8 weeks. Erythrocyte sedimentation rate (ESR) and serum levels of C-reactive protein (CRP) and 12 pro- and anti-inflammatory cytokines including tumor necrosis factor (TNF-α), interleukin-1α (IL-1α), IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, monocyte chemoattractant protein (MCP-1), interferon γ (IFN-γ), epidermal growth factor (EGF), and vascular endothelial growth factor (VEGF)] were measured at baseline and at the end of the intervention. The EORTC-QLQ-C30 instrument was used to assess the quality of life before and after the intervention. Statistical analyses were performed using SPSS software. RESULTS: A total of 67 subjects completed the study as three and two subjects were lost to follow-up in the curcuminoid and placebo groups, respectively. A significant change in CRP (p = 0.002) and ESR (p = 0.0001) was observed in patients supplemented with curcuminoids at the end of 8 weeks compared to placebo. Moreover, IL-1α showed a decreasing trend after curcuminoid supplementation compared to placebo (p = 0.077). A significant improvement in functional (p = 0.002) and global quality of life (p = 0.020) scales was observed in the curcuminoid group. CONCLUSIONS: The results showed that curcuminoids supplementation for a period of 8 weeks (500 mg/day) can improve ESR and serum levels of CRP in stage-3 CRC subjects and improve the global quality of life and functional scales compared to placebo.

The Effects of Curcumin on the Side Effects of Anticancer Drugs in Chemotherapy: A Randomized Controlled Trial.

Curcumin, the active ingredient of the spice turmeric, has been shown to have anticancer activities in several preclinical and clinical studies. The prophylactic effect of curcumin against chemotherapy-induced damage and side effects was evaluated in a double-blind, placebo-controlled randomized trial. Eighty cancer patients on standard chemotherapy regimens were randomly assigned to receive curcumin as adjuvant therapy (500 mg per 12 hours) and matched control group to receive placebo for 9 weeks. Pre- and post-intervention, the changes in the health-related quality-of-Life (QoL) score (based on the University of Washington Quality-of-Life (UW-QoL) questionnaire, version 3), clinical symptoms, and hematological and biochemical parameters were assessed. Comparison between groups based on total QoL score showed that curcumin supplementation was not associated with improved QoL (P = 0.102). Hematological and biochemical analysis showed no statistical differences between the groups at the end of the trial (P > 0.05). However, during the trial, significant differences were observed in hemoglobin (Hb), hematocrit (HCT), lactic acid dehydrogenase (LDH), serum glutamic-oxaloacetic transaminase (SGOT), and anaplastic lymphoma kinase (ALK) between the groups (P < 0.05). Future studies in a larger homogenous population of cancer patients are required to confirm the adjuvant effect of curcumin on chemotherapy-induced QoL.

Effects of Spinal-Z in Patients with Gastroesophageal Cancer.

OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of spinal-Z, derived from Peganum harmala seeds and Dracocephalum Kotschyi Boiss leaves, in patients with esophageal and stomach adenocarcinoma, and squamous cell carcinoma of the esophagus. METHODS: Sixty-one patients with malignancies of the upper gastrointestinal tract were randomly assigned to one of two groups (treatment or control) in a double-blind fashion. Six capsules of Spinal-Z were prescribed to the patients with the regimen of 600 mg/m2/day, and placebo to the control group, for six months. RESULTS: There were no significant differences between the two groups with regard to age, sex, duration of cancer, type of cancer and family history of cancer. There were significant differences in abdominal pain, heartburn, constipation and vomiting between the two groups, following spinal-Z therapy. Evaluation of drug side effects showed no difference in cough or other respiratory symptoms, itching, headache or dizziness between the two groups, both before and after treatment. CONCLUSION: This study indicates that Spinal-Z is safe and efficacious in the management of patients with upper gastrointestinal tract cancers.

COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

This article published in Cell J (Yakhteh), Vol 20, No 2, Jul-Sep 2018, on pages 267-277, four affiliations (1, 4, 5, and 10) were changed based on authors request.

COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial.

OBJECTIVES: The regenerative potential of bone marrow-derived mononuclear cells (MNCs) and CD133+ stem cells in the heart varies in terms of their pro-angiogenic effects. This phase II/III, multicenter and double-blind trial is designed to compare the functional effects of intramyocardial autologous transplantation of both cell types and placebo in patients with recent myocardial infarction (RMI) post-coronary artery bypass graft. MATERIALS AND METHODS: This was a phase II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI (CD133, Placebo, MNCs - recent myocardial infarction) conducted in accordance with the Declaration of Helsinki that assessed the safety and efficacy of CD133 and MNCs compared to placebo in patients with RMI. We randomly assigned 77 eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or a placebo. Patients underwent gated single photon emission computed tomography assessments at 6 and 18 months post-intramyocardial transplantation. We tested the normally distributed efficacy outcomes with a mixed analysis of variance model that used the entire data set of baseline and between-group comparisons as well as within subject (time) and group×time interaction terms. RESULTS: There were no related serious adverse events reported. The intramyocardial transplantation of both cell types increased left ventricular ejection fraction by 9% [95% confidence intervals (CI): 2.14% to 15.78%, P=0.01] and improved decreased systolic wall thickening by -3.7 (95% CI: -7.07 to -0.42, P=0.03). The CD133 group showed significantly decreased non-viable segments by 75% (P=0.001) compared to the placebo and 60% (P=0.01) compared to the MNC group. We observed this improvement at both the 6- and 18-month time points. CONCLUSIONS: Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and efficient with superiority of CD133+ cells for patients with RMI. Although the sample size precluded a definitive statement about clinical outcomes, these results have provided the basis for larger studies to confirm definitive evidence about the efficacy of these cell types (Registration Number: NCT01167751).

A systems medicine approach for finding target proteins affecting treatment outcomes in patients with non-Hodgkin lymphoma.

Autoantibody profiling with a systems medicine approach can help identify critical dysregulated signaling pathways (SPs) in cancers. In this way, immunoglobulins G (IgG) purified from the serum samples of 92 healthy controls, 10 pre-treated (PR) non-Hodgkin lymphoma (NHL) patients, and 20 NHL patients who underwent chemotherapy (PS) were screened with a phage-displayed random peptide library. Protein-protein interaction networks of the PR and PS groups were analyzed and visualized by Gephi. The results indicated AXIN2, SENP2, TOP2A, FZD6, NLK, HDAC2, HDAC1, and EHMT2, in addition to CAMK2A, PLCG1, PLCG2, GRM5, GRIN2B, GRIN2D, CACNA2D3, and SPTAN1 as hubs in 11 and 7 modules of PR and PS networks, respectively. PR- and PS-specific hubs were evaluated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. The PR-specific hubs were involved in Wnt SP, signaling by Notch1 in cancer, telomere maintenance, and transcriptional misregulation. In contrast, glutamate receptor SP, Fc receptor-related pathways, growth factors-related SPs, and Wnt SP were statistically significant enriched pathways, based on the pathway analysis of PS hubs. The results revealed that the most PR-specific proteins were associated with events involved in tumor development, while chemotherapy in the PS group was associated with side effects of drugs and/or cancer recurrence. As the findings demonstrated, PR- and PS-specific proteins in this study can be promising therapeutic targets in future studies.

An Updated Review of Natural Products Intended to Prevent or Treat Oral Mucositis in Patients Undergoing Radio-Chemotherapy.

Oral mucositis is a major clinical challenge in oncology and is characterized by pain and inflammation of the mucous membrane surface resulting from radiotherapy for head and neck cancer or from chemotherapeutic agents. Manifestations range from a burning sensation to ulcer formation that affect the patients' quality of life by producing pain and discomfort on swallowing, ultimately leading to malnutrition and dehydration. Due to complications arising from the use of chemical drugs, in recent decades, increasing attention has been paid to natural-based agents. The results from several studies evaluating natural products for the prevention or reduction of chemotherapy- and radiotherapy-induced oral mucositis are promising. This comprehensive review aims to provide updated information concerning the natural agents that are effective against mucositis in cancer patients receiving radiotherapy and/or chemotherapy.

Environmental Toxicant Exposure and Cancer: The Role of Epigenetic Changes and Protection by Phytochemicals.

Exposure to environmental toxicants is a well-documented predisposing factor for cancer. Although genetic alterations have long been known to occur through exposure to some environmental carcinogens, there is another layer of genome regulatory system named epigenetic system. Epigenetics is defined as any reversible and heritable change in cellular patterns of gene expression that does not alter DNA sequence. This layer of gene control plays a key role in early stages of carcinogenesis by reprogramming cells to what is known as cancer stem cells, a process with great similarities to somatic cell reprogramming into "induced pluripotent stem cell". Environmental toxicants could directly promote carcinogenesis through disturbing promoter CpG island hypermethylation, and silencing of tumor suppressor genes, hypomethylation of transposable elements and genomic instability induced by environmental toxicants. Environmental toxicants could also indirectly affect epigenetic programming of nucleus through inducing inflammatory signaling pathways that converge on NF-κB or STAT3 activation. Considering the reversibility of epigenetic alterations and their pivotal role in early carcinogenesis, reversion of these alterations could be a promising approach for chemoprevention. Selected phytochemicals have shown desirable effects through regulation of the most important epigenetic mechanisms including DNA methylation, histone modifications and microRNA expression, as well as modulation of SIRT-1 and STAT-3 signaling pathways. The present review aims to outline the epigenetic mechanisms underlying carcinogenic effects of environmental toxicants, and the protective effects of phytochemicals in reversing epigenetic aberrations in the regulatory pathways steering normal cell homeostasis.

"Coffee plus honey" versus "topical steroid" in the treatment of chemotherapy-induced oral mucositis: a randomised controlled trial.

BACKGROUND: Oral mucositis is one of the common complications of cancer chemotherapy and about 40% of the patients who take chemotherapy protocols, experience this irritating problem. The purpose of this study was to draw comparison between the therapeutic effects of our treatment modalities (topical steroid, honey, honey plus coffee) in patients suffering from oral mucositis. METHODS: This was a double blinded randomised clinical trial of a total of 75 eligible adult participants which they randomly fell into three treatment groups. For all the participants a syrup-like solution was prepared. Each 600 grams of the product consisted of "20 eight-mg Betamethasone solution ampoules" in the Steroid (S) group, "300 grams of honey plus 20 grams of instant coffee" in the Honey plus Coffee (HC) group, and "300 grams of honey" for the Honey (H) group. The participants were told to sip 10 ml of the prescribed product, and then swallow it every three hours for one week. Severity of lesions was clinically evaluated before the treatment and also one week after the initiation of the intervention. This study adhered to the principles of the Declaration of Helsinki and guidelines of Good Clinical Practice. RESULTS: This study showed that all three treatment regimens reduce the severity of lesions. The best reduction in severity was achieved in HC group. H group and S group took the second and third places. In other words, honey plus coffee regimen was the most effective modality for the treatment of oral mucositis. CONCLUSION: Oral mucositis can be successfully treated by a combination of honey and coffee as an alternative medicine in a short time. Further investigations are warranted in this field. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT: 201104074737N3, (9 May 2011).

Adjuvant therapy with bioavailability-boosted curcuminoids suppresses systemic inflammation and improves quality of life in patients with solid tumors: a randomized double-blind placebo-controlled trial.

Curcuminoids are bioactive polyphenolics with potent antiinflammatory properties. Although several lines of in vitro and preclinical evidence suggest potent anticancer effects of curcuminoids, clinical findings have not been conclusive. The present randomized double-blind placebo-controlled trial aimed to evaluate the efficacy of curcuminoids as adjuvant therapy in cancer patients. Eighty subjects with solid tumors who were under standard chemotherapy regimens were randomly assigned to a bioavailability-boosted curcuminoids preparation (180 mg/day; n = 40) or matched placebo (n = 40) for a period of 8 weeks. Efficacy measures were changes in the health-related quality of life (QoL) score (evaluated using the University of Washington index) and serum levels of a panel of mediators implicated in systemic inflammation including interleukins 6 (IL-6) and 8 (IL-8), TNF-α, transforming growth factor-ß (TGFß), high-sensitivity C-reactive protein (hs-CRP), calcitonin gene-related peptide (CGRP), substance P and monocyte chemotactic protein-1 (MCP-1). Curcuminoid supplementation was associated with a significantly greater improvement in QoL compared with placebo (p < 0.001). Consistently, the magnitude of reductions in TNF-α (p < 0.001), TGFß (p < 0.001), IL-6 (p = 0.061), substance P (p = 0.005), hs-CRP (p < 0.001), CGRP (p < 0.001) and MCP-1 (p < 0.001) were all significantly greater in the curcuminoids versus placebo group. In contrast, the extent of reduction in serum IL-8 was significantly greater with placebo versus curcuminoids (p = 0.012). Quality of life variations were associated with changes in serum TGFß levels in both correlation and regression analyses. Adjuvant therapy with a bioavailable curcuminoid preparation can significantly improve QoL and suppress systemic inflammation in patients with solid tumors who are under treatment with standard chemotherapy protocols.

Normobaric hyperoxia preconditioning ameliorates cisplatin nephrotoxicity.

BACKGROUND: Cisplatin is a potent anticancer drug, but its nephrotoxicity limits the clinical use of it. To reduce the Cisplatin-induced nephrotoxicity, various interventions have been implicated. The aim of this study was to examine whether preconditioning with normobaric hyperoxia would prevent Cisplatin-induced nephrotoxicity in patient with solid tumor. METHODS: In a prospective study, 80 adult patients with solid tumor who were treated with Cisplatin between February 2011 and December 2011 were included. Forty-three patients were exposed to pure oxygen via non-rebreathing reservoir mask which increased the provided oxygen rate to 60% oxygen for 2 hours at 48, 24, and 6 hours before intravenous administration of Cisplatin and 37 patients received only Cisplatin as a control group. Estimated glomerular filtration rate (eGFR) calculated in all patients on day 1 before and on days 1, 3, 6, 30 after Cisplatin exposures. RESULTS: Patients treated with Cisplatin and 60% oxygen showed a mild improvement in eGFR and mild reduction of serum creatinine after 30 days with statistically mild significant differences (p = 0.048). CONCLUSION: This study showed that normobaric and intermittent precondition of 60% oxygen prior to Cisplatin treatment had an acute transient adverse effect on renal function; however, the improvement of renal function will be seen after 30 days. Thus, it may help to prevent Cisplatin nephrotoxicity.

Serum levels of interleukins 2, 4, 6, and 10 in veterans with chronic sulfur mustard-induced pruritus: a cross-sectional study.

Inflammation is a key component in the pathogenesis of sulfur mustard (SM)-induced skin complications. Here, the levels of interleukin (IL) -2, IL-4, IL-6, and IL-10 were evaluated in patients with chronic SM-induced complications. Seventy-four serum samples were collected from SM-injured veterans (SM group; n = 37) and nonchemically injured patients (control group; n = 37) with skin pruritus. The levels of IL-2, IL-4, IL-6, and IL-10 were evaluated by sandwich enzyme-linked immunosorbant assay technique in both nil and mitogen medium. No significant difference was found in pruritus score between SM (74.16 +/- 5.93) and control (74.48 +/- 6.15) groups (P > .05). The mean serum concentrations of IL-2 and IL-6 were found to be significantly elevated in the control compared with the SM group (P < .05). However, no significant difference was observed between the study groups regarding serum levels of IL-4 and IL-10 (P > .05). Serum IL-2 (in both SM and control groups) and IL-6 (in the control group) concentrations were significantly correlated with pruritus score while no significant association was found for IL-4 and IL-10. Serum concentrations of IL-2, IL-6, and IL-10 are significantly decreased in SM-exposed patients with chronic pruritus. Such alterations might represent a plausible mechanism for tissue damage and skin itching following SM exposure. Therefore, variation of ILs may also contribute to skin pruritus induced by SM.

Investigation of the effects of Chlorella vulgaris supplementation on the modulation of oxidative stress in apparently healthy smokers.

BACKGROUND: Smoking is among the established yet modifiable risk factors for cancers, cardiovascular diseases, and pulmonary disorders. Oxidative stress has been proposed as a key mechanism mediating the deleterious consequences of smoking. The present study evaluated the effect of supplementation with Chlorella vulgaris, a nutrient and bioactive green microalgae with proven antioxidant capacity, on the burden of oxidative stress in Iranian smokers. METHODS: Thirty-eight smokers (mean age: 37.11 +/- 1.69 years; females: 18.4%) were administered C. vulgaris extract (3600 mg/day) for a period of 6 weeks. Fasted serum samples collected at baseline and after the completion of study were analyzed for the concentrations of vitamin C, vitamin E, glutathione, and malonedialdehyde (MDA) as well as activities of superoxide dismutase, glutathione peroxidase, and catalase. Total antioxidant capacity of serum was also determined by the ability of serum to inhibit the formation of ferryl myoglobin radical species. RESULTS: Six-week supplementation with C. vulgaris extract in smokers was associated with marked elevation of all assessed serum antioxidant measures (p < 0.001) and significant reduction of MDA levels (p = 0.002). After gender segregation, a similar pattern of changes was observed for both male and female subjects apart from lack of significant change in serum vitamin E status in females. Although the magnitude of change in serum vitamin E was significantly greater in males compared to females (p = 0.014), there was no significant change in the magnitude of changes for other assessed parameters between the genders. CONCLUSIONS: Supplementation with C. vulgaris extract significantly improves antioxidant status and attenuates lipid peroxidation in chronic cigarette smokers. Hence, C. vulgaris might prevent the disease burden and mortality rate associated with smoking.

Relationship between levels of IFNγ, TNFα, and TGFß and pruritus in sulfur mustard-exposed veterans.

One of the foremost negative effects of sulfur mustard (SM) is chronic pruritus, which affects the quality-of-life. In the present study, pruritus was assessed in relation with inflammatory factors in the blood. Seventy-two blood samples were collected from SM-injured veterans of the Iran-Iraq War (Case Group; n = 36) and non-exposed patients (Control Group; n = 36) suffering from skin pruritus. Pruritus severity in all subjects was assessed, as were levels of IFNγ, TGFß, and TNFα. The results indicated that total pruritus severity did not significantly differ between the two groups. While WBC counts in Control patients were significantly higher than among the exposed veterans, there were no significant differences in levels of any specific WBC sub-classes. Levels of serum IFNγ and TGFß in the control subjects were significantly greater than those in the exposed veterans. In contrast, serum TNFα in the SM-exposed group appeared to be in the normal range, albeit significantly higher than that of the control group. A positive correlation between pruritus and each of the evaluated cytokines was noted in the Case Group. As for the non-SM-exposed veterans, correlations were significant only in the cases of IFNγ (stimulated) and TGFß. The results of the present study suggested that there might be a relationship between cytokine alterations and pruritus in SM-exposed veterans. Based on these studies, designing of new treatments to modulate blood levels of mediators might be helpful to decrease the problem of SM-induced pruritus, thereby improving the quality-of-life in exposed veterans.

A randomized controlled trial on the anti-inflammatory effects of curcumin in patients with chronic sulphur mustard-induced cutaneous complications.

BACKGROUND: Chronic cutaneous complications such as pruritus are among the very frequent complaints of sulphur mustard (SM)-exposed patients. The present trial investigated the impact of curcumin on serum inflammatory biomarkers and their association with pruritus severity and quality of life (QoL). METHODS: This was a randomized, double-blind trial among 96 male Iranian veterans (age 37-59 y) who were suffering from chronic SM-induced pruritic skin lesions. Patients were randomly assigned to curcumin (1 g/d, n = 46) or placebo (n = 50) for four weeks. Serum concentrations of interleukins 6 (IL-6) and 8 (IL-8) together with high-sensitivity C-reactive protein (hs-CRP) and calcitonin gene-related peptide (CGRP) were measured at baseline and at the end of the trial. Assessment of pruritus severity was performed using the pruritus score and QoL using the Dermatology Life Quality Index (DLQI). RESULTS: Serum IL-8 and hs-CRP were significantly reduced in both groups but the magnitude of reduction was greater in the curcumin group (P < 0.001). Serum CGRP was only decreased in the curcumin group (P < 0.001). No significant change was observed in serum IL-6. There were significant correlations between CGRP and IL-6 changes (P = 0.011) and between DLQI and IL-8 changes (P = 0.026) in the curcumin group. In the curcumin group, changes in serum IL-8 concentrations were found as the significant predictor of DLQI scores (P = 0.026) but none of the independent variables could predict pruritus scores. CONCLUSIONS: Curcumin supplementation effectively mitigates inflammation in patients suffering from chronic SM-induced cutaneous complications. This anti-inflammatory effect might account for the observed pruritus alleviation and QoL improvement by this phytochemical.

Effect of ginger on acute and delayed chemotherapy-induced nausea and vomiting: a pilot, randomized, open-label clinical trial.

BACKGROUND: Nausea and vomiting are among the most prevalent and disturbing side effects of chemotherapy. Therefore, there is a need for additional antiemetic agents that could effectively reduce chemotherapy-induced nausea and vomiting (CINV), whether alone or in combination with current standard therapies. Since clinical data on the effectiveness of ginger in patients with advanced breast cancer is lacking, the present study aimed to evaluate the effects of ginger against both acute and delayed forms of CINV in a population with advanced breast cancer as the main malignancy. METHODS: In this pilot, randomized, open-label clinical trial, 100 women (mean age = 51.83 ± 9.18 years) with advanced breast cancer who were initially assigned to standard chemotherapy protocol with docetaxel, epirubicin, and cyclophosphamide (the TEC regimen) were randomized to receive ginger (1.5 g/d in 3 divided doses every 8 hours) plus standard antiemetic regimen (granisetron plus dexamethasone; the ginger group) or standard antiemetic regimen alone (control group). The duration of treatment with ginger was specified to 4 days from the initiation of chemotherapy. Prevalence, score, and severity of nausea, vomiting, and retching were assessed using a simplified form of Rhodes index in the first 6 hours, between 6 to 24 hours, and days 2, 3, and 4 postchemotherapy. RESULTS: A significantly lower prevalence of nausea was observed in the ginger group during 6 to 24 hours postchemotherapy. Despite this effect, no other significant additional benefit from ginger (1.5 g/d) was observed against prevalence or severity of nausea, vomiting, and retching in any of the assessed periods. CONCLUSION: Addition of ginger (1.5 g/d) to standard antiemetic therapy (granisetron plus dexamethasone) in patients with advanced breast cancer effectively reduces the prevalence of nausea 6 to 24 hours postchemotherapy. However, there is no other additional advantage for ginger in reducing prevalence or severity of acute or delayed CINV.

Hepatitis B virus genotype in Iranian patients with hepatocellular carcinoma.

OBJECTIVE: Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC). HBV appears to be the most common cause of HCC in Iran. To date, no study has been carried out on the HBV genotype in Iranian HCC patients. This study was undertaken to determine the HBV genotype in Iranian patients with HCC. METHODS: Paraffin-embedded tissue samples from 40 patients (31 males and nine females) with HBV-associated HCC were collected from different pathology centers during 2000-2007. Genotyping of HBV was performed by nested PCR-mediated amplification of the target sequence. PCR products were sequenced, and the genotype of each HBV sequence was determined by comparison with sequences of known genotypes in the GenBank. A phylogenetic tree was constructed. RESULTS: Phylogenetic analysis revealed that all of the HBV isolates were clustered in genotype D. CONCLUSIONS: Our results concur with other reports from Iran, all showing that genotype D is the only detectable genotype in the different clinical forms of HBV infection in this country.