Hepatitis Monthly
Year:2013 | Volume:13 | Issue:8|Papers Count:20

Context: Cystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emergedespecially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF.Evidence Acquisition: A literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library.Results: CF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause ofmortalityin CF (the third after pulmonary disease and transplant complications), only about the 33%ofCF patients presents clinically significant hepatobiliary disease.Conclusions: Liver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed atdelaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of fibrosis prevention and to avoid its progression prior to development its related complications.

Background: Liver transplantation (LT) is the only treatment option for patients with advanced liver disease. Currently, liver donation to these patients, considering priorities, is based on the Model for End-Stage Liver Disease (MELD). MELD score is a tool for predicting the risk of mortality in patients with advanced liver disease. However, few studies have so far been conducted in Iran on the efficacy of MELD score of these patients.Objectives: This study reviews the present status of the MELD score and introduces a new model for optimal prediction of the risk of mortality in Iranian patients with advanced liver disease.Patients and Methods: Data required were collected from 305 patients with advanced liver disease who enrolled in a waiting list (WL) in Imam Khomeini Hospital from May 2008 to May 2009. All of the patients were followed up for at least 3 years until they died or underwent LT. Cox regression analysis was applied to select the factors affecting their mortality. Survival curves were plotted. Wilcoxson test and receiver operating characteristics curves for survival predictive model were used to compare the scores. All calculations were performed with the SPSS (version 13.0) and R soft wares.Results: During the study, 71 (23.3%) patients died due to liver cirrhosis and 43 (14.1%) underwent LT. Viral Hepatitis (43.7%) is the most common cause of end-stage liver disease among Iranian patients. A new model (NMELD) was proposed with the use of the natural logarithms of two blood serum variables (total bilirubin and albumin) and the patients' age (year) by applying the Cox model: NMELD = 10 × (0.736 × ln (bilirubin) – 1.312 × ln (albumin) + 0.025 × age + 1.776).Conclusions: The results of the Wilcoxon test showed that there is a significant difference between the usual MELD and our proposed NMELD scores (P<0.001). Receiver operating characteristics curve for survival predictive model indicated that the NMELD score is more efficient compared with the MELD score in predicting the risk of mortality. Since serum creatinine was not significant in NMELD score, further studies to clarify this issue are suggested.

Background: Trans-arterial chemoembolization (TACE) is associated with better survival in BCLC-stage B patients with hepatocellular carcinoma (HCC) and Child-Pugh A whereas in Child-Pugh B there is no definite evidence of benefit.Objectives: To assess the safety and efficacy of TACE during routine clinical practice in a consecutive Greek cohort of patients with unrespectable HCC.Patients and Methods: Seventy one patients enrolled for this study (mean follow-up:24.6 months). 100 mg cisplatin, 50 mg doxorubicin and 10 ml lipiodol as well as embolic materials were used. CT-scans and blood tests were obtained prior and post-TACE. Kaplan–Meier method and Cox proportional hazard model were used to evaluate survival and factors affecting survival.Results: Survival at 1-year, 2-years, 3-years and 5-years was 73.2%, 45.4%, 33.2% and 14.9% respectively. Procedure-related mortality was 1.4%. Multivariate analysis showed lesion diameter, Child-Pugh classification, alcohol abuse, tumor response and AFP prior TACE as independent prognostic factors of survival. Patients diagnosed during surveillance had significantly better survival rates compared to those diagnosed after development of symptoms (HR = 0.58, 95%CI: 0.33-1.01, P < 0.05).Conclusions: TACE is safe and efficient for unrespectable HCC. Alcohol abuse, tumor burden, response criteria, Child-Pugh and AFP prior to the session were identified as independent predictors of survival whereas, adherence to surveillance programs resulted in significantly better survival in these patients.

Background: Occult hepatitis C virus (HCV) infection is a new entity described by the presence of HCV-RNA in liver biopsy and/or peripheral blood mononuclear cell (PBMC) specimens, and undetectable levels or absence of HCV-RNA and in the absence or presence of anti HCV antibodies in plasma by current laboratory methods.Objectives: To evaluate the detection of HCV-RNA in PBMC specimens of the liver transplant candidates with cryptogenic cirrhosis by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR).Patients and Methods: From November 2007 to March 2013, 45 patients from Liver Transplant Center of Imam Khomeini Hospital, Tehran, were enrolled in this cross sectional study. PBMC specimens were separated from the peripheral blood sample. After extraction of RNA from plasma and PBMC specimens, HCV-RNA status was tested by RT-nested PCR. The 5′-untranslated region (5′-UTR) genotyping of HCV-RNA amplified from PBMC specimens was performed by a standard methodology with the INNO-LiPATM HCV II kit. The PCR products of 5′-UTR were sequenced after cloning into the pJET1.2 / blunt cloning vector.Results: Of 45 patients, 4 (8.9% [95% CI: 4.4-15.6]) had detectable genomic HCV-RNA in their PBMC specimens. HCV genotypes were determined in the PBMCs of these subjects showed that 2 (50.0%) subjects with occult HCV infection had HCV subtype 3a, and 2 (50.0%) had HCV subtype 1b.Conclusions: This study found that 8.9 % of the Iranian candidates for liver transplant with cryptogenic cirrhosis had occult HCV infection. Therefore, designing prospective studies focusing on the diagnosis of occult HCV infection in these subjects prior to liver transplantation could be valuable.

Dear Editor, Liver plays the role of detoxifier and excreter of destructive agents against body intoxication. Liver injury occurs following by histopathological changes including degeneration, necrosis, and atrophy of liver parenchymal cells with interstitial connective tissue as well as increasing in liver enzymes, such as aspartate aminotransferase/alanine aminotransferase (AST/ALT), alkaline phosphatase (ALP), and plasma total bilirubin level (TBili) (1). Acute Hepatic Encephalopathy (AHE) is described as a neuropsychiatric syndrome which can be pursued by urea cycle defect as well as acute (ALF) and chronic liver failure (CLF)(2). Clinical neuropsychiatric symptoms, such as attention impairment, memory loss, response inhibition, confusion, lethargy, and coma, can be found in these patients (3). Ammonium toxins releasing in blood as a result of liver dysfunction was reported to be a cause of AHE…

Background: In many regions of southern Italy, hepatitis C virus (HCV) infection represents a major health problem (with a prevalence rate between 6% and 13%). HCV is associated with different kinds of neoplasms such as non-Hodgkin lymphomas (NHL), and with auto-immune diseases (cryoglobulinemia), which develop after the virus has caused immune system alterations.Objectives: To provide updated information on trends in mortality in a major metropolitan area of southern Italy from NHL, multiple myeloma and Hodgkin disease we analyzed cancer mortality data from 1988 to 2009.Materials and Methods: Mortality data were extracted from National death certificates by age groups, gender, residence and cause of death by the Italian national institute of statistics (ISTAT). Age-standardized mortality rates (SMR) were computed applying the direct method and using the world standard population. To quantify the recent direction of temporal trends in older populations over time, truncated age-adjusted mortality rates were calculated for people aged 65 years and older. Cancer mortality trends were described using their estimated annual percent change (EAPC) and related 95% Confidence Interval (CI).Results: Statistically significant increasing EAPC was found among women for NHL (+2.0% / year), while statistically significant decrease was found among men and women for HD (-3.5% / year, -3.4% / year, respectively). No statistically significant EAPC was found for multiple myeloma.Conclusions: The association between viral hepatitis and NHL in the area of interest might provide some degree of explanation to this finding. Our data confirm that due to epidemic infection of HCV in the area of Naples, a high mortality for NHL persists, moreover the adoption of standard therapeutic protocols administered in full accordance with an evidence-based approach and current guidelines explain reduced mortality from Hodgkin lymphomas.

Background: Infantile hepatic hemangioendothelioma (IHH) and hepatoblastoma (HBL) are respectively the most common benign and malignant liver tumors in children.Objective: To study the clinical manifestations and the ultrasound features of the pediatric patients for distinguishing IHH from HBL.Patients and Methods: Between 2002 and 2012, thirteen children with IHH and 38 children with HBL under the age of 10 years were included. We retrospectively reviewed the clinical and the ultrasound features of the two groups, especially including parameters as follows: age at diagnosis, gender, alpha-fetoprotein (AFP) elevation, venous involvement and Doppler ultrasound.Results: Compared with HBL group, the age of IHH group was much younger (5.8 months vs. 35.1 months, P = 0.000), the AFP elevation was less likely to be detected in IHH group (23.1% vs. 89.5%, P = 0.000). Although the color flow were the same commonly observed (61.5% vs. 52.6%, P>0.05), the spectral Doppler showed IHH was less likely to appear as arterial flow with resistance index (RI) > 0.7 (12.5% vs. 75.0%, P<0.05), characterized by arterial flow with RI < 0.7 and/or venous flow. Combined the clinical features including age (<6 months) and normal AFP level yielded high capability in differential diagnosis, with sensitivity, specificity and Youden index of 77% (10.13), 95% (36.38), and 0.72, respectively. When combined clinical features (age and AFP) and spectral Doppler as the diagnostic criterion for distinguishing these cases with positive color flow signals, the sensitivity, specificity, accuracy and Youden Index were 88%, 95%, 89% and 0.83, respectively.Conclusions: The clinical features are effective indicators for distinguishing IHH from HBL, and the spectral Doppler may be a useful adjunct parameter for differential diagnosis.

Background: Cyclosporine A (CsA)-induced hepatotoxicity could be due to a reduction in a2b1 integrin expression that may either be from the direct effect of CsA itself or from reactive oxygen species (ROS) overproduction.Objectives: In this study we aimed to identify the cellular mechanisms underlying CsA-induced hepatic injury by investigating the activation patterns of the antioxidant enzymes, using HepG2 as an in vitro model.Materials and Methods: HepG2 cells were cultured with different concentrations of CsA (0, 0.1, 1, 10 mg/ml) for 72 h. Effect of CsA on, 1) cellular integrity, 2) glutathione reductase (GR) and glutathione peroxidase (GPx) activity, 3) cellular levels of glutathione (GSH), 4) intracellular ROS, 5) ALT and AST activities, 6) urea production and 7) a2b1 integrin expression were assayed.Results: CsA treatment demonstrated a dose dependent increase in intracellular levels of ROS, GPx activity and decrease in GSH levels (P<0.05). GR activity was mildly attenuated in 1 and 10 mg/ml concentrations of CsA. Alanine aminotranferase (ALT) and aspartate aminotransferase (AST) levels increased in CsA treated cells, while urea synthesis was significantly decreased following treatment with higher concentrations of CsA (P<0.05). Significant down-regulation of β1integrin expression was observed in 1 and 10 mg/ml CsA treated cells while α2 integrin mRNA was significantly down-regulated in all CsA treated cells.Conclusions: The observed reduction of a2b1 integrin expression following CsA treatment could be proposed as a possible pathway of CsA-induced hepatotoxicity. Further studies are required to elucidate whether this attenuated expression is due to the direct effect of CsA or caused by overproduction of ROS.

Introduction: Cutaneous Mucormycosis is a rare opportunistic infection caused by Zygomycetes class of fungi that is often fatal, requiring aggressive local control as well as systemic therapy. Few cases of mucormycosis were described in patients with liver cirrhosis, mostly rhino-orbital. To our knowledge, only two cases of upper extremity involvement was reported in cirrhosis while a few cases were reported in the post-transplant setting. We report herein the third case of upper extremity mucor infection in the setting of liver cirrhosis.Case Presentation: We described a rare case of forearm infection originating in a traumatic intravenous access portal in a 25 year-old woman with liver cirrhosis secondary to autoimmune hepatitis.Discussion: She developed acute on chronic liver failure during the last trimester of pregnancy, which was terminated. Painful, erythematous lesion was noted on her right forearm in the area of intravenous access, which later became necrotic. Extensive debridement was done and histopathological examination confirmed the diagnosis of mucormycosis. The patient started on Amphotericin B. Her condition continued to deteriorate and ended up with above elbow amputation followed by right shoulder disarticulation. She died two days later due to multi-organ failure. In conclusion, forearm mucromycosis in liver cirrhosis can be fatal.

Dear Editor, In their recent article Kelishadi et al. (1) analyzed in a clear and concise way a number of key aspects of obesity-related NAFLD, deepening in particular the role of gut microflora and its potential therapeutic modulation by probiotics…

Context: The modern practice of anesthesia is highly dependent ona group of anesthetic drugs which many of them are metabolized in the liver.Evidence Acquisition: The liver, of course, usually tolerates this burden. However, this is not always an unbroken rule. Anesthetic induced apoptosis has gained great concern during the last years, especially considering the neurologic system.Results: However, we have evidence that there is some concern regarding their effects on the liver cells. Fortunately not all the anesthetics are blamed and even some could be used safely, based on the available evidence.Conclusions: Besides, there are some novel agents, yet under research, which could affect the future of anesthetic agents' fate regarding their hepatic effects.

Background: Injecting drug users (IDUs) are a major and most important risk factor for rising hepatitis C virus (HCV) prevalence in Iran.Objectives: The objective of this study was to determine the effectiveness of methadone maintenance treatment (MMT) in prevention of HCV infection transmission among IDUs.Patients and Methods: A mathematical modeling has been used to estimate number of HCV infections averted. The input parameters used in the model were collected by self-reported method from 259 IDUs before registering and one year after MMT. Nonparametric statistical tests have been used to compare risky injecting and sexual behaviors among IDUs before and after participating in MMT program. Deterministic sensitivity analyses were done to show the effects of parameters’ uncertainty on outcome.Results: Of the 259 participants, 98.4% (255) were men, the mean age ± SD was 33.1 ± 7.58 years and HCV prevalence was 50%. The studied IDUs reported lower rate of risky injecting and sexual behavior after participation in MMT program. The cumulative incidence of HCV per 100 IDUs due to sharing injection and unsafe sexual contact with MMT program were 13.84 (95% CI: 6.17 -21.51), 0.0003 (0.0001 - 0.0005) and without it 36.48 (25.84 - 47.11) and 0.0004 (0.0002-0.0006) respectively.Conclusions: The MMT program is an effective intervention to prevent HCV infection transmission, although it is essential to compare its effectiveness with other interventions before implementing it in nationwide.

Background: Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease. Seven genotypes and more than 80 subtypes have been identified for HCV so far. To date, 10 subtypes (3a to 3i; and 3k) of HCV genotype 3 have been identified. In 2006, two HCV isolates were reported from Iran that belonged to a new subtype of genotype 3. However, considering the consensus proposal for HCV genotype nomenclature, the available sequences of the new subtype did not correspond to the regions that are required to be analyzed prior to subtype assignment. During a study on the molecular epidemiology of HCV in Iran, an HCV isolate (FSM165) which seemed to belong to a new subtype of genotype 3 was obtained from a patient residing in Tehran, Iran.Objectives: The aim of this study was to assess the relatedness of isolate FM165 together with several sequences retrieved from the database to the new HCV-3 subtype reported from Iran in 2006.Materials and Methods: Various parts of the genome including the core/E1 region and two segments of the NS5B region were amplified and sequenced for isolate FSM165. Furthermore, using the Basic Local Alignment Search Tool (BLAST), the HCV database was searched for sequences that had a high level of similarity with sequences of FSM165 isolate and such sequences were retrieved from the database. To investigate the relatedness of isolate FSM165 and also the retrieved sequences to a new HCV-3 subtype reported previously, phylogenetic analyses were performed using the Kimura two-parameter model and the neighbor joining method.Results: Phylogenetic analysis of the partial NS5B region demonstrated the relatedness of isolate FSM165 to the new subtype reported from Iran in 2006. Moreover, some core/E1 and NS5B sequences that had a high level of similarity with FSM165 isolate were found through searching the HCV database. These sequences were previously either misclassified or could not be accurately classified. Phylogenetic analyses showed that all of the described sequences belonged to the new subtype of HCV genotype 3.Conclusions: Data suggests that the new subtype has a vast geographical distribution in Iran. The core/E1 and the NS5B sequences described in this paper can be used as references for the new HCV-3 subtype in future studies.

Background: Hepatitis delta virus (HDV) is a defective RNA virus dependent on Hepatitis B virus (HBV) infection for its replication and expression. All patients with HBV infection should be tested for the presence of HDV infection. It is estimated that approximately 5% of hepatitis B surface antigen (HbsAg) carriers in the world are HDV infected patients. HBV-HDV co-infection may lead to more severe acute disease and higher risks of fulminant hepatitis, cirrhosis, and hepatocellular carcinoma than those having HBV infection alone. Also, HBV infected patients with HDV super-infection have a higher rate of progression to chronic disease and serious complications.Objectives: Our aim was to determine the prevalence of HDV infection among chronic hepatitis B (CHB) patients attending Birjand Hepatitis Clinic, East of Iran.Materials and Methods: A cross-sectional analytical study was conducted on 413 CHB patients in 2012. Serology test for anti-HDV was measured by ELISA in these patients. CHB patients had positive hepatitis B surface antigen for at least 6 months before the study entrance.Results: The mean age of CHB patients was 38.5± 11.9 years and 55.9% of them (231 patients) were male. There were 13 cases (3.1%) with HDV infection. There was no association between positive anti-HDV serology and factors such as age, gender, carrier state, liver enzymes, and positive hepatitis B e antigen (HBeAg) serology.Conclusions: Although HDV had a low prevalence in our area, it is important for healthcare providers and policy makers to plan preventive strategies for HDV spread as well as HBV prevention programs among high risk population.

Background: Hepatocyte transplantation is being used in patients with liver-based metabolic disorders and acute liver failure. Hepatocytes can be isolated from unused/rejected livers under sterile conditions.Objectives: The quality of the hepatocytes is very important and the main and initial step in hepatocyte transplantation is hepatocyte isolation. In this study we tried to set up the methods of hepatocyte isolation in order to use the high quality cells in acute liver failure or congenital metabolic disorders.Materials and Methods: In this study, during a year, hepatocytes were isolated from 7 unused/rejected livers among more than 300 harvested livers in Shiraz University of Medical Sciences. The two step collagenase perfusion method was used under GMP (Good manufacturing practice) for hepatocyte isolation.Result: Highly quality hepatocytes with high viability and low contamination were isolated. The mean viability was 71.8%±21.7. In the first 4 cases microbial contamination by Staphylococci, Diphtheroid and Klebsiella was detected, however the last 3 cases were free of any microorganisms. After 5 weeks of cryopreservation in -140oC, the cell viability was still acceptable.Conclusion: Hepatocyte isolation can be performed as the main and initial step for cell transplantation from unused/rejected liver. It is the first experience in Iran.

Background: Hepatitis C virus (HCV) was found to have a major role in human liver disease by its ability to face the host-cell defenses and the immune system. Heterogeneity of HCV was the key for its adaptation to its host and represented a significant hurdle for the development of both effective vaccines as well as for novel therapeutic interventions.Objectives: Due to the heterogeneity of HCV virus because of both high replication and high mutation rate in vivo, this study was conducted to analyze different isolates of Egyptian patients of genotype 4, of the most mutant regions of the virus (E1 and E2) as they played an important role in viral persistence by escaping from the immune system of the host body.Patients and Methods: This study was conducted through PCR amplification of E1 and E2 regions, sequencing and phylogenetic analysis, calculating synonyms and non-synonyms substitutions, finding the possible glycosylation sites and different epitope domains.Results: The present work figured out that the heterogeneity of the quasispecies of our local strains 4a was high showing up 15% diversity. This study also showed four glycosylation sites that play an important role in the entry of the virus and protein folding. Besides, different epitpoes were identified in different regions of the E1 and E2 domains, a finding which would help in determining the neutralizing and non- neutralizing antibodies.Conclusions: This study would help in understanding the driving forces of genetic diversity and would be fundamental for representing potential candidate targets for antibodies and the development of vaccine trials.

Background: Hepatitis E Virus (HEV) infection is a significant public health concern and responsible for large outbreaks of acute hepatitis in poor sanitary and living conditions.Objectives: To investigate the impact of population movements on virus spreading, a large-scale population-based survey was performed in a pilgrimage- tourism area, the great Mashhad, capital city of Khorasan province.Patients and Methods: A cross-sectional study was carried out among 1582 randomly selected individuals from general population of Mashhad, north east of Iran, between May to September 2009. Serum samples were tested for total anti-HEV antibody using a specific enzyme linked immunoassay (ELISA) kit.Results: The prevalence of HEV infection was 14.2% (225.1582) with a maximum of 25.5 % (14.55) in densely populated areas. The highest prevalence was observed in visitant areas (³20%) near the holly shrine with crowded hotels and inns. The differences between these areas and other districts were statistically significant (P<0.001). The findings indicated that 13.2% (95.718) of males and 15.0% (130.864) of females were HEV positive, this difference is not significant. Seroprevalence increases with age rising, from 12.8% in subjects less than five years to 28.6% in individuals with more than 65 years old. Although, there were no meaningful differences between HEV seropositivity and socio-economic status, Illiterate individuals were significantly at higher risk for infection than educated persons (P<0.001).Conclusions: These findings demonstrated that, high prevalence of HEV is related to populated district, which can reach to the highest rate in hotels and inns close to visitants. Traditional sanitation and water supplying systems are the second important factor for the virus transmission. Therefore, it can be concluded that such areas need efficient surveillance systems to prevent the spreading of infectious diseases.

Background: Zinc deficiency has been reported frequently in hepatitis C patients in the literature. Furthermore, a decrease in zinc level has been shown in beta thalassemia major as well. Iranians consume a large amount of phytate in their regimens which can bind with zinc and decrease its gastrointestinal absorption.Objectives: This study was designed to determine plasma zinc level in an Iranian sample with the diagnosis of hepatitis C with or without concomitant beta thalassemia major.Patients and Methods: Between April 2011 and April 2012, plasma zinc level was determined via atomic absorption method, in 130 hepatitis C patients with or without beta thalassemia major in a known referral center of hepatic diseases in Tehran, Iran.Results: Mean±standard deviation (SD) of plasma zinc levels was determined as 0.78 ± 0.22 mg/L. Also zinc level was 0.76±0.19 mg/L and 0.80±0.24 mg/L in thalassemic and non thalassemic patients, respectively. T-test analysis showed that there is no significant difference between these two groups regarding plasma zinc level (P=0.235).Conclusions: It is concluded that zinc level of studied patients is less than which is reported in normal Iranian population. Moreover, there is not a significant difference in plasma zinc levels between thalassemic and non thalassemic patients and it seems to be a common problem in both ones. Addition of zinc supplement may be recommended in both groups in order to optimize the nutritional support and probably improve the treatment response.

Background: The study of weight gain after transplantation and its associated factors is necessary to propose strategies to prevent and treat this problem.Objectives: This study aims to investigate factors affecting the development of obesity after liver transplantation (LTx).Patients and Methods: Medical records of 343 liver transplantation cases, which were followed between January 2001 and January 2010 at Dokuz Eylul University, were retrospectively analyzed. Patient pre-liver transplantation height, body weight, body mass index (BMI) measurements, as well as changes in body weight at the beginning, 6 months, 12 months, and 5 years post-transplantation were observed. BMI measurements with records of immunosuppressive therapies were obtained.Results: The study was carried out with the records of 226 patients. 151 patients (66.8%) were male, 75 (33.2%) were female. The mean age was 46.19±10.2 years. 123 of these liver transplants were performed from living donors, while 103 were from cadaveric donors. The causes of liver transplantation were hepatitis D virus (HDV) infection (28%), hepatitis B virus (HBV) infection (24%), hepatitis C virus (HCV) infection (24%), alcoholic liver disease (9%), cryptogenic liver disease (9%), autoimmune hepatitis (4%), and other (2%). In this study, the prevalence of obesity was 21% at the end of the second year, decreasing to 14% by the end of the fifth year. The mean BMI gradually increased during the follow-ups, reaching 25.1 kg/m2 and 26 kg/m2 six months after liver transplantation and at the end of the first year, respectively (P < 0.002). Obesity developed in 18.2% of post-transplant patients who were receiving a calcineurin inhibitor (CNI). Regarding the development of obesity after transplantation, no statistically significant difference was found between patients using cyclosporine (CsA) and tacrolimus (TAC) (P=0.07). Six months after liver transplantation, the mean body weight gain in the groups receiving steroids and not receiving steroids were 4.71 kg and 2.7 kg, respectively (P = 0.03). In the post-transplant period, there was no significant difference in patients who had received TAC and CsA for development of diabetes mellitus (DM), hypertension (HT), or hyperlipidemia (HL) (P=0.30).Conclusions: Obesity prevalence before and after liver transplantation was comparable. Education of obese patients prior to surgery and recommendation of medical nutrition therapy should be appropriate. Similar medical care for the non-obese subjects could prevent increase in obesity prevalence. Non-corticosteroid immunosuppressive agents had no significant effect on the development of weight gain and obesity. Avoiding the use of long-term steroid therapy and obesity education are the key measures for preventing obesity after liver transplantation.

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.