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.
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 softwares.
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)
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.
Liver Transplantation; End-Stage Liver Disease; Allocation; Liver Cirrhosis
Probiotics; Non-Alcoholic Fatty Liver Disease; Children; Obesity
Liver; Rat; Pathology
The modern practice of anesthesia is highly dependent ona group of anesthetic drugs which many of them are metabolized in the liver.
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.
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.
Besides, there are some novel agents, yet under research, which could affect the future of anesthetic agents' fate regarding their hepatic effects.
Liver; Apoptosis; Anesthesiology; Pharmacology
Injecting drug users (IDUs) are a major and most important risk factor for rising hepatitis C virus (HCV) prevalence in Iran.
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.
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.
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.
Hepatitis C; Effectiveness; Methadone; Maintenance; Incidence; Iran
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.
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.
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.
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.
Hepatitis C; Genotype; Phylogeny; Iran
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.
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.
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.
HDV should be suspected in HBV carriers with unusual clinical and virological pictures. Relatedness of Iranian HDV isolates to Italian and Turkish sequences proposed a common Caucasian origin for the distribution of HDV genotype I in this ethnic group.
Hepatitis Delta Virus; Prevalence; Antibodies
Cyclosporine A (CsA)-induced hepatotoxicity could be due to a reduction in α2β1 integrin expression that may either be from the direct effect of CsA itself or from reactive oxygen species (ROS) overproduction.
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 μg/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) α2β1 integrin expression were assayed.
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 µg/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 µg/ml CsA treated cells while α2 integrin mRNA was significantly down-regulated in all CsA treated cells.
The observed reduction of α2β1 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.
Cyclosporine; Antioxidant; Enzymes; Integrin alpha2beta1
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.
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.
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).
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.
Zinc; Beta-Thalassemia; Hepatitis C; Iran
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.
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.
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.
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.
Hepatitis C Virus; Occult Infection; Peripheral Blood Mononuclear Cells; Cryptogenic; Cirrhosis; Liver Transplantation
The study of weight gain after transplantation and its associated factors is necessary to propose strategies to prevent and treat this problem.
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.
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).
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.
Liver Transplantation; Obesity; Immunosuppressive Agents; Metabolic Diseases
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.
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.
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.
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.
Hepacivirus; Phylogenetic Analysis; Polysaccharides; Epitopes
Glomerular Filtration Rate; Liver Cirrhosis; Liver Transplantation; Kidney Function Tests
Background: Chronic HCV represents one of the common causes of chronic liver disease worldwide with Egypt having the highest prevalence, namely genotype 4. Interleukin IL-28B gene polymorphism has been shown to relate to HCV treatment response, mainly in genotype1.
Objectives: We aim to evaluate the predictive power of the rs12979860 IL28B SNP and its protein for treatment response in genotype 4 Egyptian patients by regression analysis and decision tree analysis.
Patients and Methods: The study included 263 chronic HCV Egyptian patients receiving peg-interferon and ribavirin therapy. Patients were classified into 3 groups; non responders (83patients), relapsers (76patients) and sustained virological responders (104 patients). Serum IL 28 B was performed, DNA was extracted and analyzed by direct sequencing of the SNP rs 12979860 of IL28B gene.
Results: CT, CC and TT represented 56 %, 25 % and 19% of the patients, respectively. Absence of C allele (TT genotype) was significantly correlated with the early failure of response while CC was associated with sustained virological response. The decision tree showed that baseline alpha fetoprotein (AFP ≤ 2.68 ng/ml) was the variable of initial split (the strongest predictor of response) confirmed by regression analysis. Patients with TT genotype had the highest probability of failure of response.
Conclusions: Absence of the C allele was significantly associated with failure of response. The presence of C allele was associated with a favorable outcome. AFP is a strong baseline predictor of HCV treatment response. A decision tree model is useful for predicting the probability of response to therapy.
Hepatitis C Virus; IL28B Protein, Human; Decision Trees; Data Mining; Peginterferon Alfa-2a
Dietary intake might have important role in non-alcoholic fatty liver diseases (NAFLD). Although, there are some reports on dietary intake and anthropometrics measurements, few studies have focused on the markers of assessing whole diet like dietary quality indices.
Therefore, our aim was to determine the diet quality indices and biochemical parameters among patients with NAFLD and healthy individuals.
Patients and Methods
This case-control study was performed on 100 patients with NAFLD and 100 healthy subjects who were attending to Gastrointestinal Research Center, Baqiyatallah University, Tehran, Iran during the recent years. Usual dietary intake was assessed by three dietary records (one weekend and two week days). Healthy eating index (HEI), dietary diversity score (DDS), dietary energy density (DED), mean adequacy ratio of nutrients (MAR) were assessed according to the standard methods.
Patients with NAFLD had higher body mass index, weight and waist circumference compared to the healthy group (P < 0.05). Serum levels of liver enzymes, triglyceride, LDL, BUN, and uric acid were higher in patients with NAFLD (P < 0.05). Although patients with NAFLD had higher energy, carbohydrate and fat intake, their values for antioxidant vitamins, calcium and vitamin D were lower than healthy subjects (P < 0.05). HEI and MAR were higher among healthy group, and DED was lower among them. Nutrient adequacy ratio for calcium, vitamin D, and antioxidant micronutrients were lower in patients with NAFLD (P < 0.05).
It seems that dietary quality indices may be associated with NAFLD. Calcium, vitamin D, and antioxidant micronutrients intake might be lower among patients with NAFLD based on this case-control study. Further prospective studies should be conducted in this regard.
Diet Therapy; Healthy People Programs; Biochemical Processes; Non-alcoholic Fatty Liver Disease
Hepatitis B virus (HBV) is one of the most common chronic viral infections in the world. Iran has a low to intermediate HBV prevalence and approximately 1.5 million people are living with HBV infection. The impact of HBV in Iran is unknown and given the very low levels of alcohol consumption, this region provides an opportunity to examine the impact of isolated chronic HBV infection.
To examine and evaluate outcome and prognosis of HBV in Iran.
Patients and Methods
A longitudinal cohort study dating from 2003-2010 was performed. The patients were assessed six months after their first visit and then during periodic visits for the subsequent seven years. The patients’ medical history, route of diagnosis of infection, family history, and liver diseases status including: carrier state of HBV, chronic HBV, cirrhosis, and HCC were recorded. Descriptive and analytic statistics were performed, using SPSS software version 18.
275 HBsAg positive patients, who had completed a 7 year follow up period, were selected. The annual incidence rate for chronic hepatitis B in inactive carrier states and cirrhosis were 0.46% and 0.2% respectively. Over seven years, the rate of inactive carriers decreased by eight percent (They turned into chronic HBV or became HBSAg negative). No significant association was found between HBSAg seroclearance, HBeAg seroconversion and the outcome in the end of each year of follow up. Different treatment regimens did not have any statistically significant difference regarding HBeAg seroconversion. There was no significant association between the outcome and different habitual characteristics, especially smoking, as well as family history on HBsAg, HBsAb, HBeAg, and Anti-HBeAg. Values of platelets and ALT showed a significant change during the follow ups. Annual incidence rate of HCC in the present study was in the range of other studies.
These data confirm and extend data from other populations showing a low incidence of significant change in chronic HBV infection in short term with good responses to currently available therapeutics.
Hepatitis B; Hepatitis B Surface Antigens; Longitudinal Studies; Confounding Factors (Epidemiology)
Liver transplantation is considered as the standard treatment for both children and adults with end-stage liver diseases. Using this method, children who have no chance for life can live a much longer life .Shiraz Transplant Center is the major pediatric liver transplant center in Iran. Therefore, determining patients’ survival and its effective factors can help clinical programming for increasing such patients’ survival after liver transplantation.
The present study aimed to investigate the survival of patients below-18-years-old undergoing liver transplantation and the factors affecting their survival.
Patients and Methods
The present historical cohort study was conducted on 392 patients below-18-year-sold who had undergone liver transplantation for the first time in the Namazi hospital liver transplant center, Shiraz, Iran between 2000 and 2011. In this study, 1-, 3-, 5-, and 10-year survival of the patients was assessed using Kaplan-Meier and life table methods. The effect of factors related to the recipients, donors, and the transplantation process on the patients’ survival was also investigated.
According to the results, 1, 3, 5 and 10-year survival of patients was 73%, 67%, 66%, and 66%, respectively. Besides, 1 ,3, 5, and 10-year survival of the patients who survived 1 and 3 months after the transplantation was 84%, 78%, 77%, and 77% and 89%, 82%, 81%, and 81%, respectively. In the univariate analysis, age, patients’ weight at transplantation, initial diagnosis, PELD/MELD score, existence of post-transplant complications, and year of transplantation were found to be effective factors on the patients’ survival. In the multivariate analysis, only the type of graft, PELD/MELD score, and existence of post-transplant complications were the prognostic variables.
In this study, the patients’ survival rate was 73%, which is quite low compared to the survival rate reported in other studies. Although we only have a 12-year experience with pediatric liver transplantation, the survival rate has increased in our center through the recent years (2008-2011). However, the survival rate of the patients who had survived 3 months after the transplantation was 89% which is comparable to other studies. Overall, cholestatic diseases (biliary atresia was the most prevalent), type of transplantation (split), PELD/MELD score > 20, and existence of post-transplant complications increased the risk of death after the transplantation.
Survival; Pediatrics; Liver Transplantation; Iran
Hepatocellular carcinoma is a highly progressive cancer in the case of late diagnosis which is frequently associated with HBV and HCV viral infections.
To identify differentially expressed serum proteins among three main stages of HCV infection and healthy individuals, and their comparisons with sera from patients with the same stage of HBV infection.
Patients and Methods
Two-dimensional polyacrylamide gel electrophoresis combined with liquid chromatography-tandem mass spectrometry was performed on 47 sera from healthy volunteers, those with chronic active hepatitis, cirrhosis and HCC patients associated with HBV and HCV infections.
Among these, 62 spots were differentially expressed (≥ 1.5 fold; P < 0.05), of which 42 spots that corresponded to 15 proteins were identified by liquid chromatography-tandem mass spectrometry. CD5-like antigen (CD5L) was differentially expressed between cirrhosis and HCC patients with HCV infection. Leucine-rich α2-glycoprotein (LRG) and haptoglobin (HP) α2 isoforms differed in the HCC that was associated with either HCV or HBV infections.
CD5L might be a useful biomarker for early diagnosis of HCC in HCV cirrhotic patients. LRG and HP α2 isoforms could be potential markers for distinguishing viral HCC. Our results also further support the presence of varying molecules involved in hepatocarcinogenesis in HBV when compared with HCV infection.
Cirrhosis; Hepatitis B Virus; Hepatitis C Virus; Hepatocellular Carcinoma
Y-box binding protein 1 (YB-1) overexpression has been shown in various tumor cells including hepatocellular carcinoma (HCC); moreover, this protein can be actively secreted.
The aim of this study was to establish a method to quantify serum YB-1 and evaluate its clinical application in the clinical diagnosis of HCC.
Patients and Methods
Recombinant YB-1 and two populations of its antibodies were prepared. A monoclonal antibody was specific to the N-terminus of YB-1 amino acids 134-160; and another was a polyclonal antibody. A sandwich-type chemiluminescence immunoassay (CLIA) was developed and evaluated. Levels of YB-1 and alpha fetoprotein (AFP) in serum samples from 105 HCC patients, 25 hepatitis B virus patients, 25 cirrhosis patients, and 50 healthy donors were detected using the established method and an AFP electrochemiluminescence kit.
The developed method was linear to 150 μg/L of YB-1 with a minimum detection limit of 0.01 μg/L. The average recoveries were between 93.9% and 109.0%. The mean intra- and inter-assay coefficients of variation (CVs) were 4.0-4.8% and 8.2-10.2%, respectively. The relationship between the concentration of diluted YB-1 and the dilution ratios gave a good linear correlation coefficient of 0.9986. The YB-1 concentration was increased in serum of HCC patients (33.0 ± 23.39 μg/L) compared to healthy individuals (13.2 ± 5.29 μg/L, P < 0.0001), patients with HBV (17.9 ± 7.49 μg/L, P = 0.0003), and patients with HBV cirrhosis (20.7 ± 8.75 μg/L, P < 0.05). Moreover, the combination of YB-1 and alpha-fetoprotein had a high sensitivity (89.5%) and reasonable specificity (62.0%) in identifying HCC.
The established method has an acceptable performance in quantifying YB-1. In addition, serum YB-1 may aid in the diagnosis of HCC.
Y-Box-Binding Protein 1; Carcinoma; Hepatocellular; Tumor Marker
Needle Sticks; Blood Borne Pathogen; Healthcare Workers
Hepatitis B virus; Genotype
Serum apoptotic cytokeratine 18 neoepitope M30 (CK-18 M30) and matrix metalloproteinase 2 (MMP-2) have been popular markers for detecting liver fibrosis in recent years. CK-18 is a major intermediate filament protein in liver cells and one of the most prominent substrates of caspases during hepatocyte apoptosis. MMP-2 plays an important role in tissue remodeling and repairing processes during physiological and pathological states.
The objective of this study was to investigate the significance of CK-18 M30 and MMP-2 levels for clinical use in patients with chronic hepatitis B (CHB), as well as their sensitivity in determining cirrhotic patients.
Patients and Methods
This study included 189 CHB patients and 51 healthy controls. A modified Knodell scoring system was used to determine the fibrosis level in chronic hepatitis B patients. CK-18 M30 levels were determined with an M30-Apoptosense ELISA assay. MMP-2 levels were determined with the ELISA assay.
The study group consisted of 132 (69.8%) males and 57 (30.2%) females, and the control group consisted of 25 males (49.0%) and 26 females (51%). Patients’ CK-18 M30 levels were higher than values of the control group (308 [1–762] vs. 168 [67–287], P=0.001). Serum MMP-2 levels were found to be statistically higher in the patient group with respect to the controls (3.0 [1.1–6.8] vs. 2.0 [1.2–3.4], P=0.001). The highest serum CK-18 M30 and MMP-2 levels were measured in patients with cirrhosis. Serum apoptotic CK-18 M30 levels positively correlated with advanced age, fibrosis stage, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (P= 0.001, 0.033, 0.001, and 0.001, respectively). Serum MMP-2 levels positively correlated with fibrosis stage, serum ALT, and AST levels (P= 0.001, 0.001, and 0.001, respectively).
Our study indicated that CK-18 M30 and MMP-2 levels were higher in CHB patients compared to healthy controls and they were in association with significant hepatic fibrosis, especially cirrhosis.
Hepatitis B, Chronic; Cirrhosis; Liver Cirrhosis; Matrix Metalloproteinase 2
Various aspects of adherence to HCV treatment such as frequency, risk factors as well as causes of non-adherence, and its real role in clinical and virological outcome of the infected patients have remained largely unknown.
The current study aimed to evaluate patients’ adherence to anti-HCV medications in Iran.
Materials and Methods
From October 2010 to March 2011, socio-demographic characteristics, features of HCV infection, clinical properties, and habitual history of 190 patients were collected. Adherence of each patient to anti-HCV medications was determined at months 1, 3, and 6 of treatment by self-reporting and pill or empty ampoule counting. Adherence to anti-HCV treatment regimen was determined based on the 80/80/80 rule.
Adherence rate to interferon, ribavirin, or a combination of them over the first 6 months of therapy in Iranian HCV patients measured by both methods of self-reporting and pill counting were 35.4-65.8%, 46.3-56.8%, and 28.4-51.1%, respectively. Delay in receiving new prescription, financial issues, and adverse drug reactions were the most common causes of non-adherence in the patients. Adherence to ribavirin was identified as an independent predictor of achieving the end of treatment response, or sustained virological response.
The rate of adherence to interferon and ribavirin varied significantly according to the method of calculation. Over the treatment course, adherence to interferon alpha and ribavirin, each or their combination, diminished significantly.
Hepatitis C, Chronic; Medication Adherence; Iran
Leptin and adiponectin are two hormones, which are released from adipocytes in order to control energy expenditure. Both hormones are also involved in glucose homeostasis through control of insulin secretion from pancreatic islets. Since Pdx1, PPARγ, and foxm1 play important roles in islets function, it is essential to understand how these genes are regulated in the islets of Langerhans.
We have designed an experiment to identify the effect of leptin and adiponectin treatment on Pdx1, PPARγ, and foxm1 transcription.
Materials and Methods
Islets were isolated from adult male rats by collagenase and incubated with different concentrations of leptin and adiponectin for 24 hours. Next, by means of real time PCR, we evaluated the gene transcription related to a housekeeping gene. The effect of leptin and adiponectin on insulin secretion was evaluated by ELISA.
Leptin decreased PPARγ transcription and insulin secretion, while adiponectin significantly increased Pdx1 and PPARγ transcription and insulin secretion in rat islets. The transcription of foxm1 did not change in the islet cells treated with leptin or adiponectin.
These findings indicate the possibility that Pdx1 and PPARγ transcription is a mediator of leptin and adiponectin function in control of insulin secretion and glucose homeostasis in pancreatic islets.
Leptin, Adiponectin; PPAR gamma; Islets of Langerhans; Insulin
Pegylated interferon alfa plus ribavirin protocol is currently considered the most efficient hepatitis C treatment. However, no evidence of costs comparison among common viral genotypes has been published.
We aimed to assess core drivers of hepatitis C medical care costs and compare cost effectiveness of this treatment among patients infected by hepatitis C virus with genotypes 1 or 4 (group I), and 2 or 3 (group II).
Patients and Materials
Prospective bottom-up cost-effectiveness analysis from societal perspective was conducted at Infectious Diseases Clinic, University Clinic Kragujevac, Serbia, from 2007 to 2010. There were 81 participants with hepatitis C infection, treated with peg alpha-2a interferon plus ribavirin for 48 or 24 weeks. Economic data acquired were direct inpatient medical costs, outpatient drug acquisition costs, and indirect costs calculated through human capital approach.
Total costs were significantly higher (P = 0.035) in group I (mean ± SD: 12,751.54 ± 5,588.06) compared to group II (mean ± SD: 10,580.57 ± 3,973.02). In addition, both direct (P = 0.039) and indirect (P < 0.001) costs separately were significantly higher in group I compared to group II. Separate comparison within direct costs revealed higher total cost of medical care (P = 0.024) in first compared to second genotype group, while the similar tendency was observed for total drug acquisition (P = 0.072).
HCV genotypes 1 and 4 cause more severe clinical course require more care and thus incur higher expenses compared to HCV 2 and 3 genotypes. Policy makers should consider willingness to pay threshold differentially depending upon HCV viral genotype detected.
Cost-Benefit Analysis; Interferons; Ribavirin; Hepatitis C, Chronic