Post liver transplant complications of Budd-Chiari syndrome.

BACKGROUND/PURPOSE: Budd-Chiari syndrome (BCS) is a rare, life-threatening disease characterized by hepatic venous outflow obstruction. Liver transplantation (LT) is widely accepted as an effective therapeutic measure for irreversible liver failure due to BCS. There is debate on differences in the post LT course and complications in patients with BCS as compared to non-Budd-Chiari (NBC) patients. METHOD: In this retrospective study, data on all patients who received a liver transplant for BCS at the Shiraz Organ Transplantation Center between January 1996 and September 2017 were reviewed and compared to data of a control group who had received liver transplants over the same period but due to other causes (NBC). RESULTS: Out of 4225 patients who received liver transplants in the study period, 108 had BCS and an age- and gender-matched control group consisted of 108 NBC cases. The mean ± standard deviation (SD) of model for end-stage liver disease (MELD) scores were 19.1 ± 3 and 20 ± 3 for BCS and NBC groups, respectively (p = 0.33). One-, 3-, 5-, and 10-year survival rates in the BCS group were as follows: 82%, 78%, 76%, and 76% compared with the NBC rates of 83%, 83%, 83%, and 76%, respectively (p = 0.556). There was no difference between the two groups in complication rates after 6 months. In the later period, vascular thrombosis was more common in BCS. CONCLUSIONS: Whole-organ LT from deceased donors in patients with BCS had comparable outcomes with LT due to other causes of end-stage liver disease. In most instances, these patients should receive lifelong anticoagulation.

The Investigation of Drug Resistance Substitutions in NS3 Protease Sequence of Hepatitis C Virus from Non-Responder Patients.

Background: Even with the fantastic successes of direct-acting antivirals (DAA) in the treatment of Hepatitis C Virus (HCV) infection, natural drug resistance remains a challenging obstacle for their impacts. The data regarding protease inhibitors (PIs) resistance in Iran population are limited. The aim of this study was to investigate the variations in NS3 protease of HCV from non-responder patients. Methods: In this cross-sectional study, 14 HCV infected patients with genotype 1(N=5) and 3(N=9) who have not responded to Interferon-related regime were enrolled from Liver Clinic, Shiraz. The NS3 protease region was amplified by Nested-PCR followed by product gel extraction. Besides, some amplified protease regions were cloned into a cloning vector to improve the sensitivity of mutation detection. Both crude and cloned sequences were then introduced into sequencing. The obtained sequences were compared with the NS3 reference sequences and analyzed by Geno2pheno available software to find possible substitutions. In the end, the phylogenetic tree was constructed. Results: Among variations responsible for PIs resistance, only one out of 14 (7%) sample who was infected with genotype 1a, harbored R117C+N174S double mutation, which causes reduced susceptibility to Telaprevir. Any another resistance mutation was not found among the studied population. The most frequent substitutions were determined as I52M(N=9), S102A(N=9), S166A(8) and V170I(8) for genotype 3a, and F147S/A(4) for genotype 1. However, some uncharacterized substitutions on scored position, including I132L(N=1), I170V(N=3) and N174S(N=2) were also determined among sequences. Phylogenetic analysis demonstrated that the protease region has enough power to correctly classify enrolled samples into relevant clusters on the tree. There were 2, 3 and 9 cases of sub-genotypes 1a, 1b, and 3a, respectively. Conclusion: A low frequency of PIs resistance mutations in our HCV infected population is a hopeful point of starting these drugs in HCV infected patients.

Association of HBsAg mutation patterns with hepatitis B infection outcome: Asymptomatic carriers versus HCC/cirrhotic patients.

INTRODUCTION AND OBJECTIVES: The hepatitis B virus (HBV) surface antigen (HBsAg) variations suggested having some effects on infection outcome. Due to some controversial issues, the aim of this study was to compare the pattern of HBsAg variation between asymptomatic carriers and HCC/cirrhosis patients. MATERIALS AND METHODS: In this cross-sectional study, 19 HCC/cirrhotic and 26 asymptomatic patients were enrolled. After viral DNA extraction, HBs gene was amplified using an in-house nested-PCR. Then, PCR products were introduced into bi-directional Sanger sequencing. The retrieved sequences were compared with references, to investigate the variation of immunologic sites, major hydrophilic region (MHR) of HBsAg as well as reverse transcriptase (RT), and also to determine genotype/subtype. RESULTS: The analysis of MHR and epitopes on HBsAg showed dozens of substitution, which occurred more prevalently in I110, P120, Y134, G159, S193, Y206, S207, I208, L213 and P214 positions. However, Y134N/F/L (P=0.04) and P120T/S (P=0.009) were significantly detected in MHR and B-cell epitope of HCC/Cirrhotic group. A number of truncation-related mutations were higher in HCC/Cirrhotic group (P>0.001), albeit only C69* stop codon was statistically significant (P=0.003). In RT, some potentially resistant substitutions such as Q215S, V191I and V214A, were revealed. Phylogenetic analysis showed that all of isolates belonged to genotype D, and the major serotype was ayw1. CONCLUSION: The higher frequency of substitutions in MHR and immune epitopes at positions such as Y134 and P120 as well as stop codons such as C69* in HCC/cirrhotic group might candidate them as predictive factors for infection outcome.

Associations of ICOS and PD.1 Gene Variants with Colon Cancer Risk in The Iranian Population

Background: Positive and negative co-stimulatory molecules are important factors determining the outcome of immune responses to the presence of tumors. Since co-stimulatory molecule expression may be affected by gene polymorphisms, we aimed to investigate associations between variants of PD.1 and ICOS and susceptibility to colon cancer. Material and methods: ICOS (-693A/G), ICOS (+1720C/T) and PD.1 (-538G/A) gene polymorphisms were evaluated by the PCR-RFLP method in 76 colon cancer patients and 73 healthy controls. Results: The frequencies of the GG genotype and the G allele at position -693 of the ICOS gene were significantly higher in the patient group (P=0.014 and p=0.0002), while the AA genotype was significantly more common in controls (P=0.0016). At position -538 of PD.1, GG genotype and G allele frequencies were higher in the patient group (P<0.0001and P<0.0001). Again, AA and also AG genotypes significantly predominated in controls (P<0.0001 and P=0.012). Regarding genotypes and alleles of ICOS at position +1720. Frequencies of GCG and GTG haplotypes were higher in patients compared to those of controls (P=0.016 and P<0.0001), while, frequencies of GTA, ATA and ATG haplotypes were higher in controls (P=0.0017, P<0.0001 and P=0.015). GTG/GTG and GTG/GCG double haplotypes were more frequent in patients compared to controls (P=0.0147 and P=0.0071). Conclusion: Our study clarified that PD.1 (-538G/A) and ICOS (-693A/G) gene polymorphisms can be considered as genetic risk factors for the development of colon cancer among Iranian patients.

Recommendations for the Clinical Management of Hepatitis C in Iran: A Consensus-Based National Guideline.

CONTEXT: Hepatitis C virus (HCV) infection is a major public health issue worldwide, including Iran. The new direct-acting antiviral agents (DAAs) with high efficacy have changed the landscape of HCV treatment. This guideline provides updated recommendations for clinical management of HCV infection in Iran. EVIDENCE ACQUISITION: The recommendations of this guideline are based on international and national scientific evidences and consensus-based expert opinion. Scientific evidences were collected through a systematic review of studies that evaluated efficacy and safety of DAA regimens, using PubMed, Scopus and Web of Science. Expert opinion was based on the consensus of Iran Hepatitis Scientific Board (IHSB) in the 3rd national consensus on management of Hepatitis C in Iran, held on 22nd of July 2016. RESULTS: Pegylated Interferon alpha (PegIFN), Ribavirin (RBV), Sofosbuvir (SOF), Ledipasvir (LDV) and Daclatasvir (DCV) are currently available in Iran. Pre-treatment assessments include HCV RNA level, HCV genotype and resistance testing, assessment of liver fibrosis, and underlying diseases. In HCV genotype 1 and 4, DCV/SOF and LDV/SOF are recommended. In HCV genotype 2, SOF plus RBV and in HCV genotype 3, DCV/SOF is recommended. Additional care for underlying diseases should be considered. CONCLUSIONS: Affordable new HCV treatment regimens are available in Iran, providing an opportunity for HCV elimination. Recommendations provided in this current national guideline can facilitate evidence-based management of HCV infection.

The Role of Interferon Gamma Gene Polymorphism (+874A/T, +2109A/G, and -183G/T) in Response to Treatment Among Hepatitis C Infected Patients in Fars Province, Southern Iran.

BACKGROUND: Hepatitis C virus (HCV) infection as a worldwide health problem is associated with cirrhosis and hepatocellular carcinoma. With current treatment regimen, pegylated interferon (PEG-IFN) plus ribavirin, sustain virological response (SVR) is achieved in only 50% of infected individuals. In HCV infection, an inappropriate ratio of cytokines may affect the benefit of antiviral therapy. Given the polymorphisms in regulatory regions of cytokines genes may influence cytokines production. OBJECTIVES: We aimed to investigate both the frequency of genotypes and alleles of interferon gamma (IFN-γ) gene at +874A/T, +2109A/G, and -183G/T loci in HCV-infected patients and their associations with response to therapy. PATIENTS AND METHODS: A total of 158 patients were included and treated with PEG-IFN plus ribavirin. The presence of HCV infection in patients was confirmed by reverse transcription polymerase chain reaction, and genomic DNA was extracted from peripheral leukocytes using salting out method. IFN-γ gene polymorphisms were identified by polymerase chain reaction using sequence specific primers and restriction fragment length polymorphism analysis on genomic DNA. RESULTS: Of 158 patients, 110 (69.5%) subjects achieved SVR and 48 (30.5%) subjects did not respond to therapy. The frequency of AA genotype (P = 0.001; OR: 11.2; CI: 2.26-63.21) and A allele (P = 0.01; OR: 3.23; CI: 1.23 8.56) of IFN-γ gene at +2109 locus were significantly different between the responder and non-responder subjects infected with genotype 1. Regardless of HCV genotype, the frequency of AG genotype was also higher in responder group than those who did not respond to therapy (P = 0.041; OR: 05.05; CI: 1.05-33.25)). In case of IFN-γ gene at +874 locus, there was no difference in genotypes and alleles frequencies between the responder and non-responder subjects infected with HCV genotypes 1 and 3. Haplotype analysis showed no association between haplotypes and response to therapy. All participants had G/T genotype at -183 locus. CONCLUSIONS: Our findings indicate that heterogeneity at +2109 locus of IFN-γ gene but not at +874 locus could interfere with successful therapy in patients infected with HCV genotype 1.

Does kidney transplantation with deceased or living donor affect graft survival?

BACKGROUND: There are growing numbers of patients with end-stage renal disease globally at an unexpected rate. Today, the most serious challenge in transplantation is organ shortage; hence, using deceased donor is increasingly encouraged. OBJECTIVES: The aim of the study was to investigate the differences in survival rates between kidney transplant recipients with deceased donor and living donor. PATIENTS AND METHODS: In a retrospective cohort study, 218 patients who had undergone kidney transplantation in our institute from April 2008 to September 2010 were recruited. Demographics and post-transplantation follow-up data including immunosuppression regimens, rejection episodes, and survival rates were evaluated. The patients were assigned to two groups according to the donor kidney transplantation: group I, living donor kidney transplants; and group II, deceased donor kidney transplants. RESULTS: Although there were no significant differences in one-year survival rates of patient and graft between study groups, three-years survival rates of patient and graft were significantly longer in living donor kidney transplants in comparison with the deceased donor kidney recipients (P = 0.006 and P = 0.004, respectively). In Cox-regression model after adjusting for other confounding factors such as age, sex, diabetes mellitus, and first- or second-time transplantation, overall patient and graft survivals were also significantly shorter in deceased kidney transplantation than those who received kidney from a living donor (HR, 3.5; 95% CI, 1.2-10.4; and P = 0.02 for patient survival; and HR, 5.4; 95% CI, 1.5-19.5; and P = 0.009 for graft survival). CONCLUSIONS: We found acceptable short-term survival in both groups; however, living donor recipients continue to have better long-term patient and graft survival rates.