METHODS: Heparinized peripheral blood and liver biopsy specimens were collected from 13 patients with PBC and 11 patients with chronic viral hepatitis (CVH). Surgically removed liver tissues distant from the tumor in 10 patients with metastatic liver tumors were used as control livers (Control). Mononuclear cells were separated by Ficoll-gradient, and then various surface markers were investigated by flow cytometry. mRNA expression was

quantified by real-time PCR. Cytokine production was investigated using peripheral blood MAIT cells after stimulation with anti-CD3/ CD28-coupled beads in the presence or absence C646 purchase of IL-7. We also investigated the distribution of Vβ7.2+ CD161+ cells in the liver by immunohistochemical staining. RESULTS: In the Controls, CD3+ TCR-ββ- CD161high Vβ7.2+ MAIT cells comprised 6.8% (median) (range 1.1-17.9) of the total T cells in the liver but only 1.6% (0.1-6.7) of the total T cells in the blood. Intra-hepatic MAIT cells constituted a significantly lower proportion in PBC patients (1.9%, 0.7-8.8) than in CVH patients (8.9%, 0.2-20.7) and Controls. We found a significant decrease www.selleckchem.com/screening/gpcr-library.html in the proportion of activated CD69+ MAIT cells in the liver of patients with PBC compared to patients with CVH and Controls. After the normalization of alkaline phosphatase by treatment with ursodeoxycholic acid, MAIT cells increased in the blood. Although MAIT cells express high levels

of the IL-7 receptor (IL-7R), MAIT cells medchemexpress in the liver of patients with PBC expressed less IL-7R (66.8%, 60.0-70.5) than in the liver of patients with CVH (76.3%, 44.4-93.7) and Controls (89.1%, 38.5-94.8). We also confirmed that the functions of MAIT cells were dynamically regulated by the presence of IL-7. Disclosures: The following people have nothing to disclose: Toru Setsu, Satoshi Yamagiwa, Kentaro Tominaga, Naruhiro Kimura, Hiroki Honda, Hiroteru Kamimura, Masaaki Takamura, Minoru Nomoto Background

and aims: Serum metabolomic profile and changes before and after treatment with albumin dialysis using the molecular adsorbents recirculating system (MARS) were assessed in patients with cholestatic pruritus to identify metabolites potentially associated with the pathogenesis of itch Patients and Methods: Serum samples were obtained from 85 patients with primary biliary cirrhosis, 21 with pruritus (9 with resistant pruritus before MARS) and 64 without pruritus. Moreover, serum samples before and after MARS and albumin dialyzate were taken in the 9 patients with resistant pruritus. Metabolite extraction was accomplished by fractionating the samples into pools of species with similar physicochemical properties, and three different platforms were used to perform optimal profiling of: a) fatty acyls, bile acids, steroids and lysoglycerophospholipids; b) amino acids; and c) glycerolipids, sterol lipids, sphingolipids, and glycerophospholipids. The analyses were performed by UPLC-ESI-TOF-MS and multivariate and univariate analyses.

HBV cccDNA is not affected directly by the currently available anti-HBV nucleos(t)ide analogs, and Veliparib mw therefore is an important cause of HBV recurrence after current anti-HBV treatment. In this phase, the carrier is now HBeAg-negative and anti-HBe-positive. The virus replication is minimal, the hepatocytes are spared from attacks by the host immune cells. Serum HBV DNA decreases to low levels and the liver disease becomes quiescent at this stage. The prognosis is generally

good.19 However, the underlying pathological changes in the liver at the onset of this stage is crucial in determining the clinical outcome for the HBsAg carrier. In the absence of hepatic inflammation, the disease processes will

cease and hepatic fibrosis may regress. However, if cirrhosis is already well-established, the likelihood of remitting to normal hepatic architecture is low.8 Although after entering the residual HBV integrated phase the activity of liver disease becomes quiescent, a certain proportion of HBeAg-negative, anti-HBe-positive HBsAg carriers will have chronic hepatitis again. Thus, HBV replication reactivates and serum HBV DNA increases again, frequently accompanied by active hepatic injury. The course is refractory and clinical sequelae will follow. Although a single nucleotide mutation at position 1896 in the precore region from G to A (which creates a stop codon and abolishes the production of HBeAg)

was identified,20 whether this is associated find more with the reactivation is uncertain, because the same mutation has also been identified in healthy anti-HBe-positive HBsAg carriers.21 In addition, hepatitis B core promoter mutants with point mutations A1762T and G1764A have also been claimed to affect the formation of HBeAg, because these mutations may abort the transcription of pre-C mRNA but not that of pregenomic RNA.22 These mutations have been found to correlate with lower serum HBV DNA levels and lower expression of HBcAg in the liver.23 In a case–control study, the mutation was shown to increase the risk of HCC in HBsAg carriers.24 The results were confirmed recently in a community-based cohort study.25 With long-term medchemexpress follow up, these mutations were found to increase the risk of HCC (hazard ratio = 1.76, 95% CI = 1.19–2.61). Intriguingly, the precore G1896A mutation was associated with a decreased risk of HCC in this study.25 A thorough understanding of the natural history of HBV infection can indicate the directions and the possible means to control the infection. Figure 2 illustrates the three essential components of HBV infection: (i) an infection source; (ii) a susceptible host; and (iii) an established route of transmission. In the past, preventing susceptible individuals from HBV infection was thought to be the only way to control HBV infection.

The effects were most pronounced in younger patients. In terms of endoscopist assessment, the patients in the midazolam group were rated as easier to intubate by the endoscopist compared with the placebo

group, but there was no difference between the midazolam group and either the pharyngeal anesthesia or control groups. Interestingly, the midazolam group had a higher STI571 endoscopist rating for overall difficulty and retching during the procedure compared with the pharyngeal anesthesia group. Another study showed that performing endoscopic ultrasound without sedation, while less well tolerated, did not lead to longer procedure times, higher risks or increased reluctance to undergo a repeat procedure.12 In this study, however, there was no control group—only blinded (to both patients and endoscopists) sedation and placebo buy CH5424802 groups. More recently, male sex, previous colonic resection, a high body mass index (BMI) and the absence of gynecological surgery were shown to be associated with higher colonoscopy completion rates in unsedated patients.13 Hypnosis has also been used to facilitate endoscopy.14 Compared with intravenous midazolam, however, its use was associated with greater patient discomfort

(as assessed by the patient) and less amnesia for the procedure. There was also a trend towards its being associated with greater technical difficulty on the part of the endoscopist. However, use of hypnosis led to less patient agitation as assessed by independent observers compared with both patients receiving pharyngeal spray without intravenous sedation and those receiving midazolam. The use of pharyngeal local anesthetic sprays as a prelude to endoscopy is widespread, although only a few studies have evaluated MCE their efficacy. A recent meta-analysis15 of five randomized controlled trials comprising 500 patients showed that the use of pharyngeal spray led to less procedure-related discomfort and less technical difficulty as rated by the endoscopist. Whether it also leads to a reduction in intravenous sedation requirements is not clear. There is a small risk of methemoglobinemia,16

particularly with benzocaine, and some evidence that aspiration may be more likely to occur following pharyngeal spraying with local anesthetics.17 A recent meta-analysis of six prospective, randomized, controlled trials, found that listening to music before the procedure was associated with lower doses of analgesia and shorter procedure times.18 Anxiety levels were also lower in the ‘music’ group, and there was a trend towards a reduced level of sedative agents but this did not achieve statistical significance. Patients undergoing endoscopy should be fully informed of the risks of intravenous sedation in a preoperative consultation setting. Written information should be made available and there should be opportunity to ask questions.

Bending stiffness was not measured, but this finding suggests that the mechanical properties of feathers that degrade over time might be behind the impaired flight performance. The function PF-6463922 in vitro of moult is to maintain plumage function. There is considerable variation in the temporal and spatial scheduling of moult for both non-migratory and migratory birds (Svensson & Hedenström, 1999; Barta et al., 2006, 2008) and this variation provides us with an

opportunity to study the proximate mechanisms behind life-history trade-offs and their resolution under different ecological circumstances. The old world warblers, family Sylviidae, have attracted considerable attention because they show interesting variation with respect to moult and migration schedules (Svensson & Hedenström, 1999). The adults of most species moult flight feathers once per year after breeding and embark on migration to the wintering grounds with fresh feathers. Some species moult once on the

wintering grounds and willow warblers Phylloscopus trochilus moult twice per year, once on the breeding grounds and once on the wintering grounds (Salomonsen, 1945; Prŷs-Jones, 1991; Underhill et al., 1992). Great reed warblers Acrocephalus arundinaceus selleckchem moult on the stopover during migration (Hedenström et al., 1993). The ultimate causes behind this variation are still unclear, but theoretical work suggests that temporal and spatial variations in food supply are responsible (Barta et al., 2008). Weber et al. (2005) have shown that flight feathers of willow warblers, a migratory species with two annual moults, fatigue faster 上海皓元 than flight feathers of the closely related chiffchaff Phylloscopus collybita, which follows the more common pattern for the Sylviidae warblers of moulting only once each year immediately after breeding (Fig. 1). Weber et al. (2005) find that the shafts (rachis)

of willow warbler flight feathers have a larger outer diameter than the shafts of the chiffchaffs’ flight feathers. They argue that this co-variation between fatigue and structure suggests a possible trade-off between a material and a structural property of the rachis. Physiological stress during moult may force birds to deposit low-quality keratin in the growing feathers (see Murphy, King & Lu, 1988; Dawson et al., 2000). An increased diameter stiffens the rachis and compensates for a lower keratin quality. This may, however, cause a higher rate of fatigue damage accumulation in the outer layers of the rachis because of the constant radius of curvature strains that are proportional to the distance from the unstretched and uncompressed midline (Fig. 2a). The outer diameter of the feather shaft is, though, not a reliable measure of the structural contribution to bending stiffness.

Therefore, HBsAg is not a reliable marker in monitoring the effectiveness of treatment in patients with oral antivirals. Key Word(s): 1.

Hepatitis B; 2. HbsAg; 3. HBV-DNA; 4. Interferon; Presenting Author: KAMRANB. LANKARANI Additional Authors: FARIBORZ GHAFFARPASAND, MOJTABA MAHMOODI, Cabozantinib ic50 MEHRZAD LOTFI, NIMA ZAMIRI, SEYED TAGHI HEYDAR, MOHAMMAD KAZEM FALLAHZADEH, NAJMEH MAHARLOUEI, MEISAM BABAEINEJAD, SOHEILA MEHRAVAR Corresponding Author: KAMRANB. LANKARANI Affiliations: Health Policy Research Center, Shiraz University of Medical Sciences; Health Policy Research Center, Shiraz University of Medical Sciences; Health Policy Research Center, Shiraz University of Medical Sciences; Health Policy Research check details Center, Shiraz University of Medical Sciences; Health Policy Research Center, Shiraz University of Medical Sciences; Health Policy Research Center, Shiraz University of Medical Sciences; Health Policy Research Center, Shiraz University of Medical Sciences; Health Policy Research Center, Shiraz University of Medical Sciences; Health Policy Research Center, Shiraz University of Medical Sciences Objective: The prevalence and associated

risk factors of NAFLD may vary in different geographical region. Population based studies on prevalence and risk factors of NAFLD in Iranian population are few. The main aim of this population-based study was to determine the prevalence of NAFLD and its risk factors in a sample of adult Iranian population of southern Iran. Methods: This was a cross-sectional study being performed in Shiraz, southern Iran during a 10-month period from November 2010 to September 2011 through cluster random sampling of Iranian general population in Shiraz region. All individuals underwent anthropometric and blood pressure measurements and thorough medical history and physical examinations. Laboratory measurements included fasting blood glucose (FBS), lipid profile, complete blood count (CBC) and liver

function tests. NAFLD was diagnosed by transabdominal ultrasonography. Results: Overall we included 819 subjects in this study among which there were 340 males (41.5%) and 479 females (58.5%) with the mean age of 43.1 ± 14.1 上海皓元 years. NAFLD was diagnosed in 176 (21.5%) subjects. Patients with NAFLD were significantly older (p < 0.001), had higher proportion of male gender (p = 0.004) and had higher BMI (p < 0.001). They also had higher prevalence of hypertension (p < 0.001), high FBS (p < 0.001), high cholesterol (p = 0.026), high triglyceride (p < 0.001) and high waist circumference (p < 0.001). Taking all these together, patients with NAFLD had significantly higher prevalence of metabolic syndrome when compared to healthy subjects (p < 0.001). Conclusion: The prevalence of NAFLD in this group of Iranian adult general population is 21.5%. NAFLD in Iranian population is associated with male gender, old age, obesity, and features of metabolic syndrome. Key Word(s): 1. NAFLD; 2. Prevalence; 3.

Polymorphisms in lectin pathway genes determine their functional activity. We assessed the relationship between these polymorphic genes and clinically significant bacterial infections, i.e., sepsis, pneumonia, and intra-abdominal infection, and mortality within the first year after OLT, in relation to major risk factors in two cohorts from different transplant centers. Single-nucleotide polymorphisms in the mannose-binding lectin gene (MBL2), the ficolin-2 gene (FCN2), and the MBL-associated serine protease gene (MASP2) of recipients and donors were determined. Recipients

receiving a donor liver in the principal cohort with polymorphisms in all three components i.e., MBL2 (XA/O; O/O), FCN2+6359T, and MASP2+371A, had a cumulative risk of an infection buy AZD6738 of 75% as compared to 18% with wild-type donor livers (P = 0.002), an observation confirmed in the second cohort (P = 0.04). In addition, a genetic (mis)match between donor and

recipient Palbociclib research buy conferred a two-fold higher infection risk for each separate gene. Multivariate Cox analysis revealed a stepwise increase in infection risk with the lectin pathway gene profile of the donor (hazard ratio = 4.52; P = 8.1 × 10−6) and the donor-recipient (mis)match genotype (hazard ratio = 6.41; P = 1.9 × 10−7), independent from the other risk factors sex and antibiotic prophylaxis (hazard ratio > 1.7 and P < 0.02). Moreover, patients with a lectin pathway gene polymorphism and infection had a six-fold higher mortality 上海皓元 (P = 0.9 × 10−8), of which 80% was infection-related. Conclusion: Donor and recipient gene polymorphisms in the lectin complement pathway are major determinants of the risk of clinically significant bacterial infection and mortality after OLT. (HEPATOLOGY 2010;) The occurrence of infectious complications is a major clinical problem after orthotopic liver transplantation (OLT).1 Immunosuppressive agents that prevent graft rejection interfere with the adaptive immune response and thereby increase the susceptibility to infections. These drugs do not affect, however,

the innate immune system that is crucial for the first line of immunological defense. Lectins, humoral pattern recognition molecules of the innate immune system, recognize pathogen-associated carbohydrate motifs on microorganisms and elicit activation of multiple processes of innate immunity. In order to execute the elimination of microorganisms, these lectins, such as mannose-binding lectin (MBL) and ficolins, cooperate with phagocytes and other humoral factors, including complement. Upon pathogen binding, both lectins activate the complement system via MBL-associated serine proteases (MASPs), leading to C3b-mediated opsonization of the microorganism followed by phagocytosis and the formation of a complement membrane attack complex that directly kills the pathogen.

C57BL/6J mice were maintained according to protocols approved by the Animal Care Committee of the University of British Columbia following guidelines established by the Canadian Council on Animal Care. Endoderm isolation was previously described.12 Hepatoblast isolation is described in the Supporting Methods. Adult liver was obtained

from a 6-month-old female mouse. Small RNA preparation and library construction was previously described.13 Libraries were sequenced on Illumina GAIIx. Reads were aligned to NCBI37/mm9 reference genome and miRNA annotation was based on miRBase V15. Read processing, quantification, and annotation was previously described.13 Expression of miRNAs was normalized to total reads aligned to genome and expressed as reads per million (RPM). Two replicates from foregut, two from hepatoblasts, and one from selleck screening library adult liver were generated. The expression correlation between replicates was r2 = 0.9282 and r2 = 0.9718 Decitabine for foregut and hepatoblasts, respectively (Supporting Fig. S1A). We used one replicate for further analysis. miRNAs expressed at greater than 10 RPM were used in K-means clustering analysis.14 Novel miRNA prediction was previously described.13 RNA was extracted using mirVana miRNA isolation kit (Ambion). Real-time quantification was performed

using TaqMan MicroRNA Assays (Applied Biosystems) or SYBR Green (Roche) according to the manufacturer’s instructions. All expression results were normalized to U6 or Actin for miRNA and gene expression, respectively. The mir302b overexpression vector, pCMV-mir302b-IRES-GFP (302b_OE), and its control vector, pCMV-mir-IRES-GFP (Ctrl_OE), were purchased from Origene. A lentiviral-mediated gene expression system, including mir302b expression vector, pCDH302b,

and its control vector, pCDH, was purchased 上海皓元 from SBI. The mir20a knockdown vector, pCAG-d2eGFP-20a (20a_KD), and its control vector, pCAG-d2eGFP-Cxcr4 (Ctrl_KD), were subcloned from pCMV-d2eGFP-20a and pCMV-d2eGFP-Cxcr4,15 respectively (Addgene). Wildtype or mutant 3′ untranslated region (UTR) miRNA targets were cloned into pmirGLO (Promega). Tgfbr2 expression vectors, pBOS-Tgfbr2 and pBOS-Tgfbr2(Dominant negative, DN), were subcloned from pCMV5-Tgfbr2 and pCMV5-Tgfbr2(DN),16 respectively. 3TP-lux was described previously.16 TK-Renilla controlled for transfection efficiency. Western results were quantified by ImageJ. Luciferase assay is described in the Supporting Methods. ESC differentiation was previously described.17 Probes for WISH were obtained from Exiqon and experiments were performed according to Sweetman’s protocol18 at a temperature of 20° below the melting temperature of probes. No probe and mir29a served as negative controls (Fig. S2). All data presented are representative of at least three independent experiments unless indicated otherwise.

Intrahepatic transcriptional responses Selleck HKI272 were characterized by gene set enrichment analysis (GSEA), Ingenuity Pathway Analysis (IPA) and a gene module approach. Results: GS-9620 induced a broad intrahepatic immune response in HBV-infected chimpanzees, with type I interferon (IFN), T cell and B cell gene signatures prominently up-regulated. Notably, the transcriptional signature induced by GS-9620

was significantly enriched with genes induced during HBV clearance in acutely infected chimpanzees (Wieland et al. (2004) PNAS 101: 6669-74). Underscoring the parallels with natural clearance of acute infection, the HBsAg reduction by GS-9620 in HBV-infected chimpanzees was associated with up-regulation of intrahepatic CD8+ T cell and cytotoxic cell gene signatures, as well as B cell and plasma cell tran-scriptional profiles. Notably, the elevated expression of cyto-toxic cell-associated genes (e.g. perforin, granzyme B and Fas ligand) was accompanied by significant induction AZD6244 in vivo of transcrip-tional signatures consistent with hepatocyte apoptosis (e.g. caspase 3 and caspase 7), as well as hepatocyte regeneration and

proliferation (e.g. cell cycle regulatory genes). Importantly, GS-9620 also induced an intrahepatic cytotoxic T cell gene signature in chronically infected woodchucks, suggesting this is a key mechanism of antiviral response to GS-9620 in both chimpanzee and woodchuck models of CHB. Likewise, the induction of intrahepatic interferon-stimulated gene (ISG) expression suggests that antiviral ISGs may also play a role in GS-9620 treatment response in these animal models. Conclusion: These data indicate that the antiviral response induced by GS-9620 in preclinical models of CHB was likely mediated, at least in part, 上海皓元 by the cytolytic activity of CD8+ T cells. Induction of a strong intrahepatic B cell response may also have played an important role in HBsAg antigen seroconversion. Disclosures: Li Li – Employment: Gilead Sciences Peng Yue – Employment: Gilead Sciences

Robert E. Lanford – Grant/Research Support: Arrowhead Research Stephan Menne – Advisory Committees or Review Panels: Hoffman-La Roche; Consulting: Northeastern Wildlife Inc.; Grant/Research Support: Hoffmann-La Roche Congrong Niu – Employment: Gilead Science Stephane Daffis – Employment: Gilead Sciences Daniel Tumas – Employment: Gilead Sciences, Inc Abigail Fosdick – Employment: Gilead Sciences William E. Delaney – Employment: Gilead Sciences; Patent Held/Filed: Gilead Sciences; Stock Shareholder: Gilead Sciences Simon P. Fletcher – Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences Background: As hepatitis D is the result of a double infection of HDV with HBV, therapeutic goals are in relation with both viral infections. The definitive end-point of HDV therapy appears the clearance of HBsAg.

At operation, he had a contracted gallbladder and a fistula between

the fundus of the gallbladder and the transverse colon. A frozen section of the bile duct showed chronic inflammation with stenosis of the duct lumen, mucosal necrosis, granulation tissue and fibrosis in the bile duct wall (Figure 2A). The appearance was consistent with sclerosing cholangitis. An operative liver biopsy showed a mixed inflammatory infiltrate in portal tracts (Figure 2B), hepatocellular edema with cholestasis (Figure 2C) and NVP-BEZ235 datasheet degenerative changes in bile duct epithelium (Figure 2D). He was treated by cholecystectomy and prolonged T-tube drainage and is currently asymptomatic. There are now several case reports of sclerosing cholangitis in critically ill patients who required long-term treatment in intensive care units. The mechanism may be arterial hypoperfusion of the peribiliary vascular plexus that

causes ischemic injury to the bile duct. In some patients, this appears to be a progressive disease, perhaps because of infection or activation of immunological mechanisms. In the patient described above, inflammatory changes involved both the intrahepatic and extrahepatic bile ducts although the major radiological changes involved the common hepatic duct. It also seems likely that he had coexisting acalculous cholecystitis that resulted in the formation of a fistula between the gallbladder and colon. The optimal management of selleck inhibitor “ischemic” sclerosing cholangitis remains unclear. Some patients improve after endoscopic extraction of intrahepatic biliary casts while others may improve with endoscopic stents. Those with progressive disease will need to be considered for liver transplantation. Contributed by “
“Although a cancer cell line has limitations in modeling medchemexpress the physiological complexity in human

cancer, it has shown to be useful as a convenient tool to interrogate the molecular mechanism of action of cancer therapeutics.[1] Finn et al.[2] tested an intriguing idea to use a human hepatocellular carcinoma (HCC) gene signature to probe genomic profiles of hepatoma cell lines to evaluate sensitivity to a molecular targeted agent, dasatinib, although more work is needed to determine its mechanism of action. The authors identified two groups of cell lines according to the presence of a gene signature of “progenitor/HB” subtype linked to a distinct median inhibitory concentration (IC50) profile as well as cell cycle arrest and apoptosis induced by dasatinib. Of note, the classification looks concordant with positivity of alpha-fetoprotein (AFP), which has been repeatedly reported as the major determinant of global transcriptome landscape in hepatoma cells.[3, 4] We previously annotated the AFP-based subtypes of hepatoma cell lines with various molecular features and clinical phenotypes by using the gene signature assessment.

There are less data concerning the role of IL28B in other HCV genotypes. learn more The IL28B polymorphism appears to be relevant to peg-IFN therapy for genotype 4 (G4) HCV,6,31 with a similar effect size to that observed in the setting of G1 HCV. In a recent small study of peg-IFN and RBV treatment in genotype 6 (G6) HCV patients of Chinese ancestry, 23 of

24 carried the good-response genotype for rs12979860. All attained an SVR. Only one patient carried a poor-response genotype, and this patient relapsed after 48 weeks of treatment.32 The relationship between the IL28B genotype and treatment response in G6 HCV is therefore not clear. IL28B genotyping is less relevant to the treatment of G2/3 HCV, and for now, it should not be performed routinely, but rather reserved for research protocols. It will be particularly important to investigate the relevance of the IL28B genotype selleck products in

G3 patients with other unfavorable IFN-response characteristics, especially cirrhosis and non-RVR, where the IL28B genotype might be relevant to the decision to extend therapy from 24 to 48 weeks. This should be prospectively evaluated. For G4 HCV, the IL28B polymorphism appears to have a similar clinical utility to G1 HCV. The association between peg-IFN and RBV treatment response and the IL28B genotype in HCV mono-infected patients has been replicated in the setting of HIV/HCV co-infection. In a retrospective candidate gene study of Spanish patients with HIV/HCV co-infection, the good-response IL28B genotype was associated with higher rates of SVR compared to poor-response variants (rs12979860, 75% vs 38% SVR rate, respectively, P < 0.0001).31 The IL28B polymorphism remained a significant independent predictor,

even after adjusting for other important clinical factors, such as HCV genotype, HCV—RNA concentration, the absence of fibrosis,31 and serum low-density lipoprotein level.33 Similar findings have been reported in other HIV/HCV co-infected cohorts.34–36IL28B variation is associated with improved phase I kinetics, as is seen during treatment MCE公司 of HCV mono-infected patients.37,38 The strength of the association also varies according to HCV genotype, where a strong effect is seen in G1/4 HCV, but the effect is much weaker in G2/3 HCV. HIV co-infection does not appear to modulate the association between the IL28B polymorphism and spontaneous clearance, with similar OR for spontaneous clearance compared to HCV mono-infected individuals.6,9 Although very relevant to HCV outcomes in HIV/HCV co-infection, the IL28B genotype appears to have no impact on HIV outcomes.39,40 The clinical course of HCV post-transplantation is frequently aggressive.