Subgenomic analysis of the HCV core gene indicated that five patients developed delayed recurrence of HCV infection. Overall, the cumulative recurrence rate of HCV infection was 2.3% (0.4%/year; 95% confidence interval [CI], 0.9%-5.5%). The cumulative HBsAg seroclearance rate was 30.0% (95% CI, 21.5%-42.0%); with 33.1% (95% CI, 21.8%-50.1%) in the 48-week combination therapy group and 24.3% (95% CI, 13.7%-42.9%) in the 24-week therapy group. Conclusion:

Peginterferon alfa-2a and ribavirin therapy provides good HCV SVR durability and a high find more accumulative HBsAg seroclearance rate in patients who are coinfected with HCV and HBV. (HEPATOLOGY 2013;) In areas where hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is endemic, a substantial number of patients are infected with both viruses.1-3 Those dually infected with HCV and HBV have been reported to carry a significantly higher risk of developing advanced liver diseases and hepatocellular carcinoma (HCC) than those with either infection alone.3-7 Consequently, this group of patients needs to be treated more actively. In patients with HCV genotype 1 infection, the rate of sustained virologic response (SVR) at 24 weeks (SVR24) after the end of combination therapy with peginterferon alfa-2a find protocol and ribavirin was 72.2% in coinfected patients versus 77.3% in monoinfected patients; for patients with HCV genotype 2/3 infection,

the SVR24 values were 82.8% and 84.0%, respectively.8 These results suggest that combination therapy is equally effective in patients with HCV monoinfection and in those with chronic Lenvatinib solubility dmso HCV/HBV coinfection. In addition, posttreatment hepatitis B surface antigen (HBsAg) seroclearance was observed in 11.2% of 161 coinfected patients.8, 9 It is noteworthy that serum HBV DNA eventually appeared

in 36.3% of the 77 coinfected patients with undetectable pretreatment levels of HBV DNA. Previous studies have suggested that hepatitis C may relapse in 0.9% to 10% of simple chronic hepatitis C patients who initially obtained SVR24 after the end of treatment.10-12 They thus concluded that in patients with chronic hepatitis C who have no detectable serum HCV RNA 24 weeks after interferon therapy, long-term sustained biochemical and virologic response is anticipated. However, whether HCV SVR24 could be maintained in patients with chronic hepatitis B and C coinfection has not been reported. For the treatment of chronic hepatitis B, the virologic and serologic responses may also not be durable.13, 14 Furthermore, previous studies suggest that therapeutic efficacy might not be seen during the treatment period but rather occur during the prolonged follow-up period in patients receiving immunomodulatory therapy such as interferon.15 Therefore, it is important to clarify the long-term treatment outcome in this dually infected population.

FFAs increase endoplasmic reticulum JQ1 mw (ER) stress, NFkB activation and nuclear TG2 (nTG2) through pancreatic ER kinase (PERK)-dependent pathway, whereas ethanol induces nTG2 via retinoid signaling. However, the molecular mechanism by which ethanol/FFAs induce nuclear localization of TG2 has been unclear. Method:  A similar nTG2-mediated cell death is induced in acyclic retinoid (ACR)-treated hepatocellular carcinoma. Using

cultured cells, we investigated how to control this novel apoptotic pathway by regulating nuclear localization of TG2. Results:  TG2 is composed of N-terminal b-sandwich, catalytic core, b-barrel 1, and C-terminal b-barrel 2 domains. In a previous work, we identified a 14 amino acid nuclear localization signal (NLS) within the b-barrel 1 domain and a putative leucine-rich nuclear export signal (NES) at position 657 to 664 (LHMGLHKL) near the C-terminus in the b-barrel 2 domain, and found that ACR downregulated exportin-1 levels, thereby accumulation of TG2 in the nucleus. Here, we found that both ethanol and FFAs provoked generation of truncated short form of TG2 (TG2-S) defects in the putative NES at least in part

through alternative splicing, thereby causing accumulation of TG2-S in the nucleus. Conclusion:  The generation of TG2-S in ethanol or FFAs-treated hepatic cells is a novel therapeutic target for prevention of hepatic cell death associated with ASH/NASH. “
“Capsule endoscopy see more is the first-line diagnostic technique for the small bowel. However, the inability to visualize the duodenal papilla is an inherent limitation of this method. In the present

study, we evaluated feasibility of a newly developed CapsoCam SV1 capsule. This Hydroxychloroquine molecular weight is a prospective dual center study of a newly developed video capsule CapsoCam SV1 from Capsovision, CA, providing panoramic 360° imaging. A high frequency of 20 frames occurs per second for the first 2 h and thereafter 12 frames/s, with a battery life of 15 h. We evaluated feasibility and completeness of small bowel examination together with secondary endpoints of duodenal papilla detection in 33 patients. Patients swallowed the capsules following colonoscopy or were prepared with 2 L of polyethylene glycol solution prior to the examination. All patients swallowed 20 mg of metoclopramide and 160 mg of simethicone 30 min before ingestion of the capsule. Thirty-one of the 33 patients’ data could be evaluated. Small bowel examination was complete in all procedures. Mean time to pass the small bowel was 258 ± 136 min. Average small bowel cleanliness was 3.3 ± 0.5. In 71% of the patients, we identified the duodenal papilla. No adverse reaction in relation to the capsule examination was observed. CapsoCam SV1 is a safe and efficient tool in small bowel examination. The duodenal papilla as the only landmark in small bowel is detected in more than 70% of the patients.

In clinical trials, TDF and ETV have

shown a good safety renal profile. However, several cases of tubular dysfunction have been reported in HIV-infected patients receiving TDF. Little is known about the impact on renal tubular function in CHB patients under long-term use of ETV and TDF. The aim of RG-7388 cell line this study is to evaluate markers of renal tubular function and bone turnover in CHB patients treated with ETV or TDF for at least two years. Patients and Methods A multicenter, cross-sectional study was conducted in CHB patients (MENTE study). Analysis of renal parameters and markers of bone turnover were performed on patients with compensated liver disease, on first line therapy with ETV or TDF for at least two years or without treatment (control group). Tubular function was assessed by: ratio retinol binding protein/creati-nine (RBP/Cr), urinary neutrophil gelatinase-associated lipocalin (NGAL), renal tubular phosphate reabsorption (RTF), tubular maximal

reabsorption of phosphate to glomerular filtration rate (TmPO4/GFR). Glomerular filtrate was assessed using CKD-EPI, MDRD4, Cockroft-Gault formulas and creatinine clearance in 24h urine. Markers of bone turnover were also assessed by: collagen type 1 C-telopeptide GSK126 purchase (CTx), Procollagen type I N-terminal propeptide (PINP). Other parameters evaluated: Vitamin D and parathormone (PTH). Results A total of 139 CHB patients (TDF- 34, ETV- 51 and control group- 54) were included. The median exposure to TDF or ETV was 39 months (IQR,31-48). Patients on the ETV-group were older with a higher rate of hypertension and a higher proportion of males. Altered excretion of RBP was more frequent in

the TDF group (24% vs 6% and 4%, p<0.004). No differences were found in NGAL excretion. Glomerular filtrate measured as CG, CKD-EPI and MDRD4 was comparable across three groups. No statistically differences were found among groups in total excretion from of phosphate, RTF and TmPO4. CTX and PINP did not show any differences among groups. More than 80% of patients in all groups were deficient in Vit D. PTH abnormal levels were more frequent in TDF group. Conclusions Though still preliminary, these findings in patients taking TDF in the long-term have a significant higher frequency of underlying tubular dysfunction compared with ETV and control groups. These differences in tubular function were not associated with concomitant glomerular filtrate reduction. Results are also in alignment with previous data in HIV patients taking TDF-based treatment.

Data derived from a single randomized Epigenetic Reader Domain inhibitor trial or nonrandomized studies, cohort or case-control analytic studies, and multiple time series where further research may change confidence in the estimate of the clinical effect. Evidence based on clinical experience, descriptive studies, opinion of respected authorities where further research is very likely to impact confidence on the estimate of clinical effect. Another aim of this

study was to evaluate the evolution of the type of recommendations issued by the AASLD. Recommendations provided in AASLD practice guidelines can be classified into three types: (1) Recommendations based on known features of a given liver disease which should prompt further evaluation (i.e.: “Wilson Disease must be excluded in any patient with unexplained liver disease along with neurological or neuropsychiatric disorder.”[33]). (2) Recommendations on specific testing for a given liver disease (i.e.: “Liver biopsy is recommended to stage the degree of liver disease in C282Y homozygotes or compound heterozygotes if liver enzymes (ALT, AST) are elevated or if ferritin is >1000 μg/L.”[30]). (3) Recommendations

on specific treatment for a given liver disease (i.e.: “UDCA in a dose of 13-15 mg/kg/day orally is recommended for patients with PBC who have abnormal liver enzyme values regardless of histological stage.”[31]). Thus, all recommendations for this analysis were classified into one of three INCB018424 manufacturer categories: (1) Feature of Disease Recommendation; (2) Diagnostic Recommendation; or (3) Treatment Recommendation. As previously discussed, three different guideline classification systems Methocarbamol have been used during the evolution of AASLD practice guidelines. Depending on the system used, certain guidelines provided information regarding benefit versus risk for a given recommendation. This information is different from the “grade” of recommendation and was designated as the “class” of recommendation. In the final part of this analysis, we evaluated the

evolution of “class” recommendations provided in multiple versions of guidelines for a specific liver disease topic. However, unlike the grade systems assessing strength and certainty, the “class” systems used over time differed greatly and the development of a composite scoring system could not be created for comparative analysis. Therefore, the “class” analysis was only performed on guidelines that used the same scoring system. From January 1998 to August 1, 2012, the AASLD issued 28 clinical practice guidelines on 17 topics, yielding a total of 991 recommendations. When examining the initial publication for each AASLD guideline topic, a total of 512 recommendations were issued.

These include the possibilities that markers might help to identify individuals at the risk of more rapid joint deterioration, that clotting factors may have additional local action within tissues, and that outcomes might be improved with therapies that directly address wound healing and inflammation. Joint assessment tools are important. Conventional radiography is frequently used, but given the possibility of subclinical joint bleeds, accurate non-invasive imaging tools are required to detect soft

tissue and cartilage changes. Magnetic selleck products resonance imaging and ultrasonography can prove valuable here. New imaging techniques should help to increase understanding of the biological basis of early events in haemophilic arthropathy. The optimal way to measure outcomes in haemophilia is to use several methods – in addition to imaging methods, a 360° approach will use physical, functional and quality-of-life instruments. In PWH, inhibitor development complicates treatment of joint bleeds and increases the risk of developing arthropathy. A new therapeutic approach for joint bleeds in inhibitor patients divides treatment into two phases: bleed control, with bypassing agent therapy until bleeding has definitely ceased, followed by regular dosing to prevent rebleeds until synovial recovery

is complete. “
“Summary.  While an estimated 13% of women with unexplained menorrhagia have von Willebrand disease (VWD), the frequency of

other potential bleeding disorders learn more has been uncertain. This study describes the relatively wide range of laboratory characteristics of women with unexplained menorrhagia and presents issues affecting diagnosis in this population. Women with pictorial blood assessment chart (PBAC) score >100 were identified at Amino acid six U.S. sites and asked to remain drug free for 10 days prior to testing. Blood was collected on one of the first four menstrual cycle days and tested at a central laboratory for procoagulant factors, VWD and fibrinolytic factors. Platelet function testing by PFA-100® (PFA) and platelet aggregation with ATP release (PAGG/ATPR) were performed locally using standardized methods. Among 232 subjects, a laboratory abnormality was found in 170 (73.3%), including 124 of 182 White (68.1%) and 34 of 37 Black (91.9%) subjects; 6.0% had VWD, 56.0% had abnormal PAGG/ATPR, 4.7% had a non-VWD coagulation defect (NVCD) and 6.5% had an abnormal PFA only. AGG/ATPR was reduced in 58.9% of subjects, with multiple agonists in 28.6%, a single agonist in 6.1% and ristocetin alone in 24.2%. Frequencies of PAGG/ATPR defects varied by study site and race; frequencies of VWD and NVCD were similar. Laboratory abnormalities of haemostasis, especially platelet function defects, were common among women with unexplained menorrhagia across multiple U.S. sites. To what degree these abnormalities are clinically significant requires further study.

Following in vivo APAP, LDK378 research buy a rapid decline in P-c-Src (not total Src) was observed in mitochondria but not cytoplasm. Knockdown of Sab with adeno-shSab prevented inactivation of mitochondrial c-Src after APAP in vivo. Next we found that DOK-4, Src binder (J Biol Chem. 280, 26383-96,2005), was expressed exclusively in mitochondria of hepatocytes. Liver mitochondria isolated after DOK-4 knockdown were resistant to direct P-JNK/ATP mediated inhibition of OCR. Knockdown of DOK-4 in vivo (adeno-shDOK-4) prevented de-phosphorylation

of active Src and markedly protected against APAP toxicity. Conclusions: The interaction of JNK with Sab leads to inactivation of intramitochondrial c-Src and impairment of respiration. The dephosphorylation of c-Src is dependent on DOK-4, a platform for binding of Src and Ptp. Knockdown of mitochondrial DOK-4 markedly protects against APAP hepatotoxicity. Therefore, dysregulation of intramitochon-drial c-Src kinase mediates the Sab dependent effects of JNK leading to impaired mitochondrial function in APAP toxicity. Disclosures: Neil Kaplowitz – Consulting: GlaxoSmithKline,

JNJ, Merck, Novartis, Hepregen, Takeda, Otsuka, Pfizer, Geron, Daiichi-Sanyo; Independent Contractor: Acetaminophen Litigation The following people have nothing to disclose: Sanda Win, Sorafenib mouse Tin A. Than Mechanisms of drug-induced liver injury (DILI) are incompletely understood. Hepatotoxicity from acetaminophen (APAP) poses widespread problems, including acute liver failure (ALF), and requires more therapeutic development. Although the Clostridium perfringens alpha toxin cell type-specific approach has typically been utilized for cytotoxic mechanisms, recent studies identified sharing of toxicity pathways and processes in a cell-agnostic manner. For instance, expression of N-methyl-D-aspartate receptors (NMDARs) is classically associated with excitoxic injury in neuronal tissues, e.g.,

ischemic or traumatic insults, Alzheimer’s, Parkinson’s, schizophrenia, etc., but rodent and human hepatocytes also expressed NMDAR activity after liver anoxia or injury. To determine whether NMDARs could contribute in APAP-induced hep-atotoxicity, we performed studies in cultured HuH-7 cells and primary mouse hepatocytes with or without NMDA and APAP, as well as NMDAR antgonists, MK801 or memantine. MTT assays were performed to assess cytotoxicity. Calcium fluxes were measured in hepatocytes with NMDA and NMDAR block-ers. Brain and liver tissues were examined for multiple NMDARs by RT-PCR, western, and immunostaining. C57BL/6 mice were used for studies with 500 mg/kg APAP with or without 30 mg/ kg memantine. Liver injury was evaluated by histology. We found HuH-7 cells and mouse hepatocytes expressed NMDARs and were sensitive to APAP-induced cytotoxicity, which was abolished by MK801 or memantine. In mouse hepatocytes, NMDA or quinolinic acid, another agonist of NMDAR, dose-de-pendently induced calcium fluxes, APAP alone did not directly stimulate calcium fluxes related to NMDARs.

The withdrawal time and experience level of the endoscopist were more important than the procedure order in detecting adenomas by colonoscopy. Key Word(s): 1. Time; 2. colon polyp; 3. adenoma; 4. procedure order Presenting Author: FUMIAKI KAWARA Additional Authors: TETSUYA YOSHIZAKI, YOSHIKO OHARA, SHINWA TANAKA, TSUKASA

ISHIDA, YOSHINORI MORITA, TAKASHI TOYONAGA, EIJI UMEGAKI, HIROSHI YOKOZAKI, TAKESHI AZUMA Corresponding Author: FUMIAKI KAWARA Affiliations: Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University PF-02341066 molecular weight Hospital, Kobe University Hospital, Kobe University Hospital, Kobe University Hospital Objective: Introduction: There remains many

unknown check details points about the diagnosis and the prognosis of duodenal polyps. In particular, little is known about the polyps which show gastric mucin phenotype by immunohistochemical staining. We report here the endoscopic and pathological findings of two duodenal polyp cases with gastric mucin phenotype. Methods: Case report: The patients were male in both cases, and the endoscopic examination revealed semipedunculated polyps over 20 mm in diameter in their duodenal bulb. Both polyps were soft and lobulated with reddish appearance, and some lobules had white deposition on them. In the Edoxaban case 1, microvascular dilation was observed at the top of the polyp by magnified narrow band imaging (NBI) system. On the other hand, the vasculature was uniform and regular without dilatation in case 2. Endoscopic mucosal resection (EMR) was performed for both cases. Pathological findings: The polyp in the case 1 was diagnosed as well differentiated tubular adenocarcinoma. It was hyperplastic polyp in the case 2. Evaluation by immunohistochemistry revealed that MUC5AC and MUC6 but not CD10 and MUC2 were expressed in both polyps, which confirmed the gastric mucin phenotype of these lesions.

Results: Discussion: Duodenal polyps with gastric mucin phenotype were thought to develop from the ectopic gastric mucosa, gastric metaplasia or Brunner’s gland. However, there are few reports about the characteristics of them, so the details are still unclear. Conclusion: We experienced both malignant and benign cases, which showed distinctive findings with NBI system. It would be important to accumulate the data of endoscopic features for the diagnosis of malignant or benign lobulated villous polyps with gastric mucin phenotype to analyze the correlation with pathological findings, which may also lead to the better understanding of the biological characteristics of these polyps. Key Word(s): 1. Duodenal polyp; 2. gastric mucin phenotype; 3.

This antisteatotic effect was probably the result of a combination of effects on key mechanisms driving the progression to hepatic steatosis,

especially those related to insulin resistance. In this regard, Alox15 deletion in ApoE−/− mice resulted in significant improvements in glucose and insulin tolerance tests in parallel with reduced JNK phosphorylation, an established marker of insulin resistance. Moreover, Alox15 disruption augmented phosphorylation of AMPK, a master regulator of glucose and lipid homeostasis, normalized the hepatic glycogen content, and up-regulated the expression of IRS-2. Given that we did not detect changes in fasting glucose, these findings are consistent with the notion that the effects on fasting glucose in ApoE−/− Alisertib order mice are modest, whereas effects on glucose tolerance and insulin tolerance are more pronounced.36 Additionally, the antisteatotic effect associated with Alox15 disruption in ApoE−/− Ivacaftor datasheet mice was related to insulin-sensitizing effects in adipose tissue. Indeed, the insulin-resistant adipokines MCP-1, TNFα, IL-6, and resistin

were significantly repressed, whereas the expression of GLUT-4 was induced in ApoE−/−/12/15-LO−/− mice. Overall, the genetic disruption of Alox15 rendered similar effects on hepatic insulin signaling to those reported in previous studies in muscle and adipose tissues and are consistent with the role of 12/15-LO as a positive modulator of the onset of insulin resistance.9, 10, 13-16 It is important to note that the antisteatotic effects accompanying Alox15 disruption in ApoE−/− mice occurred in the absence of changes in liver weight, a phenomenon that has been documented.27, 37 The mechanisms by which hepatic steatosis does not translate into increased liver weight in ApoE−/− mice are presently unknown, but it can be speculated that the ApoE protein, in addition to its role

in lipoprotein clearance and very low-density lipoprotein assembly–secretion, also modulates the chemical composition of the hepatic tissue. Moreover, disruption of Alox15 in ApoE−/− mice did not affect serum cholesterol elevations, over suggesting that amelioration of liver injury in this model is independent of serum cholesterol levels. Although this is an intriguing observation, it is in line with previous publications in which deletion of Alox15 in ApoE−/− mice did not induce changes in serum cholesterol levels.11, 12, 38 Finally, it is also important to recognize that the antisteatotic effects accompanying the disruption of Alox15 in ApoE−/− mice differ slightly from those observed after disruption of Alox5 in these mice.7 In particular, disruption of the Alox5 gene significantly reduced hepatic inflammation without modifying the degree of hepatic steatosis,7 whereas the current study demonstrates that disruption of the Alox15 gene markedly reduces both parameters of liver injury. These results suggest that in terms of NAFLD, 12/15-LO appears to be the most relevant LO pathway.

We therefore conducted a large, pooled, post hoc analysis of patients with HCV genotypes 1, 4, 5, or 6 from four trials of PEG-IFN alfa-2a and ribavirin therapy to better understand the association between KU-57788 datasheet virologic response and pharmacodynamic effects as reflected by changes in hematologic parameters and body weight. HCV, hepatitis C virus; IFN, interferon; PEG-IFN, pegylated interferon; SVR, sustained virologic response. Patients with HCV genotypes 1, 4, 5, or 6 receiving 24 or 48 weeks of combination therapy with PEG-IFN alfa-2a (Pegasys; Roche, Nutley, NJ; 180 μg/week) and ribavirin (Copegus; Roche, Nutley, NJ; 1,000 or 1,200 mg/day) were pooled from

two registration trials1, 2 and two phase 4 trials.7, 8 The registration trials were randomized, multicenter, phase 3 studies in IFN-naïve patients with chronic hepatitis C; the first trial compared the efficacy of PEG-IFN alfa-2a and ribavirin therapy with IFN alfa-2b and ribavirin therapy for 48 weeks,1 and the second trial of PEG-IFN alfa-2a and ribavirin JNK inhibitor nmr therapy compared different treatment duration and ribavirin dose combinations.2 The phase 4 studies were noncomparative, open-label studies of PEG-IFN alfa-2a

and ribavirin for 48 weeks in treatment-naïve patients with HCV genotype 1; the majority (>73%) of patients in the first study were African American patients,7 and the second study was conducted in Latino and non-Latino Caucasian patients (ClinicalTrials.gov Identifier NCT00087607).8 All studies included stopping rules for nonresponse except for the trial in African American patients.7 Patients

who received PEG-IFN monotherapy Tyrosine-protein kinase BLK or IFN alfa-2b and ribavirin combination therapy (Rebetron) and patients with HCV/human immunodeficiency coinfection were excluded from the study. The objectives of this study were: (1) to explore the association between pharmacodynamic parameters and virologic response category (SVR, relapse, breakthrough, and nonresponders); (2) to explore the association between pharmacodynamic parameters and race/ethnicity (African American, Latino Caucasians, non-Latino Caucasians, and other races); and (3) to evaluate the effects of clinically significant hemoglobin decline (>3 g/dL versus ≤3 g/dL) on SVR. The pharmacodynamic effects of interest in this analysis were hematologic parameters (hemoglobin level, neutrophil count, and platelet count) and weight loss. Maximum decrease (baseline value for the hematologic test minus the lowest value for that test while on therapy) was used to assess the change in hematologic parameters. To better adjust for the impact of baseline difference, percentage of change from baseline was used to analyze racial/ethnic group differences and body weight changes. For patients without the specified hematologic test or body weight measurement during treatment, the corresponding maximum decrease was set as missing.

Conclusion: Hepatocyte-derived type III IFNs contribute to ISG induction and antiviral activity, but are not the principal determinant of the outcome of HCV infection. (HEPATOLOGY 2012;56:2060–2070) HCV poses a significant health problem, with more than 170 million chronically infected people worldwide.1 Treatment is based on interferon (IFN)-α in combination with ribavirin and direct antiviral agents,2 but

the role of IFN-α and other IFNs in the spontaneous outcome of infection is unclear. Type I IFNs (13 IFN-α proteins plus IFN-β, IFN-ε, IFN-κ, and IFN-ϖ) form the frontline of innate host defenses by inducing an antiviral state in infected and neighboring cells, and by modulating adaptive immune responses directly and by the induction of IFN-stimulated genes ISGs.3 Whereas ISGs are strongly induced during HCV infection,4, 5 neither the ISG-inducing cytokines nor their Roxadustat price cellular Palbociclib sources have been defined. HCV has been shown to interfere with Toll-like receptor (TLR)3- and retinoic-acid–inducible gene (RIG) I–mediated induction of IFN-β and with Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling downstream of the IFN-α/β receptor,6 thus reducing IFN-α/β production to levels that are undetectable in HCV-infected patients. In vitro studies suggest that plasmacytoid dendritic cells (pDCs) may be the source of the ISG-inducing type I IFNs,7

but the role of pDCs has not been studied in the HCV-infected liver. In this context, type III IFNs have Y-27632 2HCl become of interest. This family is composed of interleuking (IL)-29, IL-28A, and IL-28B, and induced in response to several viral pathogens.8 Although signaling by the JAK-STAT pathway is shared with type I IFNs and similar sets of ISGs are induced,9 receptors for type III IFNs are distinct from those for type I IFNs10 and are expressed in a cell-type–specific manner.11 In the liver, type III IFN receptors are expressed at significant levels as a functional full-length form,10, 11 suggesting intact type III IFN signaling as part of the intrahepatic innate immune response.

Furthermore, single nucleotide polymorphisms (SNPs) near and within IL28B are strong predictive markers for spontaneous, treatment-induced HCV clearance,12-15 suggesting that variations in type III IFN expression or function affect the outcome of HCV infection. In this context, Langhans et al. reported that IL-29 serum levels do not differ between patients with acute HCV infection and healthy controls, but that they are lower in chronically infected patients.16 Whereas recombinant type III IFNs are known to suppress HCV replication in vitro,17-19 their expression level in the liver has never been studied prospectively during acute HCV infection. Thus, the relative antiviral effect of endogenously produced type I and type III IFNs is not known.