These results may produce a new therapeutic approach for NAFL and DM by targeting miR-27b. Disclosures: Yuichiro Eguchi – Grant/Research Support: BMS The following people have nothing to disclose: Takaomi Kessoku, Yasushi Honda, Yuji Ogawa, Wataru Tomeno, Kento Imajo, Hironori Mawatari, Satoru Saito, Koichiro Wada, Atsushi Nakajima Introduction: Bile acid-binding resins are synthetic polymers used to treat dyslipidemia, vascular calcification, and hyper-phosphatemia due to chronic renal disease.

They bind bile acids and phosphates in the gut and prevent their absorption leading to lower serum levels of LDL and phosphates. Recently, these agents have been reported to lower blood glucose and increase insulin sensitivity. We report that, in a mouse model of NAFLD, sevelamer

check details treatment reverses steatosis, significantly affects inflammatory cell infiltrate, and may protect against fibro-sis. Methods: Mice fed a low fat diet (LFD) or western diet (WD; high fat, sucrose, and cholesterol) for 5 months were treated with sevelamer carbonate (2% wt/wt) for the last 2 months. The extent of steatohepatitis was assessed histologically with H&E staining. Flow cytometry of liver cell isolates was used to phe-notype intrahepatic leukocytes, and RT-qPCR was performed on whole liver to further characterize the inflammatory state of each treatment group. Results: Mean NAS scores for WD control and WD sevelamer mouse liver sections were 3.5 and 2.0 respectively (down 43%). Histology Selleck YAP-TEAD Inhibitor 1 analysis revealed significant reductions in mean steatosis, lobular inflammation, and hepatocyte ballooning scores in WD sevelamer mice compared to WD control. By qPCR, expression levels of the pro-inflammatory and pro-fibrotic genes TNF-α (7 fold, p<0.01), CCL2 (16 fold, p<0.01), COL1A1 (5 fold, p=0.03), and α-SMA (9 fold, p<0.01) were decreased in WD sevelamer compared to WD control mouse liver. By flow cytometry, the fraction of Ly6Chigh monocytes (25%, p<0.01), total macrophages (50%, p=0.02), and CD86+ macrophages MCE公司 (36%, p=0.02) was reduced in WD sevelamer

compared to WD control mouse liver. Interestingly, the WD decreased the fraction of CD206+ macrophages present in mouse liver, but sevelamer reversed this effect. This same trend was also observed with NKT cells. There was no significant change in the fraction of monocytes present. Conclusions: Sevelamer administration improves WD-induced steatosis in a mouse model of NAFLD. In addition, it reverses the increase in intrahepatic pro-inflammatory monocytes and macrophages. Commercially-available sevelamer causes a shift in liver mac-rophage phenotype, decreases the fraction of Ly6Chigh liver monocytes, restores levels of protective NKT cells, and may also have anti-fibrotic effects. Disclosures: Moshe Levi – Grant/Research Support: Intercept, Genzyme-Sanofi The following people have nothing to disclose: Brett McGettigan, Rachel McMa-han, Cara Porsche, David J.

3 The ISGs responsible for controlling HCV replication in response to IFN (either endogenously induced or therapeutically given) remain ill defined, although a picture of the ISGs capable of controlling HCV replication is emerging. The ISG 2,5-OAS has been shown to inhibit HCV replication through the RNAse L pathway,5 whereas IFN-α mediated suppression of HCV replication in vitro is independent of MxA.6 A number of less well-characterized

ISGs have also been demonstrated to selleck inhibit HCV replication; studies have demonstrated that ISG6-16 can enhance the anti-HCV activity of IFN-α,7 whereas ISG56 has direct anti-HCV activity through its ability to suppress HCV internal ribosome entry site (IRES) translation.8 More recently, PKR and the 3′- to 5′-exonuclease, ISG20, have been demonstrated to inhibit HCV replication.9, 10 Clearly, anti-HCV ISG effectors remain to be discovered and characterized. Viperin is an evolutionarily

conserved type I ISG, selleck kinase inhibitor previously demonstrated by our laboratory and others to have antiviral properties against HCV in vitro,9, 11 and a number of other viruses, including human cytomegalovirus, influenza, alphaviruses, human immunodeficiency virus, and dengue, as reviewed elsewhere.12 However, the mechanism by which viperin exerts its anti-HCV effect is unknown. Viperin localizes to both the endoplasmic reticulum (ER) and lipid droplets (LDs), and considering the LD is central to the HCV life

MCE cycle, it has been hypothesized that viperin inhibits HCV replication at this location.12, 13 In this study, we show that viperin suppresses the replication of cell-culture–derived infectious HCV, and demonstrate, for the first time, that viperin interacts with nonstructural protein 5A (NS5A) at the LD interface and within the replication complex (RC). Furthermore, we also show that viperin colocalizes with the known proviral cellular factor, human vesicle-associated membrane protein-associated protein subtype A (VAP-A) within the HCV RC, strongly suggesting that viperin exerts its effect at the level of HCV RNA replication.

In other words, there are no scientifically accepted criteria for inclusion SAHA HDAC or exclusion of specific modalities as CAM or as conventional. Conventional medicine is exactly that – medicine by convention. From an operational viewpoint, it is useful to understand the differences among complementary, alternative, and integrative medicine

systems as presently applied. Complementary medicine refers to the practice of combining allopathic medicine with virtually any other medical system’s modalities. Alternative medicine is the practice of any nonconventional medical system as an “alternative” to conventional medicine. Finally, integrative medicine is a hybrid in which nonconventional modalities which have been scientifically validated by Western standards are combined with allopathic practices

but are not yet considered conventional. selleck inhibitor When, if ever, is it appropriate to discuss these nontraditional approaches with our patients? Certainly, it is one option to simply opine that you are not an expert in this area and refer the patient to someone who is, just as we might refer a patient to an endocrinologist or cardiologist. This should be done in as professional and nonjudgmental way as possible. But if we are going to integrate some of these approaches into our care plans, there are several generally accepted circumstances where this might be more appropriate. This, of course, begs the argument that all care plans should be integrative, and that will be addressed shortly. When a patient clearly expresses a preference for a particular modality, it should be discussed openly and objectively. Certainly,

if a patient is asking for a surgery to “cure” their headaches, and there is ample evidence to suggest such an intervention is extreme, risky, or ineffective, we 上海皓元 must indicate so. But if a patient wants to try something that is outside our usual armamentarium, this is an appropriate time to include that treatment if you are comfortable with it, or to refer out, if you are not. Not infrequently, patients will present with a long list of medicines they have tried, and we are unable to assess whether these trials were adequate in dosing and duration, or not well tolerated. Often, patients report they “just don’t do well” with medications. Convincing this population to revisit medicines or to try other medicines can be, at best, an uphill battle, and at worst, a futile, time-consuming, and frustrating bootless errand. Offering these patients a “fresh approach” with interventions that are nontraditional can be very helpful. A more easily defined population is one containing patients who have frank contraindications (economic, medical, religious, etc) to traditional approaches. Many patients search for qualified doctors who can offer something other than pharmacologic interventions.

“
“A woman, aged 41 years, was admitted to hospital with acute epigastric

pain and abdominal distension. She was known to have ischemic heart disease, hypertension, hyperlipidemia and diabetes and had been previously diagnosed with a sliding hiatus hernia. Her medication at the time of admission included pantoprazole, rosuvastatin, ramipril, metformin and aspirin. On physical examination, there was moderate tenderness on palpation in the epigastrium. Blood tests revealed an elevated white cell selleck inhibitor count (15.6 × 109/L) with a neutrophilia but other blood tests including an amylase and lipase were within the reference range. A plain abdominal radiograph showed a distended stomach while a computed tomography (CT) scan showed gas within the branches of hepatic portal vein (arrows) and gas in the Trametinib nmr posterior wall of the stomach (arrows) consistent with emphysematous gastritis (Figure 1). At upper gastrointestinal endoscopy, there was a well-demarcated area of erosive gastritis on the posterior wall of the body of the stomach (Figure 2). She was treated with intravenous fluids and an intravenous proton pump inhibitor and this was followed by a relatively rapid improvement in her symptoms. A repeat CT scan after 1 week showed resolution of hepatic portal venous gas and repeat

endoscopy after 3 weeks showed almost complete resolution of gastritis. Emphysematous gastritis is a rare disease characterized by the presence of gas in the wall of the stomach, usually shown on a CT scan. Bacteria associated with emphysematous gastritis have included Clostridium welchii, Streptococcal species, Escherichia coli, Enterobacter species and Staphylococcus aureus. Common predisposing factors include the MCE公司 ingestion of corrosive substances,

alcohol abuse, abdominal surgery, diabetes and immunosuppression. Some of these patients have gas in hepatic portal veins. This is usually most prominent near the periphery of the liver in contrast to air in the bile ducts (pneumobilia) that is usually more prominent in and around the hilum of the liver. Because of presumed gastric infection, most patients are treated with broad-spectrum antibiotics. Early complications include gastric perforation and some patients have been treated with gastric surgery. Mortality rates as assessed by case reports appear to be at least 50%. In the above patient, gastritis was restricted to a segment of the stomach and the patient made a spontaneous and apparently complete recovery. Contributed by “
“We read with great interest the article by Corey et al.1 In this study, they found that hepatitis C virus (HCV) infection was associated with decreased cholesterol and low-density lipoprotein (LDL) levels and this hypolipidemic effect disappeared with successful hepatitis C treatment but persisted in nonresponders.

Here we evaluate the effects of activation of the bile acid receptor pathways MAPK Inhibitor high throughput screening in liver sinusoidal endothelial cells using microarray analysis. Methods: A murine LSEC line was treated with a dual FXR/TGR5 agonist (INT767, 30uM) and/or free fatty acids (palmitic acid and oleic acid, 0.66mM) for 24 hours. RNA was isolated and gene expression analysis was performed using the GeneChip Mouse Gene 2.0 ST Array. Analysis of deferentially

expressed genes, canonical signaling pathways and upstream regulators was analyzed using the Ingenuity Pathway Analysis (IPA) software. Differential regulation was defined as 1.5-fold difference from untreated LSEC (p<0.05, ANOVA). Results: Gene expression analysis revealed that 29 genes were uniquely downregulated following treatment with INT-767. A number of these downregulated genes have been shown to be important in fibrosis and inflammation. IL-33,

a member of the IL-1 super-family, was significantly decreased following treatment with the agonist (p=0.009). In addition, the expression targets for pro-fibrotic (TGFbeta; p=0.001) and pro-inflammatory (IL-12, p=0.04) master regulators were over-represented in our genes responding to treatment. These pathways were predicted Cabozantinib in vitro by IPA to be inhibited by treatment with INT-767. Conclusion: We demonstrate that activation of the bile acid receptor pathways in murine LSECs results in a down regulation of pro-fibrotic and pro-inflammatory genes. Understanding the effects of FXR and TGR5 activation in LSEC could be important for both NAFLD and other liver diseases. Disclosures: Luciano Adorini – Consulting: Intercept Pharmaceuticals Moshe Levi – Grant/Research Support: Intercept, Genzyme-Sanofi The following people medchemexpress have nothing to disclose: Rachel McMahan, Cara Porsche, Michael Edwards, Hugo R. Rosen Objectives:

Thyroid hormone (TH) is important for liver repair because it regulates hepatic differentiation. Both serum TH levels and hepatic deiodinases control intrahepatic TH activity. TH substrate (thyroxine, T4) is converted into active hormone (triidothyronine, T3) by deiodinase 1 (D1), but into inactive hormone (reverse T3, rT3) by deiodinase 3 (D3). D3 transcription is controlled by Hedgehog-regulated factors. Hedgehog signaling increases during liver injury. Liver injury also changes the relative expressions of D1 and D3. However, the cell types and signaling mechanisms involved are unclear. We evaluated the hypothesis that changes in hepatic deiodinases result from repair-related activation of the Hedgehog pathway in stromal cells. Methods: We localized deiodinase expression to specific liver cell types and assessed deiodinase changes during injury by performing bile duct ligation (BDL) in rats.

Louis, MO) containing 1 mg/mL of Mycobacterium tuberculosis strain H37RA, and was subsequently boosted every 2 weeks with 2OA-BSA in incomplete Freund’s adjuvant (Sigma-Aldrich). Additionally, mice received 100 ng of pertussis toxin CHIR99021 (List Biological Laboratories, Campbell, CA) at the time of initial immunization with 2OA-BSA in Complete Freund’s Adjuvant. Peripheral blood samples from individual mice were obtained from the tail vein prior to the initiation of treatment with mAbs (baseline) and then at 2-week intervals. Sera was collected prior to mAb treatment, 1 week afterward, and thereafter every 4 weeks, and stored at −70°C until

use. Animals were sacrificed at 15 weeks of age. Serum titers of anti–PDC-E2 autoantibodies were measured by way of enzyme-linked immunosorbent assay using our well-standardized recombinant autoantigens.32 Peripheral blood mononuclear cells were isolated from heparinized murine blood using Accupaque (Accurate Chemical & Scientific Company, Westbury, CT) to assess levels of B cells. Cells were preincubated with anti-mouse FcR blocking reagent and then incubated at 4°C with a predetermined optimum concentration of antigen-presenting cell (APC)-conjugated anti–T cell receptor β (BioLegend), phycoerythrin-conjugated anti-mouse IgM

(Caltag), and fluorescein isothiocyanate–conjugated anti-CD19 check details (BioLegend); B cell frequency was then determined by way of flow cytometry. The liver and spleens were collected from mice immediately following sacrifice, and single-cell mononuclear cell suspensions

were prepared for multicolor flow analysis as described.23 Immediately after sacrifice, liver and spleen tissues were harvested and fixed in 10% buffered formalin, embedded in paraffin, and cut into 4-μm sections for routine hematoxylin (DakoCytomation, Carpinteria, MCE CA) and eosin (American Master Tech Scientific, Lodi, CA) staining. Evaluation under light microscopy and scoring of liver inflammation was performed on coded hematoxylin and eosin–stained sections of liver using a set of three indices by a blinded pathologist (K. T.); indices included degrees of portal inflammation, parenchymal inflammation, and bile duct damage.33 Phenotypic analysis of bile duct damage was performed as described.34 Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphate (ALP) levels were measured using the Roche Diagnostics COBAS INTEGRA 400 Plus (Indianapolis, IN). Serum levels of the proinflammatory cytokines interleukin (IL)-6, IL-10, monocyte chemotactic protein-1 (MCP-1), interferon-γ (IFN-γ), tumor necrosis factor α, and IL-12p70 were quantified using the BD Cytometric Bead Array Mouse Inflammatory Kit (BD Biosciences) as described.35 The serum samples were loaded onto the plate neat.

Louis, MO) containing 1 mg/mL of Mycobacterium tuberculosis strain H37RA, and was subsequently boosted every 2 weeks with 2OA-BSA in incomplete Freund’s adjuvant (Sigma-Aldrich). Additionally, mice received 100 ng of pertussis toxin find more (List Biological Laboratories, Campbell, CA) at the time of initial immunization with 2OA-BSA in Complete Freund’s Adjuvant. Peripheral blood samples from individual mice were obtained from the tail vein prior to the initiation of treatment with mAbs (baseline) and then at 2-week intervals. Sera was collected prior to mAb treatment, 1 week afterward, and thereafter every 4 weeks, and stored at −70°C until

use. Animals were sacrificed at 15 weeks of age. Serum titers of anti–PDC-E2 autoantibodies were measured by way of enzyme-linked immunosorbent assay using our well-standardized recombinant autoantigens.32 Peripheral blood mononuclear cells were isolated from heparinized murine blood using Accupaque (Accurate Chemical & Scientific Company, Westbury, CT) to assess levels of B cells. Cells were preincubated with anti-mouse FcR blocking reagent and then incubated at 4°C with a predetermined optimum concentration of antigen-presenting cell (APC)-conjugated anti–T cell receptor β (BioLegend), phycoerythrin-conjugated anti-mouse IgM

(Caltag), and fluorescein isothiocyanate–conjugated anti-CD19 NVP-AUY922 (BioLegend); B cell frequency was then determined by way of flow cytometry. The liver and spleens were collected from mice immediately following sacrifice, and single-cell mononuclear cell suspensions

were prepared for multicolor flow analysis as described.23 Immediately after sacrifice, liver and spleen tissues were harvested and fixed in 10% buffered formalin, embedded in paraffin, and cut into 4-μm sections for routine hematoxylin (DakoCytomation, Carpinteria, MCE公司 CA) and eosin (American Master Tech Scientific, Lodi, CA) staining. Evaluation under light microscopy and scoring of liver inflammation was performed on coded hematoxylin and eosin–stained sections of liver using a set of three indices by a blinded pathologist (K. T.); indices included degrees of portal inflammation, parenchymal inflammation, and bile duct damage.33 Phenotypic analysis of bile duct damage was performed as described.34 Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphate (ALP) levels were measured using the Roche Diagnostics COBAS INTEGRA 400 Plus (Indianapolis, IN). Serum levels of the proinflammatory cytokines interleukin (IL)-6, IL-10, monocyte chemotactic protein-1 (MCP-1), interferon-γ (IFN-γ), tumor necrosis factor α, and IL-12p70 were quantified using the BD Cytometric Bead Array Mouse Inflammatory Kit (BD Biosciences) as described.35 The serum samples were loaded onto the plate neat.

Louis, MO) containing 1 mg/mL of Mycobacterium tuberculosis strain H37RA, and was subsequently boosted every 2 weeks with 2OA-BSA in incomplete Freund’s adjuvant (Sigma-Aldrich). Additionally, mice received 100 ng of pertussis toxin check details (List Biological Laboratories, Campbell, CA) at the time of initial immunization with 2OA-BSA in Complete Freund’s Adjuvant. Peripheral blood samples from individual mice were obtained from the tail vein prior to the initiation of treatment with mAbs (baseline) and then at 2-week intervals. Sera was collected prior to mAb treatment, 1 week afterward, and thereafter every 4 weeks, and stored at −70°C until

use. Animals were sacrificed at 15 weeks of age. Serum titers of anti–PDC-E2 autoantibodies were measured by way of enzyme-linked immunosorbent assay using our well-standardized recombinant autoantigens.32 Peripheral blood mononuclear cells were isolated from heparinized murine blood using Accupaque (Accurate Chemical & Scientific Company, Westbury, CT) to assess levels of B cells. Cells were preincubated with anti-mouse FcR blocking reagent and then incubated at 4°C with a predetermined optimum concentration of antigen-presenting cell (APC)-conjugated anti–T cell receptor β (BioLegend), phycoerythrin-conjugated anti-mouse IgM

(Caltag), and fluorescein isothiocyanate–conjugated anti-CD19 RG7420 datasheet (BioLegend); B cell frequency was then determined by way of flow cytometry. The liver and spleens were collected from mice immediately following sacrifice, and single-cell mononuclear cell suspensions

were prepared for multicolor flow analysis as described.23 Immediately after sacrifice, liver and spleen tissues were harvested and fixed in 10% buffered formalin, embedded in paraffin, and cut into 4-μm sections for routine hematoxylin (DakoCytomation, Carpinteria, medchemexpress CA) and eosin (American Master Tech Scientific, Lodi, CA) staining. Evaluation under light microscopy and scoring of liver inflammation was performed on coded hematoxylin and eosin–stained sections of liver using a set of three indices by a blinded pathologist (K. T.); indices included degrees of portal inflammation, parenchymal inflammation, and bile duct damage.33 Phenotypic analysis of bile duct damage was performed as described.34 Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphate (ALP) levels were measured using the Roche Diagnostics COBAS INTEGRA 400 Plus (Indianapolis, IN). Serum levels of the proinflammatory cytokines interleukin (IL)-6, IL-10, monocyte chemotactic protein-1 (MCP-1), interferon-γ (IFN-γ), tumor necrosis factor α, and IL-12p70 were quantified using the BD Cytometric Bead Array Mouse Inflammatory Kit (BD Biosciences) as described.35 The serum samples were loaded onto the plate neat.

In this category of patients, long-term antiviral therapy is needed to prevent

rebound of viral replication. HBsAg loss, which would allow treatment cessation, is rarely observed in this group of patients [2,3]. The choice of first-line therapy is based on multiple criteria including the age of the patients, HBeAg/HBeAb status, viral load, viral genotype, results of HBsAg quantification, ALT levels and liver histology [2,3]. Depending on these criteria, a finite duration treatment with pegylated interferon may be considered, or a long-term antiviral therapy with NUCs. In patients with decompensated liver disease, pegylated interferon is contraindicated, and NUC administration has been shown to be effective [4]. It is noteworthy that tenofovir selleck kinase inhibitor is active on both HBV and HIV and therefore is often recommended for co-infected patients [5]. Prolonged antiviral therapy with entecavir or tenofovir results in very high rate of viral suppression which is associated with improvements in serum transaminase levels and in liver histology [6–9]. In treatment naive patients, antiviral drug resistance has not been observed with tenofovir and in only 1.2% of entecavir-treated patients over periods of >5 years [10–12]. In patients with previous treatment failure, the second-line treatment should be decided

based on the cross-resistance profile of the drugs with the same 上海皓元医药股份有限公司 objective of viral suppression [10]. Although there have been major breakthroughs in the treatment of chronic hepatitis B, major challenges remain [13]. Compelling evidence IWR-1 purchase connects high levels of viral replication to an increased time to HBV DNA undetectability during treatment, and an increased incidence of cirrhosis, hepatocellular carcinoma and liver-related mortality. Thus, the correct choice of a potent first-line therapy to achieve sustained long-term suppression of viral replication provides the best chance of preventing the progression

of liver disease and prolonging survival [14]. Most patients receiving treatment will need long-term treatment to meet these goals, and the development of antiviral resistance is a major concern in these cases. The correct choice of first-line treatment also provides the best chance of avoiding salvage therapy, which can be affected by cross-resistance. For economically challenged countries that have a high burden of disease, there is a need for initiatives that can deliver virological monitoring and the most efficacious drugs at affordable cost, enabling wider accessibility of antiviral treatment and improved patient management. In addition, new treatments that can eradicate the infection are needed. Although new oral medications such as tenofovir and entecavir potently suppress replication, if they are stopped, infection is often reconstituted from the cccDNA reservoir.

O’Leary – Consulting: Gilead, Jansen Laura M. Kulik – Advisory Committees or Review Panels: Bayer/ Onyx; Grant/ Research Support: Bayer/Onyx; Speaking and Teaching: Bayer/Onyx, Nordion, Gilead Shailesh Chavan – Employment: Biotest Pharmaceuticals Christopher J. Dougherty – Employment:

Biotest Pharmaceuitcals Corporation The following people have nothing to disclose: George Therapondos, Sirolimus Roshan Shrestha, Jeffrey Campsen, James Spivey, Jens Rosenau, Kalyan R. Bhamidi-marri, Lewis W. Teperman, Gerond Lake-Bakaar, Fredric D. Gordon, Daniel Maluf Fibrosing cholestatic hepatitis (FCH) is a rare but severe form of HCV-recurrence following liver transplantation (LT) leading to poor short term survival. Therapeutic options are limited. Study aims were to assess efficacy and tolerance of sofosbuvir

(SOF) and daclatasvir (DCV)-based regimens in this setting. Methods: The CUPILT study is a prospective nationwide cohort including patients with HCV-recurrence following LT treated by new antivirals. The present work focused on 21 patients diagnosed with FCH and included between Oct 2013 and Feb 2014. FCH diagnosis was based on strict criteria including histological review by an expert pathologist. Treatment regimens were prescribed at investigator’s discretion. Patients were followed at W0, W1, W2, W3, W4, W6, W8 and W12. Results: FCH was diagnosed after a median duration of 6 months [range 1-18] following LT and therapy started at 10 months [2-38] post LT. Features of patients at W0 were: median JQ1 chemical structure MCE公司 age: 53 years [36-67], men: 81%, G1: 76%, G3: 10%, G4: 14%, ALT: 128 IU/L [46-588], gGT: 595 IU [86-5,511], bilirubin: 6.0 mg/dL [0.6-19], albumin : 3.2 g/dL [1.6-4.0], HCV RNA : 6.9 log IU/ml [4.6-8.4]. Ascites was observed in 8 (38%) patients. Four (19%) were HIV-co-infected and 14 (67%) failed

to antiviral therapy containing protease inhibitors in 9 (43%) cases. The following regimens were used: Peg-IFNa + SOF + RBV (n=2), SOF + RBV (n=6), SOF + DCV (n=1) and SOF + DCV + RBV (n=12) for 24 weeks. All patients were alive without re-transplantation at W12. HCV RNA was not detectable at W2 and W4 in 1 (5%) and 3 (14%) patients, respectively. At W12, 20 (95%) patients had HCV RNA <15 IU/ml and 17 (81%) were not detectable. Early viral kinetics was not influenced by treatment regimens. The rates of ALT and gGT normalization at W12 were 76% and 52%, respectively. Median bilirubin serum levels rapidly decreased from 6.0 to 3.6 at W1 and 2.6 mg/dL at W2. The median time to achieve bilirubin levels below 2 mg/dL was 6 weeks. At week 12, 19 (90%) of patients had bilirubin below 2 mg/dl, and 13 (69%) below 1 mg/dL. Albumin levels increased from 31 to 36 g/L at W12. This was accompanied by clinical improvement including nutritional status (weight gain from 67.5 to 70.0 Kg). Ascites disappeared in 4/8 patients, but remained stable in 2 patients who had initially refractory ascites.