Results and conclusions from these studies were first grouped and summarized to provide SAHA HDAC chemical structure generalized qualitative information. Additionally, sampling rate (defined as the percentage of biopsy attempts that struck an animal and successfully retained a sample, following Best et al. 2005) and percentage values for a range of behavioral response levels were calculated so that results could be quantitatively compared across studies. Several steps were taken in an attempt to standardize behavioral reactions to facilitate statistical comparison across studies. First, all previously reported behavioral reactions were grouped into four distinct categories (see Table 3

for definitions). Second, percentage values for sampling rate and for each of the four behavioral

response categories were calculated separately for groups of cetaceans that were from different studies or were from the same study but differed by species, differed by biopsy method H 89 concentration used, or were sampled in different geographic regions (Table 4, 5). These values were then incorporated into statistical and graphical analyses to assess factors that influence sampling rate and behavioral responses following biopsy. All percentages were arcsine transformed prior to performing ANOVA and t-tests. In some cases, nonparametric analyses (ANOVA on ranks, Mann-Whitney rank sum test) were used when tests for normality or equal variance failed. Finally, based on the qualitative and quantitative findings of this extensive review, we identify specific biopsy techniques 上海皓元 that provide adequate samples while minimizing disturbance to the animals and make recommendations for additional data to be systematically collected during biopsy sampling to aid in improving the technology and better assessing the impacts of these techniques. The majority of published studies that have

employed biopsy techniques focus on reporting the findings of the sample analyses (see Table 1, 2), rather than reporting the rate of success of acquiring biopsy samples. From the limited data available, it appears that sampling rate (defined as the percentage of biopsy attempts that struck an animal and successfully retained a sample, following Best et al. 2005) is normally high but may vary by study, the specific methods used, and the species being sampled (Table 4, 5). For example, in studies conducted by the NOAA Southwest Fisheries Science Center from 1991 to 1999, samples were obtained from 68.4% of the darts that hit small odontocetes and 84% of all darts that contacted large odontocetes and mysticetes (Chivers et al. 2000). Likewise, a system specifically designed to sample humpback whales with a pneumatic gun achieved an impressive sampling rate of 95% (Lambertsen et al. 1994). Unfortunately, the data reported in the available literature were not sufficient to quantitatively assess how biological and physical factors influenced sampling rate.

Results and conclusions from these studies were first grouped and summarized to provide buy R788 generalized qualitative information. Additionally, sampling rate (defined as the percentage of biopsy attempts that struck an animal and successfully retained a sample, following Best et al. 2005) and percentage values for a range of behavioral response levels were calculated so that results could be quantitatively compared across studies. Several steps were taken in an attempt to standardize behavioral reactions to facilitate statistical comparison across studies. First, all previously reported behavioral reactions were grouped into four distinct categories (see Table 3

for definitions). Second, percentage values for sampling rate and for each of the four behavioral

response categories were calculated separately for groups of cetaceans that were from different studies or were from the same study but differed by species, differed by biopsy method ACP-196 in vivo used, or were sampled in different geographic regions (Table 4, 5). These values were then incorporated into statistical and graphical analyses to assess factors that influence sampling rate and behavioral responses following biopsy. All percentages were arcsine transformed prior to performing ANOVA and t-tests. In some cases, nonparametric analyses (ANOVA on ranks, Mann-Whitney rank sum test) were used when tests for normality or equal variance failed. Finally, based on the qualitative and quantitative findings of this extensive review, we identify specific biopsy techniques MCE公司 that provide adequate samples while minimizing disturbance to the animals and make recommendations for additional data to be systematically collected during biopsy sampling to aid in improving the technology and better assessing the impacts of these techniques. The majority of published studies that have

employed biopsy techniques focus on reporting the findings of the sample analyses (see Table 1, 2), rather than reporting the rate of success of acquiring biopsy samples. From the limited data available, it appears that sampling rate (defined as the percentage of biopsy attempts that struck an animal and successfully retained a sample, following Best et al. 2005) is normally high but may vary by study, the specific methods used, and the species being sampled (Table 4, 5). For example, in studies conducted by the NOAA Southwest Fisheries Science Center from 1991 to 1999, samples were obtained from 68.4% of the darts that hit small odontocetes and 84% of all darts that contacted large odontocetes and mysticetes (Chivers et al. 2000). Likewise, a system specifically designed to sample humpback whales with a pneumatic gun achieved an impressive sampling rate of 95% (Lambertsen et al. 1994). Unfortunately, the data reported in the available literature were not sufficient to quantitatively assess how biological and physical factors influenced sampling rate.

4 Finally, the safety concerns potentially associated with the statin use cannot be ignored.5 With such conflicting and preliminary evidence, it is necessary to exercise a cautious skepticism for a potential beneficial role

of statins for chronic HCV hepatitis. Enzo Emanuele M.D.*, * Interdepartmental Center for Research in Molecular Medicine (CIRMC), University of Pavia, Pavia, Italy. “
“In the 1950s, Catoni[1] identified S-adenosylmethionine (SAMe or AdoMet) as an active methyl donor. SAMe methylates DNA, RNA, phospholipids, creatine, proteins, histones, among other targets, and is a precursor of polyamine and glutathione. The liver is responsible for 85% of all trans-methylation reactions[2] and SAMe deficiency has been linked to liver diseases, including cancer and nonalcoholic fatty liver disease (NAFLD). SAMe selleck products supplementation may be an interesting therapeutic approach for several liver diseases, including cholestasis, alcoholic liver disease, hepatitis C, and NAFLD. Phosphatidylcholine (PC) synthesis is the likely link between decreased SAMe supply and NAFLD progression. Liver cells are unusual in that they synthesize 30% of hepatic

PC by way of the sequential methylation of phosphatidylethanolamine (PE) catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT); the rest of Histone Methyltransferase inhibitor PC is biosynthesized by way of the CDP-choline pathway.[3] Animals MCE with decreased hepatic SAMe content, either because of dietary methyl deficiency[4,

5] or disruption of genes involved in hepatic SAMe synthesis,[6, 7] have impaired PC synthesis (Fig. 1A). Hepatic PC is required for assembly/secretion of very low-density lipoproteins (VLDL). When PC synthesis is impaired, triacylglycerol (TG) accumulates in the liver. Impaired synthesis of SAMe or PC also increase hepatic TG by activating SREBP-1 and de novo lipogenesis.[5] Hence, the supply of SAMe and PC is vital for maintaining hepatic lipid homeostasis. The glycine N-methyltransferase (GNMT) knockout mouse (Gnmt−/−) reveals an additional level of complexity to the relationship between hepatic SAMe and NAFLD.[8] GNMT methylates glycine to form sarcosine (methyl-glycine). Sarcosine has no known metabolic function but is demethylated to regenerate glycine. This futile cycle enables the catabolism of excess hepatic SAMe without aberrant production of methylated products. Deletion of GNMT increased steady-state SAMe levels 40-fold and induced NAFLD in mice.[8] Gnmt−/− mice developed NAFLD by 3 months and hepatocellular carcinoma by 8 months of age. While these studies highlight a clear link between excess SAMe and NAFLD, the mechanism underlying these findings was unclear. In this issue of Hepatology, Martínez-Uña et al.[9] provide new insight into mechanisms by which both low and high SAMe levels promote hepatic lipid accumulation (Fig. 1B).

, 201 3). In the present study, we aimed to analyse further putative targets of the Ago2 neuronal miRNA complex, namely Notch 1, KLF4, and Lin28. Methods: Notch 1, KLF4, and Lin28 gene expression was quantified in primary rat HSC cultures by real time PC R. 3∽UTR sites of Notch 1, KLF4, and Lin28 transcripts, putatively targeted by neuronal miR-9, miR-125b, mTOR inhibitor miR-128, were cloned downstream to a luciferase reporter gene and used for reporter assays in myofibroblastic HSC treated with miRNA mimics

or with scrambled miRNA. Notch 1 and Lin28 were overexpressed by lentiviral vector transduction and the influence on HSC was determined by expression profiling using PCR arrays. Results: Since the pluripotency involved factors, Notch 1, KLF4, and Lin28 were suggested to be targets of posttranscriptional neuronal miRNA repression, we investigated the expression of these mediators during myofibroblastic HSC transition. Whereas the neuronal miRNAs miR-9, miR-125b, and miR-128 were highly increased,

the putative targets Notch 1 and Lin28, but not KLF4 were markedly decreased during myofibroblastic differentiation of HSC. Next, we analysed the 3∽UTR of Notch1, KLF4, and Lin28 transcripts for putative binding sites XL765 of the three neuronal miRNAs. Reporter assays of the luciferase constructs, harboring the putative 3∽UTR sites of Notch1, KLF4, and Lin28 MCE mRNA in comparison to the corresponding mutants definitively demonstrate the inhibitory interaction of all

neuronal miRNAs to Lin28 and Notch1, and of miR-128 to KLF4 mRNA. Furthermore, neuronal miRNA over-expression in HSC resulted in a prominent decrease of Notch1 and Lin28. In order to proof the impact of the neuronal miRNA Notch1 axis, lentiviral overexpression was performed. Expression profiling of Notch1 overexpressing cells revealed that members of the Notch signaling pathway were highly upregu-lated whereas some fibrogenic mediators are downregulated. Conclusion: Upregulation of neuronal miR-9, miR-125b, and miR-128 during myofibroblastic transition and the identified interaction with factors involved in pluripotency and cell differentiation suggests a prominent role of these miRNAs in HSC differentiation and activation during fibrosis. Disclosures: The following people have nothing to disclose: Jia Huang, Andrea Noetel, Moritz Perrech, Ingo Strack, Jürgen Hescheler, Reinhard Buettner, Tomo Saric, Margarete Odenthal C5a and its cognate receptor C5aR are critical modulators of both liver immunity and liver fibrosis. However, the molecular mechanism for the cross talk between the complement system and liver fibrosis is not well understood. C5a is a potent chemokine regulating the migration of cells in the innate immune system.

01 for all). Analysis of treatment-related costs yielded an average reduction of $1219.33/patient, off-setting 49.7% of the total estimated cost for 6 months of treatment with onabotulinumtoxinA. Although we are unable to distinguish onabotulinumtoxinA’s treatment effect from other potential

confounding variables, our analysis showed that severely afflicted, treatment-refractory patients with chronic migraine experienced a significant cost-offset through reduced migraine-related emergency department visits, urgent care visits, and hospitalizations in the 6 months following treatment initiation of onabotulinumtoxinA. Future analyses will assess the longer-term effect of onabotulinumtoxinA treatment and the potential contribution of regression to the mean. “
“There have been associations demonstrated between migraine and high throughput screening ischemic stroke and heart disease. Additionally, headache patients have increased cardiovascular risk factors. This article reviews available data supporting these concerns and answers the following questions: 1)  Does the association between migraine and cardiovascular disease warrant cardiovascular screening tests Ibrutinib in vitro in migraine sufferers? “
“To assess

and compare the prevalence of migraine in patients with restless legs syndrome (RLS) and matched controls. Recent studies have suggested an association between migraine and RLS. Our work is the first case–control study on this subject performed in an RLS population. A case–control study was conducted in 47 RLS patients (27 women and 20 men aged between 18 and 65 years) and 47 age- and sex-matched controls. Validated questionnaires were used to investigate the presence of migraine, anxiety, and depression (Zung Self-Rating Anxiety and Depression scales), sleep quality (Pittsburgh Sleep Quality Index), and RLS severity (International RLS scale). MCE公司 RLS patients had higher lifetime prevalence of migraine

than non-RLS controls (53.2% vs 25.5%, P = .005; matched-OR 1.3 [P = .019]; adjusted odds ratio (OR) 3.8 [P = .03]). No significant associations were found between RLS and active migraine with aura or inactive migraine (no episodes in the previous year). However, active migraine without aura was significantly more prevalent in patients with RLS than in controls (40.4% vs 12.8%, P = .001; matched OR 1.5 [P = .001]; adjusted OR 2.7 [P = .04]). Within the RLS group, patients with migraine had poorer sleep quality than those without migraine (Pittsburgh Sleep Quality Index >5:100 vs 80.9%, P = .038) but did not differ in terms of RLS severity, anxiety and depression, use of dopaminergic agonists, and body mass index. There appears to be a relationship between RLS and migraine, in particular for active migraine without aura. “
“(Headache 2010;50:1597-1611) Medication-overuse headache (MOH) can be viewed as an interaction between the worsening of the primary headache course and individual predispositions for dependence.

The patient without antibiotic prophylaxis re-presented with another episode of SBP. 3) 16 patients were identified as being ‘at high risk’ of SBP

using published criteria; of these only 2 were given appropriate primary prophylaxis. Of the 14 patients who were not given prophylactic antibiotics, one later developed SBP. Conclusion: Although buy Copanlisib the overall number of incident cases of infection in our cohort was low, our study highlights the fact that antibiotic prophylaxis may be underutilized in the inpatient setting. Particular attention is needed in recognizing ‘high risk’ patients with low protein ascites and advanced liver disease for primary antibiotic prophylaxis. R CHENG,1,2 R KANAZAKI,2 FW CHEN,2 NA SHACKEL,1,2 GW MCCAUGHAN1,2 1Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW, Australia., mTOR inhibitor 2Royal Prince Alfred Hospital, Sydney, NSW, Australia. Introduction and aims: Thromboelastography (TEG) has been routinely used to predict blood transfusion requirements in liver transplant surgery. It measures viscoelastic properties of blood during different phases of coagulation. Although cirrhotic patients are coagulopathic biochemically, some also paradoxically develop thrombotic complications. Our aim is to assess the differences between coagulation properties (measured by TEG) of patients of varying aetiology of cirrhosis. We also assessed for potential predictors of thrombotic complications

in cirrhosis. Methods: Biochemical

and clinical data were acquired from 116 consecutive patients with liver disease on the Australian National Liver Transplant Unit registry, including: TEG scores [K time (K), R time (R), alpha angle (AA), maximal angle (MA)], coagulation studies (INR, APTT, fibrinogen), full blood count, creatinine, thrombotic complications, cause of cirrhosis, and MELD score. Disease aetiology and MELD scores were compared against each parameter using unpaired t-test. Results: Patients fall into two distinct groups based on coagulation profiles: 13 have cholestatic liver disease (primary biliary cirrhosis and primary sclerosing cholangitis); 103 have non-cholestatic liver disease. When comparing parameters medchemexpress of cholestatic liver disease versus non-cholestatic liver disease, the platelet count in x109/L (129 ± 22.7 vs 73. ± 3.9, p = 0.03), fibrinogen level in g/L (2.9 ± 0.22 vs 1.7 ± 0.06, p < 0.0001), and INR (1.7 ± 0.12 vs 2.2 ± 0.14, p = 0.007) were significantly different. For the TEG items, only MA (in mm.) is significantly different (58 ± 3.2 vs 46 ± 1.0, p = 0.003). MELD score was not significantly different (23 ± 1.8 vs 21 ± 0.9, p = 0.32). In cholestatic liver disease, MELD score does not correlate with TEG or coagulation studies except with INR (p = 0.0015). In non-cholestatic liver disease, MELD score correlates significantly with K (p < 0.0001), R (p = 0.025), MA (p = 002), fibrinogen (p < 0.0001) and INR (p < 0.0001).

The patient without antibiotic prophylaxis re-presented with another episode of SBP. 3) 16 patients were identified as being ‘at high risk’ of SBP

using published criteria; of these only 2 were given appropriate primary prophylaxis. Of the 14 patients who were not given prophylactic antibiotics, one later developed SBP. Conclusion: Although this website the overall number of incident cases of infection in our cohort was low, our study highlights the fact that antibiotic prophylaxis may be underutilized in the inpatient setting. Particular attention is needed in recognizing ‘high risk’ patients with low protein ascites and advanced liver disease for primary antibiotic prophylaxis. R CHENG,1,2 R KANAZAKI,2 FW CHEN,2 NA SHACKEL,1,2 GW MCCAUGHAN1,2 1Centenary Institute of Cancer Medicine and Cell Biology, Sydney, NSW, Australia., PLX3397 cost 2Royal Prince Alfred Hospital, Sydney, NSW, Australia. Introduction and aims: Thromboelastography (TEG) has been routinely used to predict blood transfusion requirements in liver transplant surgery. It measures viscoelastic properties of blood during different phases of coagulation. Although cirrhotic patients are coagulopathic biochemically, some also paradoxically develop thrombotic complications. Our aim is to assess the differences between coagulation properties (measured by TEG) of patients of varying aetiology of cirrhosis. We also assessed for potential predictors of thrombotic complications

in cirrhosis. Methods: Biochemical

and clinical data were acquired from 116 consecutive patients with liver disease on the Australian National Liver Transplant Unit registry, including: TEG scores [K time (K), R time (R), alpha angle (AA), maximal angle (MA)], coagulation studies (INR, APTT, fibrinogen), full blood count, creatinine, thrombotic complications, cause of cirrhosis, and MELD score. Disease aetiology and MELD scores were compared against each parameter using unpaired t-test. Results: Patients fall into two distinct groups based on coagulation profiles: 13 have cholestatic liver disease (primary biliary cirrhosis and primary sclerosing cholangitis); 103 have non-cholestatic liver disease. When comparing parameters 上海皓元医药股份有限公司 of cholestatic liver disease versus non-cholestatic liver disease, the platelet count in x109/L (129 ± 22.7 vs 73. ± 3.9, p = 0.03), fibrinogen level in g/L (2.9 ± 0.22 vs 1.7 ± 0.06, p < 0.0001), and INR (1.7 ± 0.12 vs 2.2 ± 0.14, p = 0.007) were significantly different. For the TEG items, only MA (in mm.) is significantly different (58 ± 3.2 vs 46 ± 1.0, p = 0.003). MELD score was not significantly different (23 ± 1.8 vs 21 ± 0.9, p = 0.32). In cholestatic liver disease, MELD score does not correlate with TEG or coagulation studies except with INR (p = 0.0015). In non-cholestatic liver disease, MELD score correlates significantly with K (p < 0.0001), R (p = 0.025), MA (p = 002), fibrinogen (p < 0.0001) and INR (p < 0.0001).

In clinical studies the half-life was 93 h, which was five times higher than the patient’s previous product. The incremental recovery

of N9-GP was 94% and 20% higher compared with recombinant and plasma-derived products respectively [12]. Data from the clinical C646 in vitro studies phase 3 will be published in 2014. Two main technologies, one using Fc of Immunoglobulin G (IgG) and the other using Albumin as a fusion partner are established. Both, IgG as well as albumin, are abundantly expressed in humans and known to exhibit a half-life of about 20 days. Both, human albumin and the Fc-part of IgG bind to the neonatal Fc-receptor (FcRn) residing, e.g. on endothelial cells. The FcRn recycles its cargo protein back to the cell surface membrane to be released into the

bloodstream [13]. An overview of clotting factors with fusion technology in current clinical studies is given in Table 2. rFVIII-Fc is a recombinant fusion of a B-domain deleted FVIII molecule and the dimeric constant region (Fc) of IgG1 [14, 15]. The product will be likely licenced in the USA by the middle of 2014. A large data set of the phase 3 clinical studies have already been published. The terminal half-life of rFVIIIFc (19.0 h) was extended 1.5-fold vs. rFVIII (12.4 h; P < 0.001). Median annualized bleeding rates (ABR) observed in the prophylactic arms 1 (individualized prophylaxis Histone Methyltransferase inhibitor (25–65 IU kg−1 every 3–5 days) and arm 2 (weekly prophylaxis (65 IU kg−1), were 1.6 and 3.6, MCE respectively, compared to 33.6 in the arm 3 with episodic treatment [16]. At the end of study, subjects were dosed every 3 days (n = 29), twice-weekly (n = 23), every 4 days (n = 4) or every 5 days (n = 24). The corresponding on-study ABR (last 3 months) dosed with rFVIIIFc every 3 days, twice-weekly, every 4 days and every 5 days was 0.0, 0.0, 2.0 and 2.0, respectively [17]. rFIX-Fc is a recombinant fusion of a FIX molecule to the Fc-domain of human IgG1 [18]. The product

will be licenced in the USA in the second quarter of 2014. A large data set of the phase 1–3 clinical studies have been published [19, 20]. As compared with recombinant factor IX (rFIX), rFIXFc exhibited a prolonged terminal half-life (82.1 h). The median annualized bleeding rates in groups 1 (weekly dose-adjusted prophylaxis, 50 IU kg−1 to start), 2 (interval-adjusted prophylaxis, 100 IU kg−1 every 10 days to start and 3 (episodic treatment) were 3.0, 1.4 and 17.7, respectively. In group 2, 53.8% of participants had dosing intervals of 14 days or more during the last 3 months of the study [20]. Recombinant fusion of albumin and to FIX was achieved by a linker sequence that contains a cleavable sequence identical to the activation site of FIX. Upon activation of the fusion protein (rFIX-FP, CSL654), albumin and the linker is cleaved off, leaving a native-activated FIXa molecule [21, 22].

7A,B; Supporting Information Fig. 4), PBC (Fig. 7A,C), AIH, and

PSC (Fig. 7A), suggesting that OPN induction is a conserved response to chronic liver injury. Cirrhosis rarely occurs unless NAFLD progresses to NASH, a condition that is characterized by inflammation and hepatocyte death.31 However, only a minority of individuals with NASH actually develop cirrhosis. Fibrosis stage in NASH has been shown to correlate with the level of hepatic apoptotic activity.1, 32 Index liver biopsy specimens of NASH patients who eventually progress to cirrhosis also harbor more myofibroblasts (MFs) than specimens of patients who do not progress BMS-777607 to cirrhosis.3 These observations link hepatocyte apoptosis with myofibroblast accumulation and fibrosis progression in NASH. There is further evidence that

phagocytosis of apoptotic debris stimulates HSCs to become MFs.33 Recently, we identified a potentially related DAPT mechanism by which hepatocyte apoptosis promotes MF accumulation and liver fibrosis by demonstrating that dying hepatocytes produce Hh ligands.4 Biologically active Hh ligands are detected in apoptotic fragments released by ligand-producing cells.34 Hh ligands, in turn, engage various types of Hh-responsive cells, including HSCs, ductular-type cells, and NKT cells, to trigger fibrogenic responses.7, 35, 36 Consistent with these findings, we observed that Hh activity correlated with MF accumulation and fibrosis stage in NAFLD patients and in rodent models of NAFLD, suggesting that interindividual differences in Hh signaling influenced intensity of fibrogenic responses during NASH.7 The present study provides further support for this concept, because it identifies OPN as a proximal effector of Hh-mediated fibrogenesis, and demonstrate that livers of OPN-deficient mice are significantly protected from NASH-related fibrosis. A recent analysis of the OPN gene revealed binding sites for Gli transcription factors, suggesting that OPN transcription is likely to be regulated by Hh signaling.14 By demonstrating colocalization of Gli and OPN in

liver cells, and proving that expression of OPN mRNA is increased by a Smoothened agonist but decreased by a Smoothened 上海皓元医药股份有限公司 antagonist, our results support and advance this concept. In addition, our data demonstrate that changes in OPN gene expression are paralleled by changes in OPN protein content and biological activity, because OPN aptamers reverse the profibrogenic actions of OPN. The latter findings also verify that OPN is a significant downstream target of Hh signaling (rather than vice versa), because neutralizing OPN had no effect on cellular expression of the Hh target gene Gli2 but significantly diminished fibrogenic gene expression, even in Ptc-deficient cells with supranormal Hh pathway activity.

AUROC, area under the receiver operating characteristics; DDLT, deceased donor liver transplantation; F, fibrosis stage; HCV, hepatitis C virus; HVPG, hepatic venous pressure gradient; LDLT, living donor liver transplantation; LR+, likelihood ratio positive; LR−, likelihood ratio negative; LSM, liver stiffness measurements; LT, liver transplantation; MMRM, mixed model for repeated measurements; NIA, necroinflammatory activity; NPV, negative predictive value; PPV, positive predictive value; S, sensitivity; Sp, specificity. From August 2004 to January 2008, 132 consecutive patients with HCV recurrence after LT out of a total of 293 patients who underwent transplantation in our selleck chemical institution

were considered for the study. Exclusion criteria were: graft or patient survival shorter than 12 months after LT (n = 17); combined kidney and liver transplantation (n = 4); hepatitis B virus or human immunodeficiency virus coinfection (n = 3); presence of ascites (n = 6), body mass index > 33 (n = 2), chronic graft rejection (n = 5), biliary tract complications (n = 8), veno-occlusive disease JAK2 inhibitors clinical trials (n = 1), de novo autoimmune hepatitis (n = 1) and recurrence of hepatocellular carcinoma (n = 1) during the first year after LT. Therefore, the final number

of HCV-infected LT recipients included was 84 (64%). Another 19 patients who underwent LT for other etiologies were included as the control group. Patients were managed according to previously published protocols.28 Induction immunosuppression was cyclosporine A or tacrolimus and prednisone. Mycophenolate mofetil was added in patients who required cyclosporine or tacrolimus dose reduction or discontinuation. Immunosuppression therapy was recorded throughout the study. Acute rejection episodes were documented by liver histologic analysis and treated with steroid boluses if moderate or severe. After discharge,

patients were visited at the outpatient clinic, monthly for the first 3 months with complete recording of clinical and analytical variables, and every 2 or 3 months thereafter. A total of 73 HCV-infected LT recipients underwent repeated LSM at 3, 6, 9, and 12 months and a liver 上海皓元 biopsy 1 year after LT (median = 12.3 months). An HVPG measurement was available in 65 patients at the same time. The remaining 11 patients had cholestatic hepatitis.29 In these patients, liver biopsy (n = 11) and HVPG (n = 9) were performed when the clinical diagnosis was suspected (median = 6.7 months). LSM before initiation of antiviral treatment were available at 3 and 6 months in eight patients and at months 3, 6, and 9 in three. Another five non–HCV-infected patients with elevated alanine aminotransferase (≥ 40 IU/L) underwent a liver biopsy 1 year after LT (median = 13.4 months). The study was previously approved by the Investigation and Ethics Committee of the Hospital Clinic of Barcelona following the ethical guidelines of the 1975 Declaration of Helsinki.