“Fatal hepatitis B virus (HBV) reactivation in lymphoma pa


“Fatal hepatitis B virus (HBV) reactivation in lymphoma patients with “resolved” HBV infection (hepatitis B surface antigen [HBsAg] negative and hepatitis B core antibody [anti-HBc] positive) can occur, but the true incidence and severity remain unclear. From June 2009

to December 2011, 150 newly diagnosed lymphoma patients with resolved HBV infection who were to receive rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-based chemotherapy were prospectively followed. HBV DNA was checked at baseline, at the start of each cycle of chemotherapy, and every 4 weeks for 1 year after completion of rituximab-CHOP chemotherapy. Patients with documented HBV reactivation were selleck products treated with entecavir at a dosage

of 0.5 mg/day for 48 weeks. HBV reactivation was defined as a greater than 10-fold increase in HBV DNA, compared with previous nadir levels, and hepatitis flare was defined as a greater than 3-fold increase in alanine aminotransferase (ALT) that exceeded 100 IU/L. Incidence of HBV reactivation and HBV-related hepatitis flares was 10.4 and 6.4 per 100 person-year, respectively. Severe HBV-related hepatitis (ALT >10-fold of upper limit of normal) occurred in 4 patients, despite entecavir treatment. Patients with hepatitis flare exhibited significantly higher incidence of reappearance of HBsAg after HBV reactivation (100% vs. 28.5%; P = 0.003). Conclusion: In lymphoma patients with resolved HBV infections, Navitoclax molecular weight chemotherapy-induced HBV reactivation is not uncommon, but can be managed with regular monitoring of HBV DNA and prompt antiviral therapy. Serological breakthrough (i.e., reappearance of HBsAg) is the most important predictor of HBV-related hepatitis flare. (Hepatology 2014;59:2092–2100)


“Aim:  Despite advances in medical therapy, studies have reported gaps between current evidence and actual practice in many areas of medicine. Process-of-care quality indicators (QIs) are tools to measure the MCE公司 evidence–practice gap. This study aims to examine the feasibility of applying QIs for liver cancer care to the national registry database operated by the Liver Cancer Study Group of Japan. Methods:  Prior research developed a set of process-of-care QIs developed on the basis of the Japanese Clinical Practice Guidelines for hepatocellular carcinoma. Each QI describes target patients and care processes indicated for such patients. Among the 25 developed QIs, six appeared scorable using the information contained in the dataset from the 17th Nationwide Survey of Primary Liver Cancer. Results:  In total, 16 187 patients were eligible for the six QIs for 34 599 times, among which the indicated care was provided 83.9% times. The scores ranged from 64.4% (surgical therapy in patients with HCC 3–5 cm in diameter) to 91.1% (indocyanine green checkup before surgical resection).

Key Word(s): 1 Endoscopy; 2 endoscopy training; 3 Simulator; 4

Key Word(s): 1. Endoscopy; 2. endoscopy training; 3. Simulator; 4. Computer-based; Presenting Author: XIA YAN Additional Authors: XU HONG,

WANGLI BO, TAO KE Corresponding Author: XIA YAN Affiliations: The First Hospital of Jilin University Objective: To investigate high-definition endoscopic i-Scan in the detection of colorectal Precancerous lesions of clinical value. Methods: 2011-01/2013-2 in our hospital for routine endoscopy of patients, which found that the new biological Saracatinib manufacturer and polypoid colorectal lesions were 451 cases. Respectively, using conventional high-definition endoscopy, HD i-Scan Technology and staining techniques to observe the lesion to make the initial endoscopic diagnosis with histopathological diagnosis was compared. Results: Endoscopic i-Scan HD technology for cancer and non-neoplastic lesion detection rate with the dye endoscopy rather, no significant difference (P > 0.05). I-Scan technology, high-definition endoscopic diagnosis of neoplastic

lesions was 86.1% sensitivity and specificity was 95.4% overall diagnostic accuracy rate is 92.47%. Conclusion: Endoscopic i-Scan HD technology for the observation of the large intestine mucous membrane lesions was significantly better than normal selleck chemicals colonoscopy, and the operation is simple, with high clinical value. Key Word(s): 1. i-Scan Technology; 2. colon lesions; 3. staining; Presenting Author: NAOHISA YOSHIDA Additional Authors: NOBUAKI YAGI, YUTAKA INADA, YUJI NAITO,

YOSHITO ITO Corresponding Author: NAOHISA YOSHIDA Affiliations: Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine Objective: A new endoscope system with a laser light source: blue laser imaging (BLI) has been developed by Fujifilm that allows for narrow-band light observation. The aim of this study was to evaluate the diagnostic accuracy of BLI for the diagnosis of colorectal polyps. Methods: We retrospectively analyzed 314 colorectal polyps that were examined with BLI observation at Kyoto Prefectural University of Medicine between September 2011 and January 2013. The diagnostic accuracy by published NBI magnification: Hiroshima classification was analyzed. Additionally, the ability of BLI without magnification to differentiate between neoplastic or non-neoplastic polyps MCE was analyzed. Results: A total of 41 hyperplastic polyps, 168 adenomas, 80 intramucosal cancer, 11 shallowly invaded submucosal cancer, and 14 deeply invaded submucosal cancer were analyzed. The overall diagnostic accuracy of BLI magnification was 84.3% (265/314) using Hiroshima classification. The diagnostic accuracy for dSM in cancerous lesions was 94.3% (99/105). The accuracy of differentiation was 99.3% (312/314) between non-neoplastic lesions and neoplastic lesions and 85.0% (232/273) between adenomatous lesions and cancerous lesions.

Thus, it has been postulated that the tumor-suppressive functions

Thus, it has been postulated that the tumor-suppressive functions of JNK are mostly linked to their proapoptotic activity, whereas the oncogenic functions are generally based on the ability to phosphorylate c-Jun and activate AP-1. The dual function of the JNK genes in tumorigenesis is clearly reflected in Das et al.’s study.6 The investigators identify hepatocyte

JNK as crucial in tumor initiation. A major physiological role Osimertinib for JNK is the induction of apoptosis in various cell types, including JNK-null cells, has already been reported.16 Indeed, tumors show enhanced expression of antiapoptotic proteins or inactivation of proapoptotic molecules, which are mechanisms to evade cell suicide. However, the mechanism by which JNK induces apoptosis is still not selleck products clear, and studies on the effect on JNK genes in the activation of proapoptotic molecules, such as the Bcl family, need to be performed.17 On the other hand, there is a substantial body of evidence implicating JNK in tumor development.17 In fact, JNK activation

is required for transformation induced by Ras, an oncogene activated in nearly 30% of human cancers.18 Moreover, c-Jun−/− fibroblasts cannot be transformed by Ras, which suggests that c-Jun is indispensible in tumor development.19 These observations are consistent with the fact that JNK is constitutively active in tumor samples and derived cell lines.20 Indeed, JNK1−/− mice show a marked reduction of hepatocellular carcinoma (HCC) after diethylnitrosamine (DEN) administration.21 However, tissue-specific JNK involved in tumor development was not yet defined. Here, Davis et al. demonstrate, for the first time, that JNK in nonparenchymal is the only key player in tumor development, where JNK1 might be required for the expression of c-myc.13 Yet, down-regulation of p21 expression, medchemexpress usually a marker of tumor development, was not observed after compound JNK deficiency in both hepatocytes and nonparenchymal cells. In vivo studies with p21-deficient mice will

help to dissect the interaction between the JNK genes and p21. Notwithstanding, the reduction in tumor growth in compound JNK-deficient mice is, in part, contradictory. The investigators speculate that during tumor initiation, JNK is activated in hepatocytes—indeed, JNK1 is required for hepatocyte death after DEN21—to promote cell death and inflammation, which triggers activated Kupffer cells to promote compensatory proliferation and tumor development throughout the expression of cytokines, such as interleukin-6 and tumor necrosis factor.22 In conclusion, this article sheds light upon the mechanism of JNK signaling in liver regeneration and HCC. First, the finding that the role of JNK in proliferation is cell-type–dependent opens the door to new research to identify the specific tissue required for the role of JNK1 in hepatic regeneration.

On

average patients completed 11 weeks of therapy at the

On

average patients completed 11 weeks of therapy at the time of data analysis. None of the pts died while on therapy, one patient (5%) on ribavirin discontinued all treatment due to AKI and severe anemia and one patient who was listed find more for chronic rejection received re-transplantation while on therapy and his HCV RNA remained negative after transplant. In the SOF+SMV group median (IQR) creatinine levels were significantly worse at week 8 of therapy compared to BL(1.00 (0.95-1.5) to 1.7 (1.05, 1.95)), p=0.026.There was a trend towards an increase in tacrolimus level in this group (4.5 (3.9, 4.85) at baseline to 5.5 (4.1 to 6.45) on week 4), p = 0.066. There was no decline in hemoglobin level in the SOF + SMV group at weeks 4 or 8. In the SOF + RBV group, there was no effect on creatinine or TAC levels. All patients had undetectable HCV RNA with normalization of ALT/AST at week 4(Median ALT 56 to 19 and AST 78 to 22, p=0.008). Conclusion: In our experience, SOF-based regimens

were safe and effective in treating HCV recurrence. The combination of SOF+SMV was associated with an increase in creatinine levels and a mild increase in TAC levels which requires further PXD101 monitoring. Disclosures: John J. Fung – Advisory Committees or Review Panels: Astellas, Novartis; Consulting: Vital Therapies; Grant/Research Support: Sanofi Naim Alkhouri – Advisory Committees or Review Panels: Gilead

Sciences The following people have nothing to disclose: Mohammed Eyad Yaseen Alsab-bagh, Ibrahim A. Hanouneh, Binu V. John, John K. Guirguis, Bijan Eghtesad, Nizar N. Zein Background: Non-interferon based therapy for chronic hepatitis C genotype 1 is a global goal. To date, there is limited data on the use of an all-oral treatment regimen in the post-liver transplant population. Methods: Thirty seven patients transplanted for genotype 1 chronic HCV were treated using an off-label combination of sofosbuvir, simeprevir, +/− ribavirin for 12 weeks. We collected data on patient characteristics, viral response, laboratory MCE values, and adverse events. The decision to treat patients for recurrent HCV post-transplant was made by one of 6 transplant hepatologists. Patients were monitored with monthly clinic visits and lab testing every 2-4 weeks during treatment. Results: Twenty five patients had genotype 1a, 7 patients had genotype 1b, and 5 patients were undifferen-tiated. There were 27 males (73%) and 14 African Americans (38%). The average age was 57 years (range 32-69) and the average time from transplant was 4 years (range 4-334 months). Twenty patients (54%) were treatment-experienced. Eight patients (22%) had recurrent cirrhosis. Sixteen patients (43%) were treated with ribavirin;13 started ribavirin at onset of treatment and 3 had ribavirin added due to slow viral response.

Due to the longer treatment duration of the triple combination, t

Due to the longer treatment duration of the triple combination, there are no sufficient data yet for patients reaching the end of treatment for BOC. In the cohort creatinine results were recorded at baseline, week 12, week 24, and every 12 weeks thereafter until 24 weeks after end of treatment. No documentation of urine analysis was recorded. The eGFR was calculated with the recently presented Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, which may be best suited to reflect changes of eGFR in patients with normal or mildly impaired renal function.[6] For statistical analysis in a first step, univariate Vemurafenib manufacturer regression analysis

was used. All variables reaching P < 0.05 in the univariate analysis were entered in a multiple logistic regression analysis. Software used was IBM SPSS Statistics v. 21.0.0.0. Overall, 895 patients were PD-0332991 cost included, 575 on TLV, 211 on BOC, and 109 on dual therapy. Baseline demographics are shown in Table 1. As expected, HCV genotype 1 patients treated with dual

therapy were younger, had more frequently low level HCV-RNA, and had a lower proportion of patients with diabetes mellitus or arterial hypertension, reflecting a selection for variables associated with better treatment outcome or being naïve to HCV therapy. At week 12 a decrease of eGFR to <60 mL/min in patients with >60 mL/min at baseline was observed in 49/895 (5.5%) patients overall. Patients on TLV 38/575 (6.6%) and BOC 10/211 (4.7%) experienced more frequently a decrease in eGFR to <60 mL/min compared to patients on PEG/RBV 1/109 (0.9%) (P < 0.05). Risk factors associated with eGFR <60 mL/min corresponding to renal insufficiency stage 3 were age (P < 0.001), arterial hypertension (P < 0.001), diabetes mellitus (P < 0.05), a higher

serum creatinine at baseline (P < 0.001), 上海皓元 and being on triple therapy with TLV or BOC (P < 0.05). There was no association with baseline hemoglobin, smoking, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), HCV-RNA, HCV treatment history, sex, APRI score, or comedications including nonsteroidal antiinflammatory drugs. In the multiple regression analysis age (P < 0.001), a higher creatinine at baseline (P < 0.001), being on triple therapy with TLV or BOC (P < 0.01), and arterial hypertension (P < 0.05) remained significantly associated with a decrease in eGFR to <60 mL/min. Patients with a drop of eGFR to <60 mL/min had a lower absolute mean hemoglobin at week 12 with 9.7 g/dL ± 1.4 g/dL compared to 11.0 g/dL ± 1.7 g/dL in patients with an eGFR >60 mL/min (P < 0.001). The absolute decrease in hemoglobin was also different, with 5.3 g/dL ± 1.3 g/dL compared to 3.8 g/dL ± 1.6 g/dL, respectively (P < 0.001). In the second analysis a smaller patient subset which had already reached week 24 of therapy was assessed.

Due to the longer treatment duration of the triple combination, t

Due to the longer treatment duration of the triple combination, there are no sufficient data yet for patients reaching the end of treatment for BOC. In the cohort creatinine results were recorded at baseline, week 12, week 24, and every 12 weeks thereafter until 24 weeks after end of treatment. No documentation of urine analysis was recorded. The eGFR was calculated with the recently presented Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, which may be best suited to reflect changes of eGFR in patients with normal or mildly impaired renal function.[6] For statistical analysis in a first step, univariate buy Deforolimus regression analysis

was used. All variables reaching P < 0.05 in the univariate analysis were entered in a multiple logistic regression analysis. Software used was IBM SPSS Statistics v. 21.0.0.0. Overall, 895 patients were buy KPT-330 included, 575 on TLV, 211 on BOC, and 109 on dual therapy. Baseline demographics are shown in Table 1. As expected, HCV genotype 1 patients treated with dual

therapy were younger, had more frequently low level HCV-RNA, and had a lower proportion of patients with diabetes mellitus or arterial hypertension, reflecting a selection for variables associated with better treatment outcome or being naïve to HCV therapy. At week 12 a decrease of eGFR to <60 mL/min in patients with >60 mL/min at baseline was observed in 49/895 (5.5%) patients overall. Patients on TLV 38/575 (6.6%) and BOC 10/211 (4.7%) experienced more frequently a decrease in eGFR to <60 mL/min compared to patients on PEG/RBV 1/109 (0.9%) (P < 0.05). Risk factors associated with eGFR <60 mL/min corresponding to renal insufficiency stage 3 were age (P < 0.001), arterial hypertension (P < 0.001), diabetes mellitus (P < 0.05), a higher

serum creatinine at baseline (P < 0.001), 上海皓元 and being on triple therapy with TLV or BOC (P < 0.05). There was no association with baseline hemoglobin, smoking, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), HCV-RNA, HCV treatment history, sex, APRI score, or comedications including nonsteroidal antiinflammatory drugs. In the multiple regression analysis age (P < 0.001), a higher creatinine at baseline (P < 0.001), being on triple therapy with TLV or BOC (P < 0.01), and arterial hypertension (P < 0.05) remained significantly associated with a decrease in eGFR to <60 mL/min. Patients with a drop of eGFR to <60 mL/min had a lower absolute mean hemoglobin at week 12 with 9.7 g/dL ± 1.4 g/dL compared to 11.0 g/dL ± 1.7 g/dL in patients with an eGFR >60 mL/min (P < 0.001). The absolute decrease in hemoglobin was also different, with 5.3 g/dL ± 1.3 g/dL compared to 3.8 g/dL ± 1.6 g/dL, respectively (P < 0.001). In the second analysis a smaller patient subset which had already reached week 24 of therapy was assessed.

Caucasians were the predominant ethnic population in this study (

Caucasians were the predominant ethnic population in this study (n = 1443) with the frequency of the good responder IFN-λ3 rs12979860 CC and rs8099917 TT genotypes being 32% and 52%, respectively. These results were very similar to that found in Caucasians from the pivotal GWAS from North America and Australia-Europe Opaganib concentration reporting on the IFN-λ3 rs12979860 and rs8099917 SNPs, respectively.[1, 2] Asian subjects, in contrast, had a higher prevalence of good

responder genotypes, and both SNP responder alleles were of similar prevalence. The overall frequency of the IFN-λ3 rs12979860 CC was 80%, while the rs8099917 TT genotype frequency was 86%. These findings were similar to that reported in other Asian cohorts with HCV Gt1 infection, including those from Taiwan (rs12979860 CC 90%, rs8099917 TT 90%),[11] China (rs12979860 CC 88%, rs8099917 TT 85%),[12, 13] and Korea (rs8099917 TT 85%).[14] Reports from Japan have been mixed, however, with the prevalence of the rs8099917 TT genotype in HCV Gt1 varying from 71% to 86%.[3, 15] The high prevalence of good responder IFN-λ3 polymorphisms along with recent data linking favorable IFN-λ3 genotype

to improved viral clearance and kinetics[16, 17] among Asians explains much of why Asian subjects have high response rates to PEG-IFN plus RBV. To our knowledge, this study is the first to report the distribution of IFN-λ3 polymorphisms among Australian LEE011 in vivo (or non-Australian) Aboriginals with CHC. Interestingly, we found that the prevalence of favorable IFN-λ3 genotypes among the 33 Aboriginals tested was similar to that of Caucasians with the frequency of the IFN-λ3 rs12979860 CC and rs8099917 TT genotypes being 33% and 63%, respectively. Limited data exists, however, on the outcomes of PEG-IFN and RBV therapy in Aboriginal Australians with CHC to determine whether our findings have a clinical corollary. Indeed, the only relevant study of note evaluating this issue involved Aboriginal Canadians who had similar response rates to PEG-IFN plus RBV therapy compared with non-Aboriginal

Canadians.[18] Further studies are therefore needed to address the issue of the relationship of IFN-λ3 genotype and IFN responsiveness among this important ethnic 上海皓元医药股份有限公司 group. Our study is also the first to describe the distribution of IFN-λ3 polymorphisms in native New Zealanders and Pacific Islanders. Although subject numbers were small (n = 17), Maoris and Pacific Islanders both had a relatively high prevalence of good responder genotypes, with the frequency of IFN-λ3 rs12979860 CC being 75% and 78%, and rs8099917 TT genotype 88% and 89%, respectively. Thus, the IFN-λ3 distribution of both ethnic groups appears to resemble far more closely that of Asians rather than indigenous Australians.

Helmet use has been shown to significantly reduce risk of

Helmet use has been shown to significantly reduce risk of

head injury in skiing and yet only a small proportion of skiers use helmets [75, 75]. There has been little research examining the role of behaviour in sports injury prevention [76]. Despite growing evidence for a number of injury prevention strategies, behavioural change on the part of the sportsperson, the coach and sometimes the adjudicators of sport, is required to prevent injury [77]. Safe sports participation for PWH involves balancing the benefits and risks of particular activities and, where possible, ensuring adequate clotting factor levels in the blood. The focus now should be on evaluating the role of injury prevention strategies including Bcl-2 inhibitor optimal prophylactic schedules, protective equipment and preparticipation exercise programmes on bleeds risk and ensuring that proven injury prevention strategies are adopted at a community level. KF has received speaker’s fees from Baxter, CSL Behring, Pfizer, Novo Nordisk, Biotest; performed consultancy for Bayer, Baxter, Biogen, Novo Nordisk and Pfizer; and has received research support from Bayer, Wyeth/Pfizer, Baxter, and Novo Nordisk. BK has received research support from selleck products Baxter Bioscience, Biogen-Idec Hemophilia, Novo Nordisk and Octapharma, and has acted as a consultant for CSL-Behring, Pfizer, Baxter Bioscience and Biogen-Idec Hemophilia. CB has no conflicts

to declare. CMK has not declared any conflicts. “
“In patients with haemophilia A, factor VIII (FVIII) prophylaxis reduces bleeding frequency and joint damage compared with on-demand therapy. To assess the effect of prophylaxis initiation age, magnetic

resonance imaging (MRI) was used to evaluate bone and cartilage damage in patients with severe haemophilia A. In this cross-sectional, multinational investigation, patients aged 12–35 years were assigned to 1 of 5 groups: primary prophylaxis started at age <2 years (group 1); secondary prophylaxis started at age 2 to <6 years (group 2), 6 to <12 years (group 3), or 12−18 years (group 4); or on-demand treatment (group 5). Joint status at ankles and knees was assessed using Compatible Additive MRI scoring (maximum and mean ankle; maximum and mean of all 4 joints) and Gilbert scores in the per-protocol population (n = 118). All prophylaxis groups had 上海皓元医药股份有限公司 better MRI joint scores than the on-demand group. MRI scores generally increased with current patient age and later start of prophylaxis. Ankles were the most affected joints. In group 1 patients currently aged 27−35 years, the median of maximum ankle scores was 0.0; corresponding values in groups 4 and 5 were 17.0 and 18.0, respectively [medians of mean index joint scores: 0.0 (group 1), 8.1 (group 2) and 13.8 (group 4)]. Gilbert scores revealed outcomes less pronounced than MRI scores. MRI scores identified pathologic joint status with high sensitivity. Prophylaxis groups had lower annualized joint bleeds and MRI scores vs. the on-demand group.

Helmet use has been shown to significantly reduce risk of

Helmet use has been shown to significantly reduce risk of

head injury in skiing and yet only a small proportion of skiers use helmets [75, 75]. There has been little research examining the role of behaviour in sports injury prevention [76]. Despite growing evidence for a number of injury prevention strategies, behavioural change on the part of the sportsperson, the coach and sometimes the adjudicators of sport, is required to prevent injury [77]. Safe sports participation for PWH involves balancing the benefits and risks of particular activities and, where possible, ensuring adequate clotting factor levels in the blood. The focus now should be on evaluating the role of injury prevention strategies including LY294002 in vivo optimal prophylactic schedules, protective equipment and preparticipation exercise programmes on bleeds risk and ensuring that proven injury prevention strategies are adopted at a community level. KF has received speaker’s fees from Baxter, CSL Behring, Pfizer, Novo Nordisk, Biotest; performed consultancy for Bayer, Baxter, Biogen, Novo Nordisk and Pfizer; and has received research support from Bayer, Wyeth/Pfizer, Baxter, and Novo Nordisk. BK has received research support from RXDX-106 Baxter Bioscience, Biogen-Idec Hemophilia, Novo Nordisk and Octapharma, and has acted as a consultant for CSL-Behring, Pfizer, Baxter Bioscience and Biogen-Idec Hemophilia. CB has no conflicts

to declare. CMK has not declared any conflicts. “
“In patients with haemophilia A, factor VIII (FVIII) prophylaxis reduces bleeding frequency and joint damage compared with on-demand therapy. To assess the effect of prophylaxis initiation age, magnetic

resonance imaging (MRI) was used to evaluate bone and cartilage damage in patients with severe haemophilia A. In this cross-sectional, multinational investigation, patients aged 12–35 years were assigned to 1 of 5 groups: primary prophylaxis started at age <2 years (group 1); secondary prophylaxis started at age 2 to <6 years (group 2), 6 to <12 years (group 3), or 12−18 years (group 4); or on-demand treatment (group 5). Joint status at ankles and knees was assessed using Compatible Additive MRI scoring (maximum and mean ankle; maximum and mean of all 4 joints) and Gilbert scores in the per-protocol population (n = 118). All prophylaxis groups had medchemexpress better MRI joint scores than the on-demand group. MRI scores generally increased with current patient age and later start of prophylaxis. Ankles were the most affected joints. In group 1 patients currently aged 27−35 years, the median of maximum ankle scores was 0.0; corresponding values in groups 4 and 5 were 17.0 and 18.0, respectively [medians of mean index joint scores: 0.0 (group 1), 8.1 (group 2) and 13.8 (group 4)]. Gilbert scores revealed outcomes less pronounced than MRI scores. MRI scores identified pathologic joint status with high sensitivity. Prophylaxis groups had lower annualized joint bleeds and MRI scores vs. the on-demand group.

All three patients (two viral and one alcoholic cirrhosis, who ha

All three patients (two viral and one alcoholic cirrhosis, who had nadolol stopped for impotence) remained abstinent during all follow-ups (range, 50-80 months), and none of them rebled. On the other hand, the two patients with dose reduction and loss of hemodynamic response rebled (at 13 and 17 months, respectively). Both patients in this

subgroup had mixed viral and alcohol cirrhosis and had resumed alcohol drinking prior to the rebleeding episode. Drug therapy in the remaining 43 patients was Tamoxifen datasheet well tolerated, and all of them were kept during all follow-up on the same maximal tolerated doses they had at the moment of the second HVPG. To evaluate whether the differences between alcohol abstinents and nonabstinents in long-term response and outcomes may have been related to baseline differences or beta-blocker doses received compliance, a comparison of the most relevant among these parameters was performed (Table 4). Both subgroups were comparable. Cox multivariate analysis identified Cilomilast order loss of hemodynamic response (HR, 7.5; 95% CI, 2.1-27.0; P = 0.002) and history of previous variceal bleeding

(HR, 8.6; 95% CI, 2.1-34.5; P = 0.002) as risk factors for rebleeding, and viral etiology (HR, 4.1; 95% CI, 1.0-18.6; P = 0.05) and Child-Pugh score at 1 year (HR, 1.5; 95% CI, 1.1-2.1; P = 0.015) as main determinants of death/LT. It is currently accepted in clinical guidelines1, 2 that, in an HVPG-guided prophylactic strategy after a variceal hemorrhage, those patients meeting the accepted criteria

of hemodynamic response are reasonably MCE protected from rebleeding under drug therapy alone. This view is supported by longitudinal and randomized trials in which the responder status is based on HVPG measurements taken shortly (from 2 weeks to 3 months) after the index hemorrhage, with no subsequent reassessments during the usual 2-year follow up of these studies (range, 8-28 months).5, 6 Nevertheless, although it is assumed that these patients should be kept indefinitely on drug therapy only, there is no evidence that the initial hemodynamic response is maintained after this 2-year period. In this longitudinal observational study, we followed up for a median of 4 years a large cohort of hemodynamic responders treated with beta-blockers and nitrates after a variceal bleeding, and found that this response was lost in the long term in one out of three patients, an observation that was associated with a clear negative impact on their outcomes. This is the only available report in which sequential protocol HVPG measurements were performed in responders after a variceal bleeding to check their hemodynamic status. The previous study by Merkel et al.10 shared a similar approach and reported analogous results, but it was performed in patients with no previous history of bleeding, a setting with clearly lower baseline risk of progression of portal hypertension and incidence of related complications.