Queiroz et al. [26] studied the mechanism leading to those changes. Higher IL-1β and TNF-α gastric concentrations were observed in H. pylori positive than in negative children. Multiple linear regression models revealed gastric IL-1β, but not TNF-α, as a significant predictor of low ferritin and hemoglobin concentrations. The authors concluded

that high gastric levels of IL-1β could be the link between H. pylori infection and iron deficiency or iron-deficiency anemia in children. Hepcidin, a key regulator of iron homeostasis, increases when inflammation and infections occur. It plays a critical role in macrophage iron retention, which underlies anemia caused by inflammation/infection. Ozkasap et al. [27] in their prospective study examined Tamoxifen mouse prohepcidin (hepcidin’s precursor) in iron deficiency and iron-deficiency anemia in H. pylori-infected children. The pretreatment prohepcidin levels were significantly higher in children with iron-deficiency anemia and H. pylori infection compared with the control group. The authors concluded that increased serum prohepcidin might indicate the role of inflammation in the etiology

Wnt inhibitor of anemia concurrent with H. pylori infection. Azab et al. [28] compared the serum hepcidin level and the response to oral iron therapy in 60 children with iron-deficiency anemia. Serum hepcidin was significantly lower in H. pylori noninfected children (p < .01) and significantly higher in H. pylori-infected children with iron-deficiency anemia. Hepcidin increased significantly in noninfected children after 3 months

of oral iron therapy. A negative correlation was demonstrated between hepcidin and serum ferritin, Hb, iron, and transferrin in H. pylori-infected children with iron-deficiency anemia. The 上海皓元医药股份有限公司 serum hepcidin level was associated with a diminished response to the oral iron therapy in children with iron-deficiency anemia and H. pylori infection. Uğraş et al. [29] directed their attention to a frequent intestine parasite infestation in children with H. pylori infection. In this study, among children living in low socioeconomic conditions, 5.7% of them had Blastocytosis hominis and 2 (1.9%) had Lamblia intestinalis. The co-existence of H. pylori infection and intestinal parasites has a negative effect on thriving and iron status in a growing child. Recently, guidelines on H. pylori infection in children recommend that children with refractory IDA should be tested for H. pylori infection [30]. Wang et al. [31] analyzed the association between asthma and H. pylori infection. In the presented meta-analysis, pooled OR for all included studies was 0.81 (95% Cl; 0.72–0.91) in children and 0.81 (95% Cl; 0.71–1.08) in adults. The authors found a weak evidence for an inverse association between asthma and H. pylori infection both in children and in adults, To the contrary, Karimi et al.

[9, 10] Among many lipid mediators, S1P is essential for the trafficking and activation of immunocompetent cells.[11] S1P is a metabolite of sphingomyelin from both the host cell plasma

membrane and diet.[12] Sphingomyelin is degraded into ceramide by alkaline sphingomyelinase and subsequently to sphingosine by ceramidase. Sphingosine is then phosphorylated to generate S1P by sphingosine kinases.[11] S1P is formed in most cells, but is simultaneously irreversibly degraded by S1P lyase or dephosphorylated by S1P phosphatases.[11] Therefore, S1P levels are extremely low in most tissues but high in the blood and lymph because of the lack of S1P degrading INCB024360 clinical trial activity of erythrocytes, platelets, and lymphatic endothelial cells; the difference creates an S1P gradient between these types of tissues.[13, 14] Cells expressing S1P receptors sense the S1P gradient and traffic toward high concentrations of S1P. Among five closely related S1P receptors, the type 1 S1P

receptor (S1P1) is preferentially expressed by lymphocytes and thus determines lymphocyte emigration from and retention in the lymphoid tissue.[15] this website Naïve lymphocytes express high levels of S1P1, and their activation is associated with downregulation of this receptor. However, S1P1 expression recovers in fully differentiated activated lymphocytes. These dramatic changes in S1P1 determine whether the lymphocytes are retained in the lymphoid tissues or emigrate from them into the blood or lymph circulation. We and others have shown that S1P regulates the innate and acquired phases of gut immune responses and the development of intestinal immune diseases (reviewed

in Reference[12]). For instance, S1P regulates the trafficking of B cells in the PPs and subsequent intestinal IgA production.[16] In the PPs, B cells differentiate into IgA+ plasmablasts. During B cell differentiation in the PPs, the B cells change their expression of S1P1; high expression is noted on immunoglobulin M+ naïve B cells but is downregulated during class switching to IgA. The low level of S1P1 allows newly formed IgA+ B cells to be retained in the PPs so that they can differentiate into IgA+ plasmablasts. The IgA+ plasmablasts show recovery of S1P1 expression, MCE resulting in their emigration from the PPs.[16] In agreement with this finding, when mice were treated with the immunosuppressant FTY720 to induce downregulation of S1P1 expression,[17] IgA+ plasmablasts selectively accumulated in the PPs, and their population was decreased in the lamina propria.[16] As a result, FTY720-treated mice showed reduced intestinal IgA responses against orally administered protein Ag.[16] We have also reported that IgA PCs originated from peritoneal cavity, along with unique subsets of IELs require S1P for their trafficking into the intestine.

, 2001b). Other suggested reasons why it might benefit subordinates to defer breeding include reduced foraging skills and associated energetic constraints, negative effects of breeding at the same time as dominants on the fitness of their own offspring, and costs to indirect components of their fitness if dominants are close relatives

(Young, 2009). Evidence of these effects has led to a debate over whether subordinate infertility should be interpreted as a consequence of constraints on subordinate click here breeding imposed by dominants or of voluntary restraint by subordinates caused by the need to avoid attracting aggression from dominants or by high costs of breeding associated with reduced condition or inferior foraging skills (Saltzman, Digby et al., 2009; Young, 2009). However, the distinction between these arguments is not as clear as it may initially appear since subordinates may commonly show restraint because dominants constrain their reproductive

options (Young, 2009). For example, subordinates may respond to the presence of dominants by down-regulating their physiological systems because dominants are likely to evict them if they attempt to breed, so that the likely fitness benefits of competing to breed are low (a reproductive constraint). Evidence that other factors modify the frequency of breeding by subordinates

(such as condition or the absence of unrelated partners) does not necessarily argue for interpretations based on restraint, for effects of this Dabrafenib molecular weight kind would be expected under both scenarios. Perhaps the most realistic view is that subordinates commonly show restraint because dominants constrain their reproductive options (Young, 2009). Attempts 上海皓元医药股份有限公司 by dominant females to prevent other females from breeding or to reduce their success in rearing offspring are sometimes regarded as examples of spite since they can occur at times when the benefits of reproductive suppression are not obvious or resources are abundant (Stockley & Bro-Jorgensen, 2011). However, although this is theoretically possible (Gardner & West, 2004), the fitness costs of attacks on subordinates and their offspring may often be low while simultaneous breeding by subordinates may often have long-term costs to dominants and their dependents (Clutton-Brock et al., 2010). Consequently, it is probably more realistic to regard attempts by dominants to suppress reproduction by subordinates as an example of selfish behaviour rather than spite. While infanticide by females has attracted less attention than infanticide by males, it is probably more widespread (Rödel et al., 2008) and frequently represents a threat for group-living females (Digby, 2000).

MicroRNAs involved in regulating epithelial–mesenchymal transition and cancer stem cells as molecular targets for cancer therapeutics. Cancer Gene Therapy 2012; 19(11):723-30), we have therefore further investigated the potential molecular roles of miR-216a/217 in the development of resistance to sorafenib in HCC cancer

cells. Our results demonstrated that the over-expression of miR-216a/217 acted as a positive feedback regulator for the TGF-β pathway and the canonical pathway involved in the activation of the PI3K/Akt signaling in HCC cells (Fig. 6A). In addition, the activation of TGF-β and PI3K/Akt signaling Selleckchem AZD3965 pathways in HCC cells resulted in the acquired resistance click here to sorafenib (Fig. 6B). In comparison, blocking the activation of TGF-β pathway overcame miR-216a/217-induced sorafenib resistance (Fig. 6C and 6D) and decreased the metastatic ability of HCC cells in a mouse model (Fig. 6E and 6F). We concluded that over-expression of miR-216a/217 activated the PI3K/Akt and TGF-β pathways by targeting PTEN and SMAD7, contributing to hepatocarcinogenesis and tumor recurrence (Fig. 7). Figure S2. (A and B) Expression of epithelial marker E-cadherin and mesenchymal marker Vimentin in a panel of liver cancer cell lines. Epithelial HCC cells such as HepG2

and PLC/PRF/5 gave high expression of E-cadherin and low expression of vimentin while HCC cells with mesenchymal phenotype such as SNU-449 and HLE demonstrated low expression of

E-cadherin and high expression of vimentin (P<0.05). (C and D) RT-qPCR was employed to validate the significant increase of miR-216a and miR-217 in stably-transfected HepG2-miR-216a/217 and PLC/PRF/5-miR-216a/217 MCE公司 cells. (E) HepG2-miR-216a/217 and PLC/PRF/5-miR-216a/217 stably-transfected cells demonstrated significant morphological change from an epithelial cobblestone phenotype to an elongated fibroblastic phenotype, indicative of EMT. Figure S3. Silencing of miR-216a and 217 in the HLE, mesenchymal phenotype, HCC cells. Antagomir-miR-216a/217 was transfected into HLE cells. (A) Expression of miR-216a and miR-217 was examined by qRT-PCR and significant silencing of miR-216a/217 was demonstrated. (B) A dramatic morphological change from mesenchymal to epithelial transition was observed. (C) Up-regulation of E-cadherin, an epithelial biomarker and the reduced expression of vimentin, a mesenchymal biomarker, was detected with the simultaneous increased in the expression of SMAD7 and PTEN was also observed.Figure S4. Effects of miR-216a/217 on the proliferation and apoptosis of liver cancer cells.

90 (p = 0.113, I2 = 0.438).

Conclusion: IGRA is negative impacted by IST. Current guidelines suggesting TB screening before anti-TNF therapy may be inadequate in patients already on IST. Latent TB testing appears best performed prior to the initiation of IST in IMID patients. Key Word(s): 1. inflammatory disease; 2. crohn’s disease; 3. ulcerative colitis; 4. tuberculosis; Presenting Author: SHINJI www.selleckchem.com/products/ch5424802.html SATO Additional Authors: HIDENARI NAGAI, HIROSHI MORITA, HIDENORI KURAKATA, YASUKIYO SUMINO, YOSHINORI IGARASHI Corresponding Author: SHINJI SATO Affiliations: Toho University Omori Medical Center Objective: Evaluation of bile acids (BA) is a useful method for assessing changes of the intestinal flora in patients with ulcerative colitis (UC). During enterohepatic circulation, conjugated BA is deconjugated to free BA by intestinal bacteria. The presence of intestinal microflora (Clostridium and Eubacterium) leads to 7α-dehydroxylation of cholic acid (CA) and chenodeoxycholic acid (CDCA), yielding deoxycholic acid (DCA) and lithocholic acid, respectively. It was reported that the Lachnospiraceae subgroup of Firmicutes (including Clostridium) are decreased in the colon R428 of UC patients compared

to controls without inflammatory bowel disease. We have already reported that the serum %CDCA is significantly higher in patients with UC than in healthy volunteers (HV), while serum %DCA is significantly lower in UC patients than in HV, and these changes 上海皓元医药股份有限公司 do not depend on the activity or extent of UC. The aim of the present study was to elucidate the effects of daikenchuto (DKT) in patients with UC by examining the serum BA profile. Methods: The study population was 10 patients in whom UC was diagnosed from endoscopic and histological findings. All patients underwent ileocolonoscopy with appropriate biopsies. Treatment was given with mesalazine or salazosulfapyridine (5-ASA) and all patients

achieved remission. After entering remission, they were treated with by 5-ASA plus the DKT (7.5–15.0 g/day) for 4 weeks. The control group was composed of 8 HV. Routine laboratory tests were performed on the basis of clinical need, while fasting serum samples for measurement of BA were obtained before and after treatment with 5-ASA plus DKT for 4 weeks. Serum BA fractions were analyzed by HPLC. Results: There were no significant differences of serum total BA among the 2 groups. Before treatment, %CDCA was significantly higher in the UC groups than in the HV group, while %DCA was significantly lower than in the HV group. In the UC group, %CDCA was significantly lower and %DCA was significantly higher after 4 weeks of DKT treatment. There were no significant differences in the ratio of conjugated BA to total serum BA among the 2 groups.

pylori infection, which is related to polymorphisms of pro-inflammatory factors, may reduce NSAID- or aspirin-related injury.32,48 The renin-angiotensin system (RAS) consists of angiotensinogen (AGT), angiotensin I, angiotensin II, renin, and angiotensin-converting enzyme (ACE) inhibitor, and the activity of angiotensin II is mediated through the activation of AT1R. A series of RAS gene polymorphisms significantly influence the rate of

gene transcription and is associated with clinically significant renal and cardiovascular disease.49,50 In vivo and in vitro studies have shown that the AGT-20C allele works as the high-producer allele of AGT and the AGT plasma concentration linearly increased ICG-001 order according to genotype (i.e. AA < AC < CC).50–52 The AGT-20 CC genotype has been shown to increase the risk

for peptic ulcer bleeding (OR 4.94, 95% CI 1.21–20.2) among Japanese LDA users, especially in the subgroup with ACE inhibitor or ARB co-treatment.9 RAS may play an important role in the development of upper GI mucosal injury induced by LDA. A wide variety of anionic compounds, including statins, ACE inhibitors, and ARBs, are actively transported from the portal blood into hepatocytes by the OATP 1B1, which is encoded by SLCO1B1.53–55 Among more than 40 mutations identified in SLCO1B, A388G (Asn130Asp) and T521C (Val174Ala) occur frequently and have been extensively investigated. The T521C SNP has been consistently linked with reduced transport activity of OATP1B1, both in vitro54,56–58 and in vivo.53,59,60 The collective evidence indicates that statin blood concentrations are higher in subjects with the 521C allele, and a recent genome-wide Dabrafenib study elucidated that the 521C allele is associated with an increased risk of simvastatin-induced myopathy.61 Two haplotypes with non-synonymous variations, *1b harboring A388G and *15

harboring A388G and T521C, have been frequently reported in Japanese, and the pravastatin blood concentration was significantly lower in *1b/*1b subjects than in *1a/*1a subjects.62 Another major haplotype, SLCO1B1*15, has been reported to show impaired plasma membrane expression 上海皓元 and reduced transport activity in vitro.54,58 In our recent study,63 the SLCO1B1 521TT genotype and the SLCO1B1*1b haplotype were significantly associated with the risk of peptic ulcer and bleeding in patients taking low-dose enteric-coated aspirin. SLCO1B1*1b is thought to have the highest transport activity and may diminish the preventive effect of statins or ARBs, probably by reducing the concentration in the stomach. The SLCO1B1*1b haplotype could be a new risk marker for aspirin-induced mucosal injury. No potential conflict of interest has been declared by the authors. “
“The duodenum, so named for its length of 12 fingers, is a prime segment of the gastrointestinal (GI) tract regarding luminal chemosensing due to its strategic positioning between the pylorus and the pancreaticobiliary ducts.

We also need to consider the effect of fibrosis on the L/S ratios. By multivariate analysis, fibrosis stage did not influence the L/S ratio as shown in Tables 2 and 3. However, L/S ratios tended to show increased values in advanced stage NASH as shown in Figure 5. Though the statistical differences were not obtained in this studied population, there is a possibility that severity of fibrosis influences the L/S ratios. We should take into account these AZD1208 manufacturer facts and cases be increased to elucidate the real relationship between

fibrosis and L/S ratio in the future study. The limitation of this study was that relatively small numbers of patients were studied, and further analysis and validation would be desirable. In conclusion, we analyzed the relationship between L/S ratio and histological findings to

accurately diagnose fatty liver by imaging such as CT. We identified that the optimal cut-off value of L/S ratio to exclude steatosis was 1.1, and the AUROC for the diagnosis of steatosis was 0.886. Also, we identified the L/S ratio equivalent to histologically diagnosed steatotic grades. Accordingly, L/S ratio on CT would be useful for the detection of steatosis, speculating the buy BKM120 steatotic grade, and even for monitoring the disease progression or the response to therapy. “
“The role of clinical symptoms, transabdominal ultrasound scan (USS), and liver function tests

(LFTs) in evaluating common bile duct (CBD) stones in patients suspected to have pancreatobiliary disease has been studied. However, it is unclear whether these predictive models are useful in different age cohorts. The aim of this study is to investigate the clinical presentations from different age cohorts with and without CBD stones. Four hundred and forty-three patients with pancreatobiliary MCE diseases were divided into cohorts according to decades as follows: young (Y, 18–64 years old, n = 143), young-old (YO, 65–74 years old, n = 168), old-old (OO, 75–84 years old, n = 97), and very old (VO, ≥ 85 years old, n = 35). The clinical symptoms, LFTs, and USS findings were demonstrated and compared among patients. Y- and YO-group patients were more likely to develop symptoms such as biliary colic in the presence of CBD stones. The proportion of abnormal serum aspartate aminotransferase and alanine aminotransferase were significantly greater in Y-, YO-, and OO-group patients with than in those without CBD stones. Sensitivity of USS for CBD stones in Y: 0.15; YO: 0.45; OO: 0.57; and VO: 0.68. Accuracy of USS for detected CBD stone in Y: 48%; YO: 62.5%; OO: 70.1%; and VO: 71.4%. Combined evaluation of clinical symptoms, biochemical and USS findings may help predict the presence of CBD stones. In Y, YO, and OO patients with CBD stones, the incidences of abnormal LFTs were higher.

Several studies tested neutralizing antibodies against mature VEGF proteins, blockade of VEGF receptors by VEGF receptor antibodies, soluble VEGF receptor mutants or fusion-proteins, and intra-cellular interference with VEGF mRNA or kinase signaling pathways in the target cell. Inhibiting the process of angiogenesis by knocking out the activity of VEGF has a significant impact selleckchem on tumor growth and patient survival. However, it does not seem to be enough for a complete cure. So it is still necessary to explore as many regulatory steps as possible in the complex sequence of tumor-induced angiogenesis. Besides the VEGF, FGF and its family of receptors (FGFR) are potent

inducers of angiogenesis in HCC.4,5 Elevated serum FGF levels are an important prognostic factor in HCC,6 and the aberrant activation of FGFR has been shown to drive hepatocarcinogenesis.7 FGF might also modulate the resistance to VEGF/VEGFR inhibition. For example, FGF2 has been shown to synergistically augment the VEGF-mediated HCC development and angiogenesis8 and might play a central role in the “escape mechanisms” implicated in VEGF/VEGFR targeting. Clinical and translational studies suggest that FGF blockade might circumvent resistance to

the VEGFR modulating agents.9 In a study of patients undergoing surgery for HCC, the high serum levels of FGF2 was shown to be a predictor for invasiveness and recurrence.10 Although the VEGF inhibitors can reduce the growth of the primary tumors, there are data click here showing that they might also 上海皓元医药股份有限公司 promote the invasiveness and metastasis of the tumor.11 Accordingly, novel anti-angiogenic therapies targeting FGF to synergize with VEGF-mediated anti-angiogenesis might provide a mechanism to overcome resistance to VEGF-targeted agents in HCC. So we should use the knowledge to inhibit the process of angiogenesis at a more sensitive point of angiogenesis, or at several

points simultaneously. To achieve this goal, the newly developed in vitro models of tumor growth and of blood vessel formation could be helpful. Actually, several agents that target the VEGF pathway have been tested in patients with advanced HCC, such as the oral multikinase inhibitors, sorafenib and sunitinib, whose antitumor effects are partly as a result of the inhibition of VEGF receptors. Although the SHARP trial showed only a 2.8-month improvement in median overall survival rate (P = 0.0006), along with very limited increased time to disease progression and disease control rate, and a 2.3% response rate, sorafenib became the first targeted agent approved to use in advanced HCC by the USA Food and Drug Administration.12 The monoclonal antibody against VEGF, bevacizumab, either used alone or in combination with erlotinib, has shown improved survival in advanced HCC patients. In this issue of the Journal, Jie et al.

Jessica Parkinson assisted in the preparation of the article. Kristin Stephan, PhD, provided article and editorial coordination support. Jonathan Kirk provided graphical design support. All are employees/stockholders of Vertex Pharmaceuticals Inc. All authors were either employed by Vertex Pharmaceuticals Inc. (V.G., J.E.L., K.A., P.N., and X.L.) or Tibotec (R.v.H.) at the time of the study. J.E.L. is currently employed by the U.S. Food and Drug Administration, Silver Spring, MD. Her contribution to this article was based on her prior employment

and the content of the work does not necessarily reflect any position of the Food and Drug Administration. NVP-AUY922 clinical trial “
“Pegylated interferon-α (PEG-IFN-α) forms an integral part of the current treatment for hepatitis C virus (HCV) infection. PEG-IFN-α suppresses HCV production by augmenting the innate antiviral immune response. Recent studies have reported the induction of hepcidin, the iron regulatory hormone, by IFN-α in vitro. As hepcidin plays an important Everolimus in vivo role in innate immunity,

we hypothesized that this finding may be of clinical relevance to HCV and investigated the changes in iron homeostasis during the first 24 hours of treatment. Blood samples were obtained from HCV patients immediately prior to and 6, 12, and 24 hours following the first dose of PEG-IFN-α/ribavirin (RBV). Samples were 上海皓元 analyzed for hepcidin, cytokine, iron levels, and HCV viral load, and hepcidin messenger RNA (mRNA) expression was quantified in peripheral blood mononuclear cells. Hepcidin induction by IFN-α was further analyzed in cell culture. In HCV patients a single dose of PEG-IFN-α/RBV resulted in a

significant increase in serum hepcidin, peaking at 12 hours, coinciding with a 50% reduction in serum iron and transferrin saturation over the 24-hour period. Patients with a ≥2 log decline in HCV viral load over the first 24 hours had significantly lower SI and TS levels at 12 and 24 hours. Moreover, 24-hour SI levels were an independent predictor of the immediate HCV viral decline, an indicator of ultimate treatment outcome. In cell culture, a direct induction of hepcidin by IFN-α was seen, controlled by the STAT3 transcription factor. Conclusion: Hepcidin induction occurs following the initiation of PEG-IFN-α treatment for HCV, and is mediated by way of STAT3 signaling. The subsequent hypoferremia was greatest in those with the most significant decline in viral load, identifying systemic iron withdrawal as a marker of immediate interferon-α efficacy in HCV patients. (HEPATOLOGY 2012) Chronic hepatitis C virus (HCV) infection is a leading cause of endstage liver disease worldwide.1 Current therapy involves pegylated interferon alpha (PEG-IFN-α) in combination with the nucleoside analog ribavirin (RBV).

[41] Probiotics are live microbial food supplements or components of bacteria, and may have beneficial effects on human health. Emerging data suggest that probiotics treatment improve liver chemistry tests and reduce liver

fat in NASH patients.[42, 43] Future research should focus on placebo-controlled, clinical trials using histological end-points to address the effects of prebiotics on NAFLD and NASH. There is growing evidence that diet and nutrients can affect the pathophysiology of NAFLD. The selleck chemicals llc influence of the dietary nutrients is important and can help to treat NAFLD and associated metabolic comorbidities. In general, hypercaloric diet, high dietary SFA and cholesterol, and soft drinks seem to increase stimulate hepatic lipid accumulation and progression into NASH, whereas reducing total caloric intake, increasing soy protein and whey consumption, and the supplements of MUFA,

omega-3 fatty acids, and probiotics have preventive and therapeutic effects. Gradually and maintaining weight loss by lifestyle intervention is the most effective treatment for NAFLD, and a sustained adherence to caloric restriction (either low in carbohydrates or low in fats) is a major predictor of weight loss. In addition, a healthy dietary pattern and some Neratinib supplier nutrients have benefits beyond weight reduction on NAFLD patients. Therefore, diet and nutrient management should be a component of any treatment plan for patients with NAFLD, these patients should follow a well-balanced diet (Table 5). However, research focusing on specific dietary components predisposing to NAFLD or used for treatment of NAFLD has shown conflicting results to date. Currently, well-designed dietary intervention trials are needed to create MCE definitive evidence-based dietary guidelines for NAFLD. Funding was provided by the State Key Development Program for Basic Research of China (2012CB517500), the National Natural Science Foundation of China (81070322 & 81270491), the Program of the Shanghai Committee of Science and Technology (09140903500 & 10411956300), the 100 Talents Program of the Shanghai Board of Health (XBR2011007). “
“Few studies

have evaluated the risk of cancers other than hepatocellular carcinoma associated with hepatitis B virus (HBV) infection. This study aimed to estimate incidence rates of intrahepatic cholangiocarcinoma (ICC) and non-Hodgkin lymphoma (NHL) and its major subtypes in a nationwide cohort of parous women and to assess their associations with chronic HBV infection. We conducted a cohort study including 1,782,401 pregnant Taiwanese women whose HBV serostatus was obtained from the National Hepatitis B Vaccination Registry. Newly diagnosed ICCs and NHLs were ascertained through data linkage with the National Cancer Registry. Risks of ICC and NHL were assessed using Cox proportional hazards regression models. After a mean of 6.