In this study, the effect of photon

irradiance and temperature on brown spot development was evaluated. The concentration of total soluble sugars (fructose, glucose and sucrose) in rice leaves was also evaluated. Rice plants of cv. ‘Oochikara’ were inoculated with selleck products B. oryzae and kept in a greenhouse [20 ± 2°C (night time) and 35 ± 2°C (day time), ≈ 1000 μmol photons/m2/s] or two different mist chambers (25 or 32 ± 2°C, ≈ 15 μmol photons/m2/s at the top canopy). Plants kept in a mist chamber at 32 ± 2°C, under low photon irradiance, showed reduced incubation period (IP) and increase in the rate of lesion expansion. Brown spot severity in rice leaves was 67.8% at 32 ± 2°C, 27.8% at 25 ± 2°C and 11.4% under greenhouse conditions. The highest brown spot severity was found on plants grown under low photon irradiance, in which soluble sugar concentrations were lowest, suggesting that disease development was boosted under these particular growing conditions. Based on the results of this study, a continuous high temperature and low photon irradiance, in the presence of high relative humidity,

and low soluble sugars contribute to an increase in brown spot development. “
“A virus detected in symptomatic Trifolium pratense L. plants in the Czech Republic had bacilliform virions which in thin sections occurred solely Wnt mutation in phloem tissues and measured 220–500 nm by 30–31.5 nm. The virus was mechanically transmitted to Nicotiana occidentalis Wheeler, accession 37B. The partial nucleotide sequence (540 bp; accession number JX069965) with similarity to open reading frame III of the badnavirus genome was amplified from total genomic DNA, extracted from the plants. The new sequence had 74.4% nucleotide identity to that of Ananas comosus endogenous virus in the polyprotein

gene covering reverse transcriptase. The results suggest that the Czech isolate from clover should be regarded as a new member of the genus Badnavirus, for which the name Red clover bacilliform virus is suggested. This is the first report of a tentative member of Badnavirus genus occurring in forage crops. “
“In an area reforested with Brazilian this website pine (Araucaria angustifolia) located in Paraná State, southern Brazil, 20- to 40-year-old trees representing 0.2% of the surveyed area had symptoms of root and crown rot, yellowing and browning of leaves from the uppermost branches and death. Three Phytophthora isolates obtained from diseased plant tissue were tested against 1-year-old Brazilian pine seedlings and found to display positive pathogenicity. Based on their morphological and physiological characteristics, the isolates were identified as Phytophthora cinnamomi. A GenBank BLAST search of partial sequences from the β-tubulin and elongation factor-1α genes, as well as the ITS regions and 5.8S gene of rDNA, confirmed the species identification.

In the absence of both Akt and FOXO1, the mice were able to maintain glucose homeostasis through fasting and feeding. This demonstrates that FOXO1 is intrinsically glucogenic and in its

absence, glucose homeostasis can be maintained without Akt activation. The primary function of insulin-induced Akt activation is to counteract FOXO1 and click here thus reduce glucose production during the fed state. This study also demonstrated that FOXO1 does not inhibit the insulin mediated upregulation of anabolic processes such as glycogen and lipid synthesis.[16] The activity of FOXO1 as a regulator of blood glucose is also modulated by processes other than Akt phosphorylation. The balance between acetylation and deacetylation is a second order of regulation.

Deacetylation by NAD-dependent deacetylase sirtuin-1 (Sirt1) under conditions of cellular stress, such as that induced by oxygen free radicals, activates transcription, overriding the nuclear exclusion effect of Akt and causing nuclear translocation/retention and expression of FOXO1 target genes including those involved in gluconeogenesis.[17] Other deacetylases contribute CHIR-99021 molecular weight to FOXO1 activation as well. Class IIa histone deacetylases (HDACs) have been shown to be positive regulators of hepatic FOXO1 in response to glucagon signaling during fasting. They are phosphorylated by adenosine monophosphate activated protein kinase (AMPK) and translocated to the nucleus where they deacetylate and activate FOXOs, inducing transcription of gluconeogenic

genes.[18] Several other more novel mechanisms have also been observed to play a role in FOXO1 regulation and hepatic glucose metabolism. XBP-1, a transcription factor involved in the unfolded protein response that induces expression of genes involved in endoplasmic reticulum (ER) membrane folding, has been shown to increase insulin sensitivity. This activity is independent of its transcriptional effects but can be accounted for by its direct selleck inhibitor binding to FOXO1, acting as a chaperone to direct it to proteosomal degradation.[19] Another mechanism that appears to play a specific role in regulation of the glucuneogensis function of FOXO1 is O-GlcNAc modification.[20, 21] This glylcosylation event activates transcriptional activity of FOXOs independently of nuclear translocation and results in upregulation of glucose 6-phosphatase (G6Pase) and other gluconeogenic genes. Paradoxically, it is induced by hyperglycemia and appears to result from peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) binding to O-GlcNAc transferase and targeting it to nuclear FOXO1.[22] The second area of liver metabolic function regulated by FOXO is lipid metabolism. FOXO1 has an important role in the insulin-dependent regulation of hepatic very low density lipoprotein (VLDL) production and persistence of VLDL in the circulation.

Aim was to find out the causes of hospital mortality in patients admitted with decompensated cirrhosis and to evaluate for the biochemical and hematological

parameters that are related to mortality during hospitalization selleck inhibitor Methods: Cirrhotic patients admitted at the Department of Gastroenterology at Govt Stanley Medical College from April 2010 to may 2011 were studied. Patients with decompensated cirrhosis liver who died during admission were selected as cases. Patients admitted with cirrhosis and its complications and who improved with treatment followed by discharge were selected as controls. Data collected included demographics; etiology of cirrhosis; indication for hospital admission; presence or absence of decompensation buy Palbociclib and portal hypertension; and the corresponding Child Pugh, MELD, and MELD-Na scores. Other hematological and biochemical markers were studied. The clinical diagnosis of cirrhosis was made by a history of portal hypertension excluding other etiology, liver function tests, clotting parameters, radiology criteria. The cause of death was also determined. Exclusion criteria were patients with portal hypertension not due to primary cirrhosis of liver cirrhosis complicated by hepatocellular carcinoma were excluded. Ethical committee approval was obtained for the study. Results: Total

number of cases was 140 (70 each for cases and controls). The Mean age was 46.33 years and 45.56 for controls. The mean duration of disease in cases was 20.01 months and 12.76 months for controls. The most common cause was ethanol related. The number of hepatic and non hepatic complications in both groups was similar and most patients had 2 or more comorbid conditions. The most common cause of admission was hepatic encephalopathy in both groups. While evaluating for Child status in click here both groups, 11.4 % of patients

in both groups had Child’s A. 48.6% of cases had Child’ s B while 52.9% of controls had Child’s B. 40.0% cases and 35.7% controls had Child’s C cirrhosis. The mean MELD and MELD-Na was significantly ( < 0.001) higher for the cases group compared to the control group. The most common causes of death are due to cirrhosis related complications associated with decompensation like hepatic encephalopathy, hepatorenal syndrome, UGI bleeding and infections. On univariate analysis revealed that increasing levels of MELD, MELD- Na, serum creatinine, INR, WBC, albumin, neutrophilia and duration of disease were significantly ( < 0.0001) associated with increased risk of death. On multivariate forward stepwise logistic regression, an elevated WBC count (p = 0.02, OR 1.2) and creatinine (p = 0.003, OR 1.2) were the only factors significantly associated with death. Conclusion: In hospital mortality in cirrhosis is predominantly due to hepatic dysfunction.

Aim was to find out the causes of hospital mortality in patients admitted with decompensated cirrhosis and to evaluate for the biochemical and hematological

parameters that are related to mortality during hospitalization AZD1208 Methods: Cirrhotic patients admitted at the Department of Gastroenterology at Govt Stanley Medical College from April 2010 to may 2011 were studied. Patients with decompensated cirrhosis liver who died during admission were selected as cases. Patients admitted with cirrhosis and its complications and who improved with treatment followed by discharge were selected as controls. Data collected included demographics; etiology of cirrhosis; indication for hospital admission; presence or absence of decompensation HSP inhibitor and portal hypertension; and the corresponding Child Pugh, MELD, and MELD-Na scores. Other hematological and biochemical markers were studied. The clinical diagnosis of cirrhosis was made by a history of portal hypertension excluding other etiology, liver function tests, clotting parameters, radiology criteria. The cause of death was also determined. Exclusion criteria were patients with portal hypertension not due to primary cirrhosis of liver cirrhosis complicated by hepatocellular carcinoma were excluded. Ethical committee approval was obtained for the study. Results: Total

number of cases was 140 (70 each for cases and controls). The Mean age was 46.33 years and 45.56 for controls. The mean duration of disease in cases was 20.01 months and 12.76 months for controls. The most common cause was ethanol related. The number of hepatic and non hepatic complications in both groups was similar and most patients had 2 or more comorbid conditions. The most common cause of admission was hepatic encephalopathy in both groups. While evaluating for Child status in learn more both groups, 11.4 % of patients

in both groups had Child’s A. 48.6% of cases had Child’ s B while 52.9% of controls had Child’s B. 40.0% cases and 35.7% controls had Child’s C cirrhosis. The mean MELD and MELD-Na was significantly ( < 0.001) higher for the cases group compared to the control group. The most common causes of death are due to cirrhosis related complications associated with decompensation like hepatic encephalopathy, hepatorenal syndrome, UGI bleeding and infections. On univariate analysis revealed that increasing levels of MELD, MELD- Na, serum creatinine, INR, WBC, albumin, neutrophilia and duration of disease were significantly ( < 0.0001) associated with increased risk of death. On multivariate forward stepwise logistic regression, an elevated WBC count (p = 0.02, OR 1.2) and creatinine (p = 0.003, OR 1.2) were the only factors significantly associated with death. Conclusion: In hospital mortality in cirrhosis is predominantly due to hepatic dysfunction.

Aim was to find out the causes of hospital mortality in patients admitted with decompensated cirrhosis and to evaluate for the biochemical and hematological

parameters that are related to mortality during hospitalization BMS-777607 cell line Methods: Cirrhotic patients admitted at the Department of Gastroenterology at Govt Stanley Medical College from April 2010 to may 2011 were studied. Patients with decompensated cirrhosis liver who died during admission were selected as cases. Patients admitted with cirrhosis and its complications and who improved with treatment followed by discharge were selected as controls. Data collected included demographics; etiology of cirrhosis; indication for hospital admission; presence or absence of decompensation HM781-36B ic50 and portal hypertension; and the corresponding Child Pugh, MELD, and MELD-Na scores. Other hematological and biochemical markers were studied. The clinical diagnosis of cirrhosis was made by a history of portal hypertension excluding other etiology, liver function tests, clotting parameters, radiology criteria. The cause of death was also determined. Exclusion criteria were patients with portal hypertension not due to primary cirrhosis of liver cirrhosis complicated by hepatocellular carcinoma were excluded. Ethical committee approval was obtained for the study. Results: Total

number of cases was 140 (70 each for cases and controls). The Mean age was 46.33 years and 45.56 for controls. The mean duration of disease in cases was 20.01 months and 12.76 months for controls. The most common cause was ethanol related. The number of hepatic and non hepatic complications in both groups was similar and most patients had 2 or more comorbid conditions. The most common cause of admission was hepatic encephalopathy in both groups. While evaluating for Child status in check details both groups, 11.4 % of patients

in both groups had Child’s A. 48.6% of cases had Child’ s B while 52.9% of controls had Child’s B. 40.0% cases and 35.7% controls had Child’s C cirrhosis. The mean MELD and MELD-Na was significantly ( < 0.001) higher for the cases group compared to the control group. The most common causes of death are due to cirrhosis related complications associated with decompensation like hepatic encephalopathy, hepatorenal syndrome, UGI bleeding and infections. On univariate analysis revealed that increasing levels of MELD, MELD- Na, serum creatinine, INR, WBC, albumin, neutrophilia and duration of disease were significantly ( < 0.0001) associated with increased risk of death. On multivariate forward stepwise logistic regression, an elevated WBC count (p = 0.02, OR 1.2) and creatinine (p = 0.003, OR 1.2) were the only factors significantly associated with death. Conclusion: In hospital mortality in cirrhosis is predominantly due to hepatic dysfunction.

3B). UDCA treatment did not affect serum 4β-HC or 24S-HC concentrations but selleck products increased the 27-HC concentration significantly. Treatment with bezafibrate clearly increased serum 4β-HC levels, whereas it significantly reduced the 24S-HC and 27-HC levels. Differentiated HepaRG cells exhibit a gene expression pattern similar to primary human hepatocytes and human liver tissues and maintain significant levels of hepatic cell functions, including CYP and transporter activities.26 Rifampicin and carbamazepine are classical inducers of CYP3A4 by way of the activation of PXR,27 whereas GW4064 is one of the most potent agonists of FXR.28 As shown in Fig. 4A, bezafibrate, as well as rifampicin

and carbamazepine, induced both CYP3A4 mRNA expression

and activity in a dose-dependent manner. The DPX2 cell-based luciferase reporter gene assay demonstrated that in comparison with rifampicin, bezafibrate was a weak but significant activator of human PXR as well as carbamazepine (Fig. 4B). It is noteworthy that GW4064 activated human PXR at concentrations higher than 3 μM. Among the nuclear receptors and related coactivators (Fig. 5A), PXR expression was induced by bezafibrate to a greater degree than that by rifampicin, which suggests that PXR is a target gene of PPARs, as reported.29 In contrast, the small heterodimer partner (SHP; NR0B2), a target of FXR, and LXRα were down-regulated by bezafibrate, as well as rifampicin and carbamazepine. FXR and peroxisome proliferator-activated ITF2357 receptor-γ coactivator-1α (PGC1α) expressions were significantly down-regulated by rifampicin and carbamazepine but not by bezafibrate. The MDR1 (ABCB1) and MRP2 (ABCC2) transporters (Fig. 5B) were up-regulated

by bezafibrate, similar to rifampicin, whereas MDR3, ABCG5, and ABCG8 were up-regulated by bezafibrate but not by rifampicin. In addition, Na+/taurocholate cotransporting polypeptide (NTCP) was down-regulated by this website bezafibrate but did not change significantly by rifampicin. It is notable that significant messenger RNA (mRNA) expression of BSEP was observed in HepaRG cells treated with GW4064, whereas only a trace amount of BSEP expression was detected in control cells and those treated with other compounds. Enzymes involved in cholesterol, bile acid, and fatty acid syntheses and LDL receptor expression are summarized in Fig. 5C. CYP7A1, CYP7B1, and CYP27A1 were down-regulated and CYP8B1, fatty acid synthase (FAS), and LDL receptor (LDLR) were up-regulated by bezafibrate, which was the same as the effects of rifampicin. HMG-CoA reductase (HMGCR), the rate-limiting enzyme in the cholesterol biosynthetic pathway, was down-regulated by rifampicin but was slightly up-regulated by bezafibrate. Our results clearly showed that the combination therapy of bezafibrate and UDCA significantly improved cholestasis in early-stage PBC patients who were refractory to UDCA monotherapy.

6, showed superior outcome prediction than MELD (c-statistic for SOFT = 0.7; for MELD = 0.63; 3-month post-LT survival) with the main variables being previous LT and pre-LT life support.26 In 2010, SF was reported as a prognostic parameter in patients on the waiting list.17 This observation is interesting,

because SF not only represents a parameter for iron homeostasis27 but has also been linked to systemic inflammatory and cytokine-mediated processes spanning conditions including metabolic syndrome,28 Talazoparib rheumatological disease,29, 30 and hemodialysis,19 in which it is associated with increased mortality.19 We observed that patients with high SF concentrations before LT exhibited an inferior survival following LT.31 In this study, we therefore analyzed survival, SF, and transferrin

saturation (TFS) in two independent LT cohorts. The results suggest that elevated SF in combination with low TFS prior to LT is an important predictor of mortality following LT. AIH, autoimmune hepatitis; HCC, hepatocellular carcinoma; ICU, intensive care unit; INR, international normalized Vadimezan solubility dmso ratio; LT, liver transplantation; MELD, Model for End-Stage Liver Disease; NPV, negative predictive value; PBC, primary biliary cirrhosis; PPV, positive predictive value; PSC, primary sclerosing cholangitis; SALT, survival after liver transplantation; SD, standard deviation; SF, serum ferritin; TFS, transferrin saturation. In this retrospective cohort study, all consecutive adult patients with chronic end-stage liver disease, who underwent a first LT at Hannover Medical School, Hannover, Germany, between January 1, 2003, and April 1, 2008,

were included. After the exclusion of patients with fulminant liver failure (n = 38), multiple organ transplantation (n = 39), living donor LT (n = 16), and 16 patients with a diagnosis of hemochromatosis, 354 patients remained to be analyzed. Laboratory data on the last clinic visit prior to the day of LT were obtained from the patient’s medical documentation record. Based on these data, we calculated the MELD and the SALT scores as described.1, 25 Serum sodium was measured immediately prior LT in addition to the documentation of demographics and etiologies of liver diseases. SF (immunochemical selleckchem assay; Roche Diagnostics, Mannheim, Germany),32 TFS, and serum iron were routinely measured at the time of evaluation for LT. In 92.7% of the 354 patients fulfilling the inclusion criteria, pretransplant SF was available; therefore, 328 of 354 patients remained for further analyses. The mean time from transplant evaluation measurement of SF and TFS to the day of LT was 393 ± 575 days. The end of the study period was April 1, 2010, so that all patients were followed either until death or for at least 2 years after LT. The primary endpoint of this study was patient survival at the end of follow-up.

6, showed superior outcome prediction than MELD (c-statistic for SOFT = 0.7; for MELD = 0.63; 3-month post-LT survival) with the main variables being previous LT and pre-LT life support.26 In 2010, SF was reported as a prognostic parameter in patients on the waiting list.17 This observation is interesting,

because SF not only represents a parameter for iron homeostasis27 but has also been linked to systemic inflammatory and cytokine-mediated processes spanning conditions including metabolic syndrome,28 STA-9090 rheumatological disease,29, 30 and hemodialysis,19 in which it is associated with increased mortality.19 We observed that patients with high SF concentrations before LT exhibited an inferior survival following LT.31 In this study, we therefore analyzed survival, SF, and transferrin

saturation (TFS) in two independent LT cohorts. The results suggest that elevated SF in combination with low TFS prior to LT is an important predictor of mortality following LT. AIH, autoimmune hepatitis; HCC, hepatocellular carcinoma; ICU, intensive care unit; INR, international normalized this website ratio; LT, liver transplantation; MELD, Model for End-Stage Liver Disease; NPV, negative predictive value; PBC, primary biliary cirrhosis; PPV, positive predictive value; PSC, primary sclerosing cholangitis; SALT, survival after liver transplantation; SD, standard deviation; SF, serum ferritin; TFS, transferrin saturation. In this retrospective cohort study, all consecutive adult patients with chronic end-stage liver disease, who underwent a first LT at Hannover Medical School, Hannover, Germany, between January 1, 2003, and April 1, 2008,

were included. After the exclusion of patients with fulminant liver failure (n = 38), multiple organ transplantation (n = 39), living donor LT (n = 16), and 16 patients with a diagnosis of hemochromatosis, 354 patients remained to be analyzed. Laboratory data on the last clinic visit prior to the day of LT were obtained from the patient’s medical documentation record. Based on these data, we calculated the MELD and the SALT scores as described.1, 25 Serum sodium was measured immediately prior LT in addition to the documentation of demographics and etiologies of liver diseases. SF (immunochemical selleckchem assay; Roche Diagnostics, Mannheim, Germany),32 TFS, and serum iron were routinely measured at the time of evaluation for LT. In 92.7% of the 354 patients fulfilling the inclusion criteria, pretransplant SF was available; therefore, 328 of 354 patients remained for further analyses. The mean time from transplant evaluation measurement of SF and TFS to the day of LT was 393 ± 575 days. The end of the study period was April 1, 2010, so that all patients were followed either until death or for at least 2 years after LT. The primary endpoint of this study was patient survival at the end of follow-up.

In the whole population, the dose-adjusted strategy was more cost-effective than the full dose in terms of both LYG and QALY. Specifically, compared with BSC the full-dose strategy had an ICER of €63,197 for LYG and of €69,344 for QALY, while dose-adjusted strategy had an ICER of €25,874 for LYG and of €34,534 for QALY. As in the entire SOFIA cohort, in the BCLC B patients the dose-adjusted strategy was more cost-effective than the full dose in terms of both LYG and QALY. Specifically, compared with BSC the full-dose

strategy had an ICER of €44,794 for LYG and of €57,385 for QALY, while the dose-adjusted strategy had an Ku-0059436 order ICER of €41,782 for LYG and of €54,881 for QALY. Similarly, in BCLC C patients, considering both LYG and QALY, the dose-adjusted strategy was more cost-effective than the full dose. Specifically, compared with BSC the full-dose strategy had an ICER of €59,922 for LYG and of €65,551 for QALY, while the dose-adjusted strategy had an ICER of €20,896 for LYG and of €27,916 for QALY. Performing analysis in the subgroup of the SOFIA cohort obtained after excluding patients with early radiologic progression, ICER per QALY in dose-adjusted sorafenib strategies

marginally improved. Specifically in this subgroup of patients, dose-adjusted sorafenib strategy had an ICER per QALY of €25,569 for BCLC C and of €58,265 for BCLC B patients. One-way selleck chemicals llc sensitivity analysis was done selleck products for two dominant strategies: dose-adjusted sorafenib therapy for both BCLC B and C HCC patients. Figure 3 summarizes the results of one-way sensitivity analyses, using tornado diagrams. Analyses showed that the results of the model were most sensitive to an assumption on survival rates of BSC patients, sorafenib treatment duration, and type of survival distribution. Changes in survival rates in patients managed with BSC had a great effect on cost-effectiveness. In fact, sensitivity

analysis with a hypothesized variation of survival of ±30% in BSC patients showed that ICER for QALY ranged significantly from €41,325 to €100,544 in BCLC B (Fig. 3A) and from €24,450 to €36,032 in BCLC C (Fig. 3B) patients treated with dose-adjusted sorafenib. The cost effectiveness of dose-adjusted sorafenib was sensitive to change (±30%) in the treatment duration. With a longer time of therapy, the ICER for QALY impairs both the BCLC B and BCLC C patients. Instead, for the sensitivity analysis on the disease costs, a variation of ±30% was assessed, and the model had low sensitivity. With an increase in the disease costs, the ICER for LYG and for QALY marginally increased in both BCLC B (Fig. 3A) and BCLC C (Fig. 3B) dose-adjusted strategies. Lower variations were found for both strategies by applying a discount rate ranging from 0% to 5%.

In the whole population, the dose-adjusted strategy was more cost-effective than the full dose in terms of both LYG and QALY. Specifically, compared with BSC the full-dose strategy had an ICER of €63,197 for LYG and of €69,344 for QALY, while dose-adjusted strategy had an ICER of €25,874 for LYG and of €34,534 for QALY. As in the entire SOFIA cohort, in the BCLC B patients the dose-adjusted strategy was more cost-effective than the full dose in terms of both LYG and QALY. Specifically, compared with BSC the full-dose

strategy had an ICER of €44,794 for LYG and of €57,385 for QALY, while the dose-adjusted strategy had an www.selleckchem.com/products/Deforolimus.html ICER of €41,782 for LYG and of €54,881 for QALY. Similarly, in BCLC C patients, considering both LYG and QALY, the dose-adjusted strategy was more cost-effective than the full dose. Specifically, compared with BSC the full-dose strategy had an ICER of €59,922 for LYG and of €65,551 for QALY, while the dose-adjusted strategy had an ICER of €20,896 for LYG and of €27,916 for QALY. Performing analysis in the subgroup of the SOFIA cohort obtained after excluding patients with early radiologic progression, ICER per QALY in dose-adjusted sorafenib strategies

marginally improved. Specifically in this subgroup of patients, dose-adjusted sorafenib strategy had an ICER per QALY of €25,569 for BCLC C and of €58,265 for BCLC B patients. One-way check details sensitivity analysis was done find more for two dominant strategies: dose-adjusted sorafenib therapy for both BCLC B and C HCC patients. Figure 3 summarizes the results of one-way sensitivity analyses, using tornado diagrams. Analyses showed that the results of the model were most sensitive to an assumption on survival rates of BSC patients, sorafenib treatment duration, and type of survival distribution. Changes in survival rates in patients managed with BSC had a great effect on cost-effectiveness. In fact, sensitivity

analysis with a hypothesized variation of survival of ±30% in BSC patients showed that ICER for QALY ranged significantly from €41,325 to €100,544 in BCLC B (Fig. 3A) and from €24,450 to €36,032 in BCLC C (Fig. 3B) patients treated with dose-adjusted sorafenib. The cost effectiveness of dose-adjusted sorafenib was sensitive to change (±30%) in the treatment duration. With a longer time of therapy, the ICER for QALY impairs both the BCLC B and BCLC C patients. Instead, for the sensitivity analysis on the disease costs, a variation of ±30% was assessed, and the model had low sensitivity. With an increase in the disease costs, the ICER for LYG and for QALY marginally increased in both BCLC B (Fig. 3A) and BCLC C (Fig. 3B) dose-adjusted strategies. Lower variations were found for both strategies by applying a discount rate ranging from 0% to 5%.