Immunohistochemical staining were done for Ki67 (hepatocyte replication) & CK19 (HPC & intermediate hepatocytes) for characterization of nature of hepatic regeneration & CD68 (liver tissue macrophages) CD163 (M2 macrophages)

for analysis of macrophages in liver tissue samples from patients with ACLF (n=15), ALF (n=21), CLD, (n=22). Expression CD68 & CD163 macrophages were correlated with hepatocyte replication, HPC activation & maturation. Results RT-PCR analysis documented significant increase in M2 gene markers CD163 CD206 & TGM2 (p=.001, .001 & .002) & decrease in M1 markers iNOS & CD80 (p=.001, .001) in ACLF comparison to CLD. Similarly there was significant

increase in M2 gene markers CD163, CD206 & TGM2 (p=.002, .002 & .002) & decrease in M1 markers iNOS CD80 (p=.002, p=.002) in ACLF comparison to ALF. Immunohistochemical analysis shows increase in Ki67+ hepatocytes BMS-777607 in ALF as compared to ACLF & CLD (p=.0001, .0001). Further, the number of CK19+ HPC & its maturational lineages was increased in ACLF than ALF & CLD (p=.0001, .0002). Using spearman rho correlation shows that CD163 positivity & M2/M1 macrophage ratio is significantly associated with extant of HPC differentiation to hepatocyte (p=.0001, .0004). Further Pu1 (yolk sac originated Kupffer Cells) & Myb (bone marrow originated monocyte derived macrophage) expression suggest significant increase in Pu1 expression relative to CD68 in ACLF in comparison to ALF & CLD (p=0.002, 0.001) suggesting majority of M2 macrophage in ACLF are kupffer Selleck Neratinib MCE cells.

Conclusions Alternatively activated M2 macrophages are major population in ACLF liver which promotes differentiation of HPC to hepatocyte. These M2 macrophages are of kupffer cell origin. Disclosures: The following people have nothing to disclose: Dhananjay Kumar, Sheetalnath Rooge, Smriti Shubham, Adil Bhat, Charvi Syal, Archana Rastogi, Chhagan Bihari, Viniyendra Pamecha, Anupam Kumar, Shiv K. Sarin Background/aim: Patients with HCV/HIV co-infection show faster progression of liver fibrosis, in part associated with miRNA dysregulation and more severe inflammation. The HIV protein gp120 modulates directional migration and expression of pro-fibrogenic cytokines in hepatic stellate cells (HSC), through engagement of the chemokine receptor CCR5. The NALP3 inflammasome is a critical pathway in the generation of pro-inflammatory signals during liver injury. Aim of this study was to evaluate the role miRNAs and inflammasome activation in mediating the effect HSC. Methods: HSC were isolated from normal human liver tissue. Inflammasome complex gene expression was measured by qRT-PCR. Levels of mature IL-1 β were assayed by ELISA. miRNA expression was evaluated via RT-PCR.

The patient was alive and well for 1 month after systemic antibiotics treatment with catheter drainage for peudocyst. On follow-up CT showed an interval decrease in size of the pseudocyst. Key Word(s): 1. IPMN;

2. pseudomyxoma; 3. pseudocyst; Presenting Author: ZHONGGU PING Corresponding Author: ZHONGGU PING Affiliations: yichun Objective: To study diagnosis of early diabetes-related pancreatic cancer. Methods: 117 cases of pancreatic cancer, 126 cases of diabetes, and 156 cases of gastrointestinal cancer were included in this case-control study for the comparison of diabetes case and serum Amyloid polypeptide (IAPP). Results: 22 cases of diabetes were in 117 cases of pancreatic cancer and 3 cases of diabetes were in 156 cases of gastrointestinal cancer, Dasatinib purchase the difference was statistically significant. 19 of 22 (86.3%) pancreatic cancer cases with diabetes which course of diabetes were less more than 2 years, however course of type 2 diabetes patients were most than 2 years (105/126, 83.3%) alwalys. The content of IAPP in pancreatic cancer with diabetes group, gastrointestinal cancer group and type 2 diabetes

group was respectively 21.2±11.4, 7.3±3.2 and 3.7 Selleck BGB324 ±2.8 (pmol/L). Conclusion: Pancreatic cancer patients, especially accompanying a history of less than 2 years with type 2 diabetes, might have abnormal glucose metabolism in early. The detection of serum IAPP would also help the early diagnosis of pancreatic cancer. Key Word(s): 1. pancreatic MCE公司 cancer; 2. diabetes-related ; 3. early diagnosis; Presenting Author: YIQI DU Additional Authors: MINGHAO LIU, JUN GAO, ZHAOSHEN LI Corresponding Author: YIQI DU Affiliations: Changhai Hospital, Second Military Medical University Objective: MiR-196a levels inversely correlated with survival in pancreatic adenocarcinoma patients. However, the functional contributions of miR-196a to pancreatic cancer remain unclear. Methods: Three lentiviral vectors encoding microRNA miR-196a precursor,

inhibitor and scrambled miRNA oligomer were transfected into Panc-1 cells, respectively. Then we explored the regulation of inhibitor of growth 5(ING5) expression by miR-196a and its impact on apoptosis, invasion and growth of pancreatic cancer cells. The lentiviral transfected Panc-1 cells were surgically implanted into the pancreas of mice. In vivo tumor growth and ING5 expression were measured. Results: Down-regulation of ING5 expression was detected in cells transfected with miR-196a precursor (P<0.01), accompanied by less apoptosis, increased invasion and proliferation compared to control cells (P<0.05). Cells transfected with miR-196a inhibitor revealed an opposite trend(Fig 1). Smaller detectable tumors were found in only 60% of mice after implantation of Lenti. miR-196a inhibitor – transfected Panc-1 cells compared to controls (360.7±303.6 mm∧3 versus < 511.58±365.9 mm∧3 in controls; P<0.01, Fig 2).

The patient was alive and well for 1 month after systemic antibiotics treatment with catheter drainage for peudocyst. On follow-up CT showed an interval decrease in size of the pseudocyst. Key Word(s): 1. IPMN;

2. pseudomyxoma; 3. pseudocyst; Presenting Author: ZHONGGU PING Corresponding Author: ZHONGGU PING Affiliations: yichun Objective: To study diagnosis of early diabetes-related pancreatic cancer. Methods: 117 cases of pancreatic cancer, 126 cases of diabetes, and 156 cases of gastrointestinal cancer were included in this case-control study for the comparison of diabetes case and serum Amyloid polypeptide (IAPP). Results: 22 cases of diabetes were in 117 cases of pancreatic cancer and 3 cases of diabetes were in 156 cases of gastrointestinal cancer, PD0332991 order the difference was statistically significant. 19 of 22 (86.3%) pancreatic cancer cases with diabetes which course of diabetes were less more than 2 years, however course of type 2 diabetes patients were most than 2 years (105/126, 83.3%) alwalys. The content of IAPP in pancreatic cancer with diabetes group, gastrointestinal cancer group and type 2 diabetes

group was respectively 21.2±11.4, 7.3±3.2 and 3.7 Midostaurin purchase ±2.8 (pmol/L). Conclusion: Pancreatic cancer patients, especially accompanying a history of less than 2 years with type 2 diabetes, might have abnormal glucose metabolism in early. The detection of serum IAPP would also help the early diagnosis of pancreatic cancer. Key Word(s): 1. pancreatic MCE公司 cancer; 2. diabetes-related ; 3. early diagnosis; Presenting Author: YIQI DU Additional Authors: MINGHAO LIU, JUN GAO, ZHAOSHEN LI Corresponding Author: YIQI DU Affiliations: Changhai Hospital, Second Military Medical University Objective: MiR-196a levels inversely correlated with survival in pancreatic adenocarcinoma patients. However, the functional contributions of miR-196a to pancreatic cancer remain unclear. Methods: Three lentiviral vectors encoding microRNA miR-196a precursor,

inhibitor and scrambled miRNA oligomer were transfected into Panc-1 cells, respectively. Then we explored the regulation of inhibitor of growth 5(ING5) expression by miR-196a and its impact on apoptosis, invasion and growth of pancreatic cancer cells. The lentiviral transfected Panc-1 cells were surgically implanted into the pancreas of mice. In vivo tumor growth and ING5 expression were measured. Results: Down-regulation of ING5 expression was detected in cells transfected with miR-196a precursor (P<0.01), accompanied by less apoptosis, increased invasion and proliferation compared to control cells (P<0.05). Cells transfected with miR-196a inhibitor revealed an opposite trend(Fig 1). Smaller detectable tumors were found in only 60% of mice after implantation of Lenti. miR-196a inhibitor – transfected Panc-1 cells compared to controls (360.7±303.6 mm∧3 versus < 511.58±365.9 mm∧3 in controls; P<0.01, Fig 2).

5%] versus 29 of 102 [28.4%]; P = 0.752) or between patients buy PCI-32765 with simple hepatic steatosis and corresponding controls (18 of 72 [25.0%] versus 24 of 72 [33.3%]; P = 0.359). Histopathology of the underlying liver for patients with SH and simple hepatic steatosis

is summarized in Table 2. Severe hepatocellular damage (as measured by moderate/heavy lobular inflammation and/or many ballooned hepatocytes per HPF) occurred in a minority of SH patients. Median NAS among SH patients was 4 (range, 3-5). Similarly, only 16.7% of patients with simple hepatic steatosis had severe steatosis. Perisinusoidal and/or portal/periportal fibrosis was present in 78.4% and 29.2% of patients with SH and simple steatosis, respectively. For the entire study cohort (n = 348), postoperative mortality, overall morbidity, severe morbidity, and any hepatic-related morbidity occurred in 9 (2.6%), 153 (44.0%), 58 (16.7%), and 73 (21.0%) patients, respectively. Postoperative hepatic decompensation, surgical hepatic complications, and hepatic insufficiency occurred in 37 (10.6%), 46

(13.2%), and 16 (4.6%) patients, respectively. Median intraoperative estimated blood loss (EBL) was 250 mL (range, 150-450), and 19.5% (68 of 348) patients received an RBC transfusion within 30 days after liver resection. SH patients had higher 90-day overall (56.9% versus 37.3%; P = 0.008) and any hepatic-related (28.4% versus 15.7%; P = 0.043) morbidity, compared to corresponding Decitabine supplier controls (Table 3). Rates of postoperative hepatic decompensation (16.7% versus 6.9%; P = 0.049), surgical hepatic complications (19.6% versus 8.8%; P = 0.046), and PHI (6.9% versus 2.0%; P = 0.170) were also higher among SH patients, although the latter difference was not statistically significant. Peak postoperative TBIL levels for SH patients with PHI were 34.7, 24.9, 18.9, 17.2, 13.3, MCE 9.0, and 7.0 mg/dL. Corresponding levels for control patients with PHI were 9.7 and 9.0 mg/dL. There were no differences in 90-day postoperative mortality or severe morbidity, EBL, or 30-day RBC transfusion rates between SH patients and corresponding controls (Table 3). There was no significant difference in

any endpoint between patients with simple hepatic steatosis and corresponding controls (Table 3). Peak postoperative TBIL levels for patients with simple hepatic steatosis and PHI were 19.4, 10.7, 10.7, and 10.4 mg/dL, whereas corresponding levels for controls with PHI were 21.0, 14.8, and 11.6 mg/dL. Specific postoperative complications are summarized in Table 4. Gender, patient age, malignant diagnosis, hypertension, MetS, ASA score ≥3, liver resection approach, extent of liver resection, and underlying SH were associated with overall morbidity on univariable analysis among SH and corresponding control patients (Table 5). Factors independently associated with overall morbidity on multivariable logistic regression were resection of four or more liver segments (OR, 4.228; 95% CI: 2.215-8.072; P < 0.

5%] versus 29 of 102 [28.4%]; P = 0.752) or between patients Selleckchem Gemcitabine with simple hepatic steatosis and corresponding controls (18 of 72 [25.0%] versus 24 of 72 [33.3%]; P = 0.359). Histopathology of the underlying liver for patients with SH and simple hepatic steatosis

is summarized in Table 2. Severe hepatocellular damage (as measured by moderate/heavy lobular inflammation and/or many ballooned hepatocytes per HPF) occurred in a minority of SH patients. Median NAS among SH patients was 4 (range, 3-5). Similarly, only 16.7% of patients with simple hepatic steatosis had severe steatosis. Perisinusoidal and/or portal/periportal fibrosis was present in 78.4% and 29.2% of patients with SH and simple steatosis, respectively. For the entire study cohort (n = 348), postoperative mortality, overall morbidity, severe morbidity, and any hepatic-related morbidity occurred in 9 (2.6%), 153 (44.0%), 58 (16.7%), and 73 (21.0%) patients, respectively. Postoperative hepatic decompensation, surgical hepatic complications, and hepatic insufficiency occurred in 37 (10.6%), 46

(13.2%), and 16 (4.6%) patients, respectively. Median intraoperative estimated blood loss (EBL) was 250 mL (range, 150-450), and 19.5% (68 of 348) patients received an RBC transfusion within 30 days after liver resection. SH patients had higher 90-day overall (56.9% versus 37.3%; P = 0.008) and any hepatic-related (28.4% versus 15.7%; P = 0.043) morbidity, compared to corresponding OTX015 nmr controls (Table 3). Rates of postoperative hepatic decompensation (16.7% versus 6.9%; P = 0.049), surgical hepatic complications (19.6% versus 8.8%; P = 0.046), and PHI (6.9% versus 2.0%; P = 0.170) were also higher among SH patients, although the latter difference was not statistically significant. Peak postoperative TBIL levels for SH patients with PHI were 34.7, 24.9, 18.9, 17.2, 13.3, medchemexpress 9.0, and 7.0 mg/dL. Corresponding levels for control patients with PHI were 9.7 and 9.0 mg/dL. There were no differences in 90-day postoperative mortality or severe morbidity, EBL, or 30-day RBC transfusion rates between SH patients and corresponding controls (Table 3). There was no significant difference in

any endpoint between patients with simple hepatic steatosis and corresponding controls (Table 3). Peak postoperative TBIL levels for patients with simple hepatic steatosis and PHI were 19.4, 10.7, 10.7, and 10.4 mg/dL, whereas corresponding levels for controls with PHI were 21.0, 14.8, and 11.6 mg/dL. Specific postoperative complications are summarized in Table 4. Gender, patient age, malignant diagnosis, hypertension, MetS, ASA score ≥3, liver resection approach, extent of liver resection, and underlying SH were associated with overall morbidity on univariable analysis among SH and corresponding control patients (Table 5). Factors independently associated with overall morbidity on multivariable logistic regression were resection of four or more liver segments (OR, 4.228; 95% CI: 2.215-8.072; P < 0.

Associations of HLA class II genes with DILI have also been reported

for the antituberculosis drugs isoniazid (DRB1*03), rifampin (DQA1*0102), learn more and ethambutol (DQB1*0201).74 The recognition of the role of immune response regulation and universal downstream mechanisms in DILI defined related genetic variants as new targets for genetic association studies. Polymorphisms affecting the expression of the cytokine system may favor T cell–mediated immune responses, or may also promote hepatotoxicity regardless of the initial mechanism. The first CGAS that investigated IL-10 and IL-4 polymorphisms as risk factors for diclofenac-induced DILI therefore represents a conceptual landmark. This STA-9090 clinical trial study found indeed that variants with low IL-10 (−627 AA/AC), and high IL-4 (−590 TT/CT) gene transcription are more frequently associated with DILI, and concluded that these may promote a T helper 2–mediated immune response to neoantigen formation.29 Another study found no association between IL-10, IL-4, and TNF-alpha variants and mixed DILI cases, but a low IL-10–producing variant was associated with DILI for subgroups of patients without peripheral blood eosinophilia and patients with serious DILI.31 Furthermore, variants of IL-6 were associated with increased aminotransferases under treatment with tacrine.75 Oxidative stress and antioxidant defense are involved

in many hepatotoxic mechanisms, including direct toxicity of reactive metabolites, upstream and downstream immune and inflammatory reactions, and MPT. Studies on DILI pharmacogenetics of oxidative stress relating to CYP450 enzymes and GST have

been discussed above. Considering the central mechanistic role of mitochondria in DILI mitochondrial manganese superoxide dismutase (SOD2) may be of particular interest because its function is essential for the scavenging of mitochondrial superoxide. Indeed, SOD2 knockout mice (SOD2 +/−) showed increased susceptibility to DILI caused by nimesulide76 MCE and troglitazone.10 In humans, one study found that patients with a SOD2 mutant c allele have an elevated risk of DILI caused by various drugs.68 Furthermore, it may be of interest that antioxidant defense is under the master control of nuclear factor erythroid-derived 2-like (NFE2L), which has also been shown to be involved in DILI77, 78 and may therefore represent a potential target for future genetic association studies. The bile salt export pump (BSEP, ABCB11 gene) mediates the efflux of bile acids from hepatocytes into the bile canaliculus.79 Impairment of normal BSEP function results in intracellular accumulation of bile acids and consequent liver injury. Genetic variants of ABCB11 have been studied intensely in the context of various cholestatic disorders, including DILI.

If silymarin truly inhibits NS5B polymerase activity, it should be able to inhibit HCV replication in replicon cell lines that do not produce infectious virus. Figure 3A-C depicts the effects of various doses

of silymarin on HCV protein and RNA expression in genotype 1b BB7 subgenomic and FL-NEO genomic replicon cell lines. Silymarin did not significantly inhibit viral protein expression in either cell line when assessed by western blot (Fig. 3A) or by immunofluorescence (Fig. 3B). Silymarin did not inhibit HCV RNA expression in either cell line (Fig. 3C). HCV replication was also not inhibited by silymarin in Luc-ubi-neo/ET cells, an independent genotype 1b replicon (Fig. 3D), or in a subgenomic Hydroxychloroquine price genotype 1a replicon cell line (Fig. 3E). In contrast, treatment with IFN-α caused robust suppression of HCV RNA production MLN2238 solubility dmso from the HCV-1a replicon. We tested concentrations of silymarin up to 1000 μM but failed to see any suppression of HCV RNA from the 1a replicon that was independent

of cytotoxicity, measured as GAPDH messenger RNA levels (Supporting Fig. S4). NS5A protein expression was not affected by silymarin in JFH-1-derived genotype 2a SGR7 (Fig. 3F) or SGR7.5 replicon cell lines (data not shown). Furthermore, extended treatment of FL-NEO replicon cells (or BB7 cells; data not shown) for 13 days did not affect the levels of HCV NS5A protein (Supporting Fig. S5). Therefore, silymarin had no antiviral

activity against replicon cell lines that did not produce infectious virus. The data in Figs. 2 and 3 suggest that silymarin inhibition of NS5B polymerase activity is not a significant component of silymarin’s anti-HCV activity in the HCVcc system. HCV assembles at lipid droplets,27, 28 and the virus is thought to exit the infected liver cell by hitching a ride on the apolipoprotein assembly and secretion pathway, in particular MTP-dependent very-low-density lipoprotein MCE release.20, 29, 30 Because silymarin blocked infectious virus production (Fig. 1), we determined whether silymarin also inhibits MTP activity and apoB secretion. In these studies, silymarin was added to cells that were either fully infected (96 hours postinfection) or chronically infected for 14 days. Thus, the experimental design effectively eliminated antiviral effects involving blockade of virus entry and instead allowed us to focus on the effects of silymarin on production of progeny viruses. Silymarin inhibited MTP activity in a dose-dependent manner in 14-day chronically infected cells by 25% ± 15% and in noninfected cells by 66% ± 1% at 80 μM (Fig. 4A). Naringenin, shown recently to block MTP-dependent virus release,22 also blocked MTP activity. Silymarin inhibition of MTP activity correlated with reduced apoB secretion in both mock and JFH-1-infected Huh7.5.1 cells (Fig. 4B).

If silymarin truly inhibits NS5B polymerase activity, it should be able to inhibit HCV replication in replicon cell lines that do not produce infectious virus. Figure 3A-C depicts the effects of various doses

of silymarin on HCV protein and RNA expression in genotype 1b BB7 subgenomic and FL-NEO genomic replicon cell lines. Silymarin did not significantly inhibit viral protein expression in either cell line when assessed by western blot (Fig. 3A) or by immunofluorescence (Fig. 3B). Silymarin did not inhibit HCV RNA expression in either cell line (Fig. 3C). HCV replication was also not inhibited by silymarin in Luc-ubi-neo/ET cells, an independent genotype 1b replicon (Fig. 3D), or in a subgenomic Ruxolitinib purchase genotype 1a replicon cell line (Fig. 3E). In contrast, treatment with IFN-α caused robust suppression of HCV RNA production RG7204 datasheet from the HCV-1a replicon. We tested concentrations of silymarin up to 1000 μM but failed to see any suppression of HCV RNA from the 1a replicon that was independent

of cytotoxicity, measured as GAPDH messenger RNA levels (Supporting Fig. S4). NS5A protein expression was not affected by silymarin in JFH-1-derived genotype 2a SGR7 (Fig. 3F) or SGR7.5 replicon cell lines (data not shown). Furthermore, extended treatment of FL-NEO replicon cells (or BB7 cells; data not shown) for 13 days did not affect the levels of HCV NS5A protein (Supporting Fig. S5). Therefore, silymarin had no antiviral

activity against replicon cell lines that did not produce infectious virus. The data in Figs. 2 and 3 suggest that silymarin inhibition of NS5B polymerase activity is not a significant component of silymarin’s anti-HCV activity in the HCVcc system. HCV assembles at lipid droplets,27, 28 and the virus is thought to exit the infected liver cell by hitching a ride on the apolipoprotein assembly and secretion pathway, in particular MTP-dependent very-low-density lipoprotein MCE release.20, 29, 30 Because silymarin blocked infectious virus production (Fig. 1), we determined whether silymarin also inhibits MTP activity and apoB secretion. In these studies, silymarin was added to cells that were either fully infected (96 hours postinfection) or chronically infected for 14 days. Thus, the experimental design effectively eliminated antiviral effects involving blockade of virus entry and instead allowed us to focus on the effects of silymarin on production of progeny viruses. Silymarin inhibited MTP activity in a dose-dependent manner in 14-day chronically infected cells by 25% ± 15% and in noninfected cells by 66% ± 1% at 80 μM (Fig. 4A). Naringenin, shown recently to block MTP-dependent virus release,22 also blocked MTP activity. Silymarin inhibition of MTP activity correlated with reduced apoB secretion in both mock and JFH-1-infected Huh7.5.1 cells (Fig. 4B).

18.0, Chicago, IL). A total of 658 cirrhosis patients with acute decompensation requiring hospitalization were screened during the 20-month study period. Of these, 515 were not included due to the presence of exclusion criteria (422), death between evaluation and baseline analysis (16), or refusal to participate (77) (Supporting Fig. 1). The study was therefore performed

in 143 patients. The main cause of admission in the series was infection in 61 patients (43%), followed by variceal bleeding in 29 (20%), ascites in 27 (19%), hepatic encephalopathy in 11 (8%), HRS in 8 (6%), and other causes in 7 (5%). The most common infection at inclusion was spontaneous bacterial peritonitis (26), followed by cellulitis (10), urinary tract infection (8), and pneumonia (6). Seventy-two percent of patients were men. The mean age was 57 ± 9 years. The cause of cirrhosis was alcoholism in 73 cases, hepatitis C buy ABC294640 virus (HCV) in 40, HCV plus alcohol in 20, hepatitis B virus in five, and other causes in five. Most patients were severely ill as indicated by the poor hepatic and renal function. The mean Child-Pugh and MELD scores

were 9.39 ± 2.14 and 18.21 ± 6.75, respectively. In all, 102 patients had ascites, 44 hepatic encephalopathy, and 34 gastrointestinal hemorrhage. Eight patients were in the intermediate critical care area at inclusion, seven due to variceal bleeding and one because of grade 3 hepatic encephalopathy. LGK-974 supplier Clinical characteristics at admission of patients included in the study were similar to those of patients who refused to participate or were excluded because of >24 hours from admission (data not shown). RAI was diagnosed in 37 patients of the series (26%). Prevalence of adrenal dysfunction did not significantly differ regarding the presence or absence of specific clinical decompensations at inclusion: ascites (28% versus 20%, respectively), hepatic encephalopathy (30% versus 24%), variceal bleeding (19% versus 28%), bacterial infection (19% versus 32%), MCE公司 and SBP versus non-SBP infections (15% versus 22%). Only patients with type-1 HRS showed a trend

towards a higher prevalence of RAI (57% versus 24%, P = 0.07). The prevalence of RAI was also similar across different Child-Pugh classes: 21% in Child-Pugh class A, 25% in class B and 28% in class C patients (P = 0.87). Table 1 shows the clinical and analytical characteristics of patients with and without RAI at inclusion in the study. Patients with RAI presented poorer renal function (higher blood urea nitrogen [BUN] levels and lower serum sodium concentration) and higher degree of circulatory dysfunction (lower mean arterial pressure) than patients with normal adrenal function. Liver function (Child-Pugh and MELD scores), type of decompensations (ascites, hepatic encephalopathy, hemorrhage, or bacterial infection), and inflammatory markers (serum C reactive protein levels and blood leukocyte count) did not differ between patients with normal and abnormal adrenal function.

After 5 years, the corresponding proportions were 32%, 9%, 25%, and 33% (Table 2). At inclusion, 29 patients had bleeding varices alone PD-1/PD-L1 inhibitor drugs and 16 patients without initial complications had variceal bleeding during follow-up (Table 1). These 45 patients had a median survival time of 48 months from the onset of variceal bleeding (Fig. 1). During the first month after bleeding onset they had higher mortality than patients without complications (10% versus 4%), but long-term mortality was similar

(Fig. 1). After 1 year, 64% of patients with variceal bleeding were alive without other complications, 16% were alive but had developed other complications, 11% had died without developing other complications, and 9% had died after developing other complications. After 5 years, the corresponding

proportions were 27%, 8%, 18%, and 45% (Table 2). Seven of eight deaths in this patient category were from cirrhosis, and the one remaining death was from unknown causes (Table 1). At inclusion, 20 patients had both ascites and variceal bleeding, and six of them (30%) had spontaneous bacterial peritonitis. During follow-up, 62 patients with a history of ascites developed variceal bleeding, whereas 12 patients this website with a history of variceal bleeding developed ascites (Table 1). The median survival time for the total 94 patients was 13 months from the onset of the later of the two complications (Fig. 1). After 1 year, 47% were alive without hepatic encephalopathy, 4% were alive but had developed hepatic encephalopathy, 31% had died without hepatic encephalopathy, and 18% had died after developing hepatic encephalopathy. After 5 years the corresponding proportions were 17%, 4%, 44%, and 36% (Table 2). At inclusion, 49 patients had hepatic encephalopathy, and during follow-up hepatic encephalopathy developed in nine patients who never had complications, in 66 patients with a history of ascites alone, in 10 patients with a history of variceal bleeding alone, and in 35 with a history of both ascites and variceal bleeding (Table 1). Eighty-five patients had ascites when they first developed hepatic encephalopathy, and 26% of these had spontaneous bacterial

上海皓元医药股份有限公司 peritonitis. The 169 patients with hepatic encephalopathy had a median survival time of 2.4 months from its onset; 45% died within 1 month, 64% died within 1 year, and 85% died within 5 years (Fig. 1, Table 2). Ascites was the most frequent first complication (12% of patients developed this complication within the first year after cirrhosis diagnosis), but nearly as many patients developed either variceal bleeding (6%) or hepatic encephalopathy (4%) as their first complication. Hence, 22% of patients developed one of the three complications under study during the first year after being diagnosed with alcoholic cirrhosis (Fig. 2). Patients with ascites were equally likely to develop variceal bleeding or hepatic encephalopathy as their next complication (1-year risk = 12% and 15%, respectively).