Effect Of Liver Cirrhosis Research Articles

The impact of liver cirrhosis on in-hospital outcomes among patients hospitalized for cardiogenic shock: A propensity score matched retrospective cohort study

BackgroundCardiogenic shock poses a critical challenge characterized by diminished cardiac output and organ perfusion. Timely recognition and risk stratification are essential for effective intervention. Liver cirrhosis adds complexity due to its diverse systemic manifestations. The effect of liver cirrhosis on in-hospital outcomes in cardiogenic shock remains underexplored. MethodsWe conducted a retrospective cohort study using the National Inpatient Sample database from 2016 to 2020, matching cirrhotic patients with non-cirrhotic counterparts using propensity scores. The Cochran-Mantel-Haenszel method was used to assess the impact of cirrhosis on in-hospital mortality and complications. Simple linear regression models were used to assess differences in length of stay and cost of hospitalization. ResultsThere were a total of 44,288 patients in the cohort, evenly distributed between the group with and without liver cirrhosis. Mean age of the cohort was 64 years (SD 12.5), 69.7 % were males, and 61.3 % were white. The overall in-hospital mortality rate in the cohort was 37.2 % with higher odds of in-hospital mortality in cirrhotic patients [OR = 1.3; 95 % CI (1.25, 1.35)]. Patients with cirrhosis exhibited increased risks of bowel ischemia, acute kidney injury, and sepsis compared to those without cirrhosis. Additionally, they had a heightened overall risk of major bleeding, particularly gastrointestinal bleeding, but a lower risk of intracranial hemorrhage and access site bleeding. Conversely, patients with cirrhosis had lower odds of deep vein thrombosis and pulmonary embolism, as well as arterial access site thrombosis and dissection, leading to reduced odds of peripheral angioplasty, thrombectomy, and amputation. Cirrhotic patients also had increased length of stay and cost of hospitalization. ConclusionLiver cirrhosis exacerbates outcomes in cardiogenic shock, necessitating tailored management strategies. Further research is warranted to optimize patient care and understand the underlying mechanisms.

Erythrocyte Antioxidants and Hexokinase Activity Alterations in CCl4-Induced Cirrhotic Rats Through Naltrexone Treatment

Cirrhosis is the consequence of chronic liver injury Considering the crucial role of oxidative stress in the progression of liver cirrhosis, we aimed to investigate the ameliorative effect of NTX against oxidative stress in carbon tetrachloride (CCl4)-induced cirrhotic rats. Eighty-four male Wistar rats were randomly assigned into 4 groups (21 rats /group I) receiving CCl4; (II) NTX+CCl4; (III) mineral oil (M) (as the control); (IV) NTX+M. The animals in each group were sacrificed in 3 different time-points 2 weeks, 6 weeks (early cirrhosis) and 8 weeks (advanced cirrhosis). Liver function tests, NO metabolites, GSH level, as well as the activity of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxides (GPX), and hexokinase (HK) were assessed. NTX was able to ameliorate liver injury, revealed by attenuation of ALT activity, which was significantly enhanced due to cirrhosis induction, as well as pathological evaluation. HK was also increased significantly after treatment with CCl₄ while NTX moderated this increase. Although CCl4 treatment did not have a significant effect on GSH levels, NTX was able to considerably increase GSH in blood. The activity of CAT and SOD as well as NO levels were all augmented by NTX in CCl4-treated rats. Naltrexone demonstrates antioxidative effects in liver cirrhosis and may confer a protective effect against hepatic cirrhosis through modulation of oxidative stress.

The Effect of Liver Cirrhosis on Patients Undergoing Cardiac Surgery.

The aim of this study was to investigate the impact of liver cirrhosis (LC) on postoperative complications and long-term outcomes in patients who underwent cardiac surgery. Three databases, including PubMed, Embase, and the Cochrane Library, were searched on July 24, 2022. A total of 1,535,129 patients were enrolled in the seven included studies for analysis. According to our analysis, LC was a risk factor for postoperative overall complications (OR = 1.48, 95% CI = 1.21 to 1.81, I2 = 90.35%, P = 0.00 < 0.1). For various complications, more patients developed pulmonary (OR = 1.86, 95% CI = 1.21 to 2.87, I2 = 90.79%, P = 0.00 < 0.1), gastrointestinal (OR = 2.03, 95% CI = 1.32 to 3.11, I2 = 0.00%, P = 0.00 < 0.05), renal (OR = 2.20, 95% CI = 1.41 to 3.45, I2 = 91.60%, P = 0.00 < 0.1), neurological (OR = 1.14, 95% CI = 1.03 to 1.26, I2 = 7.35%, P = 0.01 < 0.05), and infectious (OR = 2.02, 95% CI = 1.17 to 3.50, I2 = 92.37%, P = 0.01 < 0.1) complications after surgery in the LC group. As for cardiovascular (OR = 1.07, 95% CI = 0.85 to 1.35, I2 = 75.23%, P = 0.58 > 0.1) complications, there was no statistical significance between the 2 groups. As for long-term outcomes, we found that in-hospital death (OR = 2.53, 95% CI = 1.86 to 3.20, I2 = 44.58%, P = 0.00 < 0.05) and death (OR = 3.31, 95% CI = 1.54 to 5.07, I2 = 93.81%, P = 0.00 < 0.1) in the LC group were higher than the non-LC group. LC was a risk factor for cardiac surgery. Patients with LC who would undergo cardiac surgery should be fully assessed for the risks of cardiac surgery. Similarly, the surgeon should assess the patient's liver function before surgery.

Annual changes in grip strength and skeletal muscle mass in chronic liver disease: observational study

Sarcopenia is a common complication in patients with chronic liver disease (CLD); however, the progression of sarcopenia over the course of CLD is unclear. The present study therefore determined the natural course of the progression of sarcopenia in patients with CLD and the effect of liver cirrhosis (LC) on this progression. This observational study analyzed patients with chronic hepatitis (CH) (n = 536) and LC (n = 320) who underwent evaluations of the grip strength and skeletal muscle mass of the arms, trunk, and legs for sarcopenia between 2016 and 2021. A bioelectrical impedance analysis was used to evaluate skeletal muscle mass. The annual rate of change (%/year) in two tests were compared between patients with CH and LC. The annual rates of change in grip strength and skeletal muscle of arms, trunk, and legs of patients with CH and LC were − 0.84% vs. − 2.93%, − 0.54% vs. − 1.71%, − 0.43% vs. − 1.02%, and − 0.76% vs. − 1.70% for men and − 0.12% vs. − 1.71%, − 0.66% vs. − 1.71%, − 0.49% vs. − 1.31%, and − 0.76% vs. − 1.54% for women, respectively. The progression of sarcopenia was greater in LC patients than in CH patients and that the decrease in grip strength was most prominent in the progression of sarcopenia in patients with LC.

Effect of liver cirrhosis on theophylline trough concentrations: A comparative analysis of organ impairment using Child-Pugh and MELD scores.

Theophylline clearance is known to be reduced in patients with chronic liver diseases (CLDs) such as chronic hepatitis (CH) and liver cirrhosis (LC). The Child-Pugh (CP) score is generally used for pharmacokinetic evaluation, whilst a model for end-stage liver disease (MELD) has not yet been fully evaluated. This study aimed to predict theophylline clearance in patients with LC classified based on CP and MELD scores by population pharmacokinetic (PPK) analysis. PPK analysis included 433 steady-state trough concentrations from 192 Japanese bronchial asthma patients with and without CLDs and was performed using NONMEM. The severity of LC was assessed by CP and MELD scores. The final CP and MELD models which described apparent theophylline clearance (CL/F) were obtained. The CP model showed that the mean CL/F in patients without CLDs, CH patients and LC patients with CP class A, B and C was 0.0473, 0.0413, 0.0330, 0.0280 and 0.0209 L/h kg-1 , respectively. The MELD model predicted that CL/F in patients without CLDs, CH patients and LC patients with MELD scores of <10, 10-14, 15-19, 20-24 and ≥25 was 0.0472, 0.0413, 0.0324, 0.0268, 0.0230, 0.0197 and 0.0155 L/h kg-1 , respectively. CL/F in various stages of LC was evaluated, and a change in CL/F was highly dependent on the severity of CLDs in both models. The MELD model provided a more accurate and precise description of theophylline clearance in LC than the CP model, which may be due to the wider dynamic range of the MELD score.

Effect of liver cirrhosis on erectile function in rats: A study combining bioinformatics analysis and experimental research.

To explore the mechanism through which liver cirrhosis (LC) causes erectile dysfunction (ED). Bioinformatic analysis was used to predict the potential signalling pathways in LC-induced ED, and N-nitrosodiethylamine was used to establish a rat model of LC. H&E staining, Western blotting and RT-qPCR were used to detect pathological tissue damage and changes in mRNA and protein expression levels. In addition, the expression levels of sex hormones such as estradiol (E2), prolactin (PRL) and testosterone (T) were measured. The hypoxia-inducible factor (HIF) pathway was an important pathway in our bioinformatics prediction. Pathological damages were detected in the liver and penile tissues of the model rats. Compared with the normal group's serum hormone levels, E2 and PRL were increased in LC rats, while T was decreased (p<0.01). The mRNA and protein expression results from penis tissues showed that endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) were both downregulated, and HIF-1α was upregulated in the model group compared to the normal group (p<0.01). These data suggest that LC hinders erectile function and causes histopathological changes in the penis by affecting the expression of HIF-1α, eNOS, iNOS, E2, PRL and T.

Myocardial Dysfunction in Cirrhotic Cardiomyopathy is Associated with Alterations of Phospholamban Phosphorylation and IL-6 Levels

Decreased cardiac contractility has been observed in cirrhosis, but the mechanisms that initiate and maintain cardiac dysfunction are not entirely understood. We test the hypothesis that cirrhotic cardiomyopathy is related to deterioration of myocardial contractility due to alterations in calcium-handling proteins expression. In addition, we evaluated whether cardiac pro-inflammatory cytokine levels are associated with this process. Cirrhosis was induced by thioacetamide (TAA, 100mg/kg/i.p., twice weekly for eight weeks). The myocardial performance was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic challenge. The cardiac calcium handling protein expression was detected by Western blotting. Cardiac TNF-α and IL-6 levels were measured by ELISA. Thioacetamide induced liver cirrhosis, which was associated with cirrhotic cardiomyopathy characterized by invivo left ventricular diastolic and systolic dysfunction as well as cardiac hypertrophy. Invitro baseline myocardial contractility was lower in cirrhosis. Also, myocardial responsiveness to post-rest contraction stimulus was declined. Protein expression for RYR2, SERCA2, NCX, pPBL Ser16 and L-type calcium channel was quantitatively unchanged; however, pPBL Thr17 was significantly lower while IL-6 was higher. Our study demonstrates that cirrhotic cardiomyopathy is associated with decreased cardiac contractility with alteration of phospholamban phosphorylation in association with higher cardiac pro-inflammatory IL-6 levels. These findings provided molecular and functional insights about the effects of liver cirrhosis on cardiac function.

Effects of liver cirrhosis and patient condition on clinical outcomes in intrahepatic cholangiocarcinoma: a retrospective analysis of 156 cases in a single center.

The incidence of intrahepatic cholangiocarcinoma (iCCA) has been increasing over the past few decades. Liver cirrhosis is an independent risk factor for the development of iCCA. This study aimed to examine the prognostic impact of liver cirrhosis and patient condition on the treatment of iCCA. We retrospectively analyzed the cases of 156 patients diagnosed with iCCA between 1990 and 2014 in our center. Patients were divided into subgroups depending on the presence and severity of liver cirrhosis and the type of treatment. Clinical data, patient characteristics, and overall survival were compared between these groups. Forty-seven (30%) of 156 patients had liver cirrhosis, predominantly with Child-Pugh scores A (n=27) and B (n=12). The median survival differed between patients receiving tumor resection (34 months), chemotherapy (10 months), and best supportive care (2 months). An Eastern Cooperative Oncology Group Performance Status score more than 1 was a predictor of poor survival in all patients (P<0.001), independent of the presence of cirrhosis. Resection could be performed less frequently in cirrhotic patients (6 vs. 31 patients; P=0.04). If resection was performed, the presence of cirrhosis A/B did not influence survival. Cirrhosis A/B did not influence the outcome in patients receiving chemotherapy either. In cirrhotic patients receiving chemotherapy, cancer antigen 19-9 levels above 129 U/ml were associated with a significantly shorter survival (22.5 vs. 3 months, P=0.0003). The presence of liver cirrhosis in iCCA has been underestimated. There was no difference in survival between noncirrhotic patients and patients with compensated cirrhosis. Patients' general condition seems to be of more prognostic value in the treatment of iCCA than the presence of cirrhosis. Therefore, the presence of cirrhosis A/B should not prevent patients with a good Eastern Cooperative Oncology Group Performance Status score from receiving tumor resection or chemotherapy.

Outcomes and Effects of Hepatic Cirrhosis in Patients Who Underwent Transcatheter Aortic Valve Implantation

Comparative outcomes of transcatheter aortic valve implantation (TAVI) in patients with and without liver cirrhosis are scarce. This study aimed to assess the clinical outcomes and impact of liver cirrhosis on patients who underwent TAVI. Patient with liver cirrhosis who underwent TAVI 2011 to 2014 were identified in the National Inpatient Sample database using the International Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM). The primary outcome was the effect of liver cirrhosis on inpatient mortality. Secondary outcomes were the impact of liver cirrhosis on post-TAVI complications. We also evaluated the length of hospital stay and the cost of hospitalization. Propensity score-matched analysis was performed to address potential confounding. The cirrhotic patients who underwent TAVI had no significant increase in the risk of in-hospital mortality (odds ratio [OR] 1.12, 95% confidence interval [CI] 0.59 to 2.10, p = 0.734) or after procedural complications. Furthermore, cirrhotic patients were less likely to develop vascular complications requiring surgery (OR 0.47, 95% CI 0.23 to 0.98, p = 0.043), to develop after procedural deep vein thrombosis(OR <0.00, 95% CI <0.001 to <0.0001, p <0.0001), and to require pacemaker implantation. However, cirrhotic patients were more likely to undergo nonroutine hospital discharges (OR 1.50, 95% CI 1.15 to 1.96, p = 0.003). In conclusion, TAVI is a safe and reasonable therapeutic option for cirrhotic patients with severe aortic stenosis, requiring aortic valve replacement.

Diabetes, hepatocellular carcinoma, and mortality in hepatitis C-infected patients: A population-based cohort study.

The effect of diabetes mellitus (DM) on the development of hepatocellular carcinoma (HCC) and all-cause mortality after HCC development in chronic hepatitis C virus (HCV)-infected patients remains inconclusive. This cohort study aimed to investigate these issues using the Taiwanese National Health Insurance Research Database. We retrieved and enrolled newly diagnosed DM patients with HCV from the Longitudinal Cohort of Diabetes Patients database. Propensity score matching-including age, sex, alcohol-related liver disease, and baseline liver cirrhosis-was used to identify and enroll HCV patients without DM from the Longitudinal Health Insurance Database (n=1686). A multi-state model was used to investigate transitions from "start-to-HCC," "start-to-death," and "HCC-to-death." The multi-state model showed higher cumulative hazards for "start-to-HCC," "start-to-death," and "HCC-to-death" transitions in the DM (vs non-DM) cohort. The cumulative probability of death with or without HCC after 10years of follow-up was higher in the DM cohort than in the non-DM cohort. Multivariable transition-specific Cox models demonstrated that DM significantly increased the risk for transition from "start-to-HCC" (adjusted hazard ratio [aHR] 1.36; 95% confidence interval [CI] 1.16-1.59; P<0.001), "start-to-death" (aHR 2.61; 95% CI: 2.05-3.33; P<0.001), and "HCC-to-death" (aHR 1.36; 95% CI 1.10-1.68; P=0.005). The effect of liver cirrhosis on "start-to-HCC" and "start-to-death" transitions decreased over time, particularly within 2years. Diabetes mellitus increased the risk of HCC development in HCV-infected patients and the risk of all-cause mortality in patients with or without HCC.

Homocysteine deteriorates intrahepatic derangement and portal-systemic collaterals in cirrhotic rats.

In liver cirrhosis, the altered levels of vasoactive substances, especially endothelin-1 (ET-1) and nitric oxide (NO) lead to elevated intrahepatic resistance, increased portal-systemic collaterals and abnormal intra- and extra-hepatic vascular responsiveness. These derangements aggravate portal hypertension-related complications such as gastro-oesophageal variceal bleeding. Homocysteine, a substance implicated in cardiovascular diseases, has been found with influences on vasoresponsiveness and angiogenesis. However, their relevant effects in liver cirrhosis have not been investigated. In the present study, liver cirrhosis was induced by common bile duct ligation (BDL) in Sprague-Dawley rats. In acute study, the results showed that homocysteine enhanced hepatic vasoconstriction to ET-1 but decreased portal-systemic collateral vasocontractility to arginine vasopressin (AVP). Homocysteine down-regulated hepatic phosphorylated endothelial NO synthase (p-eNOS) and p-Akt protein expressions. Inducible NOS (iNOS) and cyclooxygenase (COX)-2 expressions were up-regulated by homocysteine in splenorenal shunt (SRS), the most prominent intra-abdominal collateral vessel. In chronic study, BDL or thioacetamide (TAA) rats received homocysteine or vehicle for 14days. The results revealed that homocysteine increased hepatic collagen fibre deposition and fibrotic factors expressions in both BDL- and TAA-induced liver fibrotic rats. Portal-systemic shunting and expressions of mesenteric angiogenetic factors [vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), PDGF receptor β (PDGFRβ) and p-eNOS] were also increased in BDL rats. In conclusion, homocysteine is harmful to vascular derangements and liver fibrosis in cirrhosis.

Comparison of Different Blockages on the Renin Angiotensin System in Murine Schistosomal Fibrosis.

The inhibition of the renin-angiotensin system (RAS) display anti-fibrogenic effects in liver cirrhosis, however RAS influence on schistosomal fibrosis has not been totally clarified. Thus, our objective was to compare the activities of different antihypertensive drugs on the inhibition of the RAS in murine schistosomal fibrosis. BALB/c mice (n=40) weighing 20g were subjected to inoculation of 50 cercariae and subdivided in three groups: the first group (n=15), animals were treated with losartan (10 mgkg-1 body weight); the second group (n=15) was treated with lisinopril (10 mgkg-1 body weight); while the third group (n=10) was treated with proportional volume of 0.9% NaCl, daily for 12 weeks. For this purpose, histological analysis, RT-PCR of genes related to hepatic fibrosis, as well as TGF􀀂1 and p42/44 MAPK protein quantification were evaluated. There was observed a decrease in the collagen deposits in animals treated with losartan (p<0.01) and lisinopril (p<0.01) once compared to the controls. This improvement was accompanied by a reduction of 􀀁-SMA labeled cells (p<0.001 and p<0.001) and procollagen 􀀁1(I) gene expression in both treated groups (p<0.05 and p<0.05). However, only losartan induced diminution of TGF􀀂1 and TIMP1 gene expression (p<0.01 and p<0.01), and TGF􀀂1 protein amount. Diversely, p42/44 MAPK protein was augmented in lisinopril group. Our findings demonstrated the effect of lisinopril and losartan on the decrease of hepatic fibrosis in murine schistosomiasis. The main mechanism of this process involves anti-fibrogenic activity via inhibition of TGF􀀂1 and TIMP1 by losartan treatment.Nevertheless, other possible mechanisms associated to lisinopril treatment may be implicated.

Effect of liver cirrhosis on metastasis in colorectal cancer patients: a nationwide population-based cohort study.

The aim of this study is to evaluate the liver metastasis risk among colorectal cancer patients with liver cirrhosis. This was a nationwide population-based cohort study of 2973 newly diagnosed colorectal cancer patients with liver cirrhosis and 11 892 age-sex matched controls enrolled in Taiwan between 2000 and 2010. The cumulative risk by Kaplan-Meier method, hazard ratio by the multivariate Cox proportional model and the incidence density were evaluated. The median time interval from the colorectal cancer diagnosis to the liver metastasis event was 7.42 months for liver cirrhosis group and 7.67 months for non-liver cirrhosis group. The incidence density of liver metastasis was higher in the liver cirrhosis group (61.92/1000 person-years) than in the non-liver cirrhosis group (47.48/1000 person-years), with a significantly adjusted hazard ratio of 1.15 (95% CI = 1.04-1.28, P = 0.007). The 10-year cumulative risk of liver metastasis for the liver cirrhosis and the non-liver cirrhosis group was 27.1 and 23.6%, respectively (P = 0.006). For early cancer stage with locoregional disease patients receiving surgery alone without adjuvant anti-cancer treatments, patients with liver cirrhosis (10-year cumulative risk 23.9 vs. 15.7%, P < 0.001) or cirrhotic symptoms (10-year cumulative risk 25.6 vs. 16.6%, P = 0.009) both still had higher liver metastasis risk compared with their counterparts. For etiologies of liver cirrhosis, the 10-year cumulative risk for hepatitis B virus and hepatitis C virus, hepatitis B virus, hepatitis C virus, other causes and non-liver cirrhosis were 29.5, 28.9, 27.5, 26.7 and 23.4%, respectively, (P = 0.03). Our study found that liver metastasis risk was underestimated and even higher in colorectal cancer patients with liver cirrhosis.

Differential effects of sorafenib on liver versus tumor fibrosis mediated by stromal-derived factor 1 alpha/C-X-C receptor type 4 axis and myeloid differentiation antigen-positive myeloid cell infiltration in mice.

Sorafenib--a broad kinase inhibitor--is a standard therapy for advanced hepatocellular carcinoma (HCC) and has been shown to exert antifibrotic effects in liver cirrhosis, a precursor of HCC. However, the effects of sorafenib on tumor desmoplasia--and its consequences on treatment resistance--remain unknown. We demonstrate that sorafenib has differential effects on tumor fibrosis versus liver fibrosis in orthotopic models of HCC in mice. Sorafenib intensifies tumor hypoxia, which increases stromal-derived factor 1 alpha (SDF-1α) expression in cancer and stromal cells and, subsequently, myeloid differentiation antigen-positive (Gr-1(+)) myeloid cell infiltration. The SDF-1α/C-X-C receptor type 4 (CXCR4) pathway directly promotes hepatic stellate cell (HSC) differentiation and activation through the mitogen-activated protein kinase pathway. This is consistent with the association between SDF-1α expression with fibrotic septa in cirrhotic liver tissues as well as with desmoplastic regions of human HCC samples. We demonstrate that after treatment with sorafenib, SDF-1α increased the survival of HSCs and their alpha-smooth muscle actin and collagen I expression, thus increasing tumor fibrosis. Finally, we show that Gr-1(+) myeloid cells mediate HSC differentiation and activation in a paracrine manner. CXCR4 inhibition, using AMD3100 in combination with sorafenib treatment, prevents the increase in tumor fibrosis--despite persistently elevated hypoxia--in part by reducing Gr-1(+) myeloid cell infiltration and inhibits HCC growth. Similarly, antibody blockade of Gr-1 reduces tumor fibrosis and inhibits HCC growth when combined with sorafenib treatment. Blocking SDF-1α/CXCR4 or Gr-1(+) myeloid cell infiltration may reduce hypoxia-mediated HCC desmoplasia and increase the efficacy of sorafenib treatment.

Liver cirrhosis in Fontan patients does not affect 1-year post-heart transplant mortality or markers of liver function

Liver cirrhosis is recognized with long-term follow-up of patients after the Fontan procedure. The effect of liver cirrhosis on the use of heart transplant (HT) and on post-HT outcomes is unknown. We reviewed Fontan patients evaluated for HT from 2004 to 2012 with hepatic computed tomography (CT) imaging, classified as normal, non-cirrhotic changes, or cirrhosis. The primary outcome was 1-year all-cause mortality, and the secondary outcome was differences in serial post-HT liver evaluation. CT imaging in 32 Fontan patients evaluated for HT revealed 20 (63%) with evidence of liver disease, including 13 (41%) with cirrhosis. Twenty underwent HT, including 5 non-cirrhotic and 7 cirrhosis patients. Characteristics at listing between normal or non-cirrhotic (n = 13) and cirrhosis (n = 7) groups were similar, except cirrhosis patients were older (median 17.6 vs 9.6 years, p = 0.002) and further from Fontan (median 180 vs 50 months, p < 0.05). Serial liver evaluation was similar, including aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin, and tacrolimus dose at 1, 3, 6, 9, and 12 months. Overall patient survival was 80% at 1 year, with no difference between cirrhosis and non-cirrhosis patients (86% vs 77%, p = 0.681). Liver biopsies were performed in 7 patients before HT, and all specimens showed architectural changes with bridging fibrosis. Most patients evaluated for HT had abnormal liver findings by CT, with cirrhosis in 41%. One-year mortality and serial liver evaluation were similar between groups after HT. Liver cirrhosis identified by CT imaging may not be an absolute contraindication to HT alone in this population.

Abstract 5078: Response-guided anti-angiogenic therapy for hepatocellular carcinoma recurrence with clinically available safety agent.

Abstract The incidence of hepatocellular carcinoma (HCC) is increasing not only in Asia but also in Europe and United States. Since the high-risk group of either primary or secondary HCC development seems to be clearer than in the other types of tumors, it is likely that chemopreventive agents will be beneficial in improving the prognosis of HCC. No chemopreventive agent, however, has been approved against HCC yet. Since neovascularization plays a pivotal role in HCC, an angiostatic agent is considered as one of the promising approaches. Although an anti-angiogenic agent, sorafenib has approved for advanced heparocellular carcinoma (HCC), most of patients show adverse effects in liver cirrhosis. Insulin resistance (IR) is reportedly involved in the progression of HCC partly mediated with neovascularization. The aim of this study was to develop the response-guided anti-angiogenic therapy with a clinically used safe agent; branched-chain amino acid (BCAA), which reportedly possess anti-angiogenic and IR improving activities, for the cumulative recurrence of HCC after curative therapy. BCAA (Livact; 12 g/day) was administered after the curative therapy for HCC, and 60-month follow-up revealed that the BCAA markedly inhibited the cumulative recurrence of HCC under the condition of IR along with suppression of VEGF. Chronological studies reveled that the VEGF and AFP-L3 were significantly decreased in patients without recurrence at 6 and 12 months after the treatment, respectively. The soluble VEGFR (sVEGFR)-2 was significantly suppressed only in patients without recurrence, whereas sVEGFR-1 was not. A marked suppression of sVEGFR-2 could be achieved within only three months after the treatment. Collectively, since BCAA is widely and safely used in the clinical practice to treat the patients with chronic liver diseases, BCAA may represent a new strategy for secondary chemoprevention for the HCC patients with IR. Moreover, our findings suggest that sVEGFR-2 could become a useful response-guided predictive marker of anti-angiogenic therapy against HCC by BCAA under the condition of IR. Citation Format: Hitoshi Yoshiji, Ryuichi Noguchi, Kosuke Kaji, Yosuke Aihara, Tadashi Namisaki, Kei Moriya, Akitoshi Douhara, Mitsuteru Kitade, Hiroshi Fukui. Response-guided anti-angiogenic therapy for hepatocellular carcinoma recurrence with clinically available safety agent. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5078. doi:10.1158/1538-7445.AM2013-5078

Serum Creatinine Levels Unrelated to Child-Pugh Status in Uncomplicated Cirrhosis of Liver with Ascites

Introduction: Liver cirrhosis and renal failure are two diseases that may occur in conjunction due to mutually related pathological processes. Liver cirrhosis causes portal hypertension that ultimately causes splanchnic vasodilatation leading to hepatorenal syndrome. Hypovolemia is another cause of renal failure in liver cirrhosis. The study presented here was done to assess the renal functions in patients with liver cirrhosis with ascites. Materials and methods: Sixty patients with uncomplicated cirrhosis of liver with ascites with normal renal function were included in this study. All patients were examined physically and biochemical. Main biochemical variables were serum bilirubin, serum albumin, serum creatinine and prothrombin time. Enrolled patients were categorized according to Child-Pugh class B and C. Serum creatinine levels were measured in all cases. Results: Mean level of serum albumin, serum creatinine and prothrombin time among Child B and C classes of liver cirrhosis patients were 27.36 vs 26.84 gm/dl, 0.79 vs 0.93 mg/dl, 15.97 vs 19.26 seconds respectively. No statistically significant change in the serum creatinine level among Child B and C were noticed. Conclusion: This study showed that the effect of liver cirrhosis on renal dysfunction would be minimal, if any.

Effect of liver cirrhosis on phenylalanine and tyrosine metabolism

Phenylalanine conversion to tyrosine (i.e., 'hydroxylation') is the first irreversible step in phenylalanine catabolism and a source of circulating tyrosine. The purpose of the present review is both to examine hydroxylation from a biochemical standpoint and to report data measured in vivo under physiological conditions, as well as in liver and kidney disease. The simultaneous infusion of phenylalanine and tyrosine tracers in humans allows us to determine the hydroxylation rate in vivo. Hydroxylation accounts for a minor ( approximately 10-20%) although significant portion of tyrosine flux. The liver and the kidney are the key organs accounting for virtually the whole-body hydroxylation rates. It is regulated by substrate availability, being acutely stimulated by mixed meal ingestion and by dietary adaptation to high phenylalanine intakes. Theoretically, it may be impaired in advanced liver and kidney disease. Nevertheless, in compensated liver cirrhosis, hydroxylation as well as tyrosine flux are not decreased but rather increased. Only in end stage liver disease hydroxylation may be impaired and is corrected by transplantation. Hydroxylation is also reduced in end stage renal disease. Phenylalanine hydroxylation in vivo appears to represent a regulatory step of phenylalanine disposal and tyrosine production under acute and/or extreme conditions.

Metabolische Störungen bei Leberzirrhose (Teil 2): Hepatogener Diabetes mellitus

Uip to 20% of patients with liver cirrhosis develop hepatogenous diabetesdue to the hepatocellular functional loss and insulin resistance. Optimizing diabetic metabolic conditions is not only important to avoid typical late complications of diabetes, but also cirrhosis-associated complications e.g. gastrointestinal bleeding, hepatic encephalopathy or the occurence of hepatocellular carcinoma. So far there have beenno recommendations orguidelines for the diagnosis and treatmentof hepatogenous diabetes. The medical teatment of a diabetic condition is mainly influenced by its side effects. The risk of hypoglycemia must be considered carefully during drug treatment, especially in patients with chronic alcohol abuse. Suitable oral antidiabetics are glinides and short-acting sulfonylureas or possibly meal-related insulin administration with short-acting insulins or rapid-acting insulin analogues. Biguanide and PPAR-gamma agonists are contraindicated because of side effects in liver cirrhosis. Regarding basic treatment, an adequate daily energy and protein supply should be ensuredbecause the majority of patients with liver cirrhosis are malnourished.

Der hepatogene Diabetes – aktueller Stand der Diagnostik und Therapie

Patients with liver cirrhosis develop frequently disturbances of glucose metabolism e. g. glucose intolerance or hepatogenous diabetes which are caused by the hepatocellular functional loss and insulin resistance due to chronic liver disease. Until now there are no recommendations comparable to guidelines on the diagnosis of and therapy for hepatogenic diabetes. Regarding basic treatment a sufficient daily energy and protein supply should be guaranteed since the majority of patients with liver cirrhosis are malnourished. The risk of hypoglycaemia must be considered carefully under pharmacological treatment of hepatogenous diabetes. Biguanide and PPAR gamma agonists are contraindicated due to side effects in liver cirrhosis. Suitable oral antidiabetics are glinides and short-acting sulfonylureas. If a sufficient diabetes adjustment does not succeed by oral antidiabetics a prandial insulin therapy using short-acting insulins or rapid-acting insulin analogues should be applied. Optimisation of diabetic metabolic conditions is not only important to avoid typical diabetic late complications but also cirrhosis-associated complications, e. g., gastrointestinal bleeding, hepatic encephalopathy or the occurrence of hepatocellular carcinoma.