Liver Function Score Research Articles

Study of The Relationship between Severity of Liver Cirrhosis and Pulmonary Function Tests

Background: Cirrhosis is a condition in which the liver does not function properly due to long-term damage. This damage is characterized by the replacement of normal liver tissue by scar tissue. Objective: The aim of this work is to study the relationship between severity of liver cirrhosis according to the ChildPugh score and pulmonary function tests (namely spirometry and arterial blood gas). Patients and Methods: The study is a cross sectional one, which was carried out on 50 patients admitted in the inpatient wards, or in regular follow-up in the out-patient’s clinics of the Gastroenterology Departments, in Al-Azhar University Hospitals between November 2018 and May 2019.They were divided into 3 groups according to Child Pugh Classification (A, B and C). Result: The prevalence of hypoxia was(30%) in all studied groups (50 patients), the hypoxia was present in patients with Child C and Child B (62%) and (29.4%) respectively but none of Child A had hypoxia. It was noted that all pulmonary functions were worst in patients Child class C when compared to other groups. However, patients Child B had also significantly worse pulmonary functions when compared to patients class A. We also showed that pulmonary functions are significantly correlated with synthetic liver function, Child and MELD score. The deterioration of liver functions and rise of patients score is accompanied by worsening of all pulmonary functions. Conclusion: Patients suffering from severe liver cirrhosis and ascites, have significant reduction in (PaO2) and (SaO2) in association with restrictive pulmonary function pattern (up to 100% of patients with massive ascites).

Liver stiffness and thrombin generation in compensated cirrhosis

BackgroundDecompensated cirrhosis is associated with coagulation abnormalities that can increase the risk of thrombosis and bleeding. It is unclear precisely when these abnormalities arise and whether they are exacerbated as compensated cirrhosis progresses. Transient elastography using FibroScan generates liver stiffness measurements (LSM) that associate with portal hypertension, clinical outcomes and provides prognostic information at an earlier stage than traditional liver function scores eg, MELD score. ObjectiveTo characterize thrombin generation in patients with compensated cirrhosis and to determine whether parameters of coagulation change throughout compensated cirrhosis, staged using LSM. Patients/MethodsBlood samples were collected from well‐compensated cirrhotic patients n = 61, All Child Pugh A stage) attending the Mater Misericordiae University Hospital, Ireland. Comprehensive clinical staging of liver disease, including LSM, was performed. Tissue Factor‐stimulated thrombin generation was measured by calibrated automated thrombography. ResultsUsing LSM to stage well‐compensated cirrhotic patients, we demonstrate a significant decrease in the rate of propagation, the rate of attenuation, and total thrombin generation as LSM increase. LSM correlated with endogenous thrombin potential, peak thrombin generation, the rate of propagation, and the rate of attenuation. This association between thrombin generation and LSM was still evident in sub‐analyses excluding patients with ongoing alcohol use, active HCV infection, or a history of decompensation. In contrast, there was no significant correlation between thrombin generation, prothrombin times, Child‐Pugh scores, or MELD scores. ConclusionLiver stiffness measurements identify differences in parameters of thrombin generation within a cohort of compensated cirrhotic patients before changes in clotting times occur.

Ursodeoxycholic acid exerts hepatoprotective effects by regulating amino acid, flavonoid, and fatty acid metabolic pathways

Ursodeoxycholic acid (UDCA) is an intestinal bacterial metabolite with hepatoprotective effects. However, molecular mechanisms underlying its effects remain unclear. The aim of this study was to investigate the mechanisms underlying the therapeutic effects of UDCA by using global metabolomics analyses in healthy subjects. Healthy Korean men were administered UDCA at dosage of 400, 800, or 1200mg daily for 2weeks. Serum samples were collected and used for liver function tests and to determine miR-122 expression levels. Urinary and plasma global metabolomics analyses were conducted using a liquid chromatography system coupled with quadrupole-time-of-flight mass spectrometry (LC/QTOFMS) and gas chromatography-TOFMS (GC/TOFMS). Unsupervised multivariate analysis (principal component analysis) was performed to identify discriminative markers before and after treatment. Alanine transaminase score and serum miR-122 levels decreased significantly after 2weeks of treatment. Through LC- and GC-based metabolomic profiling, we identified 40 differential metabolites in plasma and urine samples. Regulation of liver function scores and metabolic alternations highlight the potential hepatoprotective action of UDCA, which were primarily associated with amino acid, flavonoid, and fatty acid metabolism in healthy men.

Observation of the effect of bone marrow mesenchymal stem cell transplantation by different interventions on cirrhotic rats.

Bone marrow mesenchymal stem cells (BMSCs) transplantation has attracted attention for the treatment of liver cirrhosis and end-stage liver diseases. Therefore, in this study, we evaluated the effect of different methods of BMSCs transplantation in the treatment of liver cirrhosis in rats. Seventy-two male Sprague-Dawley rats were divided into 7 groups: 10 were used to extract BMSCs, 10 were used as normal group, and the remaining 52 rats were randomly divided into five groups for testing: control group, BMSCs group, BMSCs+granulocyte colony-stimulating factor (G-CSF) group, and BMSCs+Jisheng Shenqi decoction (JSSQ) group. After the end of the intervention course, liver tissue sections of rats were subjected to hematoxylin and eosin (H&E) and Masson staining, and pathological grades were scored. Liver function [aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB)] and hepatic fibrosis markers [hyaluronidase (HA), laminin (LN), type III procollagen (PCIII), type IV collagen (CIV)] were measured. BMSCs+JSSQ group had the best effect of reducing ALT and increasing ALB after intervention therapy (P<0.05). The reducing pathological scores and LN, PCIII, CIV of BMSCs+G-CSF group and BMSCs+JSSQ group after intervention therapy were significant, but there was no significant difference between the two groups (P>0.05). The effect of JSSQ on improving stem cell transplantation in rats with liver cirrhosis was confirmed. JSSQ combined with BMSCs could significantly improve liver function and liver pathology scores of rats with liver cirrhosis.

Ursodeoxycholic acid improves liver function via phenylalanine/tyrosine pathway and microbiome remodelling in patients with liver dysfunction

Ursodeoxycholic acid (UDCA) is a metabolic by-product of intestinal bacteria, showing hepatoprotective effects. However, its underlying molecular mechanisms remain unclear. The purpose of this study was to elucidate the action mechanisms underlying the protective effects of UDCA and vitamin E against liver dysfunction using metabolomics and metagenomic analysis. In this study, we analysed blood and urine samples from patients with obesity and liver dysfunction. Nine patients were randomly assigned to receive UDCA (300 mg twice daily), and 10 subjects received vitamin E (400 IU twice daily) for 8 weeks. UDCA significantly improved the liver function scores after 4 weeks of treatment and effectively reduced hepatic deoxycholic acid and serum microRNA-122 levels. To better understand its protective mechanism, a global metabolomics study was conducted, and we found that UDCA regulated uremic toxins (hippuric acid, p-cresol sulphate, and indole-derived metabolites), antioxidants (ascorbate sulphate and N-acetyl-L-cysteine), and the phenylalanine/tyrosine pathway. Furthermore, microbiome involvement, particularly of Lactobacillus and Bifidobacterium, was demonstrated through metagenomic analysis of bacteria-derived extracellular vesicles. Meanwhile, vitamin E treatment did not result in such alterations, except that it reduced uremic toxins and liver dysfunction. Our findings suggested that both treatments were effective in improving liver function, albeit via different mechanisms.

Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort

Studies using metabolomic data have identified metabolites from several compound classes that are associated with disease-related lifestyle factors. In this study, we identified metabolic signatures reflecting lifestyle patterns and related them to the risk of hepatocellular carcinoma (HCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Within a nested case-control study of 147 incident HCC cases and 147 matched controls, partial least squares (PLS) analysis related 7 modified healthy lifestyle index (HLI) variables (diet, BMI, physical activity, lifetime alcohol, smoking, diabetes, and hepatitis) to 132 targeted serum-measured metabolites and a liver function score. The association between the resulting PLS scores and HCC risk was examined in multivariable conditional logistic regression models, where ORs and 95% CIs were computed. The lifestyle component's PLS score was negatively associated with lifetime alcohol, BMI, smoking, and diabetes, and positively associated with physical activity. Its metabolic counterpart was positively related to the metabolites sphingomyelin (SM) (OH) C14:1, C16:1, and C22:2, and negatively related to glutamate, hexoses, and the diacyl-phosphatidylcholine PC aaC32:1. The lifestyle and metabolomics components were inversely associated with HCC risk, with the ORs for a 1-SD increase in scores equal to 0.53 (95% CI: 0.38, 0.74) and 0.28 (0.18, 0.43), and the associated AUCs equal to 0.64 (0.57, 0.70) and 0.74 (0.69, 0.80), respectively. This study identified a metabolic signature reflecting a healthy lifestyle pattern which was inversely associated with HCC risk. The metabolic profile displayed a stronger association with HCC than did the modified HLI derived from questionnaire data. Measuring a specific panel of metabolites may identify strata of the population at higher risk for HCC and can add substantial discrimination compared with questionnaire data. This trial was registered at clinicaltrials.gov as NCT03356535.

Prospective Association between Gestational Diabetes and Subsequent Abnormal Liver Function Scores 9 to 16 Years after Pregnancy

Chronic hyperglycemia is a risk factor for liver dysfunction. Women with gestational diabetes mellitus (GDM), glucose intolerance first recognized in pregnancy, may identify a population of individuals at an increased risk for liver complications. However, large prospective studies examining liver function following a GDM pregnancy are lacking. The Diabetes &amp; Women’s Health (DWH) Study (2012-2014) followed women with and without GDM in the Danish National Birth Cohort (DNBC). DNBC was a population-based cohort study of pregnant Danish women (1996-2002). At 9-16 years postpartum, the DWH Study conducted a clinical exam and collected bio-specimens on 607 of 1,274 women with GDM and 619 of a random sample of 1,457 women without GDM during the index DNBC pregnancy. Markers of liver function measured at follow-up included: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT). Liver function scoring indices were used to assess liver capacity including: nonalcoholic fatty liver disease liver fat score (NAFLD-LFS), fatty liver index (FLI), hepatic steatosis index (HSI), and liver fat percentage. The mean (standard deviation) age (years) at follow-up for women without and with prior GDM was 43.4 (4.5) and 43.8 (4.6), respectively. Women with prior GDM had an increased risk at follow-up of elevated NAFLD-LFS (Adjusted Relative risk [RR], 2.34; 95% CI, 1.68-3.27), FLI (RR, 1.59; 95% CI, 1.27-1.99), and HSI (RR, 1.44; 95% CI, 1.21-1.71) adjusted for pre-pregnancy BMI and other relevant risk factors compared to women without prior GDM. Women with prior GDM also had a significantly higher fatty liver percentage (Adjusted difference (%), 1.93; 95% CI, 1.10-2.77). Women with GDM during pregnancy were at an increased risk for subsequent abnormal liver function 9-16 years postpartum. GDM may serve as another risk indicator for the early identification and prevention of liver dysfunction. Disclosure S. Donnelly: None. S. Hinkle: None. S. Rawal: None. L. Grunnet: None. J.E. Chavarro: None. A.A. Vaag: Employee; Self; AstraZeneca. J. Wu: None. P. Damm: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. M. Li: None. A.A. Bjerregaard: None. A. Thuesen: None. R.E. Gore-Langton: None. E.C. Francis: None. F. Hu: None. M.Y. Tsai: None. S.F. Olsen: None. C. Zhang: None.

ZGN-1061 Improves Metabolic Parameters and Hepatic Pathology in an Obese Mouse Model of Diet-Induced and Biopsy-Confirmed Nonalcoholic Steatohepatitis

ZGN-1061 (1061) is a methionine aminopeptidase 2 (MetAP2) inhibitor being developed to improve glycemic control in type 2 diabetes. In diet-induced obese mice, 1061 reduces fat mass and improves glycemic control, lipid metabolism, and other metabolic parameters. This study investigated 8 weeks of treatment with 1061 (0.3 mg/kg, SC, N=11) or vehicle (N=10) on metabolic parameters, hepatic pathology, and nonalcoholic fatty liver disease (NAFLD) activity score (NAS; composite measure of steatosis, inflammation, and ballooning degeneration; range 0-8) in male mice with diet-induced and biopsy-confirmed nonalcoholic steatohepatitis (DIO-NASH). At week 8, there was a vehicle corrected weight loss of 13.1% with 1061 (p&amp;lt;0.001). 1061-treated mice had reduced liver weight (mean±SE: 2.6±0.4 g) vs. vehicle (3.8±0.8 g, p&amp;lt;0.001) and 21% reduction of liver triglyceride (p&amp;lt;0.05). There was no change in food intake. NAS was unchanged in vehicle-treated mice (BL 6.2±0.1, Wk8 6.4±0.2, ns). 1061-treated mice had reduced NAS (BL 6.2±0.2, Wk8 5.0±0.3, p=0.002). Two of the NAS component measures improved: steatosis in vehicle-treated mice was unchanged (BL 3.0±0.0, Wk8 3.0±0.0, ns), whereas ZGN-1061 reduced steatosis (BL 2.9±0.1, Wk8 2.5±0.2, p=0.02), and hepatocellular ballooning was unaffected in vehicle-treated mice (BL 0.7±0.2, Wk8 0.6±0.2, ns), whereas 1061 significantly reduced ballooning severity (BL 0.6 ± 0.2, Wk8 0.0 ± 0.0, p=0.006). There was no treatment effect on fibrosis stage or liver collagen 1A. However, liver galectin-3 was reduced with 1061 vs. vehicle. 1061 produced a reduction in terminal plasma ALT and AST vs. vehicle. In DIO-NASH mice, 1061 markedly reduced body weight in conjunction with liver weight and triglyceride content. Importantly, 1061 improved liver function, steatohepatitis and NAS composite score. These findings introduce 1061 as a promising therapy for obesity-related NASH. Disclosure B.F. Burkey: Employee; Self; Zafgen. M. Illemann: None. S. Veidal: None. M. Feigh: None. J. Vath: Employee; Self; Zafgen. Stock/Shareholder; Self; Zafgen. T.E. Hughes: Board Member; Self; Zafgen. Employee; Self; Zafgen. Stock/Shareholder; Self; Zafgen.

Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case-Control Study in EPIC.

Background: The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites.Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk.Results: Exposure-related metabolic signatures were identified. Particularly, the body mass index (BMI)-associated metabolic component was positively related to glutamic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1.23 (95% confidence interval = 0.93-1.62) and 1.40 (1.14-1.72), respectively, for BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC with natural indirect effects, respectively, equal to 1.56 (1.24-1.96) and 1.09 (1.03-1.15), accounting for a proportion mediated of 100% and 24%.Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk.Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators. Cancer Epidemiol Biomarkers Prev; 27(5); 531-40. ©2018 AACR.

Investigation of Clinical and Pathological Relationships between Adult- and Pediatric-type NASH in Korean Children.

BackgroundHistologically, nonalcoholic steatohepatitis (NASH) is categorized into adult-type (type 1) and pediatric-type (type 2). The origination of the histological difference between the two types and how they differ clinically remain uncertain. We aimed to understand the incidence and clinical characteristics of the two types of NASH in Korean children, and to investigate the association between their pathological type and clinical characteristics, using anthropometric and laboratory data.MethodsIn 38 children with confirmed NASH, we investigated hepatic pathological findings, and correlating factors between pathological type and laboratory and anthropometric data (weight percentile, body mass index (BMI) z-score, and blood pressure percentile). Adult-type NASH was noted in 21 patients and pediatric-type in 17 patients.ResultsAge, sex, BMI, transaminase levels, and insulin resistance were not significantly different between the two groups. Triglyceride (TG) levels were higher in adult-type NASH (P = 0.033). Hematocrit and albumin levels were lower in adult-type NASH (P = 0.016 and 0.013, respectively). Hepatic fibrosis was more common in pediatric-type. The fibrosis scores in patients with adult-type were mostly 0 and 1, whereas the score was 3 in patients with pediatric-type (P = 0.024, 0.004, and < 0.010, respectively). Anthropometric data, liver function, and insulin resistance scores did not differ between the two pathological NASH types. TG, hematocrit, and albumin may be potential factors to predict pathological types. Fibrosis was observed more frequently in pediatric-type NASH.ConclusionMonitoring children with pediatric-type NASH for progression to fibrosis or cirrhosis is recommended.

ALBI Score as a Predictor of Survival in Patients with Compensated Cirrhosis Resected for Hepatocellular Carcinoma: Exploratory Evaluation in Relationship to PALBI and MELD Liver Function Scores

SUMMARY – The aim of the study was to explore predictive value of the ALBI, PALBI and MELD scores on survival in patients resected for hepatocellular carcinoma with compensated liver cirrhosis and no macrovascular infiltration. In this retrospective study, longitudinal survival analysis was performed. We analyzed patient/tumor characteristics and MELD, ALBI and PALBI scores as liver function tests for predicting survival outcome. Survival was analyzed from the date of liver resection until death, liver transplantation, or end of follow-up. Patients were stratified for age, cirrhosis etiology, presence of esophageal varices, hepatocellular carcinoma stage, microvascular invasion, histologic differentiation, and resection margins. We identified 38 patients (alcoholic cirrhosis in 84.2% of patients) resected over an 8-year period. Median preoperative MELD score was 8, ALBI score -2.63, and PALBI score -2.38. During the follow-up period, 24 patients died. Estimated median survival time was 36 months. Microvascular invasion was observed in 33 patients. Higher ALBI score was associated with 23.1% higher relative risk of death. PALBI score was associated with 12.1% higher relative risk of death, whereas MELD score was not associated with the risk of death. In conclusion, ALBI score demonstrated significant predictive capabilities for survival in patients with compensated cirrhosis resected for hepatocellular carcinoma.

Maintenance Zinc Therapy After Initial Penicillamine Chelation to Treat Symptomatic Hepatic Wilson's Disease in Resource Constrained Setting

Background and Aim: Experience with zinc in treating symptomatic hepatic Wilson's disease (WD) is limited. The study was done to evaluate the efficacy of penicillamine followed by zinc in treating symptomatic hepatic Wilson's disease. Methods: We retrospectively analysed case records of 31 symptomatic hepatic WD patients in whom disease severity scores (Child's, MELD, Nazer's and New Wilson Index score) and 24-h Urinary copper were compared at 3 time points—baseline at presentation, at transition from penicillamine to zinc and at end of follow-up. Results: Of the 31 patients with symptomatic hepatic WD studied, 10 had associated neuro-psychiatric manifestations of WD. Penicillamine was changed to zinc sulfate either due to financial constraints (in 28 patients) or due to adverse effects of penicillamine (in 3). Child's grade was A in 6 patients, B in 5 and C in 17 at presentation (baseline). Duration of initial penicillamine chelation therapy was 134 (2–320) weeks, median (range) and of subsequent zinc therapy was 363 (35–728) weeks. There was significant improvement in liver function tests and disease severity scores (Nazer's, New Wilson Index, Child's and MELD score) at transition from penicillamine to zinc compared to baseline. This improvement was maintained till end of study period. 17 patients with Child C cirrhosis at presentation were treated with penicillamine for 111 (2–320) weeks followed by zinc for 344 (41–652) weeks, of whom 15 had significant improvement in liver function and disease severity scores until end of follow-up. 3 of 31 study patients died at 284, 112 and 437 weeks. No patient underwent liver transplantation. Conclusions: Penicillamine followed by zinc maybe safe and effective treatment in resource constrained setting for symptomatic hepatic WD patients in all grades of baseline disease severity. Our data also suggests that some patients with decompensated cirrhosis due to Wilson's disease may be managed with medical treatment, avoiding liver transplantation. The authors have none to declare.

Functional remnant liver assessment predicts liver‐related morbidity after hepatic resection in patients with hepatocellular carcinoma

We aimed to evaluate whether functional assessment of the future remnant liver is a predictor of postoperative morbidity after hepatic resection in patients with hepatocellular carcinoma (HCC). One hundred forty-six patients who underwent hepatic resection for HCC were enrolled in this study. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid enhanced MRI (EOB-MRI) analysis for functional liver assessment was carried out before hepatic resection. The signal intensity in the remnant liver was measured and divided by the signal intensity of the major psoas muscle (the liver to major psoas muscle ratio, LMR) for standardization. The remnant liver function was calculated using the formula (LMR on the hepatobiliary phase/LMR on the precontrast image). Computed tomography liver volumetry was also carried out. The remnant functional liver was calculated as the remnant liver volume or volumetric rate × remnant liver function by EOB-MRI. Morbidities developed in 19 (13.0%) patients. Morbidities associated with the liver occurred in 7 patients (4.7%). There was no mortality during surgery. Median remnant liver function scores using EOB-MRI and remnant functional liver using volumetric rate or volumetry were 1.82 (range, 1.25-2.96), 155.9 (range, 64.7-285.3), and 1027 (range, 369-2148), respectively. Logistic regression analysis identified the remnant functional liver volume as the only independent predictor for liver-related morbidity. Remnant functional liver volume using computed tomography liver volumetry and EOB-MRI was a significantly useful predictor for liver-related morbidity after hepatic resection in patients with HCC.

Safely Addressing Patients with Atrial Fibrillation to Early Anticoagulation after Acute Stroke

It has been widely reported that anticoagulants (ACs) are underused for primary and secondary prevention of ischemic stroke in patients with atrial fibrillation (AFib). Furthermore, precise evidence-based guidelines about the best timing for AC initiation after acute stroke are currently lacking. In this retrospective, observational study, we analyzed prescription trends in AFib patients with acute ischemic stroke who were hospitalized in four neurologic stroke units of our region (Lombardia, Italy). In-hospital antithrombotic prescription was performed in highly heterogeneous patterns. A prestroke treatment with AC was the leading factor enhancing AC prescription during hospitalization. The other factors promoting AC were male gender, younger age, lower prestroke disability and stroke severity, and smaller stroke volumes. AFib subtype influenced AC prescription only in AC-naïve patients. Interestingly, Congestive heart failure, Hypertension, Age higher than 75 years, Diabetes, previous Stroke or TIA or thromboembolism, Vascular disease, Age 64-75 years, female Sex (CHA2DS2-VASc) and Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile INRs, Elderly, Drugs and alcohol (HAS-BLED) scores were not associated with AC prescription. However, patients who were treated with AC, including early treatment (<48 hours), showed a low rate of bleeding. Our findings potentially suggest that, although apparently neglecting the common risk stratification tools, our neurologists were able to select the more suitable candidates for prompt AC treatment. Further studies are needed to develop new scoring systems to aid ischemic and hemorrhagic risk estimation in the secondary prevention of stroke.

The impact of the multiple types of treatments on OS and the decline of liver function in patients with advanced stage of HCC.

461 Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related death worldwide. Most HCCs develop in severely damaged liver. Methods: The effect of multiple treatment options on liver function (LF) and disease outcome of patients (pts) with HCC (n = 185) were examined retrospectively. Pt tumor burden (using Barcelona clinic liver cancer [BCLC] classification) and LF (Child Pugh [CP]) were assessed at time of diagnosis and then after treatment. Using Kaplan Meier with log rank and T tests, BCLC and CP scores were correlated with overall survival (OS) following individual treatment regimens. Results: We show that better BCLC and LF scores at time of diagnosis predict a better outcome (median OS; p &lt; 0.05). Pts received one or more of the following: no treatment, experimental treatment, TACE, Y90 radioembolization, radiofrequency ablation, resection, radiation, and sorafenib (SFB). Considering all treatment scenarios, LF improved in 9.5%, did not change in 33%, and worsened in 57% of pts. Sixty percent of untreated pts experienced LF decline, compared with 33, 54, 48 and 50% of pts receiving TACE, SFB, TACE/SFB, and Y90/SFB, respectively (no significant differences [NS]); 72% of pts receiving TACE/Y90/SFB (NS); and 85% of pts receiving other Y90/SFB combinations (p = 0.006). In general, pts who saw no change or an improvement in LF from baseline had longer median OS versus pts who had declining LF (p &lt; 0.002). However, pts receiving TACE/Y90/SFB (n = 29) had similar OS to those receiving TACE/SFB (n = 35), despite the toxicity difference (72% [TACE/Y90/SFB] vs. 48% [TACE/SFB] of pts had declining LF). TACE/SFB or TACE/Y90/SFB led to longer median OS than any other treatment group (p = 0.017). Conclusions: The outcome of pts with HCC depends on disease stage and LF. Most pts experience LF decline during treatment. Despite LF decline in 48% of pts receiving a SFB/TACE, these pts experienced longer median OS than pts on any other treatment. Balancing survival benefit with liver toxicities is critical to the successful treatment of pts with advanced HCC. Agents with good antitumor activity and minimal liver toxicity are desperately needed for these pts.

Current strategies for preoperative conditioning of the liver to expand criteria for resectability of hepatic metastases

Colorectal cancer (CRC) is among the most commonly diagnosed cancers, and the liver is its most frequent metastatic site. Colorectal liver metastases (CLM) are synchronous in 15–25 % of the CRC patients and metachronous in 20–25 %. In recent decades, 5-year-overall survival following curative liver resection of CLM has increased to 35–58 %. This improvement owes largely to advances in CLM multimodality treatment. In recent years, the CLM resectability criteria have also shifted, following several encouraging studies reporting the possibility of R0 resection for all tumors while preserving a sufficient volume of residual liver. In this context, multimodal approaches including portal vein embolization (PVE), associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) and two-stage hepatectomy after neoadjuvant chemotherapy were developed to induce hypertrophy of the future liver remnant (FLR) to fulfill minimal liver volume requirements. Liver function tests and scores could be a helpful tool in patient selection and prediction limit of the hepatic parenchymal reserve. Generally, at least 20 % of the total liver volume should be preserved in the case of a healthy liver, whereas at least 30–60 % should be preserved for livers impaired by chemotherapy-associated steatosis or hepatitis. Further use of ischemic or pharmacological preconditioning of FLR tissue such as stem cell transplantation could help to prepare the liver for extended resections and to avoid postoperative liver failure. Because of shifting CLM resectability criteria and encouraging survival rates following curative resection in the context of multimodality treatment, extended liver surgery for CLM is increasing. To condition the liver for extensive surgery and to ensure adequate postoperative liver function, several approaches were developed and routinely practiced in clinical centers.

Evaluation of Transient Elastography, Acoustic Radiation Force Impulse Imaging (ARFI), and Enhanced Liver Function (ELF) Score for Detection of Fibrosis in Morbidly Obese Patients

BackgroundLiver fibrosis induced by non-alcoholic fatty liver disease causes peri-interventional complications in morbidly obese patients. We determined the performance of transient elastography (TE), acoustic radiation force impulse (ARFI) imaging, and enhanced liver fibrosis (ELF) score for fibrosis detection in bariatric patients.Patients and Methods41 patients (median BMI 47 kg/m2) underwent 14-day low-energy diets to improve conditions prior to bariatric surgery (day 0). TE (M and XL probe), ARFI, and ELF score were performed on days -15 and -1 and compared with intraoperative liver biopsies (NAS staging).ResultsValid TE and ARFI results at day -15 and -1 were obtained in 49%/88% and 51%/90% of cases, respectively. High skin-to-liver-capsule distances correlated with invalid TE measurements. Fibrosis of liver biopsies was staged as F1 and F3 in n = 40 and n = 1 individuals. However, variations (median/range at d-15/-1) of TE (4.6/2.6–75 and 6.7/2.9–21.3 kPa) and ARFI (2.1/0.7–3.7 and 2.0/0.7–3.8 m/s) were high and associated with overestimation of fibrosis. The ELF score correctly classified 87.5% of patients.ConclusionIn bariatric patients, performance of TE and ARFI was poor and did not improve after weight loss. The ELF score correctly classified the majority of cases and should be further evaluated.

Post-transplant liver function score as an early surrogate marker of long-term outcome.

Currently, there is no universally accepted method to evaluate liver function post-orthotopic liver transplant (OLTx) and there are no early surrogate function markers to assess the impact of perioperative interventions in trial settings. In total, 495 patients were included in the study. On multivariate analysis, PTLF score, defined as normal (score <4) or dysfunctional (score ≥ 4), was the only significant variable for determining significant complications (P=0.014) and graft survival (P=002) during the perioperative period. In total, 495 patients were included in the study. On multivariate analysis, PTLF score, defined as normal (score <4) or dysfunctional (score ≥ 4), was the only significant variable for determining significant complications (P=0.014) and graft survival (P=002) during the perioperative period. PTLF score shows promise as an early surrogate marker of post-orthotopic liver transplantation mortality and morbidity by providing results within the first 7 days post-transplantation. PTLF score can potentially be used as a tool to assess the impact of perioperative interventions by predicting long-term outcomes early in the clinical course of transplant patients.

Lower urinary tract symptoms in patients with liver cirrhosis.

To evaluate the prevalence of lower urinary tract symptoms (LUTS) in men with liver cirrhosis. In total, 128 men with known liver cirrhosis were prospectively evaluated using the validated German version of the International Prostate Symptom Score (IPSS) questionnaire. In parallel, all men underwent a detailed examination including medical history; physical examination; Child-Pugh liver function score (CPS) assessment; and measurement of blood levels of prostate-specific antigen (PSA), total and free testosterone, sexual hormone-binding globulin (SHBG), prolactin, luteotropic hormone (LH), and follicle-stimulating hormone (FSH). Mean patient age and mean IPSS was 56 ± 9 years and 8 ± 6, respectively. Mild (IPSS: 1-7), moderate (IPSS: 8-19), and severe (IPSS: 20-35) LUTS were present in 60.2 % (77/128), 31.3 % (40/128), and 7.0 % (9/128) of the patients, respectively. Storage symptoms increased with the CPS (p = 0.04). Voiding symptoms and overall IPSS did not differ between the CPS groups (p = 0.93 and p = 0.67). No correlation was found between ascites volume and IPSS, storage symptoms, voiding symptoms, or quality of life (QoL) (p = 0.46, p = 0.26, p = 0.81, p = 0.87). From CPS groups A to C, mean PSA levels (p = 0.04), total and free testosterone levels (p < 0.001 and p < 0.001), and SHBG levels decreased (p = 0.03); however, prolactin levels increased (p = 0.03). LH and FSH levels did not differ between the CPS groups (p = 0.15 and p = 0.35). Men with liver cirrhosis commonly have LUTS, with a predominance of storage symptoms. Liver cirrhosis may also affect PSA-based prostate cancer risk assessment. Accurate diagnosis and therapy strategies are warranted to improve the QoL of these patients.

Efficacy analysis of emergency transjugular intrahepatic portosystemic shunt in the treatment of variceal bleeding in liver cirrhosis

Objective To investigate the feasibility,safety and efficacy of emergency transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of esophageal and gastric variceal bleeding (EGVB) in liver cirrhosis.Methods The clinical data of 12 patients with liver cirrhosis and EGVB undergoing emergency TIPS were retrospectively analyzed,and were compared with those of 90 patients with cirrhosis undergoing selective TIPS for preventing rebleeding.The haemostasis,rebleeding,hepaticportal vein pressure gradient (HPPG),liver function,hepatic encephalopathy and death were observed.The t-test was performed for measurement data,while Chi-square test was used for counting data and Kaplan-Meier survival curves was used to compare the cumulative rebleeding rate.Results All emergency TIPS of the 12 patients were successful,the bleeding stopped after operation.Among them,eight patients underwent HPPG examination,which significantly decreased after operation ((15.8 ±5.9) mmHg,1 mmHg=0.133 kPa) compared with that before operation ((20.7±5.0) mmHg) and the difference was statistically significant (t =4.022,P=0.005).The liver function (Child-Turcotte-Pugh,CTP) score was 6.6 ± 1.5 before operation and 6.5 ± 1.3 after operation,there was no significant difference (P＞0.05).Hepatic encephalopathy occurred in three patients of the 12 cases undergoing emergency TIPS within one week after operation.The rate of hepatic encephalopathy in selective TIPS group was 18％ (16/90) and there was no significant difference (P＞0.05).During the follow-up period,rebleeding occurred in one patient of the 11 followed up cases undergoing emergency TIPS,while the cumulative rebleeding rate was 21 ％ (19/90) in the selective TIPS group and there was no significant difference in cumulative rebleeding between two groups (P＞0.05).There was no dead case in the emergency TIPS group while the overall mortality of selective TIPS group was 13％ (12/90),in which the EGVB and liver function failure-related mortality was 9％ (8/90).Conclusion The emergency TIPS is feasible,safe and with satisfactory efficacy in the treatment of acute EGVB in liver cirrhosis. Key words: Portosystemic shunt, transjugular intrahepatic; Liver cirrhosis; Esophageal and gastric varices; Gastrointestinal hemorrhage