Child-Pugh Stage Research Articles

Angiotensin Receptor 1 Blockers Prolong Time to Recurrence after Radiofrequency Ablation in Hepatocellular Carcinoma patients: A Retrospective Study.

Inhibition of angiotensin II synthesis seems to decrease hepatocellular carcinoma recurrence after radical therapies; however, data on the adjuvant role of angiotensin II receptor 1 blockers (sartans) are still lacking. Aim of the study was to evaluate whether sartans delay time to recurrence and prolong overall survival in hepatocellular carcinoma patients after radiofrequency ablation. Data on 215 patients were reviewed. The study population was classified into three groups: 113 (52.5%) patients who received neither angiotensin-converting enzyme inhibitors nor sartans (group 1), 59 (27.4%) patients treated with angiotensin-converting enzyme inhibitors (group 2) and 43 (20.1%) patients treated with sartans (group 3). Survival outcomes were analyzed using Kaplan–Meier analysis and compared with log-rank test. In the whole study population, 85.6% of patients were in Child-Pugh A-class and 89.6% in Barcelona Clinic Liver Cancer A stage. Median maximum tumor diameter was 30 mm (10–40 mm) and alpha-fetoprotein was 25 (1.1–2100) IU/mL. No differences in baseline characteristics among the three groups were reported. Median overall survival was 48 months (42–51) in group 1, 51 months (42–88) in group 2, and 63 months (51–84) in group 3 (p = 0.15). Child-Pugh stage and Model for End-staging Liver Disease (MELD) score resulted as significant predictors of overall survival in multivariate analysis. Median time to recurrence was 33 months (24–35) in group 1, 41 (23–72) in group 2 and 51 months (42–88) in group 3 (p = 0.001). Number of nodules and anti-angiotensin treatment were confirmed as significant predictors of time to recurrence in multivariate analysis. Sartans significantly improved time to recurrence after radiofrequency ablation in hepatocellular carcinoma patients but did not improve overall survival.

Feasibility and clinical value of TIPS combined with subsequent antitumor treatment in HCC patients with refractory ascites.

BackgroundCurrently, hepatocellular carcinoma (HCC) patients with refractory ascites (RA) have a very poor prognosis, and there are no effective treatments recommended by the guidelines. A treatment strategy that utilizes a transjugular intrahepatic portosystemic shunt (TIPS) combined with subsequent antitumor treatment is explored in this study for its feasibility and clinical value.MethodsOne month after TIPS, the ascites grade and Child-Pugh scores and stages were reassessed to compare changes in the preoperative indicators.ResultsA total of 68 patients from 3 centers were enrolled. After TIPS, the following results were obtained: a complete response (CR), partial response (PR), or absent RA response (AR) of 38 [55.9%], 21 [30.9%], and 9 [13.2%], respectively. The control of RA was 86.8%. The median Child–Pugh scores prior to TIPS and one month after TIPS were 8 (IQR 7–9) and 7 (IQR 6–8), respectively. The down, unchanged, and elevated Child–Pugh stages were 26 [38.2%], 36 [53.0%], and 6 [8.8%], respectively. The postoperative Child–Pugh scores were significantly lower than the preoperative (p < 0.001). 92.6% (63/61) of the patients received subsequent anti-tumor treatment opportunities. The median overall survival (OS) was 8.7 (range, 0.4–49.6) months. The lower postoperative Child-Pugh stage(p = 0.001), downward change of the Child-Pugh stage(p = 0.027), and downward change of the Child-Pugh score (p = 0.002) were independent protected prognostic factors for OS.ConclusionAs a minimally invasive method, TIPS can effectively control ascites and improve Child–Pugh scores and stages. TIPS combined with subsequent anti-tumor therapy is a feasible and effective management for HCC patients with RA.

Stratification of portal vein-invaded hepatocellular carcinoma treated with transarterial chemoembolization monotherapy

PurposeThe study aimed to establish a prognostic prediction model and an artificial neural network (ANN) model to determine who will benefit from transarterial chemoembolization (TACE) monotherapy for patients with hepatocellular carcinoma (HCC) invading portal vein. MethodsTreatment-naïve patients with HCC and portal vein invasion who were treated with TACE monotherapy at hospital A as training cohort and hospital B as validation cohort were included. The primary endpoint was overall survival (OS). In training cohort, independent risk factors associated with OS were identified by univariate and multivariate analysis. The prognostic prediction (PP) and ANN models based on the independent risk factors were established to find out who will benefit most from TACE monotherapy. The type of portal vein tumor thrombosis was classified based on the Cheng’s Classification. The accuracy of the models was validated in validation cohort. ResultsTotally, 242 patients (training cohort: n ​= ​159; validation cohort: n ​= ​83) were included. The median OS was 7.1 and 8.5 months in training and validation cohort, respectively. In training cohort, the PP model was established based on the following five independent risk factors: Cheng’s Classification, Eastern Cooperative Oncology Group score, maximum tumor size, number of HCC nodules, and Child-Pugh stage. PP score of 17.5 was identified as cut-off point and patients were divided into two groups by PP score <17.5 and >17.5 in survival benefit and prognostication (8.8 vs. 5.5 months; P ​< ​0.001). These five factors were included and ranked based on the importance associated with OS in the ANN model. Both of the two models received high accuracy after validation. ConclusionsPortal vein invaded HCC patients with PP score <17.5 may benefit most from TACE monotherapy. For these patients, TACE monotherapy should be considered.

Abstract 2346: Clinical manifestation, staging and prognosis of hepatocellular carcinoma in Gambian patients

Abstract INTRODUCTION: The clinical manifestations of patients with Hepatocellular carcinoma (HCC) have changed significantly in the last decades in countries that have adopted screening tests. In developing countries due to the rarity of surveillance/screening programs coupled with diagnostic challenges of HCC, most patients present late. OBJECTIVE: To evaluate the clinical manifestations, staging and prognostic factors of HCC in Gambian patients. METHODS: Patients with suspected HCC referred to the main liver clinic at the Medical Research Council were recruited from June 2011 to September 2019. The diagnostic criteria for HCC comprised of ultrasound demonstration of liver mass greater than or equal to 2 cm combined with alpha-fetoprotein (AFP) level of greater than or equal to 200 ng/ml and/or histopathological confirmation. Clinical, radiological, fibroelastrography and laboratory data were collected in all patients. Kaplan -Meier, univariate and multivariate cox regression analyses were used to assess factors related to survival in these patients. RESULTS: Five hundred and seventy three patients were recruited into the study. The mean age of HCC patient was 40 years and mostly males (81%). The most common constitutional symptoms were weight loss (84.1%), easy fatiguability (86.3%) while the most common gastrointestinal symptoms were early satiety (79.9%) and abdominal pain (81.8%). The most common signs were hepatomegaly (76.6%) and abdominal tenderness (48.1%). Multi-focal lesions were more common on ultrasound scan (63.4%) compared to single lesions, and the median fibroelastography score was 74 kpa in these patients. Hepatitis B surface Antigen (HBsAg) carriage was present in 69.6% of HCC patients with a median AFP of 4044 ng/ml. WHO performance status 1, BCLC stage C and Child-Pugh stage A were most common among this patient group. HBsAg-positive patients with HCC were mostly males, much younger, most likely to have jaundice, dark urine, abdominal tenderness, raised transaminases, haemoglobin and international normalised ratio (INR) levels and decreased platelet counts. HCC patients who were HBsAg-negative tended to be older, more likely to have weight loss, easy fatiguability, hypertension and had a much better median survival (42.5 days vs 35 days). Both prognostic staging systems had good stratification of survival. Independent factors that affect survival were abdominal pain, jaundice at the time of presentation, hyponatremia and hypoglycaemia. CONCLUSIONS: HBV is a significant factor in HCC in The Gambia. Young males who are the main work-force are disproportionately affected, are more likely to be symptomatic and have much shorter survival. In resource limited countries like The Gambia where screening programmes and therapeutic interventions are limited, the prognosis and survival of patients with HCC patients is poor, emphasizing the need for early preventative strategies. Citation Format: Sheikh Omar Bittaye, Ramou Njie, Muhammed Tekanyi, Abubacarr Kambi, Saydiba Tamba, Gibril Fatty, Yusupha Bah, Abdoulie Jatta, Lamin Sanneh, Momodou Musa Sisawo. Clinical manifestation, staging and prognosis of hepatocellular carcinoma in Gambian patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2346.

Comprehensive predictive factors for CalliSpheres® microspheres (CSM) drug-eluting bead-transarterial chemoembolization and conventional transarterial chemoembolization on treatment response and survival in hepatocellular carcinoma patients

Transarterial chemoembolization (TACE) is widely applied in hepatocellular carcinoma (HCC) patients who are not suitable for surgical treatment. We aimed to investigate the treatment outcomes and comprehensive prognostic factors of CalliSpheres® microspheres (CSM) drug-eluting bead TACE (DEB-TACE) treatment and conventional TACE (cTACE) treatment in HCC patients. Three hundred and thirty-five HCC patients received DEB-TACE or cTACE treatment were consecutively enrolled in multi-center, retrospective cohort study. Treatment response was conducted at M1, M3 or M6 after treatment. Progression free survival (PFS) and overall survival (OS) were recorded. Thirty-seven baseline factors including demographic characteristics, clinical features, biochemical indexes and previous treatment histories were selected. In total patients, history of drink and largest nodule size≥7cm independently predicted worse ORR, DEB-TACE predicted better OS, while largest nodule size≥7cm, increased Child-Pugh stage, ALB abnormal, ALP abnormal or AFP abnormal predicted worse survival. For DEB-TACE group, previous cTACE and ANC abnormal independently predicted worse ORR, and hepatic vein invasion, increased Child-Pugh stage or AFP abnormal independently predicted poor survival. For cTACE group, largest nodule size≥7cm independently predicted poor ORR, and multifocal disease as well as ALB abnormal predicted poor OS. History of drink, largest nodule size≥7cm, DEB-TACE, increased Child-Pugh stage, abnormal ALB, ALP or AFP are potential prognostic factors in total patients, previous cTACE and ANC abnormal, hepatic vein invasion, increased Child-Pugh stage or AFP abnormal are potential prognostic factors in DEB-TA group, and largest nodule size≥7cm, multifocal disease and ALB abnormal are potential prognostic factors in cTACE group.

Biomarkers of liver dysfunction correlate with a prothrombotic and not with a prohaemorrhagic profile in patients with cirrhosis

Background & AimsDifferent liver dysfunction biomarkers are used to assess the bleeding risk of patients with cirrhosis, either as such or included in bleeding risk assessment scores. Since the current model of coagulation in patients with cirrhosis describes a procoagulant tendency with increasing severity according to Child-Pugh stage, we decided to investigate the relation between liver dysfunction biomarkers and thrombin generation. Our aim was to verify their adequacy for bleeding risk assessment.MethodsWe performed a prospective single-centre study including 260 patients with liver cirrhosis. Thrombin generation was measured using ST Genesia® Thrombin Generation System without and with thrombomodulin in order to assess the role of proteins C and S. Relations between thrombin generation and Child-Pugh/model for end-stage liver disease (MELD) scores, prothrombin time (PT)/international normalised ratio (INR), activated partial thromboplastin time (aPTT), factor V activity, albumin, and total bilirubin were assessed.ResultsThrombomodulin-mediated inhibition of thrombin generation was significantly decreased in patients with liver cirrhosis compared with healthy donors (p <0.0001) and in Child-Pugh B and C compared with A (p <0.0001 [A–B], 0.4515 [B–C], <0.0001 [A–C]). Thrombomodulin-mediated inhibition significantly decreased with increasing PT/INR, aPTT, and total bilirubin levels and with decreasing factor V activity and albumin levels.ConclusionsWorsening liver dysfunction biomarkers reflect an increasing prothrombotic profile in patients with liver cirrhosis. In particular, prolonged PT/INR and aPTT as well as decreasing factor V activity are related to an increasing thrombotic risk and not to an increasing bleeding risk. These parameters should not be used to assess bleeding risk due to haemostatic anomalies in patients with liver cirrhosis. Alternative biomarkers for bleeding risk assessment in patients with liver cirrhosis need to be developed.Lay summaryWe demonstrate that the laboratory parameters used to assess bleeding risk of patients with liver disease, e.g. prothrombin time/international normalised ratio (PT/INR) and activated partial thromboplastin time (aPTT), are inadequate for this purpose because they are correlated with a prothrombotic coagulation profile. In this article, we highlight the need for alternative parameters to assess bleeding risk in patients with liver disease.

Diagnostic and Therapeutic Challenges in Hepatocellular Carcinoma

Abstract Introduction: Early detection of hepatocellular carcinoma is essential to provide effective therapy to high-risk patients, including patients with viral cirrhosis (eg HBV, HCV), haemochromatosis, alpha 1 antitrypsin deficiency or alcohol users. Material and method: The group of patients studied was represented by patients from the records of the Medical Clinic I of the Clinical Hospital “Saint Andrew the Apostle” Constanța for a period of 3 years (2017-2019). We included 82 patients aged between 32 and 82 years (60.22 ± 10.66 years) of which 55 were male and 27 were female. Results: Out of a total of 82 patients, 74 (90.25%) had cirrhosis (CH) and a number of 8 patients (9.75%) had chronic hepatitis without cirrhosis. Child-Pugh stage B had the highest prevalence among patients with hepatic cirrhosis. The etiological factor was hepatitis C virus infection 46 patients (56.1%), followed by hepatitis B virus infection 23 patients (28.05%), 4 patients (4.87%) had double hepatitis virus infection ( HBV + HCV), and 9 patients (10.98%) had a mixed viral and ethanolic etiology. Most of the lesions were located in the right hepatic lobe 58 patients (70.74%), respectively right + left hepatic lobe 22 patients (26.83%) and in 2 patients (2.44%) there were no visualized liver nodules. All patients had parenchymal fibrosis. Conclusions: It is recommended to screen patients with chronic liver disease to assess the risk of developing hepatocellular carcinoma, initially by liver ultrasound that can accurately detect and locate suspected nodules later the definite diagnosis of hepatocellular carcinoma is confirmed by magnetic resonance imaging (MRI).

Changes in the management of variceal gastrointestinal haemorrhage in our department

Introduction: Variceal bleeding is a life-threatening complication of portal hypertension with a six-week mortality rate of approximately 20%. Aim: To analyse whether the changes introduced in the treatment of variceal gastrointestinal haemorrhage in our department affected the mortality rate of these patients. Method: A retrospective method was used to compare the data of patients treated with variceal bleeding in 2014 and 2015. In 2015, two changes were made in the treatment of patients with variceal bleeding: all patients were treated in the subintensive care unit and terlipressin was administered to all patients susceptible to variceal haemorrhage. Bleeding was mitigated by means of sclerotherapy and/or ligation. Significance was calculated using Student’s t-test, then we performed logistic regression to find out what treatment factors affect mortality rate. Patients: 2014 vs. 2015 figures – number of patients: 24 vs. 30, average age: 59.8 vs. 57.6 years, male (%): 70.8 vs. 66.7. There were no significant differences between the Child–Pugh stages of the two years, p = 0.53. For the analysis we also grouped patients based on whether irrespective of the year of treatment they were administered terlipressin or not. Number of patients: 22 vs. 32, average age: 60.4 vs. 57.4, male (%): 63.6 vs. 70.6. Results: Mortality in 2015 and 2014: 23% and 33%, respectively. Mortality of patients treated with terlipressin: 18.2 vs. 34.4, p = 0.09. Child–Pugh stages had the strongest influence on mortality (stage A vs. B p = 0.05, stage A vs. C p = 0.02). Terlipressin administered in Child–Pugh stage C reduced mortality at a rate bordering on significance (p = 0.055). Conclusion: Despite the comparatively small number of cases, the changes introduced in our department in 2015 in the treatment of variceal gastrointestinal haemorrhages resulted in a significant reduction of hospital mortality rates. Orv Hetil. 2020; 161(15): 583–587.

Portopulmonary hypertension in the current era of pulmonary hypertension management

Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension (PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH. Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined. Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9-15). Most patients (n= 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n= 336) or with an endothelin-receptor antagonist (n= 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p <0.001), 6-minute walk distance (6MWD) (p <0.0001) and pulmonary vascular resistance (p <0.0001). Overall survival rates were 84%, 69% and 51% at 1, 3 and 5 years, respectively. Baseline 6MWD, sex, age and MELD score or Child-Pugh stage were identified as independent prognostic factors. Survival from PoPH diagnosis was significantly better in the subgroup of patients who underwent liver transplantation (92%, 83% and 81% at 1, 3 and 5 years, respectively). Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes. Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation.

Nutritional Index as Prognostic Indicator in Patients Receiving Lenvatinib Treatment for Unresectable Hepatocellular Carcinoma

Background/Aim: Few studies have examined the details of nutritional status in patients with unresectable hepatocellular carcinoma (u-HCC) undergoing systemic chemotherapy with lenvatinib. We evaluated the prognostic/predictive value of nutritional status using Onodera’s prognostic nutritional index (O-PNI) for overall survival among patients with u-HCC treated with lenvatinib. Methods: Three-hundred and seventy-five u-HCC patients treated with lenvatinib were enrolled (median age 72 years; Child-Pugh class A/B/C: n = 312/60/3; BCLC stage A/B/C/D: n = 2/159/212/2). We examined median survival time (MST) and time to progression (TTP) in all patients (n = 375), prognosis according to the O-PNI (high/low: >40/≤40) in 298 patients with lymphocyte findings, and the prognostic/predictive values of Child-Pugh stage, albumin-bilirubin (ALBI)/modified ALBI (mALBI) grade, and O-PNI for Chemotherapy grade (OPNIC grade 1/2/3: O-PNI >40/≤40 to >36/≤36). Results: The MST and TTP were 16.6 and 8.0 months, respectively. The MST and TTP according to the O-PNI (>40/≤40) were “not reached” (NR)/12.4 months (p < 0.001) and 10.0/6.1 months (p = 0.012), respectively. There was a good correlation noted between ALBI score and O-PNI (r = −0.939, p < 0.001). The predictive value of the O-PNI for mALBI grade 2a was 36.0 (specificity/sensitivity = 0.894/0.942; area under the curve [AUC] = 0.978), while that for mALBI grade 1 was 39 (specificity/sensitivity = 0.920/0.929; AUC = 0.972), which was very similar to a high O-PNI. The MST analyzed with the OPNIC in the 298 patients was NR/16.2/10.4 months for OPNIC grade 1/2/3 (p < 0.001), respectively, and the c-index was 0.632, the same as that for mALBI grade (0.632), while that for Child-Pugh class was 0.571. Conclusions: OPNIC grading might have a potential for easy substitution of mALBI grading. A good nutritional status (OPNIC grade 1) or mALBI grade 1 is the best indication for lenvatinib use, while with an OPNIC grade 3, lenvatinib might be not suitable.

3:27 PM Abstract No. 301 Drug-eluting beads transcatheter arterial chemoembolization is effective and well-tolerated in hepatocellular carcinoma patients with portal vein tumor thrombus

The aim of this study was to investigate the efficacy and safety of drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) and prognostic factors in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). 58 HCC patients with PVTT who received DEB-TACE treatment were included in this retrospective study, and the baseline characteristics were recorded. Treatment response was assessed at 4-6 weeks post treatment according to modified Response Evaluation Criteria in Solid Tumors (mRECIST), Overall survival (OS) was calculated using the Kaplan–Meier method, and adverse events (AEs) were also recorded. Univariate and multivariate Cox regression analyses were used to evaluate the relevant clinical variables in predicting OS. The objective response rate (ORR) was 79.3% in terms of tumors and 44.8% in thrombi. The median PFS and OS of patients were 5.0 months and 9.0 months respectively. The cumulative survival rate at 3-, 6-, 9-, 12-, 18- and 24-month were 94.8%, 72.4%, 53.4%, 41.4%, 22.4% and 19.0%, respectively. In a stepwise multivariate Cox proportional hazards model, the higher Child-Pugh stage (HR = 2.279; 95% CI, 1.042–4.985, P = 0.039) and tumor burden (P = 0.008) were the significant predictors of poorer OS after adjustment for known risk factors. As to AEs, they were mainly transient elevated liver enzymes and postembolization syndrome, all of which were not severe. DEB-TACE is effective and well-tolerated in HCC patients with PVTT. The higher Child-Pugh stage and tumor burden are independent predictors for poorer OS.

Deleterious effect of proton pump inhibitors on the disease course of cirrhosis.

Proton pump inhibitors(PPIs) are widely prescribed to patients with liver cirrhosis. We hypothesized that long-standing PPI use is associated with spontaneous bacterial peritonitis(SBP) and accelerated development of disease-specific complications and liver-related death. A 5-year follow-up observational cohort study assessed the impact of long-standing PPI use on the clinical course of cirrhosis in a large referral patient cohort. Three hundred fifty patients with cirrhosis (alcohol:69.1%, Child-Pugh stage A/B/C:206/108/36) were assigned to two groups: regular PPI users (n=196) and nonusers (n=154). Occurrence of SBP, decompensation events (ascites, hepatic encephalopathy and variceal bleeding), and liver-related death were assessed. Regular PPI use was associated with an increased cumulative probability of SBP compared to nonusers [55% vs. 24.8%, hazard ratio(HR):4.25; P=0.05], in patients without previous SBP episode (n=84). A similar association was found between regular PPI use and decompensation events. The risk of the development of a first decompensation was higher in regular PPI users compared with nonusers, in patients with compensated clinical stage at enrollment (HR: 2.81, P= 0.008, n=146). The risk of liver-related death was also significantly increased among regular PPI users (P<0.001). In multivariate Cox-regression analysis, regular PPI use (HR:2.81, P=0.003) and MELD score (HR:1.21, P<0.001) was an independent predictor of mortality. In the present follow-up cohort study, long-term PPI use was associated with the development of SBP and a progressive disease course in patients with cirrhosis that may have been caused by enhanced pathologic bacterial translocation, accelerated development of bacterial translocation-dependent disease-specific complications, and liver-related death.

Comparison of chemoembolization with CalliSpheres® microspheres and conventional chemoembolization in the treatment of hepatocellular carcinoma: a multicenter retrospective study.

PurposeThis study aimed to compare the efficacy and safety between transarterial chemoembolization (TACE) with CalliSpheres® microspheres (CSM-TACE) and conventional TACE (cTACE) in patients with hepatocellular carcinoma (HCC).Patients and MethodsThree hundred and thirty-five HCC patients receiving CSM-TACE or cTACE were consecutively enrolled in this multi-center, retrospective cohort study, and then divided into CSM-TACE group and cTACE group accordingly. Complete response (CR), objective response (ORR) and disease control response (DCR) was assessed according to mRECIST criteria at 1 month (M1), 3 months(M3) and 6 months(M6) after treatment. Progression-free survival (PFS) and overall survival (OS) were assessed. Liver function indexes and adverse events (AEs) were also evaluated.ResultsCR at M3 (P=0.020) and ORR at M1 (P<0.001), M3 (P<0.001) and M6 (P=0.017) after treatment were significantly higher in the CSM-TACE compared with cTACE group. DCRs, PFS (25.3 months vs 24.2 months, P=0.503) and OS (27.8 months vs 25.3 months, P=0.203) were similar between the two groups. CSM-TACE was independently correlated with higher ORR at M1 (P=0.002) and longer OS (P=0.023). Abnormal alkaline phosphatase (ALP) (P=0.049) was independently associated with lower ORR at M3, and history of alcohol intake (P=0.019) and largest nodule size ≥7 cm (P=0.015) independently correlated with lower ORR at M6 (P=0.015). Largest nodule size ≥7 cm (P=0.029) and abnormal albumin (ALB) (P=0.046) were independently associated with shorter PFS. Child-Pugh stage B/C (P=0.023), abnormal ALB (P=0.001), ALP (P=0.008) and alpha-fetoprotein (AFP) (P=0.005) were independently associated with shorter OS. Most liver function indexes and AEs were similar between the two groups (P>0.05), except that ALP (P=0.005), total bilirubin (P=0.031), pain during procedure (P=0.034) and occurrence of fever post(treatment (P=0.017) were significantly elevated in the CSM-TACE compared with cTACE group.ConclusionCSM-TACE presents with a better treatment response and similar survival profile compared with cTACE in HCC patients.

Diagnostic value of plasma HSP90\u03b1 levels for detection of hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is a major health problem worldwide. However, the popular tumor marker, AFP, lacks sensitivity although its specificity is high. Tissue biopsy is an invasive operation and may increase the risk of needle-track metastases. Heat shock protein 90 (HSP90) is a potential biomarker for tumor diagnosis and prognosis. This study aims to determine whether levels of plasma HSP90α in HCC patients can be used as a cost-effective and simple test for the initial diagnosis of the disease.MethodsPlasma samples were collected from 659 HCC patients, 114 secondary hepatic carcinoma (SHC) patients, 28 hepatic hemangioma patients and 230 healthy donors. The levels of HSP90α were measured by ELISA.ResultsThe levels of plasma HSP90α in HCC patients were significantly higher than in healthy donors and in patients with hepatic hemangioma or SHC (144.08 ± 4.98, 46.81 ± 1.11, 61.56 ± 8.20 and 111.96 ± 10.08 ng/mL, respectively; p < 0.05 in all cases). The levels were associated with age (p = 0.001), BCLC stage (p < 0.001), levels of AFP (p < 0.001), tumor size (p < 0.001), tumor number (p < 0.001), PVTT (p < 0.001), EHM (p < 0.001) and Child-Pugh stage in the HCC cohort. In addition, the levels of plasma HSP90α showed an upward trend along with the progression of the BCLC stage. ROC curve analysis showed that compared to AFP (AUC 0.922, 95%CI 0.902–0.938) or HSP90α (AUC 0.836, 95%CI 0.810–0.860), the combination of HSP90α and AFP (AUC0.943, 95%CI 0.925–0.957) significantly improved the diagnostic efficiency for HCC patients.ConclusionThe results suggest that plasma Hsp90 α levels can be used as an initial diagnosis for patients with HCC in both rural and cosmopolitan settings.

A young patient with type 2 diabetes associated non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma

The rising prevalence of the metabolic syndrome has led to an increase of non-alcoholic fatty liver disease (NAFLD), and its progressive-inflammatory form called non-alcoholic steatohepatitis (NASH). In recent years, NAFLD and NASH have become major risk factors for developing liver cirrhosis and hepatocellular carcinoma (HCC). In this case, we report a 46-year-old patient with type 2 diabetes mellitus and metabolic comorbidities including obesity and arterial hypertension, who was referred because of rising liver enzymes. After clinical and diagnostic evaluation, the patient was diagnosed with NASH-associated liver cirrhosis, Child-Pugh stage B. A normal blood sugar level was difficult to achieve, and the patient presented with consistently elevated HbA1c-levels irresponsive to insulin therapy. Due to the underlying liver cirrhosis, the patient was enrolled in the HCC-surveillance program. Sonography during follow up showed a focal lesion. On magnetic resonance imaging (MRI), the diagnosis of HCC (BCLC stage A) was confirmed based on typical contrast enhancement and portal-venous wash-out. The patient was evaluated for liver transplantation with a labMELD of 17, and an intermittent therapy with TACE was initiated. Only 2months after liver transplantation, the patient developed severe and lethal complications. Overall, this case highlights the different medical issues of patients with metabolic syndrome developing a chronic liver disease. In this patient, a rapid progression from NASH-associated liver cirrhosis to HCC was seen, and therefore highlights the importance of close surveillance to identify and treat potential risk factors early in the course of the disease.

Red Cell Distribution Width as a Prognostic Factor in Patients with Hepatocellular Carcinoma.

The red blood cell distribution width (RDW) was reported to be related to the severity of liver diseases, but its clinical significance in patients with hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to explore the clinical significance of RDW in HCC patients. For the retrospective study, 422 HCC patients were enrolled in this study. Hematological parameters and liver biochemical indexes were analyzed. Child-Pugh grade and Barcelona Clinic Liver Cancer (BCLC) stages of the HCC patients were calculated. The diagnostic accuracy was evaluated according to the area under the receiver operating characteristic (ROC) curve. The medical records of HCC patients who were admitted to The Second Affiliated Hospital of Nanjing University of Chinese Medicine from January 2006 to August 2015 were retro-spectively reviewed. Subgroup analysis showed that RDW level of HCC patients with tumor size more than 10 cm were higher than those of HCC patients with tumor size smaller than 3 cm, 3 - 5 cm, and 5 - 10 cm (14.77 ± 2.35%, 15.27 ± 2.65%, 15.32 ± 2.40% vs. 15.97 ± 2.39%, p < 0.001). RDW level significantly increased with worsening Child-Pugh grade and BCLC stages. In addition, RDW level were negatively correlated with red blood cell (RBC) counts, hematocrit (HCT), lymphocyte (LY) counts, hemoglobin (Hb), blood platelet (PLT) counts, and positively correlated with aspartate-aminotransferase (AST), and total bile acid (TBA). ROC curve analysis showed that RDW level was 14.15% was the optimal prognostic cutoff point to determine the survival rate of HCC patients. In the univariate analysis followed by multivariate analysis, RDW level below 14.15% together with better Child-Pugh grade, better BCLC stages, and smaller tumor size were prognostic indicators for HCC patients. This indicated HCC patients with RDW level below 14.15% [hazard ratio of 0.530 (95% confidence interval, 0.395 - 0.710; p < 0.001)] had the lower mortality. RDW level was positively associated with tumor size. The prognosis was better for HCC patients with RDW levels below14.15% together with better Child-Pugh grade, better BCLC stages, and smaller tumor lesions. It suggested RDW level might be an easily obtainable and inexpensive prognostic indicator for HCC patients.

Evolutionary and Pronostic Aspects of Cirrhosis at the University Hospital of Brazzaville (Congo)

Introduction: cirrhosis is a serious pathology that leads to complications whose management remains difficult in our country. This study aimed to evaluate the evolutionary aspects of cirrhosis at the Brazzaville University Hospital. Patients and methods: this was a retrospective study over a period of 18 months (from January 2015 to July 2016), performed in the Gastroenterology Department of the Brazzaville University Hospital. All patients regularly followed for decompensated cirrhosis were included. The studied variables were the epidemiological, clinical and paraclinical characteristics, the occurrence of complications, the survival, and the causes of death. Univariate analysis was used to determine prognostic factors based on the Child Pugh score. Results: There were 43 patients, including 32 men and 11 women, with a mean age of 52 ± 9.5 years. Viral hepatitis B was the most common etiology (39.5%). Child Pugh stage C was found in 60.5%. Oesophageal varices were present in 93% of cases. Survival at 18 months was 72%. In univariate analysis, two variables were significantly associated with decreased survival, including Child Pugh stage C and esophageal varices (grade II and III). Conclusion: cirrhosis remains a worrying pathology because the diagnosis is often made at the stage of often serious complications putting at risk of vital prognosis.

Adrenal insufficiency in decompensated cirrhotic patients without infection: prevalence, predictors and impact on mortality.

Relative adrenal insufficiency (RAI) is common in compensated and decompensated chronic liver disease in the presence of sepsis. This study was performed to find out the prevalence of RAI in decompensated cirrhotic patients presenting with hepatic encephalopathy and variceal bleeding without any evidence of infection. The study prospectively included 75 cirrhotic patients with signs of decompensation. The short Synacthen test (SST) was performed on all patients after ruling out infection. Patients with positive blood, urine, sputum, ascitic and pleural fluid cultures or evidence of infection on chest X-ray and those with elevated procalcitonin levels (>0.05 ng/ml) were excluded. RAI in critical illness was defined by a delta cortisol level (difference between basal and post-stimulation cortisol) of ≤9 μg/dl after SST. The mean age of the study population was 54 ± 11 years. Upper gastrointestinal bleed and hepatic encephalopathy were seen in 56.6% and 41.5%, respectively, and both were seen in 1.9%. Of the 75 patients, 55 (73%) were in Child-Turcotte-Pugh (CTP) class C and the mean model for end-stage liver disease (MELD) score was 21 ± 7. Forty-five patients (60%) met our criteria for RAI. Those with RAI had lower serum albumin (2.4 ± 0.5 g/dl vs 2.7 ± 0.5 g/dl, p=0.03) and higher MELD scores (22 ± 7 vs 19 ± 6, p= 0.03). Prevalence of RAI in CTP class C was 65% (36 out of 55 patients) compared to 45% (9 out of 20 patients) in Child-Pugh stage A and B. Similarly, 82% (23 out of 28 patients) with MELD scores >25 had RAI compared to 54% with MELD scores <20. None of biochemical parameters were predictive of RAI on logistic regression analysis. Three-month mortality rate was not significantly different in patients with or without adrenal insufficiency (44% vs 28%, p = 0.11). The present study showed RAI to be common in noninfected decompensated cirrhotic patients, but did not predict 3-month mortality. There were no other predictive factors in those with RAI. Hence, in patients with cirrhosis without infection, the clinical utility of routine adrenal function testing needs further elucidation.

The risk factors for long-term survival outcome in solitary hepatocellular carcinoma up to 2 cm: Propensity score matching analysis in a population cohort with a high rate of HBV infection.

The American Joint Committee on Cancer staging recently classified solitary hepatocellular carcinoma (HCC) ≤ 2 cm with or without vascular invasion as stage T1a. We aimed to discuss the risk factors of these stage T1a patients. Patients diagnosed with solitary HCC ≤2 cm from September 2008 to June 2015 were included in our study. Due to the small number of patients undergoing a non-curable approach and liver transplantation, patients undergoing liver resection (LR) and radiofrequency ablation (RFA) were included. In the comparison between LR and RFA, 1:1 propensity score matching (PSM) was used. The overall survival (OS) and disease-free survival (DFS) were predicted, and the Cox proportional hazard model was used to find the prognostic factors, described as hazard ratio (HR) and 95% confidence interval (CI). In total, 273 HCC patients were involved in our study, of whom 192 patients underwent LR and 81 patients underwent RFA. The proportion of Child-Pugh A patients was higher in the LR group (91.7%) versus the RFA group (76.5%) (P = 0.001), and the tumour size was slightly larger in the LR group, with a median size of 1.9 cm versus 1.7 cm in the RFA group (P = 0.001). No difference was found in OS between LR and RFA. However, RFA was the only risk factor for recurrence (HR 1.578, 95% CI 1.006-2.467, P = 0.047). A total of 80 pairs were compared after PSM, and there was no significant difference in OS or DFS between LR and RFA after PSM (P = 0.5434 or P = 0.1642, respectively). Child-Pugh stage B was the only risk factor for OS in the multivariate analysis after PSM (HR 2.289, 95% CI 1.089-4.812, P = 0.029). RFA was comparable with LR in treating solitary HCC up to 2 cm but with a higher risk for recurrence due to the imbalanced pre-operative covariates. When the pre-operative factors were consistent, liver function was the only prognostic factor for long-term OS.

972 Predicting Transplant Free Survival in Patients With Hepatocellular Carcinoma Undergoing Locoregional Therapy

INTRODUCTION: Recently a few scoring systems have been proposed to predict survival in patients with hepatocellular carcinoma (HCC) undergoing locoregional therapy (LRT). We aimed to compare the NIACE score (tumor Nodularity, Infiltrative tumor, serum Alpha-fetoprotein level, Child-Pugh stage, ECOG performance status), hepatoma arterial embolization prognostic score (HAP), and ABCR score (alpha-fetoprotein, BCLC, change in Child-Pugh stage and radiological response after LRT) with Barcelona Clinic Liver Cancer (BCLC) staging in predicting transplant free survival (TFS) in patients with HCC undergoing LRT. METHODS: In a multi-centric United States veteran cohort, we retrospectively analyzed 207 patients who had undergone LRT between January 2012 and March 2019. Pre LRT NIACE and HAP scores and post LRT ABCR scores were calculated for all subjects. Kaplan Meier plots were created to identify sub groups with different TFS within individual BCLC stages. RESULTS: The mean age was 65.6 ± 6.3 years (73.4% Caucasians and 26.6% African Americans). Mean MELD-Na score at the time of first LRT was 14.3 ± 7.2. Predominant etiology of liver disease was nonalcoholic fatty liver disease (52.6%) followed by combination of alcohol and hepatitis C virus (18.4%). 65 (31.4%), 42 (20.3%), 84 (40.6%) subjects had BCLC A, B and C disease stages respectively. 146 (70.5%) underwent transarterial chemoembolization (TACE), 12 (5.8%) underwent ablation, and 42 (20.3%) underwent trans arterial radioembolization as first LRT. After a median follow-up of 15.2 months, the overall TFS was 34.6%. BCLC stages A, B and C had 47.5%, 26.3% and 26.2% TFS respectively. In the BCLC B cohort (Figure 1) only NIACE score (at cut off &gt; 1) identified subgroups with significant difference in TFS (52.9% vs. 5.3%, P &lt; 0.001). In BCLC C cohort, HAP score (at cut off &gt; 2; 37.2% vs. 13.9%, P = 0.002) and ABCR score (at cut off &gt; 2, 83.3% vs. 40.5%, P = 0.03) identified subgroups with different TFS. In BCLC A cohort none of these scores identified sub groups with differential TFS. On separate analysis of subjects undergoing TACE, all three scores identified subgroups with differential TFS (Table 2). CONCLUSION: In patients with HCC undergoing LRT, the BCLC B and C stages encompass patients with variable TFS. NIACE score for BCLC B, and HAP and ABCR scores for BCLC C refine differential prognosis and identify subgroups with different TFS. These scores should possibly be incorporated into treatment allocation.