Transarterial Radioembolization for Unresectable Hepatocellular Carcinoma: Real-Life Efficacy and Safety Analysis of Korean Patients

Transarterial radioembolization (TARE) has become widely used in the treatment of HCC, one of the most common causes of cancer mortality worldwide. Here we investigated the long-term clinical outcomes of patients with hepatocellular carcinoma (HCC) treated with TARE in a multi-medical center in Korea. A total of 149 patients treated with TARE from 2008–2014 were recruited. The pre-treatment HCC stage was classified according to the BCLC stage, of which C and D were defined as advanced HCC. Advanced HCC stage and Child–Turcotte–Pugh (CTP) score A were identified in 62 (42%) and 134 (90%) patients, respectively. Portal vein thrombosis (PVT) was identified in 58 patients (38.9%). The median time to progression (TTP) was 14 months, and the median overall survival (OS) and progression-free survival (PFS) were 18.6 and 8.9 months, respectively. The overall tumor response was 47%, and the disease control rate was 78%. OS and PFS differed significantly according to the presence of liver cirrhosis, extrahepatic metastasis, tumor response and curative treatment after TARE (all, p < 0.05). Multiple tumors and major PVT were other independent factors related to OS, while the des-gamma carboxy protein level predicted PFS (all, p < 0.05). Tumor size was an independent predictor of tumor response. TTP, OS and PFS all differed among BCLC stages. The serious adverse effect after TARE was clinically not significant. Therefore, TARE is safe and effective in treating early to advanced HCCs.

Combined CTP- IGF-1 Score: A New Score for Assessment of Disease Severity in HCV Related Liver Cirrhosis

Background: Liver is the largest endocrine organ in the body. It is a key organ in insulin mediated metabolism, growth hormone and insulin like growth factors (IGF) pathway. Liver cirrhosis is the end result of many chronic diseases including hepatitis C virus infection. Child-Turcotte-Pugh (CTP) score is the standard used in assessment of hepatic reserve but it has its drawbacks in the form of subjective variables, hepatic encephalopathy and ascites. The aim of this work is to assess IGF-1 in patients with liver cirrhosis, correlate it with CTP score and assess value of modified combined CTP-IGF-1 score. Patients and Methods: 170 patients with CLD (liver cirrhosis) and 72 healthy controls in the study groups were enrolled in the study. All patients were subjected to thorough history, clinical examination and laboratory assessment. IGF-1 was measured and all patients were evaluated using CTP and CTP-IGF-1 scores. Results: IGF1 showed highly significant low values in the study group in comparison to controls (42.15 ± 27.976 and 66.31 ± 33.084 ng/ml respectively, p <0.001). It showed also highly significant negative correlation to CTP score in the study group (p < 0.001) with progressive decrements with CTP score stage progression where IGF1 levels were 48.32 ± 28.611, 40.28 ± 25.869 and 18.80 ± 15.953 ng/ml (mean ± standard deviation) in relation to CTP score groups A, B and C respectively (p value < 0.001). The combined CTP-IGF-1 score in comparison to the classic CTP score showed improved area under curve (0.848 and 0.854), sensitivity (71.2% and 88%), negative predictive value (41.7% and 53.7%), false negative results (49 and 19) and accuracy (75.73% and 83.98%) but decreased specificity (97.22% and 61.1%), positive predictive value (99.2% and 91.5%) and higher false positive results (1 and 14) respectively. Conclusion: IGF-1 show progressive decrements with progression of liver cirrhosis and is negatively correlated with CTP score. Addition of IGF-1 to CTP score to formulate combined score improves the AUC, sensitivity, negative predictive value and the accuracy of CTP score and decreases the false negative results.

Prognostic value of AIMS65 score in cirrhotic patients with variceal bleeding

Background: In cirrhotic patients, variceal bleeding remains a major cause of death. After a variceal bleeding episode, mortality and rebleeding rates spike for the first 6 weeks before levelling off. We aimed to evaluate the performance of AIMS65 score in comparison with Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score in predicting 6-week mortality and rebleeding in cirrhotic patients with variceal bleeding. Method: Data were collected prospectively from patients with cirrhosis and variceal bleeding at Gastroenterology and Hepatology Department of Cho Ray hospital from September 2016 to April 2017. The primary endpoint was 6-week mortality and rebleeding. The prognostic value of AIMS65, CTP, and MELD scoring systems for 6-week mortality and rebleeding was compared by receiver operating characteristics curves (ROC) and the area under the curve (AUC). Results: Among 80 patients, 15% rebled and 25% died during 6-week follow-up. AUCROC of AIMS65, CTP, and MELD scores in predicting 6-week rebleeding were 0.68, 0.54, and 0.48, respectively. AUCROC of AIMS65, CTP, and MELD scores in predicting 6-week mortality were 0.80, 0.74, and 0.64, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AIMS65 score at the cutoff point of 2 were 95%, 55%, 41.3%, and 97%, respectively. Conclusion: AIMS65 score is a simple yet applicable tool for risk stratification in cirrhotic patients with variceal bleeding. We recommend using AIMS65 score with a cut-off point of 2 to identify patients at increased risk for 6-week mortality after variceal bleeding.

Frequency of Vitamin D deficiency in liver cirrhosis and its correlation with Child Pugh Score

Objective: To determine the frequency of vitamin D deficiency in patients with liver cirrhosis and the relationship of vitamin D deficiency with Child Pugh Class in patients with cirrhosis. Materials and Methods: Vitamin D and calcium levels were checked in patients with cirrhosis of liver aged 18 to 80 years admitted in Gastroenterology department of Lahore General Hospital. Investigations were also done to calculate Child Pugh (CTP) score and Child Class was assigned on the basis of score. Quantitative variables were expressed in terms of mean and standard deviation. Frequency and percentage were used for qualitative measures. The p-value was calculated by the contingency coefficient to find a relationship of vitamin D levels to CTP scores of liver cirrhosis. Data was analyzed using SPSS 24 Study Duration: The study was carried out from December 2019 to October 2020 Results: A total of 170 patients with mean age of 43.82 ± 9.72 (19-61) years were evaluated of which 144 (84.7%) were males, 26 (15.3%) were females. Vitamin D3 deficiency was found in 144/170 (84.7%) patients while insufficiency was found in 14/170(8.2 %). It was more common in male patients (86.1%) compared to female patients (76.9%). Mean vitamin D3 levels was 14.4 ± 9.4 ng/ ml. Patients with Child A cirrhosis 6/10 (60%) had deficiency, with child B 66/82 (80.5%) while with Child C 72/78 (92.3%) had deficiency of Vitamin D3. Conclusion: Vitamin D deficiency is common in patients with cirrhosis and level has decreased stepwise with higher Child Pugh Class. Keywords: Cirrhosis, Vitamin D, Child Pugh score

Management of Hepatitis C Virus Genotype 4 Treatment Failure: A Real-World Single Center Experience

Background: Treatment failure with direct-acting antiviral (DAA) therapy is associated with worsening of liver disease especially in cirrhotic patients. Moreover, data on retreatment of HCV genotype 4 patients (G4) with DAA failure are still very limited, since they are under- represented in most clinical trials. Aims: To evaluate the efficacy of retreatment of Egyptian HCV G4 DAA failure patients based on the use of a new DAA class from currently available first- generation DAA regimens other than the patient had relapsed to. Methods: 29 Egyptian HCV G4 DAA failure patients were retreated by switch to a new DAA class from first- generation DAA regimens than the patient had relapsed to independent of RAS testing. 25 out of these 29 patients completed retreatment and 4 patients were lost for follow–up. Results: Among other risk factors, by logistic regression analysis, only older age, high CTP score and high base-line viral load were independent predictors of DAA failure among our cohort. Also SOF/RBV regimen was the most common prior DAA regimen associated with treatment failure (48.3%). All our DAA failure patients were cirrhotics that made prompt retreatment of them a rescue strategy to halt viral replication and disease progression. After retreatment, 22 (88%) of the 25 patients who completed retreatment achieved SVR12 and the remaining 3 (12%) failed. These 3 patients completed a second retreatment, one achieved SVR and the other 2 relapsed again (re-relapsers) Conclusion: The overall SVR rate (88%) demonstrated in this real –world study, clearly shows that, the retreatment policy of DAA failure patients by switch to – or addition of a new drug class independent of RAS testing is a good retreatment option, that may be of importance for many areas of the world with no or difficult access to RAS testing or second-generation rescue regimens.

Evaluation of Neutrophil-to-Lymphocyte Ratio (NLR) and Its Correlation with Severity of Liver Cirrhosis Based on Child-TurcottePugh Score in a Tertiary Care Hospital, Barpeta, Assam

BACKGROUND Liver cirrhosis (LC) is the final common pathway for all chronic liver diseases. It is a major cause of morbidity and mortality in adults globally. Systemic inflammation has now been proposed to play a crucial role in the natural history of progressive liver damage and is one of the main causes of precipitating compensated liver cirrhosis to decompensated state. Neutrophil to lymphocyte ratio (NLR) has been considered as an important inexpensive biomarker to indicate ongoing inflammation in patients with cirrhosis. The purpose of this study was to find out if there is any significant correlation between neutrophil to lymphocyte ratio and Child Turcotte Pugh score (CTP) among liver cirrhosis patients. METHODS We conducted a cross sectional study involving patients diagnosed with liver cirrhosis in Fakhruddin Ali Ahmed Medical College & Hospital, Barpeta, from November 2019 to January 2021. All patients were diagnosed based on clinical history, examination and ultrasound. The study enrolled 101 cirrhotic patients irrespective of aetiology. Total white blood cell (WBC) count, neutrophil count and lymphocyte count were recorded and neutrophil to lymphocyte count was calculated. Child Turcotte Pugh score was calculated by taking data from medical records of the patients. RESULTS Out of the 101 patients enrolled in our study, majority were males (78). A significant correlation was found between NLR and CTP score in liver cirrhosis patients. The patients with NLR < 3 showed mean CTP score of 6.1 ± 0.55, with NLR in between 3 to 6 showed CTP score of 8.2 ± 1.2 and with NLR > 6 showed mean CTP score of 11 ± 0.76 CONCLUSIONS NLR can be used as a single independent biomarker and a simpler scoring system for assessment of severity of liver cirrhosis but needs further studies and evaluation. KEYWORDS Neutrophil-to-Lymphocyte Ratio, Child-Turcotte-Pugh Score, Cirrhosis

Correlation of aspartate aminotransferase-to-platelet ratio index with child-turcotte-Pugh score and model for end stage liver disease score in patients of liver cirrhosis

Background: Though liver biopsy is considered to be a gold standard for the diagnosis and severity of liver cirrhosis, recently many non-invasive markers have come up for the same. In the current study, we investigated the correlation of aspartate aminotransferase-to-platelet ratio index with other severity scores of liver cirrhosis namely child-turcotte-Pugh score and model for end stage liver disease score.Methods: Fifty-one patients with cirrhosis, identified on the basis of abdomen ultrasonographic findings were enrolled in the study. APRI was calculated for every patient using the formula, (AST/upper limit of normal/platelet count;109/l)×100. The MELD score was calculated according to the original formula proposed by the Mayo clinic group: 3.8×loge (bilirubin; mg/dl)+11.2×loge(INR)+ 9.6×loge (creatinine; mg/dl)+6.4. CTP scoring was calculated based on the severity of hepatic encephalopathy, ascites, total bilirubin, albumin, and INR. Correlation of APRI with MELD and CTP score was established using Pearson correlation coefficient.Results: APRI scores correlated well with the severity of the cirrhosis. With the progression of the CTP class from A to C and with increase in the MELD score, increase in the APRI index was also observed.Conclusions: APRI showed positive correlation with CTP and MELD score.

A Pilot Study for the Prediction of Liver Function Related Scores Using Breath Biomarkers and Machine Learning

Liver function test is the first step to diagnose various liver diseases by measuring certain proteins and liver enzymes from the blood sample. After getting the required data of the clinical parameters from the blood test it is possible to calculate Child-Pugh (CTP), AST to PLT ratio (APRI) and Model for end-stage liver disease (MELD) clinical scores that help the doctors about the severity of the disease progression. Volatile organic compounds (VOCs) found in-breath and monitoring their concentration may be a prevailing method for disease diagnosis. In this work, Isoprene, Limonene, and Dimethyl sulphide (DMS) are considered as a potential breath biomarker related to liver disease. A dataset is designed, that includes the biomarkers concentration analysed from the breath sample before and after study subjects performed an exercise. Four regression methods are performed to predict the clinical scores using breath biomarkers data as features set by the machine learning techniques. Regression methods on the dataset for prediction are evaluated by mean absolute error and root mean square error. A significant difference observed for isoprene concentration (p<0.01) and for DMS concentration (p<0.0001) between liver patients and healthy subjects breath sample. Ensemble regression methods are found best suited for the dataset. The mean absolute error for CTP score is 0.07, for APRI score 0.1 and for MELD score 0.7. The R-square value between actual clinical score and predicted clinical score is found to be 0.78, 0.95, and 0.85 for CTP score, APRI score, and MELD score, respectively. These results suggest that breath biomarkers hold a promising approach for non-invasive test and mass screening related to liver disease.

Low Eosinophil Count : A Predictor of Inhospital Mortality in a Cohort of Cirrhosis Patients With Sepsis

Background and Aims:Eosinopenia has recently been associated with sepsis. Thus, eosinopenia can be used as a marker of the severity of sepsis and high mortality, which helps in early identification of high risk patients, so better management can be offered to such patients. Aim of the study was to assess whether Absolute Esoinophil Count (AEC) at the time of ICU admission can be used as a predictor of inhospital mortality in cirrhotics.Materials and Methods:This study was a retrospective cohort study. The study population included cirrhosis patients admitted in ICU and High Dependency Unit with sepsis and their absolute eosinophil counts were assessed on the day of hospital admission.Results: A total of 105 patients were enrolled in the study. Among the various parameters analyzed, MELD score, CTP score, Albumin levels, Total count, CRP, ESR, ALT, Bilirubin, Creatinine, Urea, SIRS and Absolute Eosinophil Count(AEC) were statistically significant in predicting the mortality. AUROC of AEC for predicting mortality was 0.881. Cutoff of AEC by Youden’s index was 110 cells/cumm (sensitivity 91.3%, specificity 89%, positive predictive value 87.5% and negative predictive value 93%) in predicting inhospital mortality. MELD AUROC was 0.78 with cut off of > 24 (sensitivity 89%, specificity 74.6%, positive predictive value 73% and negative predictive value 89%) to predict mortality. Conclusion:In critically ill cirrhosis patients, absolute eosinophil count less than 110 cells/cumm can predict inhospital mortality.

Maternal and fetal outcomes of patients with liver cirrhosis: a case-control study

Background We aimed to describe the characteristics and outcomes in pregnant women with liver cirrhosis, and identify the predictors of adverse events of mother and fetus. Methods Retrospectively collected mothers with liver cirrhosis in our center from 6/2010 to 6/2019. Women without liver cirrhosis were selected as a control in a 1:2 ratio. The primary assessment was the frequency of maternal and fetal adverse events. The secondary assessment was the adverse events in patients continuing pregnancy or not and the factors to predict the severe adverse events. Results Of 126 pregnancies enrolled, 29 pregnancies were terminated for worrying disease progression and 97 pregnancies continued. One hundred ninety-four pregnancies without liver cirrhosis were selected as control. At baseline, patients with liver cirrhosis have a lower level of platelet, hemoglobin, prothrombin activity, and a higher level of ALT, total Bilirubin, creatinine. Compared to control, patients with liver cirrhosis had a higher frequency of adverse events, including bleeding gums (7.2%vs. 1.0%), TBA elevation (18.6%vs.3.1%), infection (10.3%vs.0.5%), cesarean section (73.6%vs.49.5%), postpartum hemorrhage (13.8% vs 2.1%), blood transfusion (28.9% vs 2.1%), new ascites or aggravating ascites (6.2% vs.0%), MODS (7.2% vs.0.5%) and intensive care unit admissions (24.1% vs 1.1%). The incidence of severe maternal adverse events was also higher (32.0% vs 1.5%). Women who chose to terminated the pregnancy had less severe adverse events (3.4% vs.32.0%). A higher frequency of fetal/infants’ complications was observed in liver cirrhosis population than control, including newborn asphyxia (10.2% vs1.1%), low birth weight infant (13.6% vs. 2.6%). In patients who progressed into the third trimester, multivariable regression analysis demonstrated that severe adverse events were associated with a higher CTP score (OR 2.128, 95% CI [1.002, 4.521], p = 0.049). Wilson’s disease related liver cirrhosis has a better prognosis (OR = 0.009, 95% CI [0, 0.763], p = 0.038). Conclusions The incidence of the adverse events was significantly increased in pregnancies complicated by cirrhosis. The predictor of severe adverse events is higher CTP score. Wilson’s disease induced liver cirrhosis have a better prognosis. Timely termination of pregnancy during the first trimester may avoid the incidence of severe adverse events.