Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization?

AIM:To evaluate the effectiveness of hepatic arterial infusion chemotherapy(HAIC) for advanced hepatocellular carcinoma(HCC) resistant to transarterial chemoembolization(TACE).METHODS:This study was conducted on 42 patients who received HAIC for advanced HCC between 2001and 2010 at our hospital.5-fluorouracil(5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir.Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU.The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010(written in Japanese);one group of patients who did not fulfill the criteria for TACE resistance(group A,n = 23),and another group who fulfilled the criteria for TACE resistance(group B,n = 19).We compared the outcomes in terms of the response and survival rates between the two groups.RESULTS:Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B(response rate:48% vs 16%,P = 0.028,tumor suppression rate:87% vs 53%,P = 0.014).Furthermore,both the progression-free survival rate and survival time were significantly superior in group A than in group B(3-,6-,12-,and 24-mo = 83%,70%,29% and 20% vs 63%,42%,16% and 0%,respectively,P = 0.040,and 9.8 mo vs 6.2 mo,P = 0.040).A multivariate analysis(Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival(P = 0.007).CONCLUSION:HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE.Other tools for treatment,i.e.,molecular-targeting agents may be considered for these cases.

Simple scoring system for predicting cirrhosis in nonalcoholic fatty liver disease

AIM:To investigate a simple noninvasive scoring system for predicting liver cirrhosis in nonalcoholic fatty liver disease(NAFLD)patients.METHODS:A total of 1048 patients with liver-biopsyconfirmed NAFLD were enrolled from nine hepatology centers in Japan(stage 0,216;stage 1,334;stage 2,270;stage 3,190;stage 4,38).The weight and height of the patients were measured using a calibrated scale after requesting the patients to remove their shoes and any heavy clothing.Venous blood samples were obtained in the morning after the patients had fasted overnight for 12 h.Laboratory evaluation was performed in all patients.Statistical analysis was conducted using SPSS version 12.0.Continuous variables were expressed as mean±SD.RESULTS:The optimal cutoff value of platelet count,serum albumin,and aminotransferase/alanine aminotransferase ratio(AAR)was set at<15.3 104/μL,<4.0g/dL,and>0.9,respectively,by the receiver operating characteristic curve.These three variables were combined in an unweighted sum(platelet count=1 point,serum albumin=1 point,AAR=1 point)to form an easily calculated composite score for predicting cirrhosis in NAFLD patients,called the PLALA(platelet,albumin,AAR)score.The diagnosis of PLALA≥2 had sufficient accuracy for detecting liver cirrhosis in NAFLD patients.CONCLUSION:The PLALA score may be an ideal scoring system for detecting cirrhosis in NAFLD patients with sufficient accuracy and simplicity to be considered for clinical use.

Quantitative multiparametric magnetic resonance imaging can aid non-alcoholic steatohepatitis diagnosis in a Japanese cohort

BACKGROUND Non-invasive assessment of non-alcoholic steatohepatitis(NASH)is increasing in desirability due to the invasive nature and costs associated with the current form of assessment;liver biopsy.Quantitative multiparametric magnetic resonance imaging(mpMRI)to measure liver fat(proton density fat fraction)and fibroinflammatory disease[iron-corrected T1(cT1)],as well as elastography techniques[vibration-controlled transient elastography(VCTE)liver stiffness measure],magnetic resonance elastography(MRE)and 2D Shear-Wave elastography(SWE)to measure stiffness and fat(controlled attenuated parameter,CAP)are emerging alternatives which could be utilised as safe surrogates to liver biopsy.AIM To evaluate the agreement of non-invasive imaging modalities with liver biopsy,and their subsequent diagnostic accuracy for identifying NASH patients.METHODS From January 2019 to February 2020,Japanese patients suspected of NASH were recruited onto a prospective,observational study and were screened using noninvasive imaging techniques;mpMRI with LiverMultiScan®,VCTE,MRE and 2DSWE.Patients were subsequently biopsied,and samples were scored by three independent pathologists.The diagnostic performances of the non-invasive imaging modalities were assessed using area under receiver operating characteristic curve(AUC)with the median of the histology scores as the gold standard diagnoses.Concordance between all three independent pathologists was further explored using Krippendorff’s alpha(a)from weighted kappa statistics.RESULTS N=145 patients with mean age of 60(SD:13 years.),39%females,and 40%with body mass index≥30 kg/m2 were included in the analysis.For identifying patients with NASH,MR liver fat and cT1 were the strongest performing individual measures(AUC:0.80 and 0.75 respectively),and the mpMRI metrics combined(cT1 and MR liver fat)were the overall best non-invasive test(AUC:0.83).For identifying fibrosis≥1,MRE performed best(AUC:0.97),compared to VCTE-liver stiffness measure(AUC:0.94)and 2D-SWE(AUC:0.94).For assessment of steatosis≥1,MR liver fat was the best performing non-invasive test(AUC:0.92),compared to controlled attenuated parameter(AUC:0.75).Assessment of the agreement between pathologists showed that concordance was best for steatosis(a=0.58),moderate for ballooning(a=0.40)and fibrosis(a=0.40),and worst for lobular inflammation(a=0.11).CONCLUSION Quantitative mpMRI is an effective alternative to liver biopsy for diagnosing NASH and non-alcoholic fatty liver,and thus may offer clinical utility in patient management.

Gamma-glutamyl transferase and cardiovascular risk in nonalcoholic fatty liver disease:The Gut and Obesity Asia initiative

BACKGROUND Gamma-glutamyl transferase(GGT)is associated with the risk of cardiovascular disease(CVD)in the general population.AIM To identify the association of baseline GGT level and QRISK2 score among patients with biopsy-proven nonalcoholic fatty liver disease(NAFLD).METHODS This was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia(referred to as“GO ASIA”)workgroup.All patients with available baseline GGT levels and all 16 variables for the QRISK2 calculation(QRISK2-2017;developed by researchers at the United Kingdom National Health Service;https://qrisk.org/2017/;10-year cardiovascular risk estimation)were included and compared to healthy controls with the same age,sex,and ethnicity.Relative risk was reported.QRISK2 score>10%was defined as the high-CVD-risk group.Fibrosis stages 3 and 4(F3 and F4)were considered advanced fibrosis.RESULTS A total of 1122 patients(73%)had complete data and were included in the final analysis;314(28%)had advanced fibrosis.The median age(interquartile range[IQR])of the study population was 53(44-60)years,532(47.4%)were females,and 492(43.9%)were of Chinese ethnicity.The median 10-year CVD risk(IQR)was 5.9%(2.6-10.9),and the median relative risk of CVD over 10 years(IQR)was 1.65(1.13-2.2)compared to healthy individuals with the same age,sex,and ethnicity.The high-CVD-risk group was significantly older than the low-risk group(median[IQR]:63[59-67]vs 49[41-55]years;P<0.001).Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk(P<0.001).Median GGT level was not different between the two groups(GGT[U/L]:Median[IQR],high risk 60[37-113]vs low risk 66[38-103],P=0.56).There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score(r=0.02).CONCLUSION The CVD risk of NAFLD patients is higher than that of healthy individuals.Baseline GGT level cannot predict CVD risk in NAFLD patients.However,advanced fibrosis is a predictor of a high CVD risk.

Nonalcoholic fatty liver disease with advanced fibrosis as a multi-systemic disease: proceed with caution

Accompanying the current epidemics of metabolic syndrome(MS)and obesity caused by westernization of lifestyles,the incidences of non-alcoholic fatty liver disease(NAFLD)and non-alcoholic steatohepatitis(NASH)have been increasing worldwide over the last few decades(1).Now,NAFLD has a global prevalence estimated at 25%of the world population,with some geographical;the highest prevalences are in the South America and Middle East.Namely,NAFLD has become recognized as the most common liver disease worldwide(2).

Will the magnetic resonance imaging proton density fat fraction replace liver biopsy as the gold standard for detecting steatosis?

Accompanied with the ongoing epidemics of obesity and metabolic syndrome arising from the westernization of lifestyles, the incidence of nonalcoholic fatty liver disease (NAFLD) has been getting higher worldwide in the last decades (1).