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.

Levovist ultrasonography imaging in intracystic hemorrhage of simple liver cyst

The differential diagnosis between intracystic hemorrhage and cystadenocarcinoma of the liver is often difficult even with the use of various imaging modalities. A 73-year-old woman was admitted to our hospital with the complaint of right upper quadrant pain. Ultrasonography (US) demonstrated a heterogeneous echogenic cyst measuring 11 cm × 8 cm in size in S2 of the liver, indicated intracystic hemorrhage of simple liver cyst or cystadenocarcinoma, but the differential diagnosis was considerably difficult. Levovist (Schering, Berlin, Germany) US revealed no enhancement of the intracystic structures, suggesting a clot in the case of intracystic hemorrhage. An operation was performed and the resected lesion showed a solitary benign liver cyst, measuring 5.5 cm × 4.7 cm × 8.5 cm containing a large blood clot. The patient had an uneventful recovery after the surgery. Levovist US may play an important role in discrimination between intracystic hemorrhage of simple hepatic cysts and cystadenocarcinoma of the liver.

Shape of Barrett's epithelium is associated with prevalence of erosive esophagitis

AIM:To test the hypothesis that the shape and length of Barrett's epithelium are associated with prevalence of erosive esophagitis.METHODS:A total study population comprised 869 patients who underwent endoscopy during a health checkup at our hospital.The presence and extent of Barrett's epithelium were diagnosed based on the Prague C & M Criteria.We originally classified cases of Barrett's epithelium into two types based on its shape,namely,flamelike and lotus-like Barrett's epithelium,and into two groups based on its length,its C extent < 2 cm,and ≥ 2 cm.Correlation of shape and length of Barrett's epithelium with erosive esophagitis was examined.RESULTS:Barrett's epithelium was diagnosed in 374 cases(43%).Most of these were diagnosed as shortsegment Barrett's epithelium.The prevalence of erosive esophagitis was significantly higher in subjects with flame-like than lotus-like Barrett's epithelium,and in those with a C extent of ≥ 2 cm than < 2 cm.CONCLUSION:Flame-like rather than lotus-like Barrett's epithelium,and Barrett's epithelium with a longer segment were more strongly associated with erosive esophagitis.

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.

Effect of sumatriptan on gastric emptying:A crossover study using the BreathID system

AIM:To determine the effect of oral sumatriptan on gastric emptying using a continuous 13 C breath test(BreathID system).METHODS:Ten healthy male volunteers participated in this randomized,2-way crossover study.The subjects fasted overnight and were randomly assigned to receive a test meal(200 kcal/200 mL) 30 min after pre-medication with sumatriptan 50 mg(sumatriptan condition),or the test meal alone(control condition).Gastric emptying was monitored for 4 h after administration of the test meal by the 13 C-acetic acid breath test performed continually using the BreathID system.Then,using Oridion Research Software(β version),the time taken for emptying of 50% of the labeled meal(T 1/2) similar to the scintigraphy lag time for 10% emptying of the labeled meal(T lag),the gastric emptying coefficient(GEC),and the regression-estimated constants(β and κ) were calculated.The statistical significance of any differences in the parameters were analyzed using Wilcoxon's signed-rank test.RESULTS:In the sumatriptan condition,significant differences compared with the control condition were found in T 1/2 [median 131.84 min(range,103.13-168.70) vs 120.27 min(89.61-138.25);P = 0.0016],T lag [median 80.085 min(59.23-125.89) vs 61.11 min(39.86-87.05);P = 0.0125],and β [median 2.3374(1.6407-3.8209) vs 2.0847(1.4755-2.9269);P = 0.0284].There were no significant differences in the GEC or κ between the 2 conditions.CONCLUSION:This study showed that oral sumatriptan significantly delayed gastric emptying of a liquid meal.

Epidemiology and Management of Drug-induced Liver Injury: Importance of the Updated RUCAM

Drug-induced liver injury(DILI)is a major cause of acute liver injury,liver failure,and liver transplantation worldwide.In recent years,immune checkpoint inhibitors have become widely used.This has led to an increase in DILI,for which pathophysiology and management methods differ significantly from the past.As the number of cases of acute liver injury and liver transplantation due to DILI is expected to increase,information about a DILI is becoming more valuable.DILI is classified into two types according to its etiology:intrinsic DILI,in which the drug or its metabolites cause liver damage that is dose-dependent and predictable;and idiosyncratic DILI,in which liver damage is also dose-independent but unpredictable.In addition,depending on the course of the disease,chronic DILI or drug-induced autoimmune hepatitis may be present.The number of DILI cases caused by antimicrobial agents is decreasing,whereas that caused by drugs for malignant tumors and health foods is increasing.The Roussel Uclaf Causality Assessment Method is widely used to assess causality in DILI.Liver injury is a type of immune-related adverse event.The pattern of hepatic injury in immune-related adverse events is mostly hepatocellular,but mixed type and bile stasis have also been reported.Sclerosing cholangitis caused by immune checkpoint inhibitors has also been reported as a unique type of injury.Treatment mainly comprises withdrawal of immune checkpoint inhibitors and steroid administration;however,mycophenolate mofetil may be considered if the disease is refractory to steroids.

Tropifexor,a selective non-acid farnesoid X receptor agonist,improved nonalcoholic steatohepatitis in a phase 2 trial,but several issues remain to be resolved

As obesity continues to escalate worldwide,nonalcoholic fatty liver disease(NAFLD)has emerged as the most prevalent form of liver disease,with a reported global prevalence of 30.1%(1).The prevalence of NAFLD,which was around 25%in the 1990s,has been increasing year by year in recent years and has exceeded 35%in the past few years(1).The spectrum of disease includes nonalcoholic fatty liver(NAFL),characterized by macrovesicular hepatic steatosis that may be accompanied by mild inflammation,and nonalcoholic steatohepatitis(NASH),which is additionally characterized by the presence of inflammation and cellular injury(2).

Early effects of oral administration of omeprazole and roxatidine on intragastric pH

Objective:The ideal medication for the treatment of acid-related diseases,e.g.,peptic ulcers,stress-related gastric bleeding,functional dyspepsia,and gastroesophageal reflux disease,should have a rapid onset of action to promote hemostasis and relieve the symptoms.The aim of our study was to investigate the inhibitory effects on gastric acid secretion of a single oral administration of a proton pump inhibitor,omeprazole 20 mg,and an H2-receptor antagonist,roxatidine 75 mg.Methods:Ten Helicobacter pylori-negative male subjects participated in this randomized,two-way crossover study.Intragastric pH was monitored continuously for 6 h after single oral administration of omeprazole 20 mg and roxatidine 75 mg.Each administration was separated by a 7-d washout period.Results:During the 6-h study period,the average pH after administration of roxatidine was higher than that after administration of omeprazole(median:4.45 vs.2.65;P=0.0367).Also during the 6-h study period,a longer duration of maintenance at pH above 2,5,and 6 was observed after administration of roxatidine 75 mg than after administration of omeprazole 20 mg(median:90.6% vs.55.2%,P=0.0284;43.7% vs.10.6%,P=0.0125;40.3% vs.3.3%,P=0.0125;respectively).Conclusions:In Helicobacter pylori-negative healthy male subjects,oral administration of roxatidine 75 mg increased the intragastric pH more rapidly than that of omeprazole 20 mg.

Pan-peroxisome proliferator-activated receptor agonist lanifibranor as a dominant candidate pharmacological therapy for nonalcoholic fatty liver disease

As obesity incidence increases worldwide,nonalcoholic fatty liver disease(NAFLD)has become the most common form of liver disease,with a reported global prevalence of 25.2%(1).Nonalcoholic steatohepatitis(NASH)is a severe form of NAFLD.However,the precise natural history of NAFLD/NASH remains unclear.NASH is rapidly becoming the leading cause of end-stage liver disorders and liver transplants and is associated with increased cardiovascular disease risk(2).As a result,it poses critical health issues globally from both medical and socioeconomic perspectives.

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).