Non-invasive diagnosis of hepatitis B virus-related cirrhosis

Chronic hepatitis B(CHB)infection is a major public health problem associated with significant morbidity and mortality worldwide.Twenty-three percent of patients with CHB progress naturally to liver cirrhosis,which was earlier thought to be irreversible.However,it is now known that cirrhosis can in fact be reversed by treatment with oral anti-nucleotide drugs.Thus,early and accurate diagnosis of cirrhosis is important to allow an appropriate treatment strategy to be chosen and to predict the prognosis of patients with CHB.Liver biopsy is the reference standard for assessment of liver fibrosis.However,the method is invasive,and is associated with pain and complications that can be fatal.In addition,intra-and inter-observer variability compromises the accuracy of liver biopsy data.Only small tissue samples are obtained and fibrosis is heterogeneous in such samples.This confounds the two types of observer variability mentioned above.Such limitations have encouraged development of non-invasive methods for assessment of fibrosis.These include measurements of serum biomarkers of fibrosis;and assessment of liver stiffness via transient elastography,acoustic radiation force impulse imaging,real-time elastography,or magnetic resonance elastography.Although significant advances have been made,most work to date has addressed the diagnostic utility of these techniques in the context of cirrhosis caused by chronic hepatitis C infection.In the present review,we examine the advantages afforded by use of non-invasive methods to diagnose cirrhosis in patients with CHB infections and the utility of such methods in clinical practice.

Characterization of focal liver masses using acoustic radiation force impulse elastography

AIM:To investigate the diagnostic performance of acoustic radiation force impulse(ARFI) elastography for characterizing focal liver mass by quantifying their stiffness.METHODS:This prospective study included 62 patients with a focal liver mass that was well visualized on conventional ultrasonography performed in our institution from February 2011 to November 2011.Among them,12 patients were excluded for ARFI measurement failure due to a lesion that was smaller than the region of the interest and at an inaccessible location(deeper than 8 cm)(n = 7) or poor compliance to hold their breath as required(n = 5).Finally,50 patients with valid ARFI measurements were enrolled.If a patient had multiple liver masses,only one mass of interest was chosen.The masses were diagnosed by histological examination or clinical diagnostic criteria.During ultrasonographic evaluation,stiffness,expressed as velocity,was checked 10 times per focal liver mass and the surrounding liver parenchyma.RESULTS:After further excluding three masses that were non-diagnostic on biopsy,a total of 47 focal mass lesions were tested,including 39(83.0%) malignant masses [24 hepatocellular carcinomas(HCC),seven cholangiocellular carcinomas(CCC),and eight liver metastases] and eight(17.0%) benign masses(five hemangiomas and three focal nodular hyperplasias,FNH).Thirty-seven(74.0%) masses were confirmed by histological examination.The mean velocity was 2.48 m/s in HCCs,1.65 m/s in CCCs,2.35 m/s in metastases,1.83 m/s in hemangiomas,and 0.97 m/s in FNHs.Although considerable overlap was still noted between malignant and benign masses,significant differences in ARFI values were observed between malignant and benign masses(mean 2.31 m/s vs 1.51 m/s,P = 0.047),as well as between HCCs and benign masses(mean 2.48 m/s vs 1.51 m/s,P = 0.006).The areas under the receiver operating characteristics curves(AUROC) for discriminating the malignant masses from benign masses was 0.724(95%CI,0.566-0.883,P = 0.048),and the AUROC for discriminating HCCs from benign masses was 0.813(95%CI,0.649-0.976,P = 0.008).To maximize the sum of sensitivity and specificity,an ARFI value of 1.82 m/s was selected as the cutoff value to differentiate malignant from benign liver masses.Furthermore,the cutoff value for distinguishing HCCs from benign masses was also determined to be 1.82 m/s.The diagnostic performance of the sum of the ARFI values for focal liver masses and the surrounding liver parenchyma to differentiate liver masses improved(AUROC = 0.853;95%CI,0.745-0.960;P = 0.002 in malignant liver masses vs benign ones and AUROC = 0.948;95%CI,0.896-0.992,P < 0.001 in HCCs vs benign masses).CONCLUSION:ARFI elastography provides additional information for the differential diagnosis of liver masses.However,our results should be interpreted in clinical context,because considerable overlap in ARFI values existed among liver masses.

Comparison of the efficacy and safety of sedation between dexmedetomidine-remifentanil and propofol-remifentanil during endoscopic submucosal dissection

AIM: To compare the efficacy and safety of sedation protocols for endoscopic submucosal dissection(ESD) between dexmedetomidine-remifentanil and propofolremifentanil.METHODS: Fifty-nine patients scheduled for ESD were randomly allocated into a dexmedetomidineremifentanil(DR) group or a propofol-remifentanil(PR) group. To control patient anxiety, dexmedetomidine or propofol was infused to maintain a score of 4-5 on the Modified Observer's Assessment of Alertness/Sedation scale. Remifentanil was infused continuously at a rate of 6 μg/kg per hour in both groups. The ease of advancing the scope into the throat, gastric motility grading, and satisfaction of the endoscopist and patient were assessed. Hemodynamic variables and hypoxemic events were compared to evaluate patient safety.RESULTS: Demographic data were comparable between the groups. The hemodynamic variables and pulse oximetry values were stable during the procedure in both groups despite a lower heart rate in the DR group. No oxygen desaturation events occurred in either group. Although advancing the scope into the throat was easier in the PR group("very easy" 24.1% vs 56.7%, P = 0.010), gastric motility was moresuppressed in the DR group("no + mild" 96.6% vs 73.3%, P = 0.013). The endoscopists felt that the procedure was more favorable in the DR group("very good + good" 100% vs 86.7%, P = 0.042), whereas patient satisfaction scores were comparable between the groups. En bloc resection was performed 100% of the time in both groups, and the complete resection rate was 94.4% in the DR group and 100% in the PR group(P = 0.477). CONCLUSION: The efficacy and safety of dexmedetomidine and remifentanil were comparable to propofol and remifentanil during ESD. However, the endoscopists favored dexmedetomidine perhaps due to lower gastric motility.

Prediction models of hepatocellular carcinoma development in chronic hepatitis B patients

Chronic hepatitis B virus(HBV) infection is a major cause of cirrhosis and hepatocellular carcinoma(HCC). Applying the same strategies for antiviral therapy and HCC surveillance to all chronic hepatitis B(CHB) patients would be a burden worldwide. To properly manage CHB patients, it is necessary to identify and classify the risk for HCC development in such patients. Several HCC risk scores based on risk factors such as cirrhosis, age, male gender, and high viral load have been used, and have negative predictive values of ≥ 95%. Most of these have been derived from, and internally validated in, treatment-na?ve Asian CHB patients. Herein, we summarized various HCC prediction models, including IPM(Individual Prediction Model), CU-HCC(Chinese University-HCC), GAG-HCC(Guide with Age, Gender, HBV DNA, Core Promoter Mutations and Cirrhosis-HCC), NGM-HCC(NomogramHCC), REACH-B(Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B), and Page-B score. To develop a noninvasive test of liver fibrosis, we also introduced a new scoring system that uses liver stiffness values from transient elastography, including an LSM(Liver Stiffness Measurement)-based model, LSM-HCC, and mR EACH-B(modified REACH-B).

Comparison of hydrocolonic sonograpy accuracy in preoperative staging between colon and rectal cancer

AIM:To compare the accuracy of hydrocolonic sonography (HUS) in determining the depth of invasion (T stage) in colon and rectal cancer. METHODS:A total of 1000-2000 mL of saline was instilled per rectum using a system for barium enemas,and then ultrasonography was conducted by a SSA-270A (Toshiba Co,Japan) sonolayer unit with a 3.75 MHz for 17 patients with colon cancer and 13 patients with rectal cancer before operation.After operation,T stage in HUS was compared with postoperative histological findings. RESULTS:Overall,the accuracy of T stage was 70%.It was 88% in colon cancer and 46% in rectal cancer.In evaluating nodal state,the accuracy of HUS was low in both colon (71%) and rectal cancers (46%) compared with conventional CT or MRI.The overall accuracy of N staging was 60%. CONCLUSION:HUS is valuable to evaluate the depth of invasion in colon cancer,but is less valuable in rectal cancer.Because HUS is low-cost,noninvasive,and readily available at any place,this technique seems to be useful to determine the preoperative staging in colon cancer,but not in rectal cancer.

Role of surgical resection for multiple hepatocellular carcinomas

AIM:To clarify the role of surgical resection for multiple hepatocellular carcinomas(HCCs)compared to transarterial chemoembolization(TACE)and liver transplantation(LT). METHODS:Among the HCC patients who were managed at Yonsei University Health System between January 2003 and December 2008,160 patients who met the following criteria were retrospectively enrolled:(1) two or three radiologically diagnosed HCCs;(2)no radiologic vascular invasion;(3)Child-Pugh class A;(4) main tumor smaller than 5 cm in diameter;and(5) platelet count greater than 50 000/mm3.Long-term outcomes were compared among the following three treatment modalities:surgical resection or combined radiofrequency ablation(RFA)(n=36),TACE(n=107), and LT(n=17).The survival curves were computed using the Kaplan-Meier method and compared with a log-rank test.To identify the patients who gained a survival benefit from surgical resection,we also investigated prognostic factors for survival following surgical resection.Multivariate analyses of the prognostic factors for survival were performed using the Cox proportional hazard model. RESULTS:The overall survival(OS)rate was significantly higher in the surgical resection group than in the TACE group(48.1%vs 28.9%at 5 years,P<0.005). LT had the best OS rate,which was better than that of the surgical resection group,although the difference was not statistically significant(80.2%vs 48.1%at 5 years,P=0.447).The disease-free survival rates were also significantly higher in the LT group than in the surgical resection group(88.2%vs 11.2%at 5 years, P<0.001).Liver cirrhosis was the only significant prognostic factor for poor OS after surgical resection. Clinical liver cirrhosis rates were 55.6%(20/36)in the resection group and 93.5%(100/107)in the TACE group.There were 19 major and 17 minor resections. En bloc resection was performed in 23 patients,multisite resection was performed in 5 patients,and combined resection with RFA was performed in 8 patients. In the TACE group,only 34 patients(31.8%)were recorded as having complete remission after primary TACE.Seventy-two patients(67.3%)were retreated with repeated TACE combined with other therapies. In patients who underwent surgical resection,the 16 patients who did not have cirrhosis had higher 5-year OS and disease-free survival rates than the 20 patients who had cirrhosis(80.8%vs 25.5%5-year OS rate, P=0.006;22.2%vs 0%5-year disease-free survival rate,P=0.048).Surgical resection in the 20 patients who had cirrhosis did not provide any survival benefit when compared with TACE(25.5%vs 24.7%5-year OS rate,P=0.225).Twenty-nine of the 36 patients who underwent surgical resection experienced recur-rence.Of the patients with cirrhosis,80%(16/20) were within the Milan criteria at the time of recurrence CONCLUSION:Among patients with two or three HCCs, no radiologic vascular invasion,and tumor diameters≤ 5 cm,surgical resection is recommended only in those without cirrhosis.

Treatment outcome of localized Helicobacter pylori-negative low-grade gastric MALT lymphoma

AIM: To investigate treatment outcome of Helicobacter pylori (H.pylori )-negative low-grade gastric mucosaassociated lymphoid tissue (MALT) lymphoma.METHODS: In this study,we retrospectively reviewed the clinical outcome and clinicopathologic factors of stage Ⅰ E H.pylori -negative low-grade gastric MALT lymphoma cases from August 1998 to June 2009.RESULTS: A total of eleven patients with H.pylori -negative low-grade gastric MALT lymphoma were enrolled in the study and received anti-H.pylori eradication treatment and/or radiotherapy or excisional therapy.Complete remission (CR) of gastric MALT lymphoma was achieved in all patients.The time to CR was 1-66 mo (median,1 mo).CONCLUSION: Eradication therapy may be offered as an initial treatment option even in cases of localized H.pylori -negative gastric MALT lymphoma.

Quantification of HBsAg:Basic virology for clinical practice

Hepatitis B surface antigen (HBsAg) is produced and secreted through a complex mechanism that is still not fully understood. In clinical fields, HBsAg has long served as a qualitative diagnostic marker for hepatitis B virus infection. Notably, advances have been made in the development of quantitative HBsAg assays, which have allowed viral replication monitoring, and there is an opportunity to make maximal use of quantitative HBsAg to elucidate its role in clinical fields. Yet, it needs to be underscored that a further understanding of HBsAg, not only from clinical point of view but also from a virologic point of view, would enable us to deepen our insights, so that we could more widely expand and apply its utility. It is also important to be familiar with HBsAg variants and their clinical consequences in terms of immune escape mutants, issues resulting from overlap with corresponding mutation in the P gene, and detection problems for the HBsAg variants. In this article, we review current concepts and issues on the quantification of HBsAg titers with respect to their biologic nature, method principles, and clinically relevant topics.

Survival outcome of patients with spontaneously ruptured hepatocellular carcinoma treated surgically or by transarterial embolization

AIM: To evaluate clinical outcomes of patients that underwent surgery, transarterial embolization (TAE), or supportive care for spontaneously ruptured hepatocellular carcinoma (HCC). METHODS: A consecutive 54 patients who diagnosed as spontaneously ruptured HCC at our institution between 2003 and 2012 were retrospectively enrolled. HCC was diagnosed based on the diagnostic guidelines issued by the 2005 American Association for the Study of Liver Diseases. HCC rupture was defined as disruption of the peritumoral liver capsule with enhanced fluid collection in the perihepatic area adjacent to the HCC by dynamic liver computed tomography, and when abdominal paracentesis showed an ascitic red blood cell count of > 50000 mm 3 /mL in bloody fluid. RESULTS: Of the 54 patients, 6 (11.1%) underwent surgery, 25 (46.3%) TAE, and 23 (42.6%) supportive care. The 2-, 4and 6-mo cumulative survival rates at 2, 4 and 6 mo were significantly higher in the surgery (60%, 60% and 60%) or TAE (36%, 20% and 20%) groups than in the supportive care group (8.7%, 0% and 0%), respectively (each, P < 0.01), and tended to be higher in the surgical group than in the TAE group. Multivariate analysis showed that serum bilirubin (HR = 1.09, P < 0.01), creatinine (HR = 1.46, P = 0.04), and vasopressor requirement (HR = 2.37, P = 0.02) were significantly associated with post-treatment mortality, whereas surgery (HR = 0.41, P < 0.01), and TAE (HR = 0.13, P = 0.01) were inversely associated with posttreatment mortality. CONCLUSION: Post-treatment survival after surgery or TAE was found to be better than after supportive care, and surgery tended to provide better survival benefit than TAE.

Prognosis of hepatocellular carcinoma expressing cytokeratin 19:Comparison with other liver cancers

AIM:To investigate whether expressing biliary phenotype predicted poor outcome after the surgical treatment in primary liver cancers. METHODS:Out of 204 patients that underwent liver resection due to hepatocellular carcinoma (HCC), liver specimens of 70 patients with HCC were evaluated for biliary components by cytokeratin (CK) 19 immunostain (CK19 - HCC and CK19 + HCC). CK19 positivity was defined as membranous and/or cytoplasmic expression in ≥ 5% of tumor cells with moderate or strong intensity. Patients with other primary liver cancers, such as com- bined HCC and cholangiocarcinoma (cHCC-CC), intrahe- patic cholangiocarcinoma (ICC) who received curative liver resection, were also included in the study. Clinical characteristics of CK19-HCC and CK19 + HCC patients, including survival outcome after curative liver resection, were compared with that of cHCC-CC and ICC patients. RESULTS: The overall survival (OS) rate of CK19 - HCC(n = 49) after the curative surgical treatment was 90.7%, and 80.4% at 1 and 5 years after the resection. OS rate of CK19 + HCC (n = 21) was 74.3%, 28.9% and OS rate of cHCC-CC (n = 22) was 66.7%, 32.2% at 1 and 5 years after the surgery. For ICC (n = 19), 1 and 5-year-OS rate was 50.2% and 14.3% after the cura-tive resection. The OS rates of CK19 + HCC and cHCC-CC were significantly lower than that of CK19-HCC, but higher than the OS rate of ICC (P = 0.000). There was no statistically significant difference in OS rate between CK19 + HCC and cHCC-CC. The disease free survival (DFS) rate of CK19-HCC was 72.0% and 54.5% at 1 and 3 years after the surgical treatment. DFS rate of CK19 + HCC was 53.3%, 34.3% and DFS rate of cHCC- CC was 51.5%, 39.2% at 1 and 3 years after the resection. For ICC, 1 and 3-year-DFS rate was 28.0% and 14.0% after the curative resection. DFS rate of CK19-HCC was significantly higher than that of ICC (P = 0.017), but marginally higher than DFS rate of either CK19 + HCC or cHCC-CC (P = 0.097, P = 0.089, respec-tively). Predictors of outcome after the surgery of primary liver cancer were pathology of the resected mass, existence of microvascular invasion and accompanying satellite nodule. CONCLUSION: Primary liver cancers with biliary components tended to show poorer surgical outcome. This suggested that immuno-phenotype of liver cancers was as important as their morphological classification.

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer

AIM To directly compare the efficacy and toxicity of standarddose FOLFIRINOX(sFOLFIRINOX) and modified-dose FOLFIRINOX(mFOLFIRINOX, 75% of standard-dose) for pancreatic cancer.METHODS One hundred and thirty pancreatic cancer patients who received sFOLFIRINOX(n = 88) or mFOLFIRINOX(n = 42) as their first-line chemotherapy from January 2013 to July 2017 were retrospectively reviewed. For efficacy analysis, the objective response rate(ORR),disease control rate(DCR), progression-free survival(PFS), and overall survival(OS) were evaluated and compared using Pearson's chi-square test, Kaplan-Meier plot and log-rank test. The adverse events(AEs) were evaluated, and severe(≥ grade 3) AEs rates of the two groups were compared for toxicity analysis.RESULTS The mFOLFIRINOX group included more female patients(30.7% vs 57.1%; P = 0.004) and older patients [age(median), 57 vs 63.5; P = 0.018] than the sFOLFIRINOX group. In the efficacy analysis, the ORR and DCR were not significantly different between the two groups(ORR: 39.8% vs 35.7%; P = 0.656; DCR: 80.7% vs 83.3%; P = 0.716). The median PFS and OS were also not different between the groups(PFS: 8.7 mo vs 8.1 mo, P = 0.272; OS: 13.9 mo vs 13.7 mo, P = 0.476). In the safety analysis with severe AEs, the rates of neutropenia(83.0% vs 66.7%; P = 0.044), anorexia(48.9% vs 28.6%; P = 0.029) and diarrhea(13.6% vs 0.0%; P = 0.009) were markedly lower in the mFOLFIRINOX group.CONCLUSION m FOLFIRINOX showed comparable efficacy but better safety compared to sFOLFIRINOX. If clinically necessary, initiating FOLFIRINOX with 75% of the standard-dose can alleviate toxicity concerns without compromising efficacy.

Successful hemostasis of intractable rectal variceal bleeding using variceal embolization

Portal hypertension causes portosystemic shunting along the gastrointestinal tract,resulting in gastrointestinalvarices.Rectal varices and their bleeding is a rare complication,but it can be fatal without appropriate treatment.However,because of its rarity,no established treatment strategy is yet available.In the setting of intractable rectal variceal bleeding,a transjugular intravenous portosystemic shunt can be a treatment of choice to enable portal decompression and thus achieve hemostasis.However,in the case of recurrent rectal variceal bleeding despite successful transjugular intravenous portosystemic shunt,alternative measures to control bleeding are required.Here,we report on a patient with liver cirrhosis who experienced recurrent rectal variceal bleeding even after successful transjugular intravenous portosystemic shunt and was successfully treated with variceal embolization.

Diagnostic evaluation of endoscopic ultrasonography with submucosal saline injection for differentiating between T1a and T1b early gastric cancer

BACKGROUND Endoscopic ultrasonography(EUS)has become a reliable method for predicting the invasion depth of early gastric cancer(EGC).However,diagnostic accuracy of EUS is affected by several factors.In particular,it is difficult to differentiate between T1a and T1b EGC through EUS.AIM To confirm whether submucosal saline injection(SSI)could improve the accuracy of EUS in distinguishing T1a and T1b lesions in EGC.METHODS Twenty-four patients with EGC were examined by EUS and subsequently by SSI combined EUS to compare the degree of tumor invasion.Then,they underwent endoscopic or surgical resection within 7 d.The diagnostic accuracy of EUS and SSI combined EUS was evaluated based on the final pathological findings postoperatively.Saline injected into the submucosa acted as an echoic contrast enhancing agent and had the effect of distinguishing the mucosal and submucosal layers clearly.RESULTS Of total 24 patients,23 were diagnosed with EGC(T1 cancer:13 as T1a,and 10 as T1b).Standard EUS identified 6 of 13 T1a cancer patients and 3 of 10 T1b cancer patients.Whereas,EUS-SSI identified 12 of 13 T1a cancer patients and 6 of 10 T1b cancer patients.In this study,SSI combined EUS was more accurate than EUS alone in diagnosing T1a and T1b lesions of EGC(75.0%and 37.5%,respectively).CONCLUSION SSI improved the diagnostic accuracy of EUS in distinguishing between the T1a and T1b stages in EGC.

Obesity is an important determinant of severity in newly defined metabolic dysfunction-associated fatty liver disease

Background: The recently proposed definition of metabolic dysfunction-associated fatty liver disease(MAFLD) is based on the co-existence of hepatic steatosis with other metabolic disorders, including obesity and metabolic risk abnormalities such as hyperglycemia, high blood pressure and dyslipidemia. This study aimed to assess MAFLD severity according to the presence of metabolic abnormalities and obesity. Methods: Using transient elastography, hepatic steatosis and fibrosis severity were assessed by measuring the controlled attenuation parameter and liver stiffness measurement. A total of 1163 patients with MAFLD were categorized into the following four groups according to metabolic risk abnormalities and obesity presence: non-obese without metabolic risk abnormality group(Group 1;reference group);nonobese with metabolic risk abnormality group(Group 2);obese without metabolic risk abnormality group(Group 3);and obese with metabolic risk abnormality group(Group 4). A multiple logistic regression analysis was performed to determine severe hepatic steatosis and fibrosis risk in each group in both unadjusted and adjusted models. Results: In the adjusted model, the odds ratios(ORs) [95% confidence interval(CI)] for severe hepatic steatosis in Groups 2, 3, and 4 were 1.07(0.61-1.88), 2.43(1.44-4.08), and 4.07(2.56-6.48), respectively( P trend < 0.001). For liver fibrosis, compared with Group 1, Group 2 showed no significant increases in OR, whereas Groups 3 and 4(obese groups) showed significant increases(OR = 4.70, 95% CI: 1.24-17.82 and OR = 6.43, 95% CI: 1.88-22.02, respectively). Conclusions: Obesity, rather than metabolic abnormality, is the principal determinant of severe hepatic steatosis and fibrosis in patients with MAFLD.

Efficacy of switching to telbivudine plus adefovir in suboptimal responders to lamivudine plus adefovir

AIM:To examine the efficacy of telbivudine(LdT)+adefovir(ADV)vs continuation of lamivudine(LAM)+ADV in patients with LAM-resistant chronic hepatitis B(CHB)who show a suboptimal response to LAM+ADV.METHODS:This was a randomized,active-control,open-label,single-center,parallel trial.All eligible patients were enrolled in this study in Severance Hospital,Yonsei University College of Medicine,Seoul,South Korea,between March 2010 and March 2011.Hepatitis Be antigen(HBeAg)-positive CHB patients whose serum hepatitis B virus(HBV)DNA remained detectable despite at least 6 mo of LAM+ADV therapy were included.Enrolled patients were randomized to either switching to LdT(600 mg/d orally)plus ADV(10 mg/d orally)(LdT+ADV group)or to continuation with LAM(100 mg/d orally)plus ADV(10 mg/d orally)(LAM+ADV group),and were followed for 48 wk.One hundred and six patients completed the 48-wk treatment period.Serum HBV DNA,HBeAg status,liver biochemistry and safety were monitored at baseline and week 12,24,36 and 48.RESULTS:The duration of prior LAM+ADV treatment was 18.3(LdT+ADV)and 14.9 mo(LAM+ADV),respectively(P=0.131).No difference was seen in baseline serum HBV DNA between the two groups[3.66(LdT+ADV)vs 3.76(LAM+ADV)log10IU/mL,P=0.729].At week 48,although there was no significant difference in the mean reduction of serum HBV DNA from baseline between LdT+ADV group and LAM+ADV group(-0.81 vs-0.47 log10IU/mL,P=0.167),more patients in the LdT+ADV group had undetectable HBV DNA levels compared to those in the LAM+ADV group(30.2%vs 11.5%,P=0.019).Three patients with LdT+ADV treatment and 2 patients with LAM+ADV treatment achieved HBeAg loss.The patients in both groups tolerated the treatment well without serious adverse events.The proportion of patients with estimated glomerular filtration rate≥90 mL/min per 1.73 m2in the LdT+ADV group increased from 49.1%(26/53)at baseline to 58.5%(31/53)at week 48,while that in the LAM+ADV group decreased from 37.7%(20/53)at baseline to 30.2%(16/53)at week 48.CONCLUSION:The switch to LdT+ADV in suboptimal responders to LAM+ADV showed a significantly higher rate of virologic response at week 48.These results suggest that LdT+ADV could be a therapeutic option for patients who are unable to use enofovir disoproxil fumarate for any reason.

Severity of ultrasonographic liver steatosis and metabolic syndrome in Korean men and women

AIM：To evaluate the association between the severity of liver steatosis and metabolic syndrome in apparently healthy Korean adults. METHODS： We examined 1022 men and women, aged 30-79 years, who participated in a health screening test. A standard interview, anthropometrics, biochemical studies, and abdominal ultrasonography were conducted for each participant. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel Ⅲ, with a modification for the waist circumference cut-off level. The severity of liver steatosis was evaluated using liver ultrasonography, and serum aspartate aminotransferase（AST）, alanine aminotransferase （ALT）, and γ-glutamyl transferase （γ-GT） levels were determined. RESULTS： Ultrasonographic liver steatosis was strongly associated with metabolic syndrome and common metabolic abnormalities. Compared with people without steatosis, people with mild, moderate, and severe steatosis had adjusted odds ratios for metabolic syndrome of 2.72 （95% CI, 1.01-2.94）, 2.89 （1.75-4.76） and 3.53 （1.25-9.98） in men, and 2.86 （1.64-5.01）, 3.19 （1.80-5.65） and 3.70 （0.82-16.73） in women, respectively. The serum AST level was not associated with metabolic syndrome. The serum ALT and γ-GT levels were significantly associated with metabolic syndrome in men but not in women.CONCLUSION： The occurrence of metabolic syndrome shows a stronger association with the severity of ultrasonographic steatosis than with the serum liver enzyme levels. The degree of fatty infiltration detected on ultrasonography can be used as an indicator of liver dysfunction attributable to metabolic abnormalities.

Multicenter phase Ⅱ trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer

AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine(GEM)-refractory unresectable pancreatic cancer(PC).METHODS This study was a prospective, multicenter, one-arm, open-label, phase Ⅱ trial. Patients with unresectable PC, who showed disease progression during GEMbased chemotherapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin(RIO; irinotecan 120 mg/m^2 and oxaliplatin 60 mg/m^2), which was set according to the phase Ⅰ study of FOLFIRINOX. The objective response rate(ORR), disease control rate(DCR), progressionfree survival(PFS), overall survival(OS), adverse events were evaluated. Additionally, changes in quality of life(QoL) were assessed using a questionnaire on QoL.RESULTS Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval(CI): 3.7-7.9] and median OS was 9.0 mo(95%CI: 6.4-11.6). Neutropenia(64.6%) was the most common grade 3-4 adverse event, followed by febrile neutropenia(16.7%). Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment(45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548).CONCLUSION FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities.

Combination of corticosteroids and 5-aminosalicylates or corticosteroids alone for patients with moderate-severe active ulcerative colitis:A global survey of physicians'practice

AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(UC). METHODS A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. RESULTS Six hundred and sixty-four questionnaires were distributed and 349 received(52.6% response rate). Of 340 eligible respondents, 221(65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108(32%) would stop the 5ASA(P < 0.001), and 11(3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340(41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most(94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. CONCLUSION Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.

FOLFIRINOX vs gemcitabine/nab-paclitaxel for treatment of metastatic pancreatic cancer: Single-center cohort study

BACKGROUND FOLFIRINOX and gemcitabine plus nab-paclitaxel(Gem+nabPTX)were recently introduced for metastatic pancreatic cancer treatment.However,studies that compared these two regimens and studies in Asian populations are lacking.AIM To compare the treatment outcomes of FOLFIRINOX and Gem+nabPTX regimen for metastatic pancreatic cancer treatment in Korean population.METHODS Patients with metastatic or recurrent pancreatic cancer treated with FOLFIRINOX(n=86)or Gem+nabPTX(n=81)as the first-line since January 2015 were identified using the Severance Hospital Pancreatic Cancer Cohort Registry.Treatment efficacy,treatment-related adverse events and economic aspects were compared.RESULTS Patients in the FOLFIRINOX group were significantly younger(54 vs 65 years;P<0.001)and had better performance statuses at diagnosis.The median overall survival(10.7 vs 12.1 mo;P=0.157),progression-free survival(8.0 vs 8.4 mo;P=0.134),and objective response rates(33.7%vs 46.9%;P=0.067)were not significantly different when compared with Gem+nabPTX group.Grade≥3 neutropenia and gastrointestinal adverse events were more common in the FOLFIRINOX group.The drug costs of both regimens were similar.CONCLUSION Treatment efficacy and economic burdens were comparable between the two regimens.But,the details of adverse event were different.Gem+nabPTX regimen might be considered preferentially in certain conditions.

Prevalence of clonorchiasis in patients with gastrointestinal disease: A Korean nationwide multicenter survey

AIM： To investigate prevalence of C/onorchis sinensis in patients with gastrointestinal symptoms, and the relation of the infection to hepatobiliary diseases in 26 hospitals in Korea. METHODS： Consecutive patients who had been admitted to the Division of Gastroenterology with gastrointestinal symptoms were enrolled from March to April 2005. Of those who had been diagnosed with clonorchiasis, epidemiology and correlation between infection and hepatobiliary diseases were surveyed by questionnaire. RESULTS： Of 3080 patients with gastrointestinal diseases, 396 （12.9%） had clonorchiasis and 1140 patients （37.2%） had a history of eating raw freshwater fish. Of those with a history of raw freshwater fish ingestion, 238 （20.9%） patients had clonorchiasis. Cholangiocarcinoma was more prevalent in C. sinensis-infected patients than nonnfected patients [34/396 （8.6%） vs 145/2684 （5.4%）, P = 0.015]. Cholangiocarcinoma and clonorchiasis showed statistically significant positive cross-relation （P = 0.008）. Choledocholithiasis, cholecystolithiasis, cholangitis, hepatocellular carcinoma, and biliary pancreatitis did not correlate with clonorchiasis. CONCLUSION： Infection rate of clonorchiasis was still high in patients with gastrointestinal diseases in Korea, and has not decreased very much during the last two decades. Cholangiocarcinoma was related to clonorchiasis, which suggested an etiological role for the parasite.