Post-treatment serum Wisteria floribunda agglutinin-positive mac-2-binding protein level is a useful predictor of hepatocellular carcinoma development after hepatitis C virus eradication.

AIMS: Recent advances of direct-acting antiviral drugs for hepatitis C virus (HCV) have dramatically improved the sustained virologic response (SVR) rate, but hepatocellular carcinoma (HCC) development rarely occurs even in patients who achieve an SVR. Wisteria floribunda agglutinin-positive mac-2-binding protein (WFA+-M2BP) was recently developed as a noninvasive biomarker of liver fibrosis. However, the association between the WFA+-M2BP level and HCC development after the achievement of an SVR is unclear. METHODS AND RESULTS: We examined the association between WFA+-M2BP and HCC development in 522 HCV patients who achieved an SVR (Interferon [IFN]-based therapy, n = 228; IFN-free therapy, n = 294). Multivariate analysis revealed that a high WFA+-M2BP level at SVR week 24 after treatment (SVR24) (hazard ratio [HR] = 1.215, P = 0.020), low platelet counts (HR = 0.876, P = 0.037), and old age (HR = 1.073, P = 0.012) were independent risk factors for HCC development regardless of the treatment regimen. Receiver operator characteristics curve analysis revealed that a WFA+-M2BP level at SVR24 of ≥1.62 cut-off index (COI) was the cut-off value for the prediction of HCC development (adjusted HR = 12.565, 95% CI 3.501-45.092, P < 0.001). The 3- and 5-year cumulative incidences of HCC were 1% and 1.6% in patients with low WFA+-M2BP at SVR24 (<1.62 COI), and 4.7% and 12.5% in patients with high WFA+-M2BP (≥1.62 COI) were, respectively (P < 0.001). CONCLUSIONS: The assessment of liver fibrosis using the WFA+-M2BP level at SVR24 is a useful predictor of HCC development after HCV eradication even in the IFN-free therapy era.

Does restricting fluid volume impact post-ERCP pancreatitis in patient with heart disease?

METHODS: Two hundred and forty seven of 480 patients with naïve papilla undergoing therapeutic ERCP between April 2013 and March 2018 were enrolled for the study. The following patient characteristics were investigated: age, sex, body mass index, previous diseases (heart disease, renal failure, cerebrovascular disorders, coexisting malignancy and pulmonary disease), history of PEP, common bile duct diameter, diverticula and volume of fluid infused 24 hours after the procedure. All ERCP cases had naïve papilla and had undergone treatment. RESULTS: The incidence of PEP was 8.5%. Significant differences were observed in the volume of fluid infused between patients without and with a history of heart disease (1,380 vs. 1,755 mL). The mean volume of the infused fluid was significantly lower in the PEP than non-PEP group (1,483 vs. 1,688 mL, P = 0.02). Moreover, PEP incidence differed according to a fluid infusion cutoff of 1,000 mL (7 vs. 11 cases of PEP in those with ≦1,000 mL and >1,000 mL fluid volume, respectively, P < 0.001). CONCLUSION: Restricted fluid volume was a newly identified risk factor for PEP, particularly in patients with heart and renal diseases as comorbidities.

Elevated serum tyrosine concentration is associated with a poor prognosis among patients with liver cirrhosis.

AIM: Chronic liver insufficiency is often associated with changes in amino acid metabolism. We evaluated whether change in serum amino acid concentrations had prognostic value among patients with liver cirrhosis. METHODS: This retrospective study evaluated 158 patients who had been hospitalized with cirrhosis. Baseline serum concentrations of branched-chain amino acids (BCAAs) and tyrosine, as well as the BCAA-to-tyrosine ratio, were evaluated. Cox proportional hazards analysis was used to calculate the hazard ratios for factors that were associated with mortality or liver transplantation. RESULTS: Among the 158 patients, baseline measurements showed decreased serum BCAA concentrations for 59 patients (37.3%), elevated serum tyrosine concentrations for 80 patients (50.6%), and a decreased BCAA-to-tyrosine ratio for 114 patients (72.2%). During a median follow-up period of 3.0 years, death or liver transplantation occurred at a rate of 0.136 cases/1 person-year. Multivariable analysis showed that transplant-free survival was independently predicted by older age, male sex, comorbid hepatocellular carcinoma, Child-Turcotte-Pugh score, and serum tyrosine concentration. Receiver operating characteristic curve analysis showed that a serum tyrosine concentration of >110 µmol/L was the optimal cut-off value for predicting transplant-free survival (adjusted hazard ratio 1.89, 95% confidence interval 1.15-3.11, p = 0.012). Kaplan-Meier analysis showed a significant difference in the 5-year transplant-free survival probability between patients with high and low serum tyrosine concentrations (42.1% vs. 60.7%, p < 0.001). CONCLUSIONS: Elevated serum tyrosine concentration, but not changes in serum BCAA concentration or the BCAA-to-tyrosine ratio, may indicate a high risk of death or liver transplantation for patients with liver cirrhosis.

Hepatitis B Surface Antigen Decline during Sofosbuvir and Ribavirin Therapy in Hepatitis B Inactive Carriers Who Were Co-infected with Hepatitis C.

Direct-acting antiviral (DAA) therapy carries a potential risk of inducing hepatitis B virus (HBV) reactivation. However, the HBV kinetics during and after DAA therapy in patients co-infected with hepatitis C virus (HCV) and HBV remain unknown. We retrospectively evaluated the HBV kinetics during and after sofosbuvir/ribavirin therapy in four HBV inactive carriers co-infected with HCV. HCV was eradicated in all patients. Changes in HBV-DNA levels during treatment differed among patients. The hepatitis B surface antigen (HBsAg) levels uniformly decreased (mean -0.530 logIU/mL) by the end of treatment and returned to near the baseline in all patients. Sofosbuvir/ribavirin therapy thus demonstrated a suppressive effect on HBsAg.

Mucinous Cystadenocarcinoma of the Pancreas with Cyst Infection in a Male Patient.

Follow-up computed tomography revealed a 40-mm pancreatic tail cyst in a 59-year-old man with type 1 diabetes mellitus. An intraductal papillary mucinous neoplasm was suspected; mucinous cystic neoplasm (MCN) was not considered because the patient was a man. During follow-up, cyst infection occurred but was improved by conservative treatment. At the 24-month follow up examination, cyst nodules had developed, corresponding to an increase in the carbohydrate antigen 19-9 level. Mucinous cystadenocarcinoma (MCC) was diagnosed pathologically based on distal pancreatectomy. A diagnosis of male MCN/MCC is often delayed, which may lead to a poor prognosis. MCN infection is also rare and poorly recognized. We observed an atypical male case of MCN/MCC.

Eosinophilic Gastroenteritis in an Ulcerative Colitis Patient During Treatment with Tumor Necrosis Factor-alpha Antagonist.

A 45-year-old man with steroid-dependent ulcerative pancolitis was hospitalized with frequent diarrhea, abdominal pain and distension 3 months after induction of golimumab, a tumor necrosis factor-alpha antagonist. Computed tomography showed wall thickening from the stomach to the colon and massive ascites. Peripheral blood test revealed eosinophilia. A large number of eosinophils were observed in the ascites fluid. Although esophagogastroduodenoscopy showed no abnormal findings and colonoscopy showed ulcerative colitis with a Mayo endoscopic subscore of 1, eosinophil infiltration was histologically observed. Based on these findings, we diagnosed him with eosinophilic gastroenteritis and started prednisolone. Consequently, his eosinophil counts and abdominal symptoms dramatically improved.

Successful Management of Hemosuccus Pancreaticus due to Pancreatic Adenocarcinoma by Chemoradiotherapy.

Management of hemosuccus pancreaticus (HP) due to pancreatic adenocarcinoma is problematic. This is the first report of the successful management of HP caused by pancreatic adenocarcinoma by chemoradiotherapy, which is a treatment option for cases with a high surgical risk that are not suitable for interventional radiology. In the present case, bloody pancreatic juice was detected in the main pancreatic duct, and anemia worsened without repeated blood transfusions. The patient ultimately underwent chemoradiotherapy comprising radiation of 3 Gy in 15 fractions concomitant with systemic chemotherapy of S-1. After the treatments, the anemia improved, and the patient was discharged on day 45.

On-treatment Serum Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Level and Risk of Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis B during Nucleot(s)ide Analogue Therapy.

We aimed to analyze the serum level of a novel fibrosis marker, Mac-2-binding protein glycosylation isomer (M2BPGi), and its predictive value for hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) under nucleot(s)ide analogue (NA) therapy. Serum M2BPGi levels were quantified in 147 CHB patients at baseline, 48 weeks after starting NA therapy, and at the patients' last visit. The serum M2BPGi level serially decreased at each time point. During the median follow-up time of 6.6 years, 14 of 147 patients developed HCC. Multivariate Cox proportional hazard analysis demonstrated that high serum M2BPGi at 48 weeks was an independent risk factor for HCC development. A cutoff value of M2BPGi at 48 weeks > 1.5 showed an adjusted hazard ratio = 34.9 (95% confidence interval, 4.3-284.9). The 3- and 5-year cumulative incidence of HCC in patients with low M2BPGi were 0.9% and 4.2%, respectively, whereas those in patients with high M2BPGi were 10.1% and 25.6%, respectively (p < 0.001). In conclusion, Serum M2BPGi level at 48 weeks is a useful predictor for HCC development in patients with CHB who receive NA therapy.

A case of primary biliary cholangitis overlapping with type 2 autoimmune hepatitis.

A 42-year-old woman was admitted to our hospital with cholestatic liver injury. Serological examination revealed anti-mitochondrial M2 antibody positivity and anti-nuclear antibody and anti-smooth muscle antibody negativity. Histological examination of the first liver biopsy revealed chronic nonsuppurative destructive cholangitis with epithelioid granulomas. Ursodeoxycholic acid therapy successfully treated her cholestasis. Sixteen months later, she developed acute icteric hepatitis with elevation of serum aspartate and alanine aminotransferase levels. Anti-mitochondrial M2 positivity and anti-nuclear antibody and anti-smooth muscle antibody negativity persisted at that time. However, it became clear that anti-liver kidney microsomal type 1 antibody was positive. Histological examination of the second liver biopsy demonstrated scarce interface hepatitis and evident parenchymal inflammation and centrilobular zonal necrosis. Her liver biochemical test results promptly improved with the addition of prednisolone therapy. Considering the findings, she was diagnosed with primary biliary cholangitis-type 2 autoimmune hepatitis overlap syndrome. According to a literature review, this is an extremely rare autoimmune overlap syndrome.

Elevated serum procalcitonin levels and their association with the prognosis of patients with liver cirrhosis.

OBJECTIVES: Bacterial infection is a major complication in patients with liver cirrhosis. Procalcitonin is an early diagnostic marker of bacterial infection. This study aimed to investigate the association between the serum procalcitonin levels and the prognosis of patients with liver cirrhosis. METHODS: We retrospectively analyzed the serum procalcitonin levels in 236 hospitalized patients with liver cirrhosis. The impact of the serum procalcitonin level on their prognoses was evaluated using multivariate Cox proportional hazards analyses and the Kaplan-Meier method. RESULTS: The serum procalcitonin level was higher (≥0.05 ng/mL) in 151 (64%) patients, and it was significantly higher in the patients with Child-Turcotte-Pugh class C than in those with Child-Turcotte-Pugh classes A/B. Patients with refractory ascites, hepatic encephalopathy, gastrointestinal bleeding, and bacterial infections had elevated serum procalcitonin levels. The multivariate analyses showed a serum procalcitonin level ≥0.05 ng/mL was an independent prognostic factor for liver cirrhosis (hazard ratio = 1.64; 95% confidence interval = 1.07-2.53; P = 0.024). During a median follow-up interval of 2.1 years, the three-year cumulative survival rates for the patients with normal and elevated serum procalcitonin levels were 72.9 and 56.0%, respectively (P < 0.001). The subgroup analyses that stratified the patients according to age, the Child-Turcotte-Pugh classification, and the presence of liver cancer showed the serum procalcitonin level was significantly associated with their prognoses. CONCLUSIONS: The patients with liver cirrhosis had higher serum procalcitonin levels, regardless of local bacterial infections, and higher procalcitonin levels were associated with poor prognoses.

Prognostic significance of serum tyrosine concentration in patients with primary biliary cholangitis under ursodeoxycholic acid therapy.

AIM: Chronic liver insufficiency is often associated with alteration in amino acid metabolism. We evaluated the prognostic value of changes in serum amino acid concentrations in patients with primary biliary cholangitis. METHODS: A total of 75 primary biliary cholangitis patients who started urusodeoxycholic acid therapy were retrospectively enrolled. Baseline serum concentrations of branched-chain amino acids and tyrosine, and branched-chain amino acid-to-tyrosine ratio were determined. The hazard ratios of factors associated with liver-related events were analyzed by Cox proportional hazard analysis. RESULTS: Of the 75 patients enrolled, 12 showed a decrease in serum branched-chain amino acid levels, and 15 showed an increase in serum tyrosine levels. The branched-chain amino acid-to-tyrosine ratio decreased in 16 patients. During a median 5.6-year follow up, liver-related events occurred in 11 patients. Multivariate analysis showed that high serum tyrosine levels at baseline and high alkaline phosphatase levels 48 weeks after starting urusodeoxycholic acid therapy were independent risk factors for event occurrence. From the receiver operator characteristics curve analysis, serum tyrosine concentration >110 µmol/L was identified as a cut-off value with an adjusted hazard ratio of 20.9 (95% confidence interval 4.3-101.5, P < 0.001). Kaplan-Meier analysis showed that the 5-year cumulative incidences of event occurrence in patients with high and low serum tyrosine concentration were 56.5% and 5.5%, respectively (P < 0.001). The 10-year survival probabilities also showed significant differences between patients with high and low serum tyrosine concentration (44.9% vs. 92.0%, P < 0.001). CONCLUSION: Elevation of serum tyrosine concentration indicates a high risk of liver-related events in primary biliary cholangitis patients receiving urusodeoxycholic acid therapy.

Budd-Chiari Syndrome Associated With Hypereosinophilic Syndrome Treated by Deceased-Donor Liver Transplantation: A Case Report.

INTRODUCTION: Budd-Chiari syndrome (BCS) associated with hypereosinophilic syndrome (HES) is very rare, and only a few reports have described its treatment. Furthermore, no report to date has described the performance of liver transplantation for the treatment of BCS associated with HES. We herein describe a 54-year-old man who underwent deceased-donor liver transplantation (DDLT) for treatment of BCS associated with HES. CASE: A 54-year-old man was found to have an increased eosinophil count during a medical check-up. After exclusion of hematopoietic neoplastic diseases and secondary eosinophilia, idiopathic hypereosinophilia was diagnosed. Oral prednisolone was administered to the patient, and his eosinophil count immediately decreased to a normal level. He had an uneventful course without complications for 11 months but then presented with bloating and malaise. Imaging studies including ultrasonography, enhanced computed tomography, and angiography revealed BCS associated with HES. Transjugular intrahepatic portosystemic shunt failed because of complete obstruction of the hepatic veins. Therefore, the patient was introduced to our hospital for liver transplantation. DDLT was performed with venovenous bypass 1 month after the patient was placed on the DDLT waiting list. The explanted hepatic veins were completely occluded and organized. The patient's eosinophil count was maintained at a normal level with prednisolone treatment after DDLT. CONCLUSIONS: Liver transplantation can be a treatment option for BCS associated with HES if neoplastic diseases and secondary eosinophilia have been excluded. Life-long oral steroid therapy is required to control HES even after liver transplantation.

A case of ischemic gastroduodenal disease in a patient who was receiving hemodialysis treatment that was managed by conservative treatment.

A 69-year-old man was under maintenance dialysis due to diabetic renal failure. He had a drop in blood pressure during dialysis, developed hematemesis, and was transported to our hospital. Emergency upper gastrointestinal endoscopy revealed diffuse erosion, mucosal sloughing, and edematous mucosa in the upper body of the stomach to the posterior wall of the antrum and to the greater curvature, which were considered to be an ischemic change. His underlying diseases included diabetic renal failure, chronic arteriosclerosis obliterans, cerebral infarction, internal carotid artery stenosis, hypertension, and myocardial infarction. Blood evaluation showed only mild inflammation and no fibrinolytic hyperactivity. Contrast-enhanced computed tomography (CECT) showed no occlusion of blood vessels. It was considered that the patient had a transient ischemic change due to blood pressure drop. The patient's condition improved with conservative treatment.

Prediction of Hepatocellular Carcinoma Development after Hepatitis C Virus Eradication Using Serum Wisteria floribunda Agglutinin-Positive Mac-2-Binding Protein.

We aimed to clarify the association between a novel serum fibrosis marker, Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA⁺-M2BP), and hepatocellular carcinoma (HCC) development in 355 patients with chronic hepatitis C who achieved sustained virologic response (SVR) through interferon-based antiviral therapy. Pretreatment serum WFA⁺-M2BP levels were quantified and the hazard ratios (HRs) for HCC development were retrospectively analyzed by Cox proportional hazard analysis. During the median follow-up time of 2.9 years, 12 patients developed HCC. Multivariate analysis demonstrated that high serum WFA⁺-M2BP (≥2.80 cut off index (COI), HR = 15.20, p = 0.013) and high fibrosis-4 (FIB-4) index (≥3.7, HR = 5.62, p = 0.034) were independent risk factors for HCC development. The three- and five-year cumulative incidence of HCC in patients with low WFA⁺-M2BP were 0.4% and 0.4%, respectively, whereas those of patients with high WFA⁺-M2BP were 7.7% and 17.6%, respectively (p < 0.001). In addition, combination of serum WFA⁺-M2BP and FIB-4 indices successfully stratified the risk of HCC: the five-year cumulative incidences of HCC were 26.9%, 6.8%, and 0.0% in patients with both, either, and none of these risk factors, respectively (p < 0.001). In conclusion, pretreatment serum WFA⁺-M2BP level is a useful predictor for HCC development after achieving SVR.

Pretreatment AKR1B10 expression predicts the risk of hepatocellular carcinoma development after hepatitis C virus eradication.

AIM: To clarify the association between aldo-keto reductase family 1 member B10 (AKR1B10) expression and hepatocarcinogenesis after hepatitis C virus eradication. METHODS: In this study, we enrolled 303 chronic hepatitis C patients who had achieved sustained virological response (SVR) through interferon-based antiviral therapy. Pretreatment AKR1B10 expression in the liver was immunohistochemically assessed and quantified as a percentage of positive staining area by using image-analysis software. A multivariate Cox analysis was used to estimate the hazard ratios (HRs) of AKR1B10 expression for hepatocellular carcinoma (HCC) development after achieving SVR. The cumulative incidences of HCC development were evaluated using Kaplan-Meier analysis and the log-rank test. RESULTS: Of the 303 chronic hepatitis C patients, 153 (50.5%) showed scarce hepatic AKR1B10 expression, quantified as 0%, which was similar to the expression in control normal liver tissues. However, the remaining 150 patients (49.5%) exhibited various degrees of AKR1B10 expression in the liver, with a maximal AKR1B10 expression of 73%. During the median follow-up time of 3.6 years (range 1.0-10.0 years), 8/303 patients developed HCC. Multivariate analysis revealed that only high AKR1B10 expression (≥ 8%) was an independent risk factor for HCC development (HR = 15.4, 95%CI: 1.8-132.5, P = 0.012). The 5-year cumulative incidences of HCC development were 13.7% and 0.5% in patients with high and low AKR1B10 expression, respectively (P < 0.001). During the follow-up period after viral eradication, patients expressing high levels of AKR1B10 expressed markedly higher levels of alanine aminotransferase and α-fetoprotein than did patients exhibiting low AKR1B10 expression. CONCLUSION: Chronic hepatitis C patients expressing high levels of hepatic AKR1B10 had an increased risk of HCC development even after SVR.