Current Status of Conversion Hepatectomy After Sorafenib and Lenvatinib Treatment for Unresectable Hepatocellular Carcinoma.

BACKGROUND/AIM: Sorafenib and lenvatinib have long been used as a first-line treatment for advanced hepatocellular carcinoma (HCC). Along with the development of systemic chemotherapy for HCC, the concept of conversion hepatectomy has recently become widespread. The present study aimed to assess the clinical outcomes of sorafenib and lenvatinib for HCC regarding the possibility of conversion hepatectomy in clinical practice. PATIENTS AND METHODS: A total of 295 patients with advanced HCC receiving sorafenib and lenvatinib, accounting for 306 treatments (sorafenib, n=157; lenvatinib, n=149, 11 patients received lenvatinib after sorafenib treatment) at five different institutions were enrolled. Patients were assessed for their clinical characteristics and therapeutic response using both Response Evaluation Criteria in Solid Tumors criteria (RECIST) and modified RECIST (mRECIST) criteria. Additionally, an indication of surgery after tyrosine kinase inhibitor administration was determined based on the tumor status of patients. RESULTS: The median survival times of patients treated with sorafenib and lenvatinib were 12.8 and 16.4 months, respectively, without significant difference (p=0.1645). The objective response rates (ORR) of sorafenib based on mRECIST and RECIST were 10.1% and 5.9%, respectively, and those of lenvatinib were 38.1% and 19.0%, respectively. Among the 306 treatments, two cases (sorafenib and lenvatinib, one each) underwent hepatectomy after systemic chemotherapy. CONCLUSION: Few cases with unresectable HCC were amenable to conversion hepatectomy after sorafenib and lenvatinib treatments due to the limited ORR by RECIST. Cautious approach must be taken when administering neoadjuvant chemotherapy aimed at conversion hepatectomy.

Factors associated with the response to atezolizumab/bevacizumab combination therapy for hepatocellular carcinoma.

Background and Aim: The purpose of this study was to analyze factors associated with the overall survival (OS) of atezolizumab/bevacizumab combination therapy for advanced hepatocellular carcinoma (aHCC). We also assessed the OS of patients with ineffective therapy and those who discontinued treatment owing to adverse events (AEs). Methods: This retrospective multicenter study involved 139 patients with aHCC who received atezolizumab/bevacizumab combination therapy between November 2020 and September 2022. Results: The median duration of treatment was 136.5 days, and the median observation period was 316 days. The overall response rate was 40%, and the disease control rate was 78% according to mRECIST criteria. Grade ≥2 AEs occurred in 63 patients (43%) and led to treatment discontinuation in 16 patients. Multivariate analysis revealed that treatment response and occurrence of grade ≥2 AEs after therapy, as well as low level of albumin-bilirubin (ALBI) grade and low level of des-gamma carboxy prothrombin (DCP) before therapy, were extracted as factors that contributed to OS. Log-rank tests with the Kaplan-Meier method showed significant differences in OS among these factors. The OS of patients who discontinued owing to AEs was significantly shorter than that of other patients. Conclusion: Not only factors before therapy but also treatment response and the appearance of AEs are involved in OS for atezolizumab/bevacizumab combination therapy. Although the development of AEs also contributed to OS, appropriate management of AEs is important to avoid discontinuing treatment with this combination.

Significance of post-progression therapy after tyrosine kinase inhibitors for advanced hepatocellular carcinoma.

Background and Aim: Molecular-targeted therapies such as sorafenib and lenvatinib have long been used as first-line treatment for advanced hepatocellular carcinoma (aHCC). However, adverse events or limited therapeutic effects may necessitate the change to another therapeutic option, known as post-progression therapy. To investigate the significance of post-progression therapy, we analyzed the outcomes of aHCC patients following first-line molecular-targeted therapy in a real-world study. Methods: This retrospective, multicenter study involved patients with aHCC who received sorafenib or lenvatinib as first-line therapy between January 2011 and September 2021. Results: In total, 513 patients were analyzed: 309 treated with sorafenib and 204 with lenvatinib. The overall response and disease control rates were 15 and 50%, respectively, in the sorafenib group and 30 and 75%, respectively, in the lenvatinib group (P < 0.001). Kaplan-Meier analysis revealed no significant differences in progression-free survival and overall survival (OS) between the two treatments. Multivariate analysis revealed that fibrosis-4 index, disease control rate, post-progression therapy, and use of an immune checkpoint inhibitor (ICI) were significantly associated with OS. OS was significantly longer in patients who received post-progression therapy than in those who did not (log-rank P < 0.001). Most patients who received an ICI as post-progression therapy had previously received lenvatinib. Among lenvatinib-treated patients, OS was significantly longer in patients who received an ICI than in patients received another or no post-progression therapy (P = 0.004). Conclusion: The introduction of newer drugs for post-progression therapy is expected to prolong survival. ICI-based regimens appear to be effective after lenvatinib.

Risk Factors for Adverse Events in Patients with Chronic Constipation Following Lubiprostone Administration.

INTRODUCTION: Lubiprostone is an effective treatment of chronic constipation (CC). However, as with other stimulant or osmotic laxatives, adverse events (AEs) can make it difficult to continue treatment. This article investigates AE risk factors associated with lubiprostone. METHODS: We retrospectively analyzed all 1,338 Japanese patients with CC treated at our hospital from October 2013 to July 2017. All patients were diagnosed with constipation as defined by the Roma III criteria. Enrolled patients received lubiprostone orally (24 or 48 µg daily), after which we investigated the incidence of AEs. The causative factors for diarrhea and nausea, the most common AEs, were examined by the backward logistic regression model. RESULTS: Two hundred eight (15.5%) experienced at least 1 AE. No serious AEs were associated with the study drug. The AEs reported by >1% of patients overall were diarrhea (6.1%) and nausea (4.2%). We performed a multivariate logistic regression using a backward variable selection method to investigate AE risk factors. Factors associated with higher incidence of diarrhea were patient age of 65 years or more (odds ratio: [95% confidence interval]; p value) (2.09: [1.05-4.16]; 0.035). Factors associated with greater likelihood of nausea included female gender (1.99: [1.10-3.61]; 0.023), and the chief complaint was a patient complaining of abdominal pain and fullness (2.07: [1.01-4.22]; 0.046). CONCLUSIONS: Understanding AE risk factors can help avoid unnecessary AEs and promote more effective treatment.

Propensity score matching analysis: incidence and risk factors for "stardust" gastric mucosa, a novel gastric finding potentially induced by vonoprazan.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, is used for acid-related diseases. Occasionally, small white protrusions called "stardust" gastric mucosa have been detected in the stomachs of some patients taking vonoprazan. AIMS: To determine the incidence of, and risk factors for, stardust gastric mucosa potentially induced by vonoprazan METHODS: In this study, we enrolled 19 503 patients who underwent endoscopy at our hospital between 2016 and 2019. Using propensity score matching, we retrospectively compared patients who received and did not receive vonoprazan. The two groups were matched for age, sex, history of proton pump inhibitor use, and atrophic gastritis. RESULTS: After 1:1 propensity score matching, each group comprised 2516 patients. Stardust gastric mucosa was detected significantly more often in the stomachs of patients receiving vonoprazan than those who had not received vonoprazan (4.9% vs 0.2%, P < 0.001). Its location was 70.7% in the upper third of the stomach, 29.3% in the middle third and none in the lower third. Histologically, this lesion had a mucus pool within a dilated duct surrounded by flattened glandular epithelium. The cumulative incidence rate of stardust gastric mucosa at 1, 2 and 3 years was 4.6%, 16.5% and 26.2%, respectively. The factors independently associated with the presence of stardust gastric mucosa were >205 days of vonoprazan oral intake (odds ratio [OR]: 6.99, 95% confidence interval [CI]: 4.60-10.88) and female sex (OR: 1.75, 95% CI: 1.20-2.58). CONCLUSIONS: Stardust gastric mucosa appeared more frequently in the stomachs of patients taking vonoprazan.

Real-World Comparison of Elobixibat and Lubiprostone Treatment in Patients with Chronic Constipation: A Propensity Score-Matched Analysis.

INTRODUCTION: Elobixibat is a new laxative, but its efficacy and adverse events (AEs) are insufficiently examined compared with those of other laxatives. Hence, by propensity score (PS) matching, we compared the effects and AEs between elobixibat and lubiprostone. METHODS: We retrospectively analyzed 1,887 Japanese patients with chronic constipation (CC) treated at our hospital between October 2013 and April 2020. Enrolled patients were divided into three treatment groups, namely, elobixibat (10 mg daily) (E10 group, n = 293), lubiprostone (24 µg daily) (L24 group, n = 772), and lubiprostone (48 µg daily) (L48 group, n = 822), as their first treatment. We then investigated the changes on the weekly average number of spontaneous bowel movements, stool consistency scores (SCSs), and AEs starting from the baseline until the end of the 2-week treatment. To adjust for patients' background, we performed one-to-one nearest neighbor matching without replacement between elobixibat- and lubiprostone-treated patients according to the individual estimated PSs. RESULTS: After treatment, for SCSs, both the L24 and L48 groups significantly improved compared with the E10 group (p < 0.05), but their stools were soft (Bristol Stool Form Scale: 4.8). Notably, the E10 group had less frequent AEs than the L24 group (26 [9.0%] vs. 43 [14.8%], p = 0.03). Particularly, nausea was significantly less in the E10 group than that in the L48 group (2 [0.7%] vs. 7 [2.4%], p = 0.01). CONCLUSION: Elobixibat is a beneficial drug for patients with mildly symptomatic CC and is safe to use, given its few AEs.

A rare case of pyogenic granuloma of the jejunum causing gastrointestinal bleeding.

Pyogenic granulomas (PG) are lobular capillary hemangiomas mostly found in the mucous membranes of the skin and oral cavity, and rarely occur in the gastrointestinal tract. Here we describe a case of an 84-year-old patient with alcoholic cirrhosis who presented with persistent melena and progressive anemia. Endoscopy showed esophageal varices and he underwent endoscopic variceal ligation (EVL) with transient resolution of anemia. However, due to worsening anemia, he underwent capsule endoscopy that revealed a bleeding tumor in the small intestine. We performed double-balloon endoscopy and found a 7-mm polyp with a white coat located in the jejunum and resected it at a later date. Histological characteristics led to the diagnosis of PG, and the patient's melena and anemia subsequently improved.

Feasibility of the lidocaine injection method during esophageal endoscopic submucosal dissection.

BACKGROUND AND AIM: Esophageal endoscopic submucosal dissection (ESD) is often technically difficult due to intraoperative body movements. The level of sedation can be increased to suppress body movements, but this may not be successful in all cases. Using local analgesics for submucosal injection during ESD may aid in conscious sedation. This study evaluated the feasibility of the lidocaine injection method (LIM) during esophageal ESD. METHODS: Twenty-nine patients with superficial esophageal cancer were enrolled in this study at Osaka Saiseikai Nakatsu Hospital, and 1% lidocaine + 0.4% hyaluronate sodium was injected into the submucosa underneath the lesion during esophageal ESD. The main outcome was body movements that disturbed the procedure. RESULTS: Most patients were male (90%), with a median age of 70 years (interquartile range [IQR]: 66-75 years old), and the median lesion size was 17 mm (IQR: 12-21 mm). The median injection volume of lidocaine was 70 mg (IQR: 55-79 mg). All lesions were successfully removed en bloc. In all cases, there were no body movements that disturbed the procedure. Regarding adverse events of sedation, five patients (17%) had hypotension, four patients (14%) had bradycardia, and seven patients (24%) had hypoxemia during ESD. Convulsions or arrhythmia as adverse events associated with lidocaine were not observed. CONCLUSIONS: Esophageal ESD with LIM did not cause body movements that disturbed the procedure. LIM may help create a stable conscious sedation method for esophageal ESD.

Barrett's adenocarcinoma with esophageal varices successfully treated by endoscopic submucosal dissection with direct varices coagulation.

A 67-year-old Japanese man with alcoholic cirrhosis underwent esophagogastroduodenoscopy (EGD), which revealed a 15-mm elevated lesion on the esophagogastric junction (EGJ). Endoscopic findings suggested that the lesion was an intramucosal cancer present on the esophageal varices. The location of the lesion at EGJ caused difficulties in endoscopic injection sclerotherapy and endoscopic variceal ligation for esophageal varices before esophageal endoscopic submucosal dissection (ESD). Direct varices coagulation treatment was therefore selected during ESD. Coagulation of bared varices with hemostatic forceps after mucosal incision enabled performing ESD without serious bleeding. 2 months afterwards, the patient underwent EGD, with no esophageal varices or carcinoma recurrence. Direct varices coagulation was effective for ESD of Barrett adenocarcinoma with esophageal varices.

Endoscopic submucosal dissection for early gastric cancer on the lesser curvature in upper third of the stomach is a risk factor for postoperative delayed gastric emptying.

BACKGROUND: Advances in Endoscopic submucosal dissection (ESD) technology have established ESD for early gastric cancer as a safe and stable technique. However, ESD may induce delayed gastric emptying and the cause of food residue retention in the stomach after ESD is not clear. This study aimed to clarify risk factors for delayed gastric emptying with food retention after gastric ESD. METHODS: We retrospectively examined for food residue in the stomach 1 week after ESD was performed for early gastric carcinoma at Osaka Saiseikai Nakatsu Hospital from February 2008 to November 2016. RESULTS: Food residue was observed in 68 (6.1%) of 1114 patients who underwent gastric ESD. The percentage of lesions located on the lesser curvature of the upper third of the stomach was 45.6% (31/68) in the food residue group and 3.5% (37/1046) in the non-food residue group, which was significantly different (P < 0.01). Multivariate logistic regression analysis revealed that lesions on the lesser curvature of the upper third of the stomach (Odds ratio [OR] 23.31, 95% confidence interval [CI] 12.60-43.61, P < 0.01), post-ESD bleeding (OR 4.25, 95%CI 1.67-9.80, P < 0.01), submucosal invasion (OR 2.80, 95%CI 1.34-5.63, P < 0.01), and age over 80 years (OR 2.34, 95%CI 1.28-4.22, P < 0.01) were independent risk factors for food retention after gastric ESD. Of the 68 patients, 3 had food residue in the stomach on endoscopic examination for follow-up observation after the ESD ulcer had healed. CONCLUSIONS: Delayed gastric emptying with food retention after gastric ESD was associated with lesions located in the lesser curvature of the upper stomach, submucosal invasion of the lesion, age older than 80 years, and post-ESD bleeding, though it was temporary in most cases.

The Effects of Switching to Vonoprazan, a Novel Potassium-Competitive Acid Blocker, on Gastric Acidity and Reflux Patterns in Patients with Erosive Esophagitis Refractory to Proton Pump Inhibitors.

BACKGROUND/AIM: The effects of vonoprazan and proton pump inhibitors (PPIs) in patients with reflux esophagitis (RE) have not yet been compared using multichannel intraluminal impedance-pH (MII-pH). METHODS: A total of 8 patients with persistent gastric mucosal injury, despite completing an 8-week standard PPI therapy, were enrolled in the study. While they were on standard PPI therapy, the baseline values of reflux parameters, holding time ratio (HTR) of gastric pH >4, and esophageal pH <4 were obtained by using 24 h MII-pH monitoring. They were re-evaluated after discontinuation of the therapy and 4 weeks of subsequent treatment with vonoprazan 20 mg/day. RESULTS: The patients were found to be CYP2C19 extensive metabolizers and negative for Helicobacter pylori infection. In 7 patients (87.5%), the mucosal lesions had healed completely after vonoprazan therapy. A significant increase in gastric pH >4 HTR was observed, from 26.5 to 78.0% (p = 0.029). A reduction in esophageal pH <4 HTR was also observed but it was not statistically significant. Furthermore, acid clearance time and the total number of reflux events, including acid and proximal reflux events, were significantly reduced. CONCLUSION: Vonoprazan may be a better therapy for the treatment of patients with PPI-refractory RE.

A Comparative Study of a New Class of Gastric Acid Suppressant Agent Named Vonoparazan versus Esomeprazole for the Eradication of Helicobacter pylori.

BACKGROUND: Helicobacter pylori eradication rates have decreased worldwide. Gastric acid inhibition during treatment is important to eradicate these bacteria successfully. A new potassium-competitive acid blocker, vonoprazan (VPZ), has been shown to achieve high eradication rates in a previous randomized controlled trial. OBJECTIVE: To determine the efficacy of VPZ for H. pylori eradication. METHODS: A total of 874 patients were enrolled; 431 received esomeprazole (EPZ) and 443 received VPZ. First-line regimens contained clarithromycin (CAM) 200 mg b.i.d., amoxicillin 750 mg b.i.d., and either EPZ 20 mg b.i.d. or VPZ 20 mg b.i.d. for 7 days. Metronidazole 250 mg b.i.d. replaced CAM in the second-line regimens. The eradication of H. pylori was assessed by 13C-urea breath tests 4-8 weeks after each therapy. RESULTS: The overall first-line eradication rate was 79.9% (341/427) with EPZ vs. 86.3% (377/439) with VPZ (p = 0.019). The second-line eradication rate was 83.3% (45/51) with EPZ vs. 91.1% (41/45) with VPZ (p = 0.900). CONCLUSION: VPZ was significantly more effective than EPZ for first-line treatment. However, for second-line treatment, there was no significant difference between EPZ and VPZ.

The serum level of NX-DCP-R, but not DCP, is not increased in alcoholic liver disease without hepatocellular carcinoma.

BACKGROUND AND AIM: Alcoholic liver disease (ALD) is the most common cause of hepatocellular carcinoma (HCC) worldwide. Des-gamma-carboxy prothrombin (DCP) is elevated in many patients with HCC, but also in severe alcoholics without HCC. We aimed to clarify whether the DCP/NX-DCP ratio (NX-DCP-R) could have a high specificity in ALD patients without HCC. METHODS: We performed a prospective cohort study on a total of 703 consecutive outpatients of liver diseases including severe alcoholics and healthy volunteers, who underwent blood biochemical examinations at Kobe University Hospital. Serum DCP was measured by electrochemiluminescence immunoassay (ECLIA) using a monoclonal antibody, MU-3. A novel parameter, serum NX-DCP, which represents predominantly DCP caused by reduced vitamin K availability, was also measured by ECLIA using monoclonal antibodies P-16 and P-11. The diagnostic accuracy of DCP and NX-DCP-R in patients with and without excessive alcohol intake was statistically examined. RESULTS: DCP was significantly higher in alcoholics than in non-alcoholics (p= 0.005), whereas the NX-DCP-R did not differ between alcoholics and non-alcoholics (p= 0.375). DCP was significantly increased in the serum of each patient with alcoholic hepatitis and alcoholic cirrhosis (p< 0.05), whereas the NX-DCP-R was not increased (p> 0.05). CONCLUSIONS: NX-DCP-R, but not DCP, was not increased in alcoholics without HCC. As for negative screening for HCC, the specificity of the NX-DCP-R in alcoholics without HCC was better than that of DCP in alcoholics without HCC, and so could be a useful negative screening tool for HCC in millions of alcoholics worldwide.

Serum level of taurine would be associated with the amelioration of minimal hepatic encephalopathy in cirrhotic patients.

AIM: A variety of treatment modalities including L-carnitine have been tried for cirrhotic patients with minimal hepatic encephalopathy (MHE), which improved MHE for some patients, but were not effective for the other patients. We aimed to identify pre-therapeutic independent factors to predict the amelioration of MHE after L-carnitine treatment. METHODS: We performed a prospective cohort study on a total of 64 consecutive outpatients of cirrhotic patients who underwent blood biochemical examinations and neuropsychiatric (NP) test at Kobe University Hospital. MHE patients diagnosed by the NP test were p.o. administrated L-carnitine for 3 months. The patients with and without MHE amelioration were compared, and the independent factors were statistically examined. Predictive scoring systems of the amelioration of MHE were established using multivariate logistic regression. RESULTS: The amelioration of MHE was found in 45.8% of MHE patients. Serum taurine before the treatment was the best predictive factor of the amelioration of MHE (P = 0.046). The predictive model using serum taurine discriminated well between patients with and without the amelioration of MHE (area under the receiver-operator curve, 0.748; 95% confidence interval, 0.531-0.901). The predictive scores of the amelioration of MHE enable the patient-specific probability to be easily looked up. CONCLUSION: Serum taurine before L-carnitine treatment was shown to be an independent factor associated with the amelioration of MHE 3 months after the treatment. The easy pre-therapeutic prediction of MHE amelioration after L-carnitine treatment would help in improving awareness of the selection of MHE patients with good response to L-carnitine, thus being beneficial from a financial perspective.

Chronic Liver Disease Questionnaire would be a primary screening tool of neuropsychiatric test detecting minimal hepatic encephalopathy of cirrhotic patients.

AIM: The neuropsychiatric test (NP test) is a clinically available modality to confirm minimal hepatic encephalopathy (MHE), but it takes at least 30 min for outpatients to complete. An easier primary screening tool of the NP test would be helpful to predict MHE in routine testing on the public. METHODS: We performed a prospective cohort study on 59 cirrhotic outpatients at Kobe University Hospital. Laboratory measurements, the NP test and the Chronic Liver Disease Questionnaire (CLDQ) were performed. As an indicator of MHE, cases with and without two abnormal subsets or more in the NP test were compared, and the independent risk factors were statistically examined. Predictive scoring systems of the risk of MHE were established using multivariate logistic regression. RESULTS: CLDQ worry (WO) was the best predictive factor of MHE diagnosed by the NP test (P = 0.006). The predictive model using CLDQ WO discriminated well between patients with and without MHE (area under the curve, 0.714; 95% confidence interval, 0.582-0.824). The predictive scores of MHE enable the patient-specific probability to be easily looked up. CONCLUSION: CLDQ WO was shown to be an independent factor associated with the NP test to diagnose MHE in cirrhotic patients. The easy predictive scoring system of the risk of MHE using CLDQ WO could become a primary screening tool before performing the NP test in a social setting.

Downregulation of CXCR4 in Metastasized Breast Cancer Cells and Implication in Their Dormancy.

Our understanding of the mechanism of cancer dormancy is emerging, but the underlying mechanisms are not fully understood. Here we analyzed mouse xenograft tumors derived from human breast cancer tissue and the human breast cancer cell line MDA-MB-231 to identify the molecules associated with cancer dormancy. In immunohistological examination using the proliferation marker Ki-67, the tumors included both proliferating and dormant cancer cells, but the number of dormant cells was remarkably increased when they metastasized to the lung. In the gene expression analysis of the orthotopic cancer cells by a single-cell multiplex real-time quantitative reverse transcription PCR followed by flow cytometric analysis, restrained cellular proliferation was associated with downregulation of the chemokine receptor CXCR4. In the immunohistological and flow cytometric analyses, the expression level of CXCR4 in the metastasized cancer cells was decreased compared with that in the cancer cells in orthotopic tumors, although the expression level of the CXCR4 ligand CXCL12 was not reduced in the lung. In addition, the proliferation of the metastasized cancer cells was further decreased by the CXCR4 antagonist administration. In the ex vivo culture of the metastasized cancer cells, the expression level of CXCR4 was increased, and in the xenotransplantation of ex vivo cultured cancer cells, the expression level of CXCR4 was again decreased in the metastasized cancer cells in the lung. These findings indicate that CXCR4 is downregulated in metastasized breast cancer cells and implicated in their dormancy.

Serum NX-DCP as a New Noninvasive Model to Predict Significant Liver Fibrosis in Chronic Hepatitis C.

BACKGROUND: Finding a noninvasive method to predict liver fibrosis using inexpensive and easy-to-use markers is important. OBJECTIVES: We aimed to clarify whether NX-des-γ-carboxyprothrombin (NX-DCP) could become a new noninvasive model to predict liver fibrosis in hepatitis C virus (HCV) related liver disease. PATIENTS AND METHODS: We performed a prospective cohort study on a consecutive group of 101 patients who underwent liver biopsy for HCV-related liver disease at Kobe University Hospital. Laboratory measurements were performed on the same day as the biopsy. Factors associated with significant fibrosis (F3-4) were assessed by multivariate analyses. A comparison of predictive ability between multivariate factors and abovementioned noninvasive models was also performed. RESULTS: Increase in serum NX-DCP was significantly related to increase in fibrosis stage (P = 0.006). Moreover, NX-DCP was a multivariate factor associated with the presence of significant fibrosis F 3-4 (median 21 of F0-2 group vs. median 22 of F3-4 group with P = 0.002). The AUC of NX-DCP showed no significant differences compared with those of the AST-to-platelet ratio index (APRI), modified-APRI, the Göteborg University Cirrhosis Index (GUCI), the Lok index, the Hui score, cirrhosis discriminating score (CDS) and the Pohl score (P > 0.05). CONCLUSIONS: NX-DCP correlated positively with fibrosis stage and could discriminate well between HCV-related patients with or without significant fibrosis. Moreover, NX-DCP had a similar predictive ability to the abovementioned models, and thereby could be a new noninvasive prediction tool for fibrosis.

Acute Hepatic Phenotype of Wilson Disease: Clinical Features of Acute Episodes and Chronic Lesions Remaining in Survivors.

BACKGROUND AND AIMS: Wilson disease (WD) is an inherited disorder of copper metabolism, and an international group for the study of WD (IGSW) has proposed three phenotypes for its initial presentation: acute hepatic, chronic hepatic, and neurologic phenotypes. Characterization of the acute hepatic phenotype may improve our understanding of the disease. METHODS: Clinical features of 10 WD patients with the acute hepatic phenotype and characteristics of chronic lesions remaining in survivors were assessed by the European Association for the Study of the Liver (EASL) guidelines. RESULTS: All six patients younger than 30 years had survived an acute episode of hemolytic anemia with residual liver disease of cirrhosis or chronic hepatitis. The acute episode was self-limiting in two of the four patients over the age of 30 years and progressed to acute liver failure in the other two patients. One of the two survivors had residual liver disease of chronic hepatitis, while the other had chronic hepatitis and neurologic disease. Neurologic disease remained in a patient who successfully received a liver transplantation. During acute episodes, serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) changed rapidly along with anemia. Liver-specific ALT levels were age-dependently correlated with hemoglobin (Hb) concentrations. Enzyme reduction was milder for AST than ALT, which resulted in a high AST/ALT ratio in the anemic stage. The anemic stage in two patients transformed to acute liver failure. CONCLUSIONS: All survivors of an acute episode of the acute hepatic phenotype had residual liver disease or both liver and neurologic diseases. The rapid changes in liver enzymes during the acute episode and the liver and neurologic diseases remaining in survivors may provide a better understanding of WD.

Branched-chain amino acid granules improve the non-protein respiratory quotient after radiofrequency ablation.

OBJECTIVE: The supplementation of oral branched-chain amino acid (BCAA) granules is known to improve energy metabolism in cirrhotic patients, but not those with hepatocellular carcinoma (HCC). We aimed to clarify whether BCAA granules improve energy metabolism in HCC patients after radiofrequency ablation (RFA). METHODS: We performed a prospective cohort study (UMIN000004624) involving 40 HCC patients who underwent RFA at Kobe University Hospital. Indirect calorimetry and urinary/blood biochemical examinations were performed before and seven days after RFA. Blood biochemical examinations were also conducted three months after RFA. The patients treated with and without BCAA supplementation were compared, and univariate factors were statistically examined. RESULTS: The non-protein respiratory quotient (npRQ) and albumin levels before RFA were significantly lower in the BCAA group than in the control group (p=0.024 and 0.005). The npRQ ratio (seven days after/before RFA) was significantly higher in the BCAA group than in the control group (p=0.019). In addition, the albumin ratio (three months after/before RFA) was significantly higher in the BCAA group than in the control group (p=0.018). CONCLUSION: Supplementation with BCAA granules improves energy metabolism in addition to the liver function after RFA. Improvements in the liver function may result in consistently adequate treatment for HCC recurrence after RFA.

Mutational diversity of NS5A and NS3 during triple therapy (telaprevir, pegylated-interferon-α 2b and ribavirin) for genotype 1b chronic hepatitis C: The Kobe Hepatitis Therapeutic Group.

Telaprevir, a non-structural (NS)3/4A protease inhibitor, is a direct-acting antiviral drug that inhibits viral replication. Triple therapy with telaprevir, pegylated interferon, and ribavirin is a standard therapeutic regimen for patients with genotype 1b chronic hepatitis C virus (HCV) infection and a high viral load. Several factors, including mutations in the NS5A gene, are important predictors of the efficacy of interferon therapy. In this study, we examined the mutational diversity of NS5A and its impact on the efficacy of triple therapy. We enrolled patients with genotype 1b chronic HCV infection and a high viral load (31 males/17 females; mean age, 57.6 years), who were treated with triple therapy. This study was conducted at Kobe University Hospital and at three affiliated hospitals in Hyogo prefecture, Japan, between November 2011 and June 2013. A sustained viral response after 12 weeks (SVR12) was achieved in 37/48 patients (77%). Based on intent-to-treat analysis, SVR12 was significantly greater in patients with the major allele than in those with the minor allele for the IL28B single nucleotide polymorphism (SNP; 88 vs. 56%; P<0.05). The prevalence of the V2334I mutation in NS5A was significantly higher in patients who achieved SVR12, while that of G2356E was significantly higher in patients who did not achieve SVR12 (P<0.05). Mutations in the NS3 region that are thought to confer resistance to telaprevir were detected in 3/27 patients who achieved SVR12 (Val36, n=3) and in 5/10 patients who did not achieve SVR12 (Val36, n=4; Thr54, n=1). In conclusion, the IL28B SNP and mutations in the NS5A region were associated with the therapeutic response to triple therapy. Half of the patients who did not achieve SVR12 had mutations conferring resistance to telaprevir. However, pre-existing mutations in NS3 did not affect the efficacy of triple therapy.