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Miwa Kawanaka,1 Ken Nishino,1 Takahito Oka,1 Noriyo Urata,1 Jun Nakamura,1 Mitsuhiko Suehiro,1 Hirofumi Kawamoto,1 Yasutaka Chiba,2 Gotaro Yamada1 1Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan; 2Clinical Research Center, Kinki University Hospital, Sayama, Japan Objective: Amino acid imbalance is often found in patients with cirrhosis, and this imbalance is associated with insulin resistance. However, the mechanism underlying the relationship between amino acid imbalance and insulin resistance remains unclear. We evaluated serum amino acid concentrations in patients with nonalcoholic fatty liver disease to determine if any of the levels of amino acids were associated with the biochemical markers and fibrosis stage of nonalcoholic steatohepatitis (NASH). Methods: In 137 patients with nonalcoholic fatty liver disease who underwent liver biopsy, plasma levels of branched-chain amino acid (BCAA), tyrosine (Tyr), and the BCAA-to-Tyr ratio values were determined using mass spectroscopy. These values were then assessed for associations with fibrosis stage, anthropometric markers (age, sex, and body mass index), biochemical markers (alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glycosylated hemoglobin), and relevant disease-specific biomarkers (homeostasis model assessment of insulin resistance [HOMA-IR], serum iron, ferritin, leptin, adiponectin, high-sensitivity C-reactive protein, and hyaluronic acid). Results: Serum albumin levels, plasma BCAA levels, and BCAA-to-Tyr ratio values were negatively associated with the fibrosis stage. In contrast, Tyr levels increased with increasing fibrotic staging. Tyr levels were also correlated with HOMA-IR results. Conclusion: Plasma BCAA levels in patients with NASH decreased with increasing liver fibrosis, while Tyr levels increased with increasing fibrotic stage. These results suggest that amino acid imbalance and insulin resistance are intimately involved in a complex pathogenic mechanism for NASH. Keywords: nonalcoholic steatohepatitis, amino acid imbalance, branched-chain amino acids, branched-chain amino acid-to-tyrosine ratio (BTR)

Miwa Kawanaka,1 Ken Nishino,1 Jun Nakamura,1 Mitsuhiko Suehiro,1 Daisuke Goto,1 Noriyo Urata,1 Takahito Oka,1 Hirofumi Kawamoto,1 Hajime Nakamura,2 Junji Yodoi,3 Keisuke Hino,4 Gotaro Yamada11Department of Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, 2Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, 3Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto, 4Department of Hepatology and Pancreatology, Kawasaki Medical School, Okayama, JapanBackground: Nonalcoholic steatohepatitis (NASH) is a common liver disease that can progress to cirrhosis. Oxidative stress is one of the central mechanisms causing hepatocellular injury in the disease. In this study, antioxidant therapy using both vitamins C and E was conducted in patients with NASH.Methods: Vitamin E 300 mg/day and vitamin C 300 mg/day were administered orally to 23 patients with NASH for 12 months. Body mass index was measured during therapy. Serum levels of alanine aminotransferase, thioredoxin (an oxidative stress marker), and high-sensitivity C-reactive protein were measured before treatment and after 12 months in all patients. Ten of the 23 patients underwent liver biopsy before and after treatment.Results: Body mass index remained unchanged during treatment with vitamins C and E. Serum alanine aminotransferase, thioredoxin, and high-sensitivity C-reactive protein levels were decreased significantly at 12 months compared with pretreatment. Liver biopsies showed improved necroinflammatory activity in eight cases and improved fibrosis staging in 4.Conclusion: Serum alanine aminotransferase, thioredoxin, and high-sensitivity C-reactive protein levels, and liver histology were clearly improved with vitamin C and E therapy. These findings suggest that combination therapy using these vitamins may be useful in patients with NASH to minimize damage from oxidative stress and slow the processes leading to cirrhosis.Keywords: vitamin E, vitamin C, nonalcoholic steatohepatitis, oxidative stress

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is associated with a variety of adverse events (AEs). One of the most important AEs is post-ERCP pancreatitis (PEP), which is most common in cases of difficult biliary cannulation. Although the precut technique has been reported as a PEP risk factor, recent studies indicate that early precut could reduce PEP, and that precut itself is not a risk factor., Aim: To evaluate the safety of the precut technique, especially in terms of PEP., Methods: We conducted a retrospective study, spanning the period from November 2011 through December 2021. It included 1556 patients, aged ≥ 20 years, who underwent their initial ERCP attempt for biliary disease with a naïve papilla at the Kawasaki University General Medical Center. We compared the PEP risk between the early precut and the delayed precut group., Results: The PEP incidence rate did not significantly differ between the precut and non-precut groups. However, the PEP incidence was significantly lower in the early precut group than the delayed precut group (3.5% vs 10.5%; P = 0.02). The PEP incidence in the delayed precut group without pancreatic stent insertion (17.3%) was significantly higher compared to other cases ( P < 0.01)., Conclusion: Our findings indicate that early precut may reduce PEP incidence. If the precut decision is delayed, a pancreatic stent should be inserted to prevent PEP., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective Gastrointestinal (GI) disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and inflammatory bowel disease (IBD) can exhibit overlapping GI symptoms, including abdominal pain and alterations in bowel habits. The symptoms of GI disorders are commonly considered to be triggered and exacerbated by fatty food intake. Therefore, this study aimed to compare the food preferences of patients with GI disorders. Methods Forty food images (including fatty and light foods) and 20 animal images were selected to evaluate food preferences. The preference score was assessed using a visual analog scale ranging from 1 to 100. GI symptoms were evaluated using the GI Symptom Rating Scale (GSRS), and correlations between the GSRS and preference scores were investigated. Results Overall, 22 healthy controls and 23, 29, 27, and 20 patients with FD, IBS, GERD, and IBD, respectively, were enrolled. The preference score for all foods in patients with FD was significantly lower than that in healthy controls and those with IBS, GERD, and IBD (52.9 vs. 66.5 vs. 68.5 vs. 69.1 vs. 70.7, p<0.01). The score of fatty foods was lower in patients with FD than in healthy controls and those with IBS, GERD, and IBD (43.8 vs. 72.3 vs. 77.5 vs. 77.4 vs. 80.7, p<0.01), whereas that of light foods and animal images was not different among the groups. No significant correlation was found between the preference score and symptom severity. Conclusions Patients with FD had a negative preference for foods, particularly fatty foods, independent of the severity of GI symptoms.

A 66-year-old male came to our hospital because of occult blood in stool and anemia. The patient was diagnosed as unresectable advanced gastric cancer,( ML/Less, type 2, tub2, cT4b[liver], cN+, cM0, cStage Ⅳ, HER2 negative). He was given oxaliplatin plus S-1 therapy. In the 3rd course of chemotherapy, he had severe anemia, and active bleeding from the tumor. To control the bleeding he underwent distal gastrectomy, lateral segmentectomy of the liver, and S4 partial hepatectomy. The patient underwent adjuvant chemotherapy with docetaxel plus S-1. Three months after surgery, lymph nodes recurrence was observed. He underwent second-line therapy with paclitaxel and ramucirumab. Seven months after surgery, lymph nodes recurrence was increased. He was switched to third-line therapy with nivolumab. He is currently arrive 12 months after surgery.

The patient was a 73-year-old man. He was diagnosed with left renal pelvic carcinoma(papillary urothelial carcinoma, pT3aN0M0, Stage Ⅱ)at the age of 69. Left nephroureterectomy and partial cystectomy were performed at our hospital. At the age of 71, he was diagnosed with a recurrent bladder tumor and underwent radical cystectomy and ureteroenterostomy at a different hospital. At the age of 73, he visited our hospital with abdominal pain. Computed tomography(CT)revealed wall thickening of the descending colon and dilation of the oral tract. Emergency colonoscopy was performed. He was diagnosed with intestinal obstruction due to descending colon cancer. Colonoscopy revealed a circumferential type 2 lesion in the descending colon that was completely stenosed. Colonic stent placement was performed. A tumor biopsy confirmed the diagnosis of micropapillary adenocarcinoma. The preoperative diagnosis was descending colon cancer cT4aN2aM0, cStage Ⅲc. One month after stent placement, an open segmental resection of the descending colon with D2 dissection was performed. Immunostaining of the specimen showed CK7(+)and CK20(-), and the postoperative diagnosis was a recurrence of left renal pelvic carcinoma in the descending colon. We report a rare case of renal pelvic carcinoma that recurred in the descending colon 4 years after initial surgery.

In a 79-year-old man, upper gastrointestinal endoscopy and CT revealed an entire circumferential type 3 tumor with stenosis from the lower thoracic esophagus to the abdominal esophagus. He was diagnosed with esophageal adenocarcinoma and underwent middle and lower esophageal resection and 2 regional lymph node dissections. The postoperative pathological diagnosis was poorly differentiated adenocarcinoma, pT3N0M0, pStage ⅡA esophagogastric junction cancer(Siewert type Ⅱ). The patient was followed-up without postoperative adjuvant chemotherapy, following the Japanese Gastric Cancer Treatment Guidelines 2021(6th edition). Six months postoperatively, contrast-enhanced CT revealed multiple lymph node, small intestinal mesenteric, and left adrenal metastases, and SOX therapy was initiated. After 4 courses of SOX therapy, the patient was brought to the emergency room and admitted with anorexia and weakness, and consciousness disorder was observed on the next day. Contrast-enhanced MRI of the head was indicative of meningeal carcinomatosis, and cytological examination of the spinal fluid revealed adenocarcinoma, which was diagnosed as meningeal carcinomatosis from esophagogastric junction carcinoma. Subsequently, his consciousness disorder worsened, and he died on the 9th day of hospitalization. We report a rare case of meningeal carcinomatosis following esophagogastric junction cancer.

Background: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are caused and exacerbated by consumption of fatty foods. However, no study has evaluated brain activity in response to food images in patients with disorders of gut-brain interaction (DGBI). This study aimed to compare food preference and brain activity when viewing food images between patients with DGBI and healthy controls., Methods: FD and IBS were diagnosed using the ROME IV criteria. Food preference was assessed using a visual analog scale (VAS). Brain activity in the prefrontal cortex (PFC) in response to food images was investigated using functional near-infrared spectroscopy (fNIRS)., Results: Forty-one patients were enrolled, including 25 with DGBI. The mean VAS scores for all foods (controls vs. FD vs. IBS: 69.1 ± 3.3 vs. 54.8 ± 3.8 vs. 62.8 ± 3.7, p = 0.02), including fatty foods (78.1 ± 5.4 vs. 43.4 ± 6.3 vs. 64.7 ± 6.1, p < 0.01), were the lowest in patients with FD among all groups. Patients with FD had significantly higher brain activity in the left PFC than those with IBS and healthy controls (mean z-scores in controls vs. FD vs. IBS: - 0.077 ± 0.03 vs. 0.125 ± 0.04 vs. - 0.002 ± 0.03, p < 0.001)., Conclusions: Patients with DGBI, particularly those with FD, disliked fatty foods. The brain activity in patients with DGBI differed from that in healthy controls. Increased activity in the PFC of patients with FD was confirmed., (© 2023. The Author(s).)

Aim: This study aimed to evaluate the age-specific characteristics, prognosis, and complications of patients with lean nonalcoholic fatty liver disease (NAFLD)., Methods: Background factors (age, sex, diabetes, dyslipidemia, hypertension, and PNPLA3 gene polymorphism), blood test results, liver histology findings, muscle mass, and grip strength were investigated in 782 patients with NAFLD who underwent liver biopsy. Prognosis and complications were compared among 549 patients with nonlean or lean NAFLD who were followed up for 6.5 years. Additionally, background factors, blood test results, liver histology findings, prognosis, and complications were compared according to age (≥60 years vs. <60 years) in patients with lean NAFLD., Results: Lean NAFLD patients showed lower aspartate aminotransferase, alanine aminotransferase, homeostasis model assessment-insulin resistance, high-sensitivity C-reactive protein, ferritin, and leptin but higher adiponectin and hemoglobin A1c (HbA1c) levels than patients with nonlean NAFLD. Furthermore, lean NAFLD patients showed less liver fibrosis, inflammation, steatosis, and ballooning. Among lean NAFLD patients, those aged 60 years and older were more frequently female, showed higher rates of hypertension, diabetes, and dyslipidemia, had higher HbA1c and type IV collagen 7S levels, lower platelet count, higher liver fibrosis and inflammation grades, and lower muscle mass and grip strength. Lean NAFLD was associated with a worse prognosis in patients aged 60 years and over than in those younger than 60 years of age and with a higher incidence of liver-related disease, cerebrocardiovascular events, and nonliver cancer., Conclusions: Age is an important consideration in patients with lean NAFLD. Compared with nonlean NAFLD, lean NAFLD was associated with a worse prognosis and higher risk of complications in patients aged 60 years and older., (© 2023 Japan Society of Hepatology.)

Background and Aim: Percutaneous drainage of intra-abdominal abscesses is often uncomfortable for the patient and may result in prolonged hospital stays. Recent studies have shown that endoscopic ultrasound-guided abscess drainage (EUS-AD) could effectively treat various abscesses and fluid collections. However, no indications or procedures have been established for EUS-AD treatments, and studies on its usefulness and safety are insufficient. The present study aimed to evaluate the efficacy and safety of EUS-AD for treating non-pancreatic abscesses., Methods: This retrospective study included 20 patients, aged ≥20 years, who underwent EUS-AD for an abscess or fluid accumulation in the abdomen or mediastinum, but not the pancreas. Patients were treated at the Kawasaki University General Medical Center between March 2013 and June 2021. All EUS-AD procedures were performed prior to a percutaneous drainage or surgical drainage., Results: Among the 20 patients who underwent an EUS-AD for abscess, 8 (40%) had liver abscesses, 6 (30%) had intraperitoneal abscesses, 3 had (15%) splenic abscesses, 1 (5%) had a mediastinal abscess, 1 (5%) had an iliopsoas abscess ( n  = 1, 5%), and 1 (5%) had an abdominal wall abscess. The technical success rate was 95% ( n  = 19/20). We inserted nasobiliary catheters in 4/20 patients (20%). The clinical success rate was 90% ( n  = 18/20). Two clinical failures required reintervention, and both were treated with percutaneous drainage. Adverse events were observed in 2/20 patients (10%). One patient experienced fever after the procedure, and the other experienced localized peritonitis., Conclusion: EUS-AD was effective and safe for abscess removal, particularly when approached from the upper gastrointestinal tract., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. The serum level of soluble CD163 (sCD163), a macrophage activation marker, is associated with liver tissue changes; however, its prognostic value is unknown. Here, we determined the utility of sCD163 as a marker for hepatocellular carcinoma (HCC) and prognostic marker for NAFLD., Methods: This retrospective study obtained data regarding serum sCD163 levels, liver histology, and background factors associated with NAFLD in 287 patients (men/women, 140/147; average age, 53 ± 14 years) with NAFLD who underwent liver biopsy. Repeated liver biopsies of 287 patients with NAFLD (5.0 ± 2.7 years) were compared regarding serum sCD163 levels and liver tissue changes (stage, grade, steatosis, and NAFLD activity score)., Results: Serum sCD163 levels increased with the progression of liver fibrosis and inflammation (both P < 0.05) and were particularly helpful in distinguishing cases of Grade 4 fibrosis (P < 0.001). Levels of sCD163 significantly decreased in patients with NAFLD exhibiting alleviated fibrosis and inflammation (P < 0.05). We could also predict the development of HCC and associated mortality based on serum sCD163 levels at the time of NAFLD diagnosis. Serum sCD163 levels were higher in patients with HCC than in patients without HCC (1074 ± 379 ng/ml vs. 669 ± 261 ng/ml; P < 0.0001), and the same trend was observed for mortality., Conclusions: The serum sCD163 level reflects the progression of fibrosis and inflammation in liver tissues, showing much promise as a noninvasive biomarker for nonalcoholic steatohepatitis and NAFLD as well as a possible predictor of HCC development and patient prognosis., (© 2023. The Author(s).)

Two adult cases of acute gastric mucosal lesions (AGML) caused by Helicobacter pylori infection were confirmed by spontaneous eradication during the follow-up period. The clinical course of the initial infection by H. pylori in adults with AGML remains unclear, whether it is transient or progresses to a persistent infection. In these two reported cases, gastric biopsies at the time of the onset revealed the presence of H. pylori; however, serum H. pylori antibodies performed at the same time were negative. Retesting for H. pylori serum antibody, after six months in one and after two months in the other, was negative, confirming spontaneous eradication.

Background and Aim: Obstructive jaundice induced by pancreatic adenocarcinoma is typically treated with biliary drainage with endoscopic retrograde cholangiopancreatography (ERCP)-guided biliary drainage (ERCP-BD). Recently, endoscopic ultrasonography-guided biliary drainage (EUS-BD) was employed as an alternative method after ERCP-BD failed. We aimed to determine the efficacy and safety of EUS-BD for primary biliary drainage., Methods: Between December 2011 and February 2019, at Kawasaki General Medical Center, we retrospectively enrolled 33 patients who had undergone endoscopic biliary drainage with a metal stent, in a first attempt to relieve obstructive jaundice caused by unresectable pancreatic adenocarcinoma. We compared the technical and clinical outcomes between ERCP-BD and EUS-BD., Results: Twenty-three patients underwent ERCP-BD and 10 underwent EUS-BD. Both groups achieved 100% technical success. The clinical success rates were similar between the groups: 91% (21/23 patients) for ERCP-BD and 100% (10/10 patients) for EUS-BD ( P  = 0.48). Biliary obstruction recurred in 6/23 patients (26%) treated with ERCP-BD and 1/10 patients (10%) treated with EUS-BD ( P  = 0.40). Other adverse events occurred in 4/23 patients (17%) in the ERCP-BD group and 1/10 patients (10%) in the EUS-BD group ( P  = 0.99)., Conclusion: We suggest that EUS-BD could be employed for primary biliary drainage in patients with obstructive jaundice caused by unresectable pancreatic adenocarcinoma., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

A 75-year-old man with fever was diagnosed with alveolar hemorrhage. Antineutrophil cytoplasmic antibodies for myeloperoxidase and proteinase 3 were absent. He received corticosteroid therapy, which immediately improved his symptoms and chest radiological findings. After the discontinuation of corticosteroids, fever and general fatigue relapsed, and renal function deteriorated with hematuria and proteinuria. A nerve conduction study revealed mononeuritis multiplex. Renal biopsy demonstrated focal necrotizing crescentic glomerulonephritis with endocapillary proliferative lesions, immunofluorescence C3 deposits, and electron-microscopic subepithelial hump-like deposits. Nephritis-associated plasmin receptor (NAPlr) and plasmin activity, biomarkers of infection-related glomerulonephritis, were positive in glomeruli. Although pathological findings suggested infection-related glomerulonephritis (IRGN), clinical manifestations, such as alveolar hemorrhage and mononeuritis multiplex, suggested systemic small vessel vasculitis. After corticosteroid therapy, systemic symptoms disappeared, and the gradual amelioration of hematuria and proteinuria was observed. Based on the clinical symptoms for which steroid therapy was effective, the patient was considered to have systemic small vessel vasculitis, the etiology of which may have been associated with infection., (© 2021. Japanese Society of Nephrology.)

We present a 56-year-old female patient diagnosed with stage 2/grade 3 non-alcoholic steatohepatitis (NASH) via liver biopsy. Over the next 14 years, six liver biopsies were performed, and the patient was followed up clinically. This was a valuable case wherein we were able to investigate the histology of the liver and the timing of changes in the AST/ALT ratio, platelets, albumin, FIB4-Index, and liver fibrosis markers.

Objective: To evaluate patient acceptability and bowel preparation efficacy of sodium picosulfate-magnesium citrate (PICOPREP) for colonoscopy., Methods: A questionnaire survey regarding the patient acceptability of bowel preparation agent PICOPREP was administered to 54 patients, and its efficacy was evaluated using the Ottawa Bowel Preparation Scale (OBPS)., Results: Eighteen (33.3%) participants reported that PICOPREP is very easy to drink, 30 (55.5%) easy, four (7.4%) acceptable, one (1.9%) difficult, and one (1.9%) very difficult. The flavor was very good as reported by eight (14.8%) participants, good by 25 (46.3%), neutral by 20 (37.0%), bad by one (1.9%), and very bad by none. The number of patients who requested PICOPREP was 42 (77.7%), indicating its high acceptability. Evaluation of the OBPS score showed that the rectosigmoid colon had significantly better polyethylene glycol (PEG) scores than PICOPREP, but the entire colon did not show a significant difference between PICOPREP and PEG scores (1.09 ± 0.65 vs. 1.17 ± 0.76, p  = 0.632 in the right colon; 0.48 ± 0.52 vs. 0.72 ± 0.66, p  = 0.079 in the mid colon, 0.93 ± 0.49 vs. 0.63 ± 0.52, p  = 0.012 in the rectosigmoid colon, and 3.28 ± 1.70 vs. 3.20 ± 1.90, p  = 0.836 in the entire colon)., Conclusion: PICOPREP is considered as one of the important options due to its good patient acceptability and high efficacy similar to PEG., Competing Interests: The authors declare that they have no conflict of interest., (© 2021 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Glomerulopathy with fibronectin deposits (GFND) is a rare hereditary kidney disease with autosomal dominant inheritance. A 21-year-old woman who had been diagnosed with GFND 10 years ago was admitted for investigation of a rapid decline in her renal function, hemolytic anemia, and cardiac dysfunction. A renal biopsy showed GFND accompanied by extraglomerular vascular lesions. Comprehensive treatments against hypertension and anemia improved the renal function. Although there have been few reports of vascular lesions in GFND, we suspect that endothelial hyperpermeability resulting from hypertension caused the fibronectin deposition and narrowing of the extraglomerular vascular lumens, thereby accelerating hypertension and inducing hemolytic anemia.

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and affects approximately 25% of the general global adult population. The prognosis of NAFLD patients with advanced liver fibrosis is known to be poor. It is difficult to assess disease progression in all patients with NAFLD; thus, it is necessary to identify patients who will show poor prognosis., Aim: To investigate the efficacy of non-invasive biomarkers for predicting disease progression in patients with NAFLD., Methods: We investigated biomarkers associated with mortality in patients with NAFLD who visited the Kawasaki Medical School General Medical Center from 1996 to 2018 and underwent liver biopsy and had been followed-up for > 1 year. Cumulative overall mortality and liver-related events during follow-up were calculated using the Kaplan-Meier analysis and compared using log-rank testing. We calculated the odds ratio and performed receiver operating characteristic curve analysis with logistic regression analysis to determine the optimal cut-off value with the highest prognostic ability., Results: We enrolled 489 patients who were followed-up for a period of 1-22.2 years. In total, 13 patients died (2.7% of total patients enrolled); 7 patients died due to liver-related causes. Poor prognosis was associated with liver fibrosis on histological examination but not with inflammation or steatosis. Blood biomarkers associated with mortality were platelet counts, albumin levels, and type IV collagen 7S levels. The optimal cutoff index for predicting total mortality was a platelet count of 15 × 10 4 /μL, albumin level of 3.5 g/dL, and type IV collagen 7S level of 5 mg/dL. In particular, only one-factor patients with NAFLD presenting with platelet counts ≤ 15 × 10 4 /μL, albumin levels ≤ 3.5 g/dL, or type IV collagen 7S ≥ 5 mg/dL showed 5-year, 10-year, and 15-year survival rates of 99.7%, 98.3%, and 94%, respectively. However, patients with two factors had lower 5-year and 10-year survival rates of 98% and 43%, respectively. Similarly, patients with all three factors showed the lowest 5-year and 10-year survival rates of 53% and 26%, respectively., Conclusion: A combination of the three non-invasive biomarkers is a useful predictor of NAFLD prognosis and can help identify patients with NAFLD who are at a high risk of all-cause mortality., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective We investigated the muscle cramp status of patients with liver cirrhosis by focusing on the degree of liver damage, skeletal muscle mass, and nutritional status. Methods All enrolled patients completed a questionnaire about muscle cramps. The degree of liver damage was examined using the Child-Pugh classification and the albumin-bilirubin (ALBI) grade. The nutritional status and skeletal muscle mass were examined using the Controlling Nutritional Status (CONUT) method and the psoas muscle index (PMI). Results Among the respondents, 55.7% of the patients reported experiencing muscle cramps. An analysis of the two patient groups-those who experienced muscle cramps and those who did not-revealed significant differences in Child-Pugh classification (muscle cramp-positive vs. muscle cramp-negative: A/B/C, 54.1%/32.4%/13.5% vs. 90.0%/10.0%/0.0%; p=0.004), ALBI grade (1/2/3, 20.5%/71.8%/7.7% vs. 54.8%/38.7%/6.5%; p=0.011), modified ALBI grade (1/2a/2b/3, 20.5%/20.5%/51.3%/7.7% vs. 54.8%/22.6%/16.1%/6.5%; p=0.008), CONUT score (normal/mild/moderate/severe, 25.6%/28.2%/41.0%/5.1% vs. 22.6%/61.3%/12.9%/3.2%; p=0.024), and PMI (3.85±1.13 cm 2 /m 2 vs. 4.94±1.86 cm 2 /m 2 ; p=0.012). Conclusion Our findings suggest that muscle cramps occur more frequently in patients with liver cirrhosis due to their decreased liver function and poorer nutritional status.

Background: Considering the fact that both alanine aminotransferase (ALT) and the triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio are useful markers for cardiovascular disease, insulin resistance (IR), and metabolic syndrome (MetS), the possible association of ALT and TG/HDL-C ratio is conceivable, but the association is not well studied. Moreover, assessment of IR and MetS by a combination lipid and liver biomarkers has rarely been carried out. Methods: A total of 11,808 Japanese subjects who underwent an annual health examination and who were not taking medications were recruited. The association between TG/HDL-C ratio and ALT level was investigated using correlation and multiple linear regression analyses. Homeostasis model assessment of insulin resistance (HOMA-IR) and the number of MetS components were evaluated after subjects were stratified by TG/HDL-C ratio and ALT levels. Results: Correlation analysis revealed that ALT levels were positively associated with TG/HDL-C ratio. Moreover, multiple linear regression analysis revealed that TG/HDL-C ratio was positively associated with ALT levels, and the association was attenuated but persisted in both men and women after additional adjustment for visceral adiposity (body mass index, waist circumference, or fatty liver) and IR (HOMA-IR). HOMA-IR and MetS component number increased with either ALT or TG/HDL-C ratio in both men and women. HOMA-IR and MetS component number were particularly high (HOMA-IR: men 2.82, women 3.22, MetS component number: men 2.6, women 2.1) in subjects with highest ALT level and TG/HDL-C ratio. Conclusions: TG/HDL-C ratio showed a positive association with ALT levels in both sexes. Assessments of IR and MetS can become more precise by evaluating TG/HDL-C ratio and ALT, simultaneously.

A 44-year-old patient progressed from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) cirrhosis. She was diagnosed with NAFL via a liver biopsy. At 56 years old, she was diagnosed with NASH stage 3 via a second liver biopsy. One year later, she was diagnosed with NASH cirrhosis via a third liver biopsy. This is the first study to report the gradual deterioration of liver histology shown via three liver biopsies and fibrosis markers in a patient who progressed from NAFL to NASH cirrhosis. Following menopause, it is necessary to be aware of the rapid development of liver fibrosis.

We herein report a case of gastric hyperplastic polyps after argon plasma coagulation (APC) for gastric antral vascular ectasia (GAVE) in the antrum of a 65-year-old man with liver cirrhosis and hypergastrinemia induced by long-term proton pump inhibitor (PPI) use. Two years after APC therapy, endoscopy demonstrated multiple gastric polyps in the antrum and angle. A gastric polyp biopsy indicated foveolar epithelium hyperplasia, which was diagnosed as gastric hyperplastic polyps. One year after switching to an H2 blocker antagonist, endoscopy revealed that the polyps and GAVE had disappeared, with normal gastrin levels suggesting that PPI-induced hypergastrinemia had caused gastric hyperplastic polyps after APC therapy, and the polyps had disappeared after discontinuing PPIs.

Results from a recent study indicate that a higher level of oleic acid/stearic acid ratio was associated with metabolically unhealthy obesity. This was further validated in cross-sectional and interventional studies; however, this was not extensively studied in a non-obese population. We recruited 260 Japanese subjects with serum free fatty acid profiles undergoing anti-aging health examinations. The determinants for oleic acid/stearic acid ratio were investigated using multiple regression analyses. To compare different markers, the subjects were classified based on oleic acid/stearic acid ratio and the combination of oleic acid/stearic acid ratio and triglyceride levels. The oleic acid/stearic acid ratio exhibited a positive correlation with the logmatic transformed triglyceride/high-density lipoprotein cholesterol ratio and the fasting triglycerides-glucose index, both of which were used as markers for insulin resistance. Multiple regression analyses revealed that the triglyceride/high-density lipoprotein cholesterol ratio and fasting triglyceride-glucose index were positively associated with the oleic acid/stearic acid ratio. Most markers were the worst in the highest triglyceride group in both oleic acid/stearic acid groups. In addition, most markers were worse in high oleic acid/stearic acid ratio group than low group. In conclusion, oleic acid/stearic acid ratio might be a useful marker for insulin resistance in non-obese Japanese subjects., Competing Interests: The authors(s) declared no potential conflict of interest with respect to the research, authority, and/or publication of this article., (Copyright © 2021 JCBNCopyright © 2021 JCBN.)

It has been reported that hepatic flare (HF), attributable to the development of immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfected patients, occurs frequently after the start of anti-retroviral therapy (ART). We have observed several cases of hepatitis B surface antigen (HBsAg) loss after IRIS. However, the factors leading to HBsAg clearance remain unknown. We measured CD4+ and CD8+ T cells, cytokines and chemokines in 16 patients coinfected HIV-1 and HBV with IRIS, and analyzed the factors leading to HBsAg clearance after IRIS. There was no significant difference in the CD4+ and CD8+ T cell counts between the HBsAg clearance and non-clearance groups, while the serum concentrations of almost all cytokines and chemokines in the HBsAg clearance group were higher than in the HBsAg non-clearance group at any time of observation. In particular, IP-10 at the ALT peak, GM-CSF and IL-12 one month after the ALT peak and TNF-α and GM-CSF after the ALT concentrations fell to within normal limits, were significantly higher in the HBsAg clearance group. It seems that HBsAg loss after IRIS requires continued immune responses against HBV, involving Th1 cytokines.

A 68-year-old woman had undergone laparoscopic high anterior resection for rectal cancer. Two years postoperatively, metachronal pulmonary metastases and cerebellar metastasis were surgically resected. Three and a half years after the primary surgery, computed tomography(CT)demonstrated a nodule at the pancreatic tail. Under suspected primary pancreatic cancer or metastasis from rectal cancer, we performed distal pancreatectomy. Histological examination of the pancreatic tumor suggested a metastasis from the rectal cancer since tumor cells were negative for CK7 and positive for CK20 and CDX2 immunohistochemically. Three months after the pancreatic resection, CT demonstrated hepatic and cerebellar metastases. After subsequent chemotherapy, liver metastasis disappeared. The cerebellar metastasis shrank with radiotherapy.

Background The relationship between growth hormone (GH)-replacement therapy and the thyroid axis in GH-deficient (GHD) children remains controversial. Furthermore, there have been few reports regarding non-GHD children. We aimed to determine the effect of GH therapy on thyroid function in GHD and non-GHD children and to assess whether thyrotropin-releasing hormone (TRH) stimulation test is helpful for the identification of central hypothyroidism before GH therapy. Methods We retrospectively analyzed data from patients that started GH therapy between 2005 and 2015. The free thyroxine (FT4) and thyroid-stimulating hormone (TSH) concentrations were measured before and during 24 months of GH therapy. The participants were 149 children appropriate for gestational age with GHD (IGHD: isolated GHD) (group 1), 29 small for gestational age (SGA) children with GHD (group 2), and 25 short SGA children (group 3). Results In groups 1 and 2, but not in group 3, serum FT4 concentration transiently decreased. Two IGHD participants exhibited central hypothyroidism during GH therapy, and required levothyroxine (LT4) replacement. They showed either delayed and/or prolonged responses to TRH stimulation tests before start of GH therapy. Conclusions GH therapy had little pharmacological effect on thyroid function, similar changes in serum FT4 concentrations were not observed in participants with SGA but not GHD cases who were administered GH at a pharmacological dose. However, two IGHD participants showed central hypothyroidism and needed LT4 replacement therapy during GH therapy. TRH stimulation test before GH therapy could identify such patients and provoke careful follow-up evaluation of serum FT4 and TSH concentrations.

A 60-year-old male, who exhibited finger tremors, obnubilation, and hyperammonemia (409 μg/dL), was admitted to our hospital. Initially, we suspected that a portosystemic shunt had caused his hyperammonemia. However, his symptoms did not improve after balloon-occluded retrograde transvenous obliteration. He was subsequently found to have some peculiar eating habits, including a fondness for bean curd and peanuts, and an aversion to alcohol and sweets. Furthermore, marked citrullinemia (454.2 nmol/mL) was revealed, which led us to suspect adult-onset type II citrullinemia (CTLN2). DNA analysis of the patient and his mother, son, and daughter confirmed that he was homozygous for the c.852&#95;855del mutation in the SLC25A13 gene, and his relatives were heterozygous for the c.852&#95;855del mutation, which led to a definitive diagnosis. A low-carbohydrate diet and the administration of L-arginine ameliorated his symptoms. It is important to be aware that CTLN2 can occur in elderly patients. Thus, patients who exhibit symptoms of CTLN2 should be interviewed about their dietary habits and subjected to plasma amino acid analysis.In this report, we consider the metabolic disorders seen in citrin deficiency and the associated compensatory mechanisms in relation to the clinical features and treatment of CTLN2.

Asians are known to be more likely than Westerners to develop fatty liver and lifestyle-related diseases in spite of their weight. However, the relationship between fat accumulation and lifestyle-related diseases in non-obese Asians is unknown. Therefore, this study aimed to analyze visceral fat and hepatic fat in participants with a normal body mass index (BMI) and examine their characteristics during a medical checkup. This cross-sectional study was conducted on 663 of 1142 patients who underwent abdominal ultrasonography and who had an alcohol intake (converted to ethanol) of <30 g/day for males and <20 g/day for females and a BMI of <25 kg/m 2 during a health checkup. Participants were classified into four groups: group A, visceral fat accumulation (VFA) (-) and fatty liver (FL) (-) ( n = 549); group B, VFA (+) and FL (-) ( n = 32); group C, VFA (-) and FL (+) ( n = 58); and group D, VFA (+) and FL (+) ( n = 24). The frequencies of lifestyle-related disease complications, liver function tests, and liver fibrosis were evaluated among the four groups. Compared with group A (control), groups B, C, and D had a higher number of males, BMI, abdominal circumference, ALT, AST, γ-GTP, triglyceride, uric acid, fasting blood sugar levels, and incidence of hyperlipidemia. Groups C and D had higher ALT, HbA1c, cholinesterase, and triglyceride levels, FIB4 index, and the number of patients with diabetes mellitus (DM) than groups A and B; however, there was no difference between groups A and B. FL is a risk factor of DM and liver fibrosis in non-obese Japanese individuals; however, VFA only is not a risk factor of DM and liver fibrosis.