First reports of clinical effects of transjugular intrahepatic portosystemic shunt in four patients with cirrhotic ascites refractory to tolvaptan.

OBJECTIVE: Ascites in patients with decompensated cirrhosis can lead to abdominal distention and decrease quality of life. Tolvaptan, a vasopressin V2 receptor antagonist, is an effective agent in the treatment of ascites, whereas some patients are refractory to tolvaptan. The efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for these patients is not known. In this study, we performed TIPS for tolvaptan-refractory cirrhotic patients and analysed its efficacy and safety in these patients. DESIGN: This retrospective analysis included patients with liver cirrhosis who received TIPS for ascites or hydrothorax refractory to tolvaptan therapy along with conventional diuretics between January 2015 and May 2018 at Tokai University Hospital. We evaluated the efficacy and safety of TIPS. RESULTS: This study included four patients. All patients presented with Child-Pugh class B liver cirrhosis and model for end-stage liver disease-sodium scores were 10/12/14/16. TIPS was generated successfully without any major complications in all patients. The body weight decreased by a mean of 4.7 (SD=1.0) kg and estimated glomerular filtration rate improved from a mean of 38.2 (SD=10.3) to 59.5 (SD=25.0) mL/min/1.73 m2 in a month after TIPS procedure. CONCLUSION: TIPS is an effective potential treatment for ascites in patients with tolvaptan refractory condition. In appropriate patients who can tolerate TIPS, the treatment may lead towards renal function improvement.

Transitional Changes in Job Stress and Psychological Adjustment of Hospital Workers During the COVID-19 Pandemic in Japan.

OBJECTIVES: The aim of the present study was to longitudinally evaluate job stress and burnout before and after the third wave of in Japan and identify transitional changes in the mental health status of a cohort of employees at a coronavirus disease 2019 (COVID-19)-dedicated hospital. METHODS: The same surveys were conducted in October 2020 and March 2021. 151 subjects who responded to both surveys were included. The Maslach Burnout Inventory-General Survey was used to evaluate burnout. Multiple logistic regression analyses were performed to determine odds ratios for factors associated with burnout using a non-burnout group as a reference. RESULTS: In the cohort, 31.1% of employees showed dropout intention and 13.2% of employees were experiencing burnout in March 2021. Hospital workers were more motivated by a sense of contribution and accomplishment, which could balance increased exhaustion in March 2021. The following factors associated with burnout remained to be solved: self-quarantine, unfavorable patient prognosis, poor communication of information, lack of sleep in comparison to the pre-COVID-19 period, and desire for good communication of information. CONCLUSION: It is important to continuously evaluate the mental health status of employees and to provide targeted prevention and intervention in order to mitigate psychological distress and avoid burnout and resignation.

Antiviral Therapy for Patients Chronically Infected with Hepatis C Virus at Tokai University Hospital.

OBJECTIVE: Hepatitis C virus (HCV) was identified in 1989. In 2020, three decades after HCV identification, three researchers won the Nobel Prize in Physiology or Medicine for the discovery of this virus. In 1992, three years after the discovery, interferon (IFN) was launched as the first anti-HCV therapy in Japan; however, the efficacy of IFN therapy was far from acceptable due to severe adverse effects. The advent of IFN-free direct-acting antivirals (DAAs) in 2014 dramatically improved the outcomes of antiviral treatment without serious adverse effects. In this study, we aimed to summarize anti-HCV therapy at the Tokai University Hospital. METHODS: We identified patients who underwent anti-HCV therapy by searching medical records from January 1992 to December 2020, analyzed their background, and compared safety and efficacy among treatments. RESULTS: A total of 1777 treatments were given to 1299 patients. The sustained virologic response rate has dramatically increased over the past 30 years, with only 7% for IFN monotherapy and 95% or higher for recent IFN-free DAA therapies. CONCLUSIONS: We documented the results of anti-HCV therapy at the Tokai University Hospital. In the 30 years since the discovery of HCV, surprisingly successful progress has been accomplished in the anti-HCV treatment.

The prevalence and natural history of hepatic cysts examined by ultrasound: a health checkup population retrospective cohort study.

The prevalence of hepatic cysts in the general population and their natural history are largely unknown. This study aimed to assess the prevalence and natural history of hepatic cysts by investigating health checkup participants. Ultrasonographic data of health checkup participants (n = 38,842) were retrospectively evaluated to calculate its prevalence. In addition, we assessed the changes in the size and characteristics of hepatic cysts over 10 years (n = 7709). We found the prevalence of hepatic cysts was 21.9%. Older age, female sex, and presence of kidney cysts or pancreatic cysts were associated with the occurrence of hepatic cysts. Younger age, female sex, and the existence of multiple hepatic cysts were associated with cyst enlargement. Among 126 individuals who had hepatic cysts with a diameter of 30 mm or larger at the first visit, two (1.6%) required treatment. Remain 124 cases showed four patterns: 44 cases with enlargement, 47 stable, 11 regression after enlargement, and 22 regression. Hyperechoic fluid inside the cysts was observed in 54.5% (18 of 33), which was significantly higher than 6.6% (6 of 91) of the non-regression (OR = 17.0). The appearance of intracystic hyperechoic fluid by ultrasound may predict subsequent regression of the hepatic cyst.

A Case of Silent COVID-19 Pneumonia Found by an Optional Chest CT Scan During a Health Check.

We experienced a case of silent Coronavirus disease 2019 (COVID-19) pneumonia that was found by an optional chest computed tomography (CT) scan during a health check. A 62-year-old man with a present medical history of hypertension visited the health screening center at Tokai University Tokyo Hospital on August 7th, 2020. Prior to entry into the hospital, his body temperature was measured and his history was obtained (called 'COVID-19 triage'), but there were no remarkable findings. Subsequently, patchy ground glass opacities were observed with peripheral distribution in bilateral multiple lobes. Based on this finding COVID-19 pneumonia was highly suspected. Subsequently, a PCR test was positive for COVID-19. Even in health check settings, we should be aware of possible encounters with COVID-19 infections. The high risk of silent spread plays a significant role in the ongoing pandemic. Chest CT scans, which can efficiently identify silent COVID-19 pneumonia, should be performed earlier during health check examinations, at least before gastroendoscopy, which causes significant droplet dispersion. Health check examination providers should not cancel or postpone health checks; rather, it is necessary for them to provide health check examinees with a safe environment with minimal delay in access to recommended health care services.

Collection of excitation-emission-matrix fluorescence of aerosol-candidate-substances and its application to fluorescence lidar monitoring.

Fluorescence lidars have the potential to identify aerosols, but it seems that the basic data of the fluorescence spectrum of various aerosols appear to be inadequate for practical use in application of fluorescence lidar monitoring. We collected the fluorescence spectrum data of 61 powders with different substances as pseudo-aerosols and organized them as EEM (Excitation-Emission-Matrix) fluorescence data. Our interest was also in the artificial substances that are discarded around our surroundings and become aerosols. Four applications of the EEM fluorescence to fluorescence lidars were discussed; designing fluorescence lidars, reconstructing aerosol fluorescence spectrums measured by fluorescence lidar, searching for new substances for fluorescence lidar measurement, and developing a database of EEM fluorescence for identifying aerosol types measured by fluorescence lidar. All EEM fluorescence data and application software were stored in one USB memory and run in the BIOS (Basic Input/Output System) independent of a computer OS (Operating System) for ease of use. Aerosol identification software worked well in general, but we have also talked a bit about improvements.

A CRISPR/Cas9-based method for targeted DNA methylation enables cancer initiation in B lymphocytes.

Targeted DNA methylation is important for understanding transcriptional modulation and epigenetic diseases. Although CRISPR-Cas9 has potential for this purpose, it has not yet been successfully used to efficiently introduce DNA methylation and induce epigenetic diseases. We herein developed a new system that enables the replacement of an unmethylated promoter with a methylated promoter through microhomology-mediated end joining-based knock-in. We successfully introduced an approximately 100% DNA methylation ratio at the cancer-associated gene SP3 in HEK293 cells. Moreover, engineered SP3 promoter hypermethylation led to transcriptional suppression in human B lymphocytes and induced B-cell lymphoma. Our system provides a promising framework for targeted DNA methylation and cancer initiation through epimutations.

Clinicopathological Features of Autoimmune Hepatitis with IgG4-Positive Plasma Cell Infiltration.

BACKGROUND: We aimed to elucidate the characteristics and prognosis of autoimmune hepatitis (AIH) patients with immunoglobulin (Ig) G4-positive plasma cell infiltration. METHODS: We enrolled 84 AIH patients. The number of IgG- and IgG4-positive plasma cells was immunohistochemically counted per high-power field in the portal area. Patients with 3 or more IgG4-positive plasma cells on average and a ratio of IgG4 to IgG-positive plasma cells ≥5% were defined as IgG4-associated AIH (IgG4-AIH), and their clinicopathological characteristics and prognosis were compared to those of the remaining classical-AIH patients. RESULTS: Ten (11.9%) and 74 patients (88.1%) were categorized as IgG4-AIH and classical-AIH patients, respectively. The median age of the IgG4-AIH patients was 67 years, the majority was female (80.0%), and the distribution was similar to that of the classical-AIH patients. The IgG4-AIH patients exhibited significantly more severe phenotypes in portal inflammation, interface hepatitis, fibrosis, and rosette formation. All clinical laboratory data were similar except for serum IgG4 levels, which were higher in IgG4-AIH patients (168.5 vs. 22.9 mg/dL, p = 0.014). During a median follow-up period of 139 months, the relapse rate was significantly lower in the IgG4-AIH group than in the classical-AIH group (11.1 vs. 49.2%; p = 0.048). Twelve (16.2%) and 6 (8.1%) classical-AIH patients underwent liver-related events and liver-related deaths, respectively. In contrast, none of the IgG4-AIH patients progressed to severe liver disease. CONCLUSIONS: The IgG4-AIH patients had more severe inflammation and advanced fibrosis in the liver. However, their prognosis was not poor compared to that of classical-AIH patients. IgG4-AIH may have a phenotype distinct from classical-AIH.

Nineteen-year prognosis in Japanese patients with biopsy-proven nonalcoholic fatty liver disease: Lean versus overweight patients.

BACKGROUND: Many studies have investigated the prognosis of nonalcoholic fatty liver disease (NAFLD); however, most studies had a relatively short follow-up. To elucidate the long-term outcome of NAFLD, we conducted a retrospective cohort study of patients with biopsy-proven NAFLD. METHODS: We re-evaluated 6080 patients who underwent liver biopsy from 1975 to 2012 and identified NAFLD patients without other etiologies. With follow-up these patients, we evaluated the outcome-associated factors. RESULTS: A total of 223 patients were enrolled, 167 (74.9%) was non-alcoholic steatohepatitis (NASH). The median follow-up was 19.5 (0.5-41.0) years and 4248.3 person-years. The risk of type 2 diabetes mellitus (T2DM) and hypertension was 11.7 (95% confidence interval [CI] 8.70-15.6) and 7.99 (95% CI 6.09-10.5) times higher, respectively, in NAFLD patients than in the general population. Twenty-three patients died, 22 of whom had NASH. Major causes of death were extrahepatic malignancy and cardiovascular disease (21.7%) followed by liver-related mortality (13.0%). All-cause mortality was significantly higher in NASH patients than in nonalcoholic fatty liver patients (P = 0.041). In multivariate analysis, older age (hazard ratio [HR] 1.09 [95% CI 1.05-1.14], P<0.001) and T2DM (HR 2.87 [95% CI 1.12-7.04], P = 0.021) were significantly associated with all-cause mortality. The factors significantly associated with liver-related events were older age, T2DM, milder hepatic steatosis, and advanced liver fibrosis. Body mass index wasn't associated with either mortality or liver-related events. CONCLUSIONS: T2DM was highly prevalent in NAFLD patients and was significantly associated with both all-cause mortality and liver-related events. The lean patients' prognosis wasn't necessarily better than that of overweight patients.

Hypothyroidism is a Predictive Factor for Better Clinical Outcomes in Patients with Advanced Hepatocellular Carcinoma Undergoing Lenvatinib Therapy.

Patients with advanced hepatocellular carcinoma (HCC) undergoing molecular targeted therapy often experience non-negligible adverse events (AEs). Paradoxically, certain AEs are reportedly associated with a good prognosis. We aimed to identify factors predictive of treatment duration and overall survival (OS) in patients with HCC undergoing lenvatinib therapy. Forty-six consecutive patients with advanced HCC who received lenvatinib therapy from April 2018 to November 2019 were prospectively followed until November 2019. Treatment efficacy was assessed according to the modified Response Evaluation Criteria in Solid Tumors for 2-3 months after therapy initiation. The disease control rate (DCR) was defined as the percentage of patients with a complete response, partial response, or stable disease. The DCR was 65.2%, with a median survival of 10.2 months. Grade 2/3 hypoalbuminemia resulted in shorter treatment duration. Factors predictive of longer OS were a Child-Pugh score of 5 at baseline and the occurrence of Grade 2/3 hypothyroidism. Conversely, Grade 2/3 hypoalbuminemia was associated with a poorer prognosis. An AE of Grade 2/3 hypothyroidism was associated with a better prognosis in patients receiving lenvatinib treatment for advanced HCC. Continuing anticancer therapy with appropriate thyroid hormone replacement may contribute to longer OS.

Increase in the Lipopolysaccharide Activity and Accumulation of Gram-Negative Bacteria in the Stomach With Low Acidity.

INTRODUCTION: Lipopolysaccharides (LPSs) of Gram-negative bacteria (GNB) are highly toxic and induce inflammation. Therefore, we investigated both the LPS activity and composition of GNB in the gastric fluid (GF) to assess the potential toxicity of them accumulated in the stomach. METHODS: GF and saliva samples were obtained from 158 outpatients who were undergoing upper gastrointestinal endoscopy and 36 volunteers using a nasogastric tube. The LPS activity was measured by assay kits including recombinant Factor C or Limulus amebocyte lysate. To assess the bacterial composition in the samples, a 16S ribosomal DNA-based operational taxonomic unit analysis was performed. We focused on the genera representing >0.1% of the whole microbiota. RESULTS: We found a high LPS activity in the GF samples with weak acidity (approximately > pH 4), whereas little/no activity in those with strong acidity (approximately < pH 2). Spearman test also demonstrated a close correlation between pH and LPS in those samples (r = 0.872). The relative abundance of GNB in the saliva showed no significant difference between the subject groups with weak- and strong-acidity GF. In addition, in the subjects whose GF acidity was weak, the GNB abundance in the GF was almost the same as that in the saliva. By contrast, in the subjects whose GF acidity was strong, the GNB abundance in the GF was significantly lower than that in the saliva. DISCUSSION: GNB that have recently moved from the oral cavity might account for the prominent LPS activity in a stomach with weak acidity.

Efficacy and safety of glecaprevir/pibrentasvir in patients with hepatitis C virus infection aged ≥75 years.

AIM: Opportunities to treat older patients with hepatitis C virus infection have increased. We investigated the efficacy and safety of glecaprevir/pibrentasvir in patients with HCV infection aged ≥75 years. METHODS: We retrospectively evaluated 131 patients with hepatitis C virus infection treated with glecaprevir/pibrentasvir at nine institutions in Japan. The patients were divided into two groups according to their age: the elderly group (n = 43, aged ≥75 years) and younger group (n = 88, aged <75 years). We compared the clinical characteristics, virologic response and adverse events between the two groups. The predictive factors for adverse events were also assessed. RESULTS: The presence of cirrhosis (27.9%), a history of hepatocellular carcinoma (23.3%) and comorbidities (88.4%) were more frequently observed in the elderly group than in the younger group. Six (14.0%) patients in the elderly group and 19 (21.6%) in the younger group dropped out before the sustained virologic response 12 assessment. In the intention-to-treat population, 86.0% in the elderly group and 78.4% in the younger group achieved sustained virologic response 12 (P = 0.30). In the modified intention-to-treat population, all patients achieved sustained virologic response 12. A total of 27.5% of patients experienced adverse events. The most frequently observed adverse events was pruritus, and was significantly associated with female sex, the presence of hemodialysis and serum albumin at baseline <4.0 g/dL. CONCLUSION: Glecaprevir/pibrentasvir therapy was effective and well tolerated, even in elderly patients with hepatitis C virus infection aged ≥75 years. Geriatr Gerontol Int 2020; ••: ••-••.

Hypozincemia is associated with human hepatocarcinogenesis in hepatitis C virus-related liver cirrhosis.

AIM: Hypozincemia is associated with the progression of chronic liver diseases, but it is unknown whether hypozincemia promotes human hepatocarcinogenesis. Our aim is to evaluate the serum zinc levels in liver cirrhosis (LC) patients and clarify the relationship between the serum zinc levels and the development of hepatocellular carcinoma (HCC). METHODS: Cirrhotic patients without HCC (n = 299) were enrolled from 14 medical institutes in Japan as a multicenter prospective study (No. 2028). Of the 299 patients, 157 were included in the present study based on reliable and consistent serum zinc levels and no history of oral zinc supplementation. Clinical parameters associated with the development of HCC were determined. Furthermore, the cumulative incidence of HCC was analyzed using Kaplan-Meier methods and was calculated using the log-rank test. A Cox regression analysis was utilized for the multivariate analysis to evaluate the predictors of hepatocarcinogenesis. RESULTS: Thirty of 157 patients (19.1%) developed HCC during an observation period of 3 years. Serum zinc levels were significantly decreased in hepatitis C virus-related LC (C-LC) patients with HCC (0.0180). The risk factors for incidence of HCC were hypozincemia (0.0014), high α-fetoprotein (0.0080), low branched chain amino acids-to-tyrosine ratio (0.0128), or female sex (0.0228). Hypozincemia (hazard ratio 1.61, 0.0324) was the only significant predictor of hepatocarcinogenesis by multivariate Cox regression analysis. CONCLUSIONS: Hypozincemia is associated with hepatocarcinogenesis in C-LC patients.

Effect of Sodium Glucose Co-Transporter 2 Inhibitors on Liver Fat Mass and Body Composition in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVE: Sodium glucose co-transporter 2 inhibitors increase urinary glucose excretion and reduce visceral adiposity and body weight, but their efficacy on patients with nonalcoholic fatty liver disease has not been sufficiently investigated. The aim of this study was to assess the effect of sodium glucose co-transporter 2 inhibitors on liver fat mass and body composition in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus. METHODS: We retrospectively analyzed 17 patients with nonalcoholic fatty liver disease and type 2 diabetes who received sodium glucose co-transporter 2 inhibitors between November 2016 and July 2017. Changes in liver fat, subcutaneous and visceral fat, body composition, and liver function-related parameters were assessed after 24 weeks of sodium glucose co-transporter 2 inhibitor treatment and compared to baseline values. RESULTS: Ten patients received dapagliflozin at 5 mg/day and seven patients received canagliflozin at 100 mg/day for 24 weeks. All patients completed the study without any serious adverse effects and achieved body weight loss and improved glycated hemoglobin levels. Liver fat mass evaluated by proton magnetic resonance spectroscopy was significantly reduced (19.1% vs. 9.2%, p < 0.01), and so were both subcutaneous and visceral fat mass. The body fat/body weight ratio decreased, whereas the skeletal muscle mass/body weight ratio increased. Liver function (aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transpeptidase) improved significantly. CONCLUSIONS: Sodium glucose co-transporter 2 inhibitor treatment not only improved glycemic control but also reduced liver fat mass in patients with nonalcoholic fatty liver disease and type 2 diabetes. Body weight loss was primarily attributable to a reduction in fat mass, especially visceral fat. Thus, sodium glucose co-transporter 2 inhibitors could potentially serve as a therapeutic agent for patients with nonalcoholic fatty liver disease and type 2 diabetes.

Isolated adrenocorticotropic hormone deficiency potentially induced by nivolumab following pseudo-progression in clear cell renal cell carcinoma: A case report.

Nivolumab is a monoclonal immunoglobulin G antibody blocking programmed death receptor-1 (PD-1) that promotes the restoration of the natural T-cell-mediated immune response against cancer cells; however, it also causes a number of autoimmune-related adverse events (irAEs) that often involve the endocrine system. The present report describes a 71-year-old man with clear cell renal cell carcinoma metastasis in the lung. Following the 14th course of nivolumab therapy, the patient complained of general malaise, loss of appetite and mild consciousness disturbance. Laboratory tests revealed a severely elevated eosinophil ratio (26.2%) and low sodium value (122 mmol/l). Endocrine system tests revealed that the patient's adrenocorticotropic hormone (ACTH; 4.5 pg/ml) and cortisol (0.1 µg/dl) levels were lower than normal, while those of other pituitary hormones were higher than normal. This case was therefore diagnosed as isolated ACTH deficiency induced by nivolumab. Magnetic resonance imaging (MRI) showed normal pituitary glands. Hydrocortisone replacement therapy improved the clinical symptoms early and enabled the patient to restart nivolumab therapy. Isolated ACTH deficiency due to nivolumab, a PD-1 immune checkpoint inhibitor antibody, is a rare occurrence. This report may be useful for avoiding delays in the diagnosis and treatment of this life-threatening irAE even if no pituitary abnormalities are identified via MRI.

Impaired Renal Function May Not Negate the Efficacy of Tolvaptan in the Treatment of Cirrhotic Patients with Refractory Ascites.

BACKGROUND AND OBJECTIVE: Tolvaptan, an oral vasopressin V2 receptor antagonist, has been widely used for the treatment of patients with cirrhosis and ascites. However, its efficacy in patients with renal dysfunction remains unknown. The objective of this study was to investigate the efficacy and safety of tolvaptan in patients with decompensated cirrhosis and severe chronic kidney disease (s-CKD). METHODS: We studied 43 patients with liver cirrhosis who received tolvaptan (7.5 mg/day) for refractory ascites. s-CKD was defined as an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2. Response to tolvaptan was defined as weight loss ≥ 1.5 kg in 7 days of treatment. RESULTS: Eighteen patients (42%) had s-CKD (s-CKD group), while the other 25 patients (58%) did not have s-CKD (n-CKD group). Rates of response to tolvaptan were similar: 68% in the n-CKD group and 56% in the s-CKD group. Urine volumes increased significantly from baseline to day 7 in both groups. Incidences of adverse events were also similar (P = 0.93). Mean eGFR did not decline even in the s-CKD group (27.3 ± 2.2 mL/min/1.73 m2 at baseline vs. 26.6 ± 2.3 mL/min/1.73 m2 on day 7; P = 0.9). The cumulative survival rate did not differ significantly between the n-CKD and s-CKD groups. In the s-CKD group, responders obtained a better prognosis than non-responders. CONCLUSIONS: Tolvaptan significantly increased urine volumes similarly in patients with s-CKD and n-CKD without affecting renal function. As responders achieved a better prognosis, tolvaptan could be a good option to treat ascites in patients with cirrhosis and s-CKD.

Chemotherapeutic Effect of CD147 Antibody-labeled Micelles Encapsulating Doxorubicin Conjugate Targeting CD147-Expressing Carcinoma Cells.

BACKGROUND: CD147 (basigin/emmprin) is expressed on the surface of carcinoma cells. MATERIALS AND METHODS: For studying the efficacy of CD147-targeting medicine on CD147-expressing cells, we studied the effect of anti-CD147-labeled polymeric micelles (CD147ab micelles) that encapsulated a conjugate of doxorubicin with glutathione (GSH-DXR), with specific accumulation and cytotoxicity against CD147-expressing A431 human epidermoid carcinoma cells, Ishikawa human endometrial adenocarcinoma cells, and PC3 human prostate carcinoma cells. RESULTS: By treatment of each cell type with CD147ab micelles for 1 h, a specific accumulation of CD147ab micelles in CD147-expressing cells was observed. In addition, the cytotoxicity of GSH-DXR-encapsulated micelles against each cell type was measured by treatment of the micelles for 1 h. The cytotoxic effect of CD147ab micelles carrying GSH-DXR was 3- to 10-fold higher for these cells than that of micelles without GSH-DXR. CONCLUSION: These results suggest that GSH-DXR-encapsulated CD147ab micelles could serve as an effective drug delivery system to CD147-expressing carcinoma cells.

The Prevalence and Implication of Zinc Deficiency in Patients With Chronic Liver Disease.

BACKGROUND: Patients with liver cirrhosis often exhibit zinc deficiency. Although zinc is involved in many bioactivities, many aspects of clinical implications of zinc deficiency in liver cirrhosis remain unclear. We aimed to reveal the prevalence and implications of zinc deficiency in liver cirrhosis by assessing associations with parameters such as clinical symptoms and laboratory data. METHODS: In 235 cirrhosis patients enrolled at multiple medical institutions in 2009, we assessed how blood zinc levels were associated with their clinical symptoms, patients characteristics, and liver function test results. RESULTS: Blood zinc levels were most strongly correlated with blood albumin levels among the study parameters (r = 0.587, P < 0.0001). When blood albumin levels were ≤ 3.5 g/dL, blood zinc levels were < 70 µg/dL in 88% of patients. Additionally, significant correlations were observed with age (r = -0.253, P = 0.0014), aspartate aminotransferase levels (r = -0.254, P = 0.0020), total bilirubin levels (r = -0.222, P = 0.0053), prothrombin time (r = -0.255, P = 0.0029), branched-chain amino acid to tyrosine ratio (r = 0.357, P < 0.0001), Child-Pugh score (r = 0.469, P < 0.0001), ammonia levels (r = -0.246, P = 0.0028), and total cholesterol levels (r = 0.314, P < 0.0001). Blood zinc levels were significantly lower in patients with edema/ascites (P < 0.0001), those with hepatic encephalopathy (P = 0.0215), those receiving oral diuretics (P = 0.0045), and those receiving oral branched-chain amino acids (P < 0.0001) than in those without these conditions. CONCLUSIONS: Zinc deficiency is prevalent in cirrhosis patients, whereas nitrogen metabolic disorders, particularly hypoalbuminemia, can be an indicator of zinc deficiency. Thus, cirrhosis patients exhibiting a nitrogen metabolic disorder should be examined for the presence of zinc deficiency.

Successful Eradication Therapy for Helicobacter pylori-positive Atrophic Gastritis at the Sixth Attempt: A Case Report.

A 74-year-old woman undergoing outpatient follow-up for reflux esophagitis and atrophic gastritis tested positive for Helicobacter pylori and underwent primary eradication therapy with lansoprazole (LPZ) 30 mg, amoxicillin (AMPC) 750 mg, and clarithromycin (CAM) 200 mg twice daily for 1 week in August 2012. A urea breath test (UBT) after this treatment revealed that eradication had failed. Secondary eradication therapy was carried out with esomeprazole (EPZ) 20 mg, AMPC 750 mg, and metronidazole (MNZ) 250 mg twice daily for 1 week, but this also failed. The third attempt at eradication consisted of EPZ 20 mg, AMPC 750 mg, and sitafloxacin (STFX) 100 mg twice daily for 1 week, but this also ended in failure. A fourth attempt using rabeprazole (RPZ) 20 mg (4 times daily) with MNZ 250 mg and STFX 100 mg twice daily for 2 weeks also failed, as did a fifth attempt in April 2015 using vonoprazan (VPZ) 20 mg, AMPC 750 mg, and MNZ 250 mg twice daily for 1 week. Eradication was finally successful after the sixth attempt, in which the patient was treated with vonoprazan 20 mg, MNZ 250 mg, and STFX 100 mg twice daily for 2 weeks.