Ipragliflozin Improves the Hepatic Outcomes of Patients With Diabetes with NAFLD.

Sodium glucose cotransporter-2 inhibitors (SGLT2is) are now widely used to treat diabetes, but their effects on nonalcoholic fatty liver disease (NAFLD) remain to be determined. We aimed to evaluate the effects of SGLT2is on the pathogenesis of NAFLD. A multicenter, randomized, controlled trial was conducted in patients with type 2 diabetes with NAFLD. The changes in glycemic control, obesity, and liver pathology were compared between participants taking ipragliflozin (50 mg/day for 72 weeks; IPR group) and participants being managed without SGLT2is, pioglitazone, glucagon-like peptide-1 analogs, or insulin (CTR group). In the IPR group (n = 25), there were significant decreases in hemoglobin A1c (HbA1c) and body mass index (BMI) during the study (HbA1c, -0.41%, P < 0.01; BMI, -1.06 kg/m2 , P < 0.01), whereas these did not change in the CTR group (n = 26). Liver pathology was evaluated in 21/25 participants in the IPR/CTR groups, and hepatic fibrosis was found in 17 (81%) and 18 (72%) participants in the IPR and CTR groups at baseline. This was ameliorated in 70.6% (12 of 17) of participants in the IPR group and 22.2 % (4 of 18) of those in the CTR group (P < 0.01). Nonalcoholic steatohepatitis (NASH) resolved in 66.7% of IPR-treated participants and 27.3% of CTR participants. None of the participants in the IPR group developed NASH, whereas 33.3% of the CTR group developed NASH. Conclusion: Long-term ipragliflozin treatment ameliorates hepatic fibrosis in patients with NAFLD. Thus, ipragliflozin might be effective for the treatment and prevention of NASH in patients with diabetes, as well as improving glycemic control and obesity. Therefore, SGLT2is may represent a therapeutic choice for patients with diabetes with NAFLD, but further larger studies are required to confirm these effects.

Treatment and outcome of COVID-19 patients in a specialized hospital during the third wave: advance of age and increased mortality compared with the first/second waves.

PURPOSE: To elucidate the clinical course of patients with coronavirus disease 2019 (COVID-19) treated at a specialized hospital mainly for those with mild and moderate severity during the third wave, and to compare that with the first and second (1st/2nd) waves. METHODS: We retrospectively reviewed the severity on admission, treatment, and outcome of a total of 581 patients from September, 2020, to March, 2021, and examined the risk factors for deterioration of respiratory condition, defined as requiring oxygen ≥ 7 L/min for 12 h. RESULTS: The median age was 78 (interquartile range 62-83) years, older than in the 1st/2nd waves (53 years), and 50% of the patients was male. The number of patients classified as mild (peripheral oxygen saturation (SpO2) ≥ 96%), moderate I, II, and severe (requiring admission to the ICU or mechanical ventilation) was 121, 324, 132, and 4, respectively. Favipiravir, ciclesonide, dexamethasone, and/or heparin were administered for treatment. Respiratory condition recovered in 496 (85%) patients. It worsened in 81 patients (14%); 51 (9%) of whom were transferred to tertiary hospitals and 30 (5%) died. Mortality rate increased by fivefold compared during the 1st/2nd waves. Age, male sex, increased body mass index, and C-reactive protein (CRP) on admission were responsible for worsening of the respiratory condition. CONCLUSION: Patients were older in the third wave compared with the 1st/2nd waves. Respiratory condition recovered in 85%; whereas 5% of the patients died. Old age, male sex, increased body mass index, and CRP would be responsible for worsening of the respiratory condition.

Clinical profiles and outcome of patients with COVID-19 in a specialized hospital in Japan.

PURPOSE: To characterize the clinical features and outcome of patients treated at a specialized hospital for coronavirus disease 2019 (COVID-19). METHODS: We retrospectively reviewed the symptoms on admission, treatment, and outcome of a total of 300 patients with mild (peripheral oxygen saturation (SpO2) ≥ 96%), moderate I (93% < SpO2 < 96%), moderate II (SpO2 ≤ 93%) and severe (requiring admission to the ICU or mechanical ventilation) COVID-19. RESULTS: Median age was 53 (interquartile range [IQR] 33-72) years and 57% was male. The number of patients with mild, moderate I, II and severe condition was 85, 138, 61 and 16, respectively. Common presenting symptoms were cough (n = 71), loss of taste (42), loss of smell (39), fever ≥ 37.5 °C (36). Dyspnea was observed only 21 cases; 57 reported no symptoms on admission. Favipiravir, ciclesonide, dexamethasone, and heparin were administered in 106, 168, 65, and 38 patients, respectively, but not remdesivir. The median duration of hospitalization was 10 (7-15) days. All patients with mild and moderate I severity were discharged. Among the 77 patients classified as moderate II or severe, 3 were transferred to tertiary hospitals for further treatment on the day of admission. The respiratory condition worsened in 21 patients; 18 required transfer to tertiary hospitals 3 (median) days after admission and 3 died. CONCLUSION: Respiratory condition recovered in 92%; whereas it worsened in 7% and the mortality rate was 1%. The ratios of male patients, of patients with diabetes mellitus in those with the decreased respiratory condition, were significantly higher than recovered.

[Solitary lymph node metastasis from early-stage hepatocellular carcinoma after transcatheter arterial chemoembolization and radiofrequency ablation: a case report and review of the Japanese literature].

A 77-year-old man with chronic hepatitis C underwent transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early-stage hepatocellular carcinoma (HCC) in segment 8 of the liver. Necrosis was confirmed radiologically. After 19 months, recurrent HCC in segment 6 was treated with TACE and RFA. There was no recurrence. Direct-acting antiviral (DAA) therapy 24 months after the initial procedure led to a sustained virologic response. AFP-L3 markedly increased 11 months after DAA therapy, and MRI 6 months after that showed a solitary lymph node near the common bile duct. Because no intrahepatic recurrence or other lymph nodes were seen, the solitary node was excised. Histopathology showed metastatic HCC. There has been no subsequent recurrence over 13 months of follow-up.

[A Resected Case of Retroperitoneal Metastasis and Small Bowel Metastasis from HCC].

A 71-year-old man underwent right hemi-hepatectomyfor a hepatocellular carcinoma(HCC)measuring 18 cm in diameter. The pathological diagnosis was poorlydifferentiated HCC. Ten months after the surgery, computed tomographyrevealed a nodule 12mm in diameter in the right lung as well as 2 nodules measuring 19 and 11mm in diameter in the retroperitoneum at the cranial aspect of the left kidney. Four months later, the nodule in the right lung had enlarged to 44 mm, while the 2 nodules in the retroperitoneum had enlarged to 68mm and 34 mm. These nodules were resected and histopathologicallydiagnosed as metastasis from HCC. Twenty-one months after liver resection, computed tomographyrevealed nodules 16 and 25mm in diameter in the retroperitoneum around the urinarybladder and jejunum, respectively. One month later, intussusception resulted from the jejunal tumor. Laparoscopic surgerywas performed for both tumors, which were diagnosed as metastases from HCC. Twenty-five months after liver resection, metastasis from the HCC appeared in the left adrenal grand, at the site of the jejunal anastomosis, and in the fattytissue around the right scapula. Twenty-nine months after liver resection, the patient died of respiratoryfailure from multiple metastases in the left lung.

Putting "sticky notes" on the electronic medical record to promote intra-hospital referral of hepatitis B and C virus-positive patients to hepatology specialists: an exploratory study.

BACKGROUND: Currently, no system for appropriate intra-hospital collaboration regarding hepatitis virus positive individuals exists, even in medical institutions with hepatologists among their staff. The main objective of this study was to explore a simple alert system to promote the referral of patients with hepatitis B surface antigen (HBsAg)- or anti-hepatitis C virus (HCV) antibodies positivity to hepatologists through electronic medical records. METHODS: Since April 2014 at Osaka City Juso Hospital, "sticky notes" have been put on the electronic medical records of patients newly diagnosed with HBsAg- or anti-HCV- antibodies positivity to recommend intra-hospital referral of those patients to specialists. In this study, we investigated the number of referrals to hepatologists before vs. after the introduction of this system (that is, in fiscal years 2013 [Period 1] and 2014 [Period 2], respectively), and the subsequent clinical courses of the patients. RESULTS: The proportions of patients with HBsAg and anti-HCV antibody positivity did not show statistically significant differences between Period 1 and Period 2 (1.6 % [43/2,757] vs. 1.3 % [39/2,891], p = 0.58; and 5.8 % [156/2,674] vs. 5.3 % [147/2,790], p = 0.39, respectively). However, the referral proportions for patients with HBsAg- and anti-HCV antibody positivity were significantly higher in Period 2 (73 % [11/15] and 65 % [41/63], respectively) than in Period 1 (28 % [5/18] and 17 % [9/54]) (p = 0.009 and p < 0.001, respectively). Among patients who were referred to hepatologists, 2 HBsAg-positive and 4 anti-HCV antibody positive patients initiated antiviral treatment. CONCLUSION: Our simple electronic medical record based alert system effectively promoted intra-hospital referral of hepatitis virus-positive patients, who have been detected by screening tests, to hepatologists.

The Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) is more useful than pre-existing laboratory tests for predicting hazardous drinking: a cross-sectional study.

BACKGROUND: It is important to screen for alcohol consumption and drinking customs in a standardized manner. The aim of this study was 1) to investigate whether the AUDIT score is useful for predicting hazardous drinking using optimal cutoff scores and 2) to use multivariate analysis to evaluate whether the AUDIT score was more useful than pre-existing laboratory tests for predicting hazardous drinking. METHODS: A cross-sectional study using the Alcohol Use Disorders Identification Test (AUDIT) was conducted in 334 outpatients who consulted our internal medicine department. The patients completed self-reported questionnaires and underwent a diagnostic interview, physical examination, and laboratory testing. RESULTS: Forty (23 %) male patients reported daily alcohol consumption ≥ 40 g, and 16 (10 %) female patients reported consumption ≥ 20 g. The optimal cutoff values of hazardous drinking were calculated using a 10-fold cross validation, resulting in an optimal AUDIT score cutoff of 8.2, with a sensitivity of 95.5 %, specificity of 87.0 %, false positive rate of 13.0 %, false negative rate of 4.5 %, and area under the receiver operating characteristic curve of 0.97. Multivariate analysis revealed that the most popular short version of the AUDIT consisting solely of its three consumption items (AUDIT-C) and patient sex were significantly associated with hazardous drinking. The aspartate transaminase (AST)/alanine transaminase (ALT) ratio and mean corpuscular volume (MCV) were weakly significant. CONCLUSIONS: This study showed that the AUDIT score and particularly the AUDIT-C score were more useful than the AST/ALT ratio and MCV for predicting hazardous drinking.

Randomized trial of combined triple therapy comprising two types of peginterferon with simeprevir in patients with hepatitis C virus genotype 1b.

Simeprevir (SMV) is a potent, macrocyclic hepatitis C virus (HCV) non-structural 3/4 A protease inhibitor. This prospective study compared the efficacy and safety of SMV in combination with peginterferon α2a + ribavirin (P2aR) and with peginterferon α2b + ribavirin (P2bR) in Japanese patients with HCV genotype 1b infection. METHODS: Hepatitis C virus genotype 1b patients were randomly assigned to receive SMV (100 mg QD) with P2aR for 12 weeks, then P2aR alone for 12 or 36 weeks; or SMV (100 mg QD) with P2bR for 12 weeks, then P2bR alone for 12 or 36 weeks. The primary endpoint was a sustained virologic response 24 weeks after completing treatment (SVR24). RESULTS: In total, 151 patients were randomly assigned to the P2aR (n = 76) or P2bR group (n = 75). Six patients dropped out. Sustained virologic response 24 weeks after completing treatment was achieved in 55 (75.3%) of 73 P2aR patients and 55 (76.4%) of 72 P2bR patients. There was no difference in the rate of SVR24 between the two groups (P = 0.88). No differences in the proportion of patients who became HCV RNA-negative were detected between the P2aR and P2bR groups. The two groups had comparable numbers of adverse events, which led to the discontinuation of treatment in 9.6% and 8.3% of participants in the P2aR and P2bR groups, respectively. CONCLUSION: Peginterferon α2a or α2b in combination with SMV + ribavirin therapy showed identical antiviral effects in patients with chronic hepatitis C. Also, the incidence of adverse events was identical for both regimens.

The Alcohol Use Disorders. Identification Test (AUDIT) score is useful for predicting alcohol consumption.

It is important to screen for alcohol consumption and drinking customs by using a stan- dardized method. The aim of this study was to investigate whether standardized questionnaire was useful for predicting alcohol consumption. A cross-sectional study using the Alcohol Use Disorders Identification Test (AUDIT) was conducted in 334 outpatients who consulted the Internal Medicine Department of Osaka City Juso Hospital. The patients completed self-reported questionnaires and underwent a diagnostic interview, physical examination, and laboratory testing. Forty (23%) male patients reported daily alcohol consumption 40 g, and 16 (10%) female patients reported consumption 20 g. The optimal cutoff values of hazardous drinking (all patients)/ drinker (male)/ drinker (female) were calculated using a 10-fold cross validation, resulting in an optimal AUDIT score cutoff of 8.2/ 7.2/ 6.1, with sensitivity of 95.5%/ 96.3%/ 88.9%, specificity of 87.0%/ 96.3%/ 88.9%, false positive rate of 13.0%/ 9.4%/6.6%, false negative rate of 4.5%/ 3.'%/ 11.1%, and area under the receiver operating characteristic curve of 0.97/ 0.98/ 0.99. In conclusion, this study showed that the AUDIT score was useful for predicting alcohol consumption.

Influenza A(H1N1)pdm09 vaccine effectiveness and other characteristics associated with hospitalization in chronic liver disease patients.

BACKGROUND & AIMS: To date, few studies have investigated the clinical effectiveness of influenza vaccine in chronic liver disease patients. The aim of this study was to examine the effectiveness of monovalent inactivated influenza A(H1N1)pdm09 vaccine and other characteristics associated with hospitalization in patients with chronic hepatitis C. METHODS: We conducted a hospital-based cohort study during influenza A(H1N1)pdm09 pandemic. A total of 408 patients (132 vaccinated, 276 unvaccinated) with detectable HCV-RNA were followed up with respect to any hospitalization using a weekly postal questionnaire. Reported hospitalizations were verified by medical records. RESULTS: During the epidemic period, 28 hospitalizations (6 vaccinated, 22 unvaccinated) were observed. After adjustment for potential confounders, vaccination decreased the odds ratio (OR) for hospitalization with marginal significance (OR = 0.43, 95%CI = 0.16-1.17). Besides, positive association with hospitalization was observed in patients with albumin levels <3.5 g/dl (OR = 8.40, 3.66-19.3) and steroid users (OR = 5.58, 0.98-31.7). CONCLUSIONS: Among patients with chronic hepatitis C, A(H1N1)pdm09 vaccine appeared to have a protective effect against hospitalization. Those patients with a higher risk for hospitalization should be carefully followed during the influenza season, even when vaccinated.

Postoperative outcomes of primary hepatic neuroendocrine carcinomas: review article.

BACKGROUND: We examined the course of a primary hepatic neuroendocrine carcinoma (PHNEC) patient and analyzed the postoperative outcome of all reported PHNEC cases. METHODS: A literature search for PHNEC cases was performed using PubMed. All reported cases and our present patient were analyzed in this study. Survival analysis was performed using the Kaplan-Meier method. Risk factors for the recurrence of PHNEC following hepatic resection were investigated. RESULTS: A total of 43 patients were analyzed in this study. The 3-, 5-, and 7-year overall survival rates were 55%, 48%, and 48%, respectively. The 3-, 5-, and 7-year overall survival rates in surgery patients were 78% each, and 25%, 17%, and 17%, respectively in nonsurgery patients. Lymph node metastasis posed a significant risk factor for postoperative recurrence. CONCLUSIONS: Hepatic surgery is an appropriate therapeutic treatment for PHNEC without distant metastasis nor lymph node metastasis. Adjuvant chemotherapy might be necessary for PHNEC patients with lymph node metastases.

Favorable factors for re-treatment with pegylated interferon α2a plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus.

AIM: Effect of re-treatment for pegylated interferon (PEG-IFN) plus ribavirin was not fully evaluated. We examined the effects of re-treatment with PEG-IFN plus ribavirin in patients with high viral loads of genotype 1 hepatitis C virus who failed to achieve a sustained virological response (SVR) with combination therapy. METHODS: We examined 38 patients who were re-treated with PEG-IFN α2a plus ribavirin for more than 60 weeks, among whom 14 were non-responders and 24 were relapsers after previous treatment with PEG-IFN α2b plus ribavirin. IL28B genotyping was done in 21 patients. RESULTS: The overall SVR rate was 34%. Analysis of baseline characteristics showed that the relapsers had a significantly higher SVR rate than the non-responders (50.0%, 12/24 vs. 7.1%, 1/14, respectively, P = 0.012) The SVR rates of re-treated patients who had turned hepatitis C virus (HCV) RNA-negative at weeks 8, 12, 24, and 48 of the previous therapy were 67% (4/6), 67% (4/6), 29% (2/7), and 25% (1/4), respectively. Re-treatment achieved an SVR in five of 12 patients with IL28B major alleles and three of nine patients with IL28B minor alleles. During the re-treatment, patients with complete viral suppression at week-12 achieved a significantly higher SVR rate (P = 0.001). CONCLUSIONS: Re-treatment with PEG-IFN α2a plus ribavirin therapy is effective in patients who relapse after a course of PEG-IFN α2b plus ribavirin therapy. Re-treatment is a particularly useful option for patients who achieve early viral clearance during previous therapy.

[A case of congenital esophageal stenosis that remained untreated until adulthood and was improved by endoscopic balloon dilatation].

A 20-year-old man had suffered from dysphagia since primary school. Upper gastrointestinal and endoscopy examinations revealed severe circumferential stenosis of the upper intra-thoracic esophagus. Secondary stenosis due to factors such as inflammation did not appear present, so congenital esophageal stenosis (CES) was diagnosed. Dysphagia improved after two endoscopic balloon dilatations. Almost all cases of CES are treated in baby-hood, and individuals who remain untreated until adulthood are rare. Check ups and diagnoses should be made taking CES into consideration, even in adults.

[A case of hepatocellular carcinoma with portal vein thrombus(Vp3)and lung metastases(stage IVB),which responded completely to treatment with Tegafur/Uracil].

A 65-year-old woman who had diffuse hepatocellular carcinoma(HCC)with tumor thrombus of right portalvein(Vp3) and lung metastases(Stage IVB)was treated by single-agent therapy with tegafur/uracil(UFT). As a result, primary and metastatic tumors were not recognized by diagnostic imaging, with a noted decrease of AFP, AFP-L3 and PIVKA-II. Generally, oral chemotherapy for HCC is not recommended because of the low response rate. However, there have been some reports including the present case which have showed a marked response with UFT. We thus conclude that UFT can be an option with low risk of crucial adverse effects in the treatment of selected HCC patients.

A case of isolated granulomatous gastritis that spontaneously resolved without Helicobacter pylori eradication.

Isolated or idiopathic granulomatous gastritis (IGG) is a rare disease and its etiology remains unclear. Some recent papers have reported that IGG is caused by Helicobacter pylori. We present herein a case of IGG that resolved spontaneously without H. pylori eradication. A 54-year-old woman displayed rigidity and thickened folds in the gastric corpus on upper gastrointestinal series. Upper gastrointestinal endoscopy revealed erythematic mucosa and thickened folds. Biopsies of gastric mucosa taken via endoscopy showed noncaseating granulomas and H. pylori infection. The patient was diagnosed with IGG, as no causes of granuloma (e.g., Crohn's disease, sarcoidosis, foreign bodies), excluding H. pylori were identified. Since this patient did not have any symptoms, she was followed without medication, including for eradication of H. pylori. Rigidity and thickened folds normalized with 6 months. Although H. pylori is suspected as the cause of IGG, this case resolved without H. pylori eradication. We thus conclude that the cause of IGG is not H. pylori alone.

Successful treatment of duodenal adenocarcinoma with multiple liver metastases by S-1 + irinotecan (CPT-11).

Unresectable duodenal adenocarcinoma excluding the ampullary region is rare, and no standard chemotherapy has been defined for this disease. Although S-1-based chemotherapy is widely administered for advanced gastric cancer, few reports have described advanced duodenal cancer treated with S-1-based chemotherapy. We present herein a case of duodenal adenocarcinoma with liver metastases. The patient was a 72-year-old man with chief complaints of epigastralgia and fever. Gastroduodenal endoscopy revealed an ulcerative lesion on the upper wall of the duodenal bulb, and biopsy specimens showed well-differentiated adenocarcinoma. Computed tomography and ultrasonography showed multiple liver metastases. S-1 (80 mg/m(2) day(-1) on days 1-21) + irinotecan (80 mg/m(2) day(-1) on days 1 and 15) were administered in 4-week intervals as first-line chemotherapy. Tumor markers subsequently normalized, and liver metastases were diminished. The progression-free term was 6 months. Grade 3 neutropenia and diarrhea were observed as adverse events. S-1 + cisplatin and S-1 + docetaxel were administered as second- and third-line chemotherapies, respectively. The patient died due to hepatic failure, with an overall survival of 15 months. S-1-based regimens appear effective and well tolerated, and S-1 may thus represent a useful option for advanced duodenal cancer.

Spontaneous regression of hepatocellular carcinoma: report of a case.

A spontaneous regression of hepatocellular carcinoma is an extremely rare phenomenon. A 69-year-old Japanese man with hepatitis C virus-related chronic hepatitis presented with a liver tumor. We diagnosed the tumor to be hepatocellular carcinoma in the course of spontaneous regression, by imaging studies and changes in the tumor markers. Because the possible presence of viable cancer cells could not be ruled out, we recommended surgery. He refused all treatments at first, but finally agreed to undergo surgery about 10 months after presentation. A hepatectomy was performed. Histologically, no viable tumor cells were found. In our case, the vascularity of the tumor according to the imaging findings was followed up during the clinical course. The patient is now doing well and without any evidence of recurrence at 37 months after surgery.