Granulocyte and monocyte apheresis therapy for patients with active ulcerative colitis associated with COVID-19: a case report.

Coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now a pandemic. Although several treatment guidelines have been proposed for patients who have both inflammatory bowel disease and COVID-19, immunosuppressive therapy is essentially not recommended, and the treatment options are limited. Even in the COVID-19 pandemic, adjuvant adsorptive granulocyte and monocyte apheresis may safely bring ulcerative colitis (UC) into remission by removing activated myeloid cells without the use of immunosuppressive therapy. Our patient was a 25-year-old Japanese male with UC and COVID-19. This is the first case report of the induction of UC remission with granulocyte and monocyte apheresis treatment for active UC associated with COVID-19.

Polymerase-chain reaction testing to prevent hospital-acquired severe acute respiratory syndrome coronavirus 2 infection in Shinjuku, an epicenter in Tokyo: The Tokyo Women's Medical University model.

Hospital-acquired severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infection is a healthcare challenge. We hypothesized that polymerase chain reaction testing of symptomatic triaged outpatients and all inpatients before hospitalization in Shinjuku, a coronavirus disease 2019 (COVID-19) epicenter in Tokyo, using the Tokyo Women's Medical University (TMWU) model would be feasible and efficient at preventing COVID-19. This retrospective study enrolled 2981 patients from March to May 2020. The prevalence of SARS-CoV-2 infection was 1.81% (95% credible interval [CI]: 0.95-3.47%) in triaged symptomatic outpatients, 0.04% (95% CI: 0.0002-0.2%) in scheduled asymptomatic inpatients, 3.78% (95% CI: 1.82-7.26%) in emergency inpatients, and 2.4% (95% CI: 1.49-3.82%) in symptomatic patients. There were no cases of hospital-acquired SARS-CoV-2 infection. This shows that the TWMU model could prevent hospital-acquired SARS-CoV-2 infection and is feasible and effective in reducing the impact of SARS-CoV-2 infection in the hospitals.

Characteristics of NAFLD Based on Hypopituitarism.

Background: Hypopituitarism and hypothalamic disorders, which induce central obesity and appetite disorder, are associated with nonalcoholic fatty liver disease (NAFLD). We retrospectively analyzed the clinical features of NAFLD patients with hypopituitarism. Patients. We examined the cases of 15 NAFLD patients with hypopituitarism (mean age, 39.4 years; males/females, 11/4). The causes of hypopituitarism were surgical in eight cases (six with craniopharyngioma and two with prolactinoma) and nonsurgical in seven cases, including unexplained hypopituitarism in five cases, Sheehan syndrome in one case, and one case that occurred after the radiation therapy. Serum adiponectin, soluble tumor necrosis factor receptor-2 (TNFR-2), and leptin levels were measured. Results: We compared the cases of the eight patients who underwent cranial surgery due to craniopharyngioma or prolactinoma and seven nonsurgical cases. The body mass index (surgery group, 30.2 ± 4.1; nonsurgery group, 29.2 ± 14.2) and the rate of diabetes (75% in surgery group, 14.3% in nonsurgery group) tended to be higher in the surgery group, and the hepatic fibrosis grade (surgery group, 3.75 ± 0.38; nonsurgery group, 1.64 ± 1.07) was significantly higher in the surgery group. The levels of adipocytokines, serum adiponectin, and serum soluble TNFR-2 showed no correlation with hepatic fibrosis, whereas the serum leptin levels were significantly correlated with liver fibrosis (R = 0.696). Conclusion: The hepatic fibrosis grade rapidly progressed in the cranial surgery cases of NAFLD patients with hypopituitarism, possibly in association with BMI, diabetes mellitus, and leptin. In such cranial surgery patients, strong interventions should be considered from the early stage, including diet education, hormone replacement, and more.

Copper deposition in oligodendroglial cells in an autopsied case of hepatolenticular degeneration.

We present a case of hepatolenticular degeneration, so-called Wilson's disease (WD), in a 31-year-old Japanese man with broader deposition of copper in the liver, kidney and brain. The liver showed severe cirrhotic changes with macronodular pseudolobule formation, but there was little difference in immunohistochemical expression patterns of the copper transporter ATP7B between the control and present case. In the brain, there were both WD-related lesions such as the scattering of Opalski cells and changes caused by hepatic encephalopathy including the appearance of Alzheimer type II glia. Of note, we identified copper deposits in the systemic organs, including hepatocytes, renal tubules, and in broad areas of the brain. Surprisingly, as a result of further pursuit, copper accumulation in the brain was rarely identified in neuronal cells, but in Olig2-positive glial cells with double immunohistochemical staining. Together, this rare autopsied case suggests a novel cellular candidate affected by abnormal copper metabolism and the necessity to perform the systemic examination of copper deposition in WD.

The Clinical Difference in the Platelet Counts between Liver Cirrhosis with Nonalcoholic Fatty Liver Disease and Hepatitis C Virus.

Objective The rate of platelet count reduction appears to differ among different liver diseases. In the present study, we investigated the difference in the platelet counts of patients with nonalcoholic fatty liver disease (NAFLD) and those with chronic liver disease due to hepatitis C virus (CLD-HCV). Methods The study population included 620 patients with NAFLD and 405 patients with CLD-HCV, all of whom were diagnosed by liver biopsy. The relationships between the grade of fibrosis and the platelet count in the two diseases were compared. The optimal cut-off value for the diagnosis of liver cirrhosis (LC) was measured. The relationships between the platelet count and anti-platelet antibodies, the serum thrombopoietin level, the grade of splenomegaly and liver stiffness were also investigated in both LC groups. Results In NAFLD patients, the platelet count was significantly higher at each grade of fibrosis in comparison to CLD-HCV. The optimal cut-off value for the diagnosis of LC was 16.0×104/µL [sensitivity, 86.7%; specificity, 87.6%; area under the curve (AUC), 0.930] in NAFLD and 12.7×104/µL (sensitivity, 57.8%; specificity, 88.2%; AUC, 0.863) in CLD-HCV. No anti-platelet antibodies were detected in patients with either type of LC. The serum thrombopoietin levels, the distribution of splenomegaly grades, and liver stiffness did not differ between the two LC groups to a statistically significant extent. As the splenomegaly grade increased, the platelet count decreased. Conclusion The optimal cut-off values for diagnosing LC differed between the two diseases and should be determined separately. The reason for the difference in platelet reduction is still unclear, and requires further investigation.

The Outcome of Cirrhotic Patients with Ascites Is Improved by the Normalization of the Serum Sodium Level by Tolvaptan.

Objective Hyponatremia is frequently observed in patients with decompensated liver cirrhosis and it is also related to a poor prognosis. The vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites and increases the serum sodium (Na) level. In this study, we investigated (i) whether or not correction of the Na level improves the prognosis of cirrhotic patients with ascites and (ii) predictors of normalization of the serum Na level after tolvaptan therapy. Methods This was a single-center retrospective study. A total of 95 Japanese cirrhotic patients (60 men, median age 63 years) were enrolled and received tolvaptan orally after hospitalization for ascites treatment. The serum Na level was monitored during the period of tolvaptan treatment. The laboratory data and survival rates of patients who achieved serum Na levels of <135 and ≥135 mEq/L after 1 week were compared. Results Patients showed serum Na levels of 136 (121-145) mEq/L, and 42.1% had a serum Na level of <135 mEq/L. Among patients with an initial serum Na level <135 mEq/L, 60.0% achieved a normal level after 1 week, and the survival rate was significantly higher in patients with a normalized serum Na level (p<0.01). The pretreatment brain natriuretic peptide (BNP) level was predictive of achieving a serum Na level of ≥135 mEq/L (odds ratio: 0.87, 95% confidence interval: 0.316-0.987, p<0.05). Conclusion Normalization of the Na level after one week was associated with a favorable outcome of tolvaptan therapy, and Na correction improved the prognosis.

Four cases of type 1 diabetes mellitus showing sharp serum transaminase increases and hepatomegaly due to glycogenic hepatopathy.

Poorly controlled diabetes mellitus (DM) patients sometimes show serum transaminase elevations due to steatohepatitis. However, we experienced four cases with type 1 DM with sharp elevations in serum transaminases that could not be explained by steatohepatitis alone and showed bright liver. They were diagnosed with glycogenic hepatopathy (GH) clinicopathologically. The four patients had a median age of 22.5 years (range, 19-29 years) and 12.5 (4-15)-year histories of type 1 DM and showed marked increases in serum transaminases (aspartate aminotransferase, 698 U/L [469-2763 U/L]; alanine transaminase, 255 U/L [216-956 U/L]). Diabetes mellitus control was poor and hemoglobin A1c was 12.7% (11-16.5%). Three cases had a past history of diabetic ketoacidosis. Hepatomegaly and hyperdense liver were seen on computed tomography scans. Magnetic resonance imaging showed low intensity in T2-weighted images. The pathological findings revealed pale and swollen hepatocytes and glycogenated nuclei. The architecture of the liver was preserved, and steatosis and fibrosis were mild. The cytoplasm of hepatocytes stained densely positive with periodic acid-Schiff, and the positive staining disappeared after diastase digestion, suggesting glycogen deposition. No other cause of hepatitis was evident, and the diagnosis was GH. Elevated transaminases improved within 1 month with good glycemic control. Transaminase elevations were observed several times in three cases with poor glycemic control. Glycogenic hepatopathy is rare, but extremely high serum elevations of transaminases are important to identify clinically. Despite showing a good clinical course in general, GH sometimes recurs and requires strict glycemic control. Clinicians should be aware of and recognize GH when dealing with uncontrolled DM patients.

Response to tolvaptan and its effect on prognosis in cirrhotic patients with ascites.

AIM: The vasopressin V2 receptor antagonist tolvaptan has been used for the treatment of cirrhotic patients with ascites; however, no predictor of efficacy and prognosis has been developed. We evaluated candidate predictors of response to tolvaptan treatment. METHODS: This was a single-center retrospective study. Overall, 97 Japanese cirrhotic patients (60 men, median age 63 years), who were hospitalized for ascites treatment including oral tolvaptan coupled with conventional diuretics, were enrolled. The efficacy of tolvaptan was defined as a urination increase of ≥500 mL or a urine volume ≥2000 mL/day on the day following treatment. The prognosis of tolvaptan treatment was evaluated by the post-treatment survival time by Kaplan-Meier analysis. RESULTS: Tolvaptan therapy was effective in 67% of cirrhotic patients. Patients showed -1.5 (-17.2 to +6.2) kg change in body weight and 40% achieved ≥2.0 kg reduction in body weight after 1 week of treatment. Platelet counts, urine sodium (Na) level, and urine Na/potassium (Na/K) ratio were higher, and the blood urea nitrogen (BUN)/creatinine (Cr) ratio was lower, in cases showing a response to tolvaptan. The combination of a BUN/Cr ratio ≥17.5 and urine Na/K ratio <3.09 was predictive of being non-responsive to tolvaptan, and the response rate in these patients was only 39% (P < 0.01). The mean post-treatment survival duration was significantly longer in patients who responded to tolvaptan therapy. CONCLUSIONS: Urinary BUN and Na excretion were predictive of a response to tolvaptan, and tolvaptan treatment may improve the prognosis of cirrhotic patients.

Successful Treatment of Ascites using a Denver® Peritoneovenous Shunt in a Patient with Paroxysmal Nocturnal Hemoglobinuria and Budd-Chiari syndrome.

A 56-year-old man was diagnosed with aplastic anemia and paroxysmal nocturnal hemoglobinuria at 43 years of age and treatment with cyclosporin A was started. Liver cirrhosis, ascites, and thrombus in the hepatic veins were found at 56 years of age and Budd-Chiari syndrome (BCS) was diagnosed according to angiography findings. He was treated with diuretics and paracentesis was performed several times, but with limited efficacy. A Denver® peritoneovenous shunt (PVS) was inserted into the right jugular vein; his ascites and renal function improved immediately and his general condition has remained good for 12 months since starting the above treatment regimen. A PVS is a treatment option for ascites due to BCS.

Safety and efficacy of long-term tolvaptan therapy for decompensated liver cirrhosis.

AIM: Recently, the short-term efficacy of the vasopressin V2 receptor antagonist tolvaptan for the treatment of ascites in cirrhosis was reported. However, the long-term effects remain unknown. Here, we report the clinical features of decompensated cirrhosis treated using long-term tolvaptan therapy, and evaluate its safety and efficacy. METHODS: Fifty-five cirrhotic patients hospitalized due to ascites, despite receiving appropriate diuretic treatment, were treated with tolvaptan. We excluded 35 patients due to liver transplant (20.0%), death (28.6%), poor general status (14.3%), improved ascites (5.7%) or other reasons (31.4%). In 20 cases treated with tolvaptan for 6 months, total body water (TBW) and extracellular fluids (ECW) were measured using bioelectric impedance analysis (BIA) with an InBody720. RESULTS: The median age of the 20 patients was 64 years (range, 48-90), and 60% were male. The etiology of cirrhosis included hepatitis C (45%), alcohol-induced (20%) and other (35%). The percentage of patients with Child-Pugh class A, B and C was 0%, 40% and 60%, respectively. Biochemical findings revealed that serum creatinine levels and estimated glomerular filtration rate were not affected during 6 months of treatment with tolvaptan, and there was no renal disturbance. The median serum sodium levels were increased from 138 to 139 mEq/L, but serious adverse events related to renal and liver function were not observed. Data also revealed that long-term treatment reduced the BIA-estimated ECW/TBW ratio. CONCLUSION: Long-term tolvaptan treatment was a safe and effective treatment for decompensated cirrhosis.

Spontaneous clearance of HCV accompanying hepatitis after liver transplantation.

Re-infection by the hepatitis C virus (HCV) occurs rapidly after liver transplantation (LT), and spontaneous clearance of HCV is rare under immunosuppressive conditions. Here, we report on two patients who underwent LT to treat liver cirrhosis and hepatocellular carcinoma. The immunosuppressants prescribed were short-term corticosteroids, tacrolimus, and mycophenolate mofetil. A 50-year-old woman underwent LT, with her brother as the donor. She acquired HCV of serological type 1 after LT; the HCV RNA level was 6.0 logIU/mL. Corticosteroids were discontinued within 24 days, with a total dose of 669 mg (adjusted) prednisolone (PSL). The serum alanine aminotransferase (ALT) level increased to 700 U/L by day 55 post-LT. Surprisingly, HCV RNA was not detected on day 87. A 52-year-old man underwent LT, with his sister as the donor. He became rapidly re-infected with HCV of serological type 2; the HCV RNA level was 6.9 logIU/mL. Corticosteroids were given for 24 days, with a total dose of 827 mg (adjusted) PSL. The serum ALT level increased continuously and his HCV cleared 115 days after LT. Both donor and recipient had the major IL28B genotype. HCV was eliminated spontaneously, even under immunosuppressive conditions, after PSL discontinuation without interferon treatment. Minimal use of immunosuppressants and the presence of hepatitis may have contributed to HCV clearance. However, it is important to evaluate additional relevant cases.

A Novel Guide-Wire Technique for Repositioning a Nasobiliary Catheter from Mouth to Nostril without Using a Nelaton Tube.

OBJECTIVE: We aimed to assess the usefulness of a novel guide-wire technique for repositioning without the use of a Nelaton tube and to compare this to the conventional technique. SUBJECTS AND METHODS: A total of 50 patients who underwent endoscopic nasobiliary drainage (ENBD) at the Yachiyo Medical Center, Chiba, Japan, were enrolled into the study. The patients were randomly divided into 2 groups according to the use of a novel guide-wire technique (n = 28) or the conventional technique (n = 22). The ENBD catheters were repositioned from the mouth to the nose. The primary end point was the procedural time from the insertion of the Nelaton tube or guide wire into the nostril until the ENBD catheter had been repositioned in the nose. The secondary end point was the success rate of the procedure. RESULTS: The mean procedure time of our technique (120.8 s) was shorter than the traditional technique (131.9 s), but this difference was not statistically significant (p = 0.56). Our technique did not involve the use of the Nelaton tube, and so could save the cost of USD 1.17 per patient. The novel technique did not require the removal of the mouthpiece with a laryngoscope or the use of a Nelaton tube, and no postural change was necessary. A single operator performed the novel procedure unassisted. No adverse events were observed relating to either the novel or the traditional technique. CONCLUSIONS: The novel guide-wire technique for repositioning ENBD catheters was effective and is recommended for use.