Yoriyuki Takamori

Outcome and prognostic factors of 391 Japanese patients with primary sclerosing cholangitis

Objectives: We performed a national survey in 2003, and demonstrated characteristic features of primary sclerosing cholangitis (PSC) patients in Japan. In this study, we aimed to clarify the outcome and prognostic factors of Japanese PSC patients.

Changes in biliary excretory mechanisms in rats with ethinyloestradiol-induced cholestasis.

Several excretory pathways for cholephilic compounds have been known. To examine the changes in excretory pathways in cholestasis induced by ethinyloestradiol, various bile acids, organic anions and organic cations were intravenously administered to ethinyloestradiol‐treated rats and their biliary excretion was studied. Biliary excretion of taurocholate was slightly delayed, but its excretory maximum was markedly decreased. Biliary excretion of lithocholate‐3‐O‐glucuronide, leukotriene C4, sulphobromophthalein and pravastatin was markedly impaired to a similar extent. Biliary excretion of vinblastine, a P‐glycoprotein substrate, was increased, suggesting increased expression of P‐glycoprotein. In contrast, biliary excretion of erythromycin, a cationic antibiotic, was markedly impaired. In conclusion, ethinyloestradiol treatment altered the biliary excretion of organic compounds, which may partly be related to changes of the canalicular transporters.

Benefit of cystatin C in evaluation of renal function and prediction of survival in patients with cirrhosis.

The assessment of renal function is of vital importance in management of patients with cirrhosis. While serum creatinine (Cr) is routinely used for this purpose, Cr‐based estimated glomerular filtration rate (eGFR) does not reflect true renal function because of muscle wasting and impaired liver function. By contrast, cystatin C (CysC) is unrelated to muscle volume and liver function. In this study, we examined whether CysC‐based GFR estimation is beneficial in assessment of renal function in patients with cirrhosis.

Validation of the Japanese version of the Chronic Liver Disease Questionnaire for the assessment of health‐related quality of life in patients with chronic viral hepatitis

Patients with chronic liver diseases (CLD) suffer from a variety of subjective symptoms, and the assessment of health‐related quality of life (HRQOL) is crucial. The Chronic Liver Disease Questionnaire (CLDQ) is the first liver disease‐specific instrument for this purpose. In this study we aimed to develop the Japanese version of CLDQ and to assess its validity and reliability in Japanese patients with chronic viral hepatitis.

Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis

Antimicrobial therapy is a mainstay of the management for patients with acute cholangitis and/or cholecystitis. The Tokyo Guidelines 2018 (TG18) provides recommendations for the appropriate use of antimicrobials for community‐acquired and healthcare‐associated infections. The listed agents are for empirical therapy provided before the infecting isolates are identified. Antimicrobial agents are listed by class‐definitions and TG18 severity grade I, II, and III subcategorized by clinical settings. In the era of emerging and increasing antimicrobial resistance, monitoring and updating local antibiograms is underscored. Prudent antimicrobial usage and early de‐escalation or termination of antimicrobial therapy are now important parts of decision‐making. What is new in TG18 is that the duration of antimicrobial therapy for both acute cholangitis and cholecystitis is systematically reviewed. Prophylactic antimicrobial usage for elective endoscopic retrograde cholangiopancreatography is no longer recommended and the section was deleted in TG18. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

Effect of tauro‐α‐muricholate and tauro‐β‐muricholate on oestradiol‐17β‐glucuronide‐induced cholestasis in rats

The effect of tauro‐β‐muricholate (βMC‐tau) and tauro‐α‐muricholate (αMC‐tau) on oestradiol‐17β‐glucuronide (E217G)‐induced cholestasis was compared with that of taurourso‐deoxycholate (UDC‐tau) in rats. Like UDC‐tau, αMC‐tau and βMC‐tau infused at the rate of 0.2 μmol/min per 100 g bodyweight (BW) completely inhibited the cholestasis induced by E217G infused at the rate of 0.06 μmol/min per 100 g BW for 20 min. These findings indicate that βMC‐tau and αMC‐tau are useful in protecting against various types of experimental cholestasis, as well as against bile acid‐induced cholestasis.

Inhibition of biliary glutathione excretion by lithocholate-3-O-glucuronide: a possible role in initiating lithocholate-3-O-glucuronide-induced cholestasis

Abstract Lithocholate-3- O -glucuronide is a cholestatic agent. Herein, the effect of lithocholate-3- O -glucuronide on biliary glutathione excretion, which has been suggested as a driving force for the bile acid independent canalicular bile flow, was examined in rats. Intravenously injected lithocholate-3- O -glucuronide (1.6 μmol/100 g body wt.) caused a transitional decrease in bile flow (67% of the basal value) and depressed biliary glutathione excretion to 15% of the basal value, which corresponded to biliary lithocholate-3- O -glucuronide excretion. A lower dose of lithocholate-3- O -glucuronide (1.0 μmol/100 g body wt.) also inhibited biliary glutathione excretion (54%) with a slight decrease in bile flow (80%). These findings indicate that a decrease in bile acid independent bile flow due to the inhibition of biliary glutathione excretion is one of the initiating factors to cause cholestasis induced by lithocholate-3- O -glucuronide.

Primary hepatic somatostatinoma developed in a patient with von Recklinghausen's disease

3), and even ERCP findings were significantly improved in 2 cases. Our retrospective investigation suggests that SASP is more effective to normalize hepatobiliary enzymes compared with other treatments. Interestingly, SASP was much more effective than oral 5-aminosalicylates (mesalazine, 5-ASA), which was used for IBD patients with PSC (Table 1). The mechanism of therapeutic action of SASP for PSC is not clear. One hypothesis is that SASP improves inflammation of the colonic mucosa, which then results in a decrease in translocation of bacteria and toxins into the portal tract. This hypothesis, however, is inconsistent with our observation because oral 5-ASA was ineffective. The majority of SASP passes directly into the colon and is digested by bacterial enzymes into sulfapyridine and 5ASA.4 5-ASA is antiinflammatory5,6 and is the primary therapeutic compound in SASP, whereas sulfapyridine has been said to be of no value for treatment of bowel inflammation. However, sulfapyridine is effective for rheumatoid arthritis and possesses antibacterial activity, and the action of this component might be an alternative explanation of the observed efficacy. A large randomized and controlled study is warranted to clarify the efficacy of SASP in patients with PSC.

Abdominal ultrasonogram of autoimmune pancreatitis: Five cases of pancreatic lesions accompanied by Sjögren syndrome.

The concept of autoimmune pancreatitis has recently been established, and ultrasonographic findings we obtained from five cases consistent with autoimmune pancreatitis are reported here. Case 1, a 77-year-old man, was admitted complaining of loss of body weight. Serum hepatobiliary enzymes and γ-globulin levels were elevated, and antinuclear antibody was positive, Abdominal ultrasonography showed dilatation of the intrahepatic bile duct, wall thickening of the common bile duct and hypoechoic swelling of the pancreatic head and body. ERCP revealed multiple stenosis of the intra-and extra-hepatic bile ducts, and diffuse irregular narrowing of the main pancreatic duct. The patient complained of thirst, and the minor salivary gland was examined histologically. Our diagnosis was Sjögren syndrome accompanied by sclerosing cholangitis and a pancreatic lesion. Obstructive jaundice also developed, and PTCD was therefore performed. Both the pancreatic swelling and multiple stenosis of the bile duct improved after steroids were administered. Case 2, a 71-year-old man, was admitted with jaundice. Abdominal ultrasonography showed hypoechoic swelling of the pancreas. ERCP showed stenosis of the common bile duct in the pancreatic head region and diffuse irregular narrowing of the main pancreatic duct. Histological examination of the minor salivary gland suggested Sjögren syndrome. Steroids were therefore administered because the presence of both hyper-γ-globulinemia and positive antinuclear antibody suggested involvement of the autoimmune mechanism. Steroid therapy improved the jaundice as well as the findings from the cholangiograms and pancreatograms. We also encountered three similar cases, all consistent with the concept of autoimmune pancreatitis. The ultrasonographic findings of the pancreatic lesion (1) showed them as homogeneous and markedly hypoechoic areas and, (2) visualized the main pancreatic duct in the lesion, which facilitated a differential diagnosis of the neoplastic lesions. (3) Steroid therapy effectively decreased the hypoechoic area; in some cases, however, a hypoechoic area remained around the main pancreatic duct.

Gilbert Syndrome with Concomitant Hereditary Spherocytosis Presenting with Moderate Unconjugated Hyperbilirubinemia

We experienced a case of a 19-year-old man with Gilbert syndrome with concomitant hereditary spherocytosis. The patient presented with moderate unconjugated hyperbilirubinemia, and inherited etiology was strongly suspected. The diagnosis of Gilbert syndrome was confirmed by the genetic analysis of the UGT1A1 gene, demonstrating UGT1A1*28 and compound heterozygote UGT1A1*6. In addition, since the laboratory findings and imaging studies revealed lysemia as well as gallstone and splenomegaly, a diagnosis of hereditary spherocytosis was made as a comorbidity. Both Gilbert syndrome and hereditary spherocytosis are hereditary diseases with a high frequency, and the hyperbilirubinemia may be exacerbated when these two diseases are concomitant.