Jun-ichi Sugihara

Removal of endotoxin and cytokines by plasma exchange in patients with acute hepatic failure.

OBJECTIVES To compare the circulating concentrations of endotoxin and cytokines in patients with fulminant hepatitis and patients with the severe form of acute hepatitis, and to assess the effects of plasma exchange on the circulating concentrations of these inflammatory mediators in patients with acute hepatic failure. DESIGN Prospective, consecutive entry study of patients meeting fulminant hepatitis criteria and the severe form of acute hepatitis criteria. SETTING University hospital, intensive care unit. PATIENTS Five patients with fulminant hepatitis, eight patients with the severe form of acute hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. INTERVENTIONS Plasma endotoxin, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were determined on admission in five patients with fulminant hepatitis and eight patients with the severe form of acute hepatitis. Circulating concentrations of the inflammatory mediators were measured before and after a single course of plasma exchange in eight patients with acute liver failure, including five patients with fulminant hepatitis, two patients with acute-on-chronic hepatic failure, and one patient with postoperative hepatic failure. MEASUREMENTS AND MAIN RESULTS TNF-alpha and IL-6 in patients with fulminant hepatitis were significantly higher than in patients with the severe form of acute hepatitis, whereas endotoxin concentrations did not differ between patients with fulminant hepatitis or the severe form of acute hepatitis. IL-1beta was not detectable in patients with either fulminant hepatitis or the severe form of acute hepatitis. Plasma endotoxin concentrations decreased immediately after plasma exchange. Serum concentrations of TNF-alpha and IL-6 were significantly lower after plasma exchange than before plasma exchange. CONCLUSION TNF-alpha and IL-6 may be important in the pathogenesis of the clinical symptoms that differentiate fulminant hepatitis from the severe form of acute hepatitis, and plasma exchange removes these inflammatory mediators from the circulation of patients with severe liver disease.

Nocturnal branched-chain amino acid administration improves protein metabolism in patients with liver cirrhosis: Comparison with daytime administration

BACKGROUND In an attempt to optimize oral branched-chain amino acid (BCAA) administration to improve serum albumin in cirrhotic patients, we compared the effects of nocturnal and daytime BCAA administration on protein metabolism in cirrhotic patients. METHODS Twelve cirrhotic patients were enrolled in a short-term study. Patients were administered either conventional daytime BCAA granule or nocturnal BCAA for a week, and metabolic analyses were performed, followed by a crossover study in the next week. Another 12 patients, who showed no improvement of serum albumin level with previous daytime BCAA administration, were randomly assigned to either a nocturnal or a daytime BCAA administration group in a long-term study. RESULTS Low Fischers ratio, reduced respiratory quotient, and low serum albumin were observed at entry in cirrhotic patients. Whereas daytime BCAA administration improved nitrogen balance and Fischers ratio, these 2 were further significantly improved after nocturnal BCAA administration. There were no changes in parameters of energy metabolism throughout the study. In the 3-month follow-up, a significant increase in serum albumin was observed in patients administered nocturnal BCAA but not in those administered daytime BCAA. CONCLUSIONS Nocturnal BCAA administration improved serum albumin in cirrhotic patients who showed no improvement in serum albumin level with daytime BCAA administration. This effect could be partly caused by the improved protein sparing with this administration method.

Inflammatory pseudotumor of the liver with primary sclerosing cholangitis

Abstract: Inflammatory pseudotumor (IPT) of the liver is a rare benign variant of hepatic masses, and its exact etiology has not been elucidated. We report a case of IPT associated with primary sclerosing cholangitis (PSC). The patient was a 50-year-old man admitted to our hospital because of jaundice. Abdominal ultrasonography (US) and computed tomography showed multiple dilations of the intrahepatic bile ducts and multiple masses in the liver. On magnetic resonance imaging, the masses were slightly hypointense on T1-weighted images and slightly hyperintense on T2-weighted images. On T1-weighted images after the bolus infusion of Gd chelate, the masses had no contrast enhancement, and they were hypointense in the arterial phase and portal venous phase. However, they were slightly enhanced and became almost isointense relative to the surrounding normal liver parenchyma in the delayed phase. Endoscopic retrograde cholangiography demonstrated multiple irregular strictures and dilations of the intrahepatic bile ducts. Angiography demonstrated no abnormal findings, but, interestingly, subsequent dynamic CO2-enhanced US showed a strongly hyperechoic string, indicating that an artery had penetrated through the hypoechoic mass. A US-guided percutaneous needle biopsy revealed that the lesions were morphologically comparable to IPT. After cholangiography and microscopic analysis of the tumor, the final diagnosis was determined to be IPT of the liver with PSC. A number of previous reports have suggested a possible relationship between IPT and PSC, based on pathological findings. This report confirmed, based on clinical findings, that PSC is one of the causes of hepatic IPT.

Insulin resistance raises the risk for recurrence of stage I hepatocellular carcinoma after curative radiofrequency ablation in hepatitis C virus‐positive patients: A prospective, case series study

Aim:  Several studies have reported that insulin resistance raises the risk of primary hepatocellular carcinoma (HCC). We conducted a prospective, case series study to test the impact of insulin resistance on the recurrence after curative radiofrequency ablation (RFA) of stage I HCC in HCV‐positive patients.

Erectile dysfunction in patients with chronic viral liver disease: its relevance to protein malnutrition

BackgroundIn patients with chronic liver disease (CLD), quality of life is generally accepted as poor, especially for physical function. However, sufficient data regarding erectile function has not been shown in patients with CLD. The international index of erectile function (IIEF) is widely used to assess erectile function, and a short form of the IIEF was recently developed (IIEF-5). Using this questionnaire, we evaluated erectile dysfunction (ED) in patients with CLD.MethodsA total of 117 Japanese patients (64 with chronic hepatitis [CH] and 53 with liver cirrhosis [LC]) were analyzed. The etiologies were hepatitis B virus (HBV) in 21, HCV in 94, and non-B non-C in 2. The IIEF-5 and Medical Outcomes Study Short Form 36 (SF-36) were administered to the patients, and biochemical analyses for items serum albumin, prothrombin time, bilirubin, and ammonia were also performed.ResultsThe incidence of ED was 85% in the total cohort with CLD, 78% in those with CH, and 92% in those with LC (P < 0.05 between CH and LC). ED was found in 50% of CLD patients under age 50 years, in 79% aged 50–59, and in 100% aged over 60 (P, overall <0.001). The scores for ED severity correlated with increasing grades of a modified Child-Pugh classification (P < 0.05). Simple regression analysis showed age (P < 0.01), physical function (P < 0.001), role physical (P < 0.001), and social functioning (P < 0.05) on the SF-36, and serum albumin (P < 0.001) as significant determinants of ED. Multiple regression analysis identified age (P < 0.001) and serum albumin (P < 0.001) as independent significant factors that determined ED.ConclusionsThese data clearly demonstrate that liver disease is the cause of ED in patients with CLD, and serum protein status could be relevant to this condition in these patients.

Endoscopic papillary balloon dilatation for common bile duct stones: efficacy of combination with extracorporeal shockwave lithotripsy for large stones.

Background Endoscopic papillary balloon dilatation (EPBD) is generally considered a safe and effective technique for removal of common bile duct (CBD) stones. However, some reports have prompted concern about the risk of pancreatitis following the procedure, and it seems to be more difficult and to require adjunctive procedures more frequently in patients with large stones. Aims To analyse the factors influencing pancreatitis after the procedure, and to examine which is the more suitable adjunct for treating large stones, mechanical lithotripsy (ML) or extracorporeal Shockwave lithotripsy (ESWL). Patients and methods EPBD was performed in 92 patients, including 40 with large stones (≥ 12 mm). These 40 patients were randomly assigned to two groups receiving ML or ESWL to fragment stones (20 patients each). Results Complete ductal clearance was obtained in all 92 patients. Significant elevation of the serum amylase level compared with the prior value (> 300 IU/I) was observed in 26 (28%), and eight (8.7%) developed clinical pancreatitis. To assess the influence of various factors on the amylase level, multivariate analysis was used. The number of stones and the time required for treatment had a significant influence on the incidence of increased amylase level (P < 0.05), and ML also significantly increased it (P < 0.05). On the other hand, the amylase level remained low in the ESWL group. ML caused elevation of amylase level in 11 patients (55%), while three (15%) had elevation after ESWL. Conclusions In patients with multiple stones, elevation of the amylase level is more frequent This seems to be because repeated cannulation and much time is required for treatment. In patients with large stones, the rate was also high if ML was used, but was low when ESWL was used. ESWL may reduce the incidence of pancreatitis.

Psychoneurological symptoms during interferon therapy in patients with chronic hepatitis: prospective study on predictive use of Cornell Medical Index and electroencephalogram

Abstract: Background/Aims: We assessed the usefulness of the Cornell Medical Index (CMI) and electroencephalogram (EEG) in the prediction and early detection of psychoneurological symptoms associated with interferon (IFN) therapy for chronic viral hepatitis.

Late Reactivation of Hepatitis B Virus after Chemotherapies for Hematological Malignancies: A Case Report and Review of the Literature

Reactivation of hepatitis B virus (HBV) is a serious complication of immunosuppressive therapy and cytotoxic chemotherapy. The optimal duration of HBV-DNA monitoring for at-risk patients depends on the clinical features of reactivation, especially the range of potency from therapies to reactivation. We present a case of very late reactivation after chemotherapy for lymphoma and review previous reports of late reactivation cases. We also underscore the significance of developing an indicator for anti-HBV immunity which can be used to determine the optimal monitoring period.

Significant effect of hepatitis C virus specific CTLs on viral clearance in patients with type C chronic hepatitis treated with antiviral agents

Aim:  To evaluate the correlation between hepatitis C virus (HCV) specific cytotoxic T lymphocytes (CTLs) and viral clearance in antiviral treated patients, we examined the number and function of HCV epitope‐specific CTLs and the viral load in 12 HLA‐A2‐positive patients with chronic hepatitis C, after undergoing interferon therapy.

A case of liver hilar tuberculous lymphadenitis complicated by biliary stricture diagnosed by endoscopic ultrasound-guided fine-needle aspiration

This report describes a case of liver hilar tuberculous lymphadenitis complicated by biliary stricture, diagnosed with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). A 44-year-old woman was referred to our center for further evaluation of abnormal liver function tests. Abdominal ultrasound/contrast-enhanced computed tomography (CT) revealed a 15-mm hypovascular mass with a weakly enhanced margin at the liver hilum. Magnetic resonance cholangiopancreatography revealed dilatation of the intrahepatic bile ducts in the left lobe of liver and gradual narrowing of the left hepatic duct. Biliary stricture associated with enlarged hilar lymph nodes due to metastasis or malignant lymphoma was suspected, but calcification on chest CT and a positive T-SPOT test did not rule out tuberculosis. After transpapillary brush cytology of the bile duct stricture failed to confirm the diagnosis, EUS-FNA of hilar lymph nodes was performed and showed positive for the acid-fast bacillus and polymerase chain reaction for Mycobacterium tuberculosis DNA as well as epithelioid granulomas on pathological evaluation. Those findings led to a diagnosis of hilar tuberculous lymphadenitis. The patient is under treatment with antituberculosis drugs. Abdominal tuberculous lymphadenitis is rare and some cases diagnosed as lymphadenopathy of unknown origin have required surgery. EUS-FNA is a safe and minimally invasive diagnostic method in such cases.