Ken Okai

Simple Resistance Exercise helps Patients with Non-alcoholic Fatty Liver Disease

To date, only limited evidence has supported the notion that resistance exercise positively impacts non-alcoholic fatty liver disease. We evaluated the effects of resistance exercise on the metabolic parameters of non-alcoholic fatty liver disease (NAFLD) in 53 patients who were assigned to either a group that performed push-ups and squats 3 times weekly for 12 weeks (exercise group; n=31) or a group that did not (control; n=22). Patients in the control group proceeded with regular physical activities under a restricted diet throughout the study. The effects of the exercise were compared between the 2 groups after 12 weeks. Fat-free mass and muscle mass significantly increased, whereas hepatic steatosis grade, mean insulin and ferritin levels, and the homeostasis model assessment-estimated insulin resistance index were significantly decreased in the exercise group. Compliance with the resistance exercise program did not significantly correlate with patient background characteristics such as age, sex, BMI and metabolic complications. These findings show that resistance exercise comprising squats and push-ups helps to improve the characteristics of metabolic syndrome in patients with non-alcoholic fatty liver disease.

Centrilobular necrosis in acute presentation of Japanese patients with type 1 autoimmune hepatitis

AIM To compare clinicopathological features of acute presentation of type 1 autoimmune hepatitis (AIH) with or without centrilobular necrosis (CN). METHODS Our study comprised 41 patients with biopsy-proven acute presentation (acute exacerbation phase 36, acute hepatitis phase 5) of type 1 AIH at our hospital from 1975 to 2009. Elevated serum alanine aminotransferase (ALT) (> 5x upper limit of normal) identified acute presentation of the disease. We compared clinicopathological features of these AIH patients with or without CN. The data used for analysis included patient background (age, sex, type of disease, presence of complications with other autoimmune diseases, human leukocyte antigen, and International Autoimmune Hepatitis Group score), clinical parameters at presentation (ALT, alkaline phosphatase, IgG, anti-nuclear antibodies, and anti-smooth muscle antibodies), histology and therapy. RESULTS CN was found in 13 (31.7%) patients with acute presentation (acute exacerbation phase 10, acute hepatitis phase 3) of AIH. Serum IgG levels of patients with CN were significantly lower than those of patients without CN (mean: 2307 mg/dL vs 3126 mg/dL, P < 0.05), while antinuclear antibody-negative rates were significantly higher (30.7% vs 3.5%, P < 0.05). However, other clinical features were similar between the two groups. The frequency of advanced fibrosis in patients with CN was significantly lower than in patients without CN (F0-2: 84.6% vs 35.7%, F3-4: 15.4% vs 64.3%, P < 0.05). Other histological features were similar between the two groups. Although there was no significant difference between groups when evaluated using the revised original score (12 vs 14), the simplified AIH score of patients with CN was significantly lower (6 vs 7, P < 0.05). Frequency of DR4 was similar between patients with and without CN. CONCLUSION CN is observed in both Japanese patients with acute hepatitis phase and acute exacerbation phase of type 1 AIH, although AIH with CN often shows clinical features of the genuine acute form.

Firing properties of neurones in the laterodorsal hypothalamic area during sleep and wakefulness

Abstract In undrugged, head‐restrained rats, neuronal activity was recorded in and around the laterodorsal hypothalamic area where orexin neurones are distributed. Among 22 neurones observed across whole sleep–waking states, half (n = 11) were most active during paradoxical sleep and least active during waking. Others were equally more active during paradoxical sleep and waking than during slow‐wave sleep (n = 6), or were most active during waking and least active during paradoxical sleep (n = 3). The majority of neurones started to increase firing activity prior to the transition of sleep–waking states. These results suggest that the area of the hypothalamus containing orexin neurones plays a role in sleep–waking regulation.

Reduced brain activity in female patients with non-alcoholic fatty liver disease as measured by near-infrared spectroscopy

Patients with non-alcoholic fatty liver disease (NAFLD) have impaired health-related quality of life including physical and mental state. Near-infrared spectroscopy (NIRS) is a useful tool for evaluation of brain activity and depressive state. This study aimed to determine the brain activity of female NAFLD patients using NIRS. Cerebral oxygenated hemoglobin (oxy-Hb) concentration during a verbal fluency task (VFT) was measured using NIRS in 24 female NAFLD patients and 15 female healthy controls. The Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire was administered to both groups before NIRS. There was no significant difference in CES-D score between groups. However, the oxy-Hb concentration and number of words during the VFT were less in NAFLD compared to healthy controls. The mean value of oxy-Hb concentration during 0–60 s VFT in the frontal lobe was also smaller in NAFLD patients compared to healthy controls (0.082 ± 0.126 vs. 0.183 ± 0.145, P < 0.001). Cerebral oxygen concentration is poorly reactive in response to VFT in female NAFLD patients. This may indicate an association between decreased brain activity and NAFLD regardless of depression.

Drug-induced Liver Injury with HHV-6 Reactivation.

Liver dysfunction was identified in a 16-year-old boy hospitalized with high fever and abdominal pain and fullness. He had received pharmacotherapy for a headache 2 months previously and other drugs for a high fever 4 days prior to being admitted to our hospital. The patients liver dysfunction was consistent with and fulfilled the criteria for drug induced liver injury, but the laboratory findings showed elevated procalcitonin levels, hyponatremia and leukocytosis. Moreover, we confirmed the presence of human herpesvirus 6 (HHV-6) DNA. The patient exhibited symptoms of high fever and abdominal pain and fullness but no exanthema. The clinical and laboratory findings did not satisfy the criteria for drug-induced hypersensitivity syndrome, and we speculate that the diversity of clinical and laboratory findings may have resulted from HHV-6 reactivation. To the best of our knowledge, this is the first case report on drug-induced liver injury with various findings due to HHV-6 reactivation. HHV-6 reactivation should be considered in patients with drug induced liver injury even in the absence of exanthema.

Reduced frontal activation during verbal fluency task in chronic hepatitis C patients with interferon-based therapy as measured by near-infrared spectroscopy

Psychiatric side‐effects are the main reason for discontinuation of interferon (IFN)‐based therapy. Recent developments in near‐infrared spectroscopy (NIRS) have enabled non‐invasive clarification of brain functions in psychiatric disorders. We prospectively evaluated brain activation in 20 chronic hepatitis C patients with or without IFN‐based therapy by using NIRS during a verbal fluency task (VFT).

Drug-induced liver injury with autoimmune features complicated with hemophagocytic syndrome.

A 60-year-old woman was admitted to our hospital with non-coma acute liver failure. Based on a 1-month history of supplement use, negative viral hepatitis markers, positive antinuclear antibody test, high IgG level, positive HLA-DR4, liver biopsy findings of centrizonal necrosis, and inflammatory cell infiltration in the portal area, she was diagnosed with drug-induced liver injury (DILI) with autoimmune features or the acute hepatitis phase of autoimmune hepatitis (AIH). Although her liver disorder was ameliorated by administration of prednisolone and plasma exchange, anemia and thrombocytopenia were observed during the course of treatment. A bone marrow examination showed hemophagocytosis. Therefore, with no other evidence suggesting infection or malignancy, we determined that the patient had DILI complicated by hemophagocytic syndrome (HPS). Although HPS is very rarely seen in patients with DILI with autoimmune features or the acute hepatitis phase of AIH, this condition should be considered if cytopenia is observed in a patient with DILI.

Case of idiopathic portal hypertension complicated with autoimmune hepatitis

We report a case of idiopathic portal hypertension (IPH) complicated with autoimmune hepatitis. A 60‐year‐old woman was admitted to our hospital with esophageal and gastric varices in February 2010. Abdominal ultrasonography and computed tomography showed splenomegaly and collateral veins without evidence of liver cirrhosis. Laboratory examinations and liver biopsy indicated that the esophageal and gastric varices were caused by IPH. She underwent endoscopic injection sclerotherapy and partial splenic embolization. Two years after these therapies, laboratory examinations showed liver dysfunction with elevated levels of aspartate aminotransferase (180 IU/L), alanine aminotransferase (190 IU/L), γ‐glutamyl transpeptidase (159 IU/L) and immunoglobulin G (2609 mg/dL). The titer of antinuclear antibodies was 1:320 and its pattern was homogeneous and speckled. Histological examination revealed plasma cell/lymphocyte infiltration and interface hepatitis in the portal tract. Based on these findings, a diagnosis of autoimmune hepatitis accompanied by IPH was made. After treatment with prednisolone (20 mg/day), liver functions were normalized immediately. Overlapping of IPH and AIH is extremely rare, but the present case is interesting considering the etiology of IPH because an autoimmune mechanism is thought to be involved in the pathogenesis of IPH.

Paralytic Ileus due to Superior Mesenteric Venous Thrombosis after Transarterial Injection for Hepatocellular Carcinoma

A 69-year-old man was admitted to hospital with abdominal pain. In the four years prior to his presentation, he had undergone repeated transarterial chemoembolizations and injections for hepatocellular carcinoma. He underwent his 8th transcatheter arterial therapy one month prior to admission. Abdominal X-rays and contrast-enhanced computed tomography showed large amounts of small intestinal gas and venous thrombosis from the portal vein to the superior mesenteric vein, respectively. The thrombosis was reduced after anticoagulation therapy (heparin, antithrombin III, danaparoid sodium and warfarin). This is the first case report of paralytic ileus due to superior mesenteric venous thrombosis after transcatheter arterial therapy for hepatocellular carcinoma with an arterioportal shunt.

Hepatitis B Virus Reactivation in a Patient with Nonalcoholic Steatohepatitis 41 Months after Rituximab-containing Chemotherapy: A Case Report

Hepatitis B virus (HBV) reactivation occasionally occurs long after immunosuppressive therapy. The characteristics of late HBV reactivation remain unclear. We herein present a case of HBV reactivation in a patient with nonalcoholic steatohepatitis (NASH) more than 3 years after rituximab-containing chemotherapy for diffuse large B-cell lymphoma. Increased transaminase levels, which were induced by NASH, were observed after chemotherapy and were alleviated with statin treatment. HBV reactivation was identified incidentally. The patient developed hepatitis that improved with entecavir therapy. Our case might indicate that the presence of NASH is associated with HBV reactivation long after treatment and that statins, as immune-modulatory agents, affect HBV reactivation.