Yukiko Kanno

Overlap of primary biliary cirrhosis and autoimmune hepatitis: Characteristics, therapy, and long term outcomes

Background:  Coexistence of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) is referred to as PBC‐AIH overlap. Pathogenesis of PBC‐AIH is not well understood and its diagnosis is challenging. We previously reported the clinical characteristics of 10 patients diagnosed with PBC‐AIH overlap.

Expression of micro-RNAs in peripheral blood mononuclear cells from primary biliary cirrhosis patients

The aim of this study was to clarify the relationship between the expression of micro‐RNAs (miRNAs) in peripheral blood mononuclear cells (PBMCs) and clinical presentation in patients with primary biliary cirrhosis (PBC).

Risk factors associated with relapse of type 1 autoimmune hepatitis in Japan.

Aim:  Patients receiving corticosteroid therapy on a tapered schedule occasionally suffer autoimmune hepatitis (AIH) relapses. The aim of this study was to assess the frequency and features of relapses, explore risk factors associated with relapses, and evaluate the effectiveness of azathioprine (AZP) therapy against relapses in Japanese patients with type 1 AIH.

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.

Autoimmune hepatitis complicated by late‐onset systemic lupus erythematosus

A 69‐year‐old man with autoimmune hepatitis (AIH) was admitted to hospital with high fever and cough. Chest roentgenogram and computed tomography showed pleural and pericardial effusion. Serological tests showed a high titer of antinuclear antibodies and positive anti‐DNA antibody and lymphocytopenia. He fulfilled the American College of Rheumatology criteria for systemic lupus erythematosus (SLE). After administration of corticosteroids, his symptoms and liver dysfunction improved. To the authors’ knowledge, this is the first male case of overlap between AIH and late‐onset SLE.

Doppler ultrasonographic characteristics of superficial and deep-flow signals in the knee joint pannus of patients with rheumatoid arthritis

Increased blood flow signals on power Doppler ultrasonography in the proliferated synovium (pannus) of patients with rheumatoid arthritis (RA) have been used to evaluate articular inflammation.1–7 Fiocco et al 5 reported that, in patients with RA after 3 months of etanercept treatment, superficial layer vascularity of the knee joint pannus8 was significantly reduced, and this occurred before deep-layer vascularity was affected. In all, 97 knee joints of 52 patients with RA were scanned longitudinally and transversely at suprapatellar recess; we …

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.