Evaluation of nailfold capillaroscopy findings in patients with primary biliary cirrhosis

博士（医学）福島県立医科大

A case of advanced intrahepatic cholangiocarcinoma successfully treated with chemosensitivity test-guided systemic chemotherapy

Intrahepatic cholangiocarcinoma (ICC) is a relatively rare and highly fatal neoplasm that arises from the biliary epithelium. Prognosis is generally poor and survival is limited to a few months. Here we present a case of advanced ICC successfully treated by chemosensitivity test-guided systemic chemotherapy combining S-1 and cisplatin (CDDP). A 65-year-old woman with a liver tumor was referred to our hospital on November 21, 2007. Abdominal ultrasonography and computed tomography (CT) showed low-density masses of 50 and 15 mm in diameter, respectively in segment VIII of the liver and in the enlarged lymph node in the para-aorta. Ultrasonography-guided fine needle biopsy diagnosed the tumors as ICC. Since the patient was inoperable for lymph node metastasis, she underwent systemic chemotherapy with gemcitabine. Six months after initiation of chemotherapy, CT revealed ICC progression in the liver and pleural dissemination with pleural effusion. The patient was admitted to our hospital for anticancer drug sensitivity testing on June 9, 2008. Based on the sensitivity test results, we elected to administer systemic chemotherapy combining S-1 and CDDP. Two months into the second chemotherapy treatment, CT revealed a reduction of the tumors in the liver and lymph node and a decrease in pleural effusion. After eight cycles of the second chemotherapy, 17 mo after ICC diagnosis, she is alive and well with no sign of recurrence. We conclude that chemosensitivity testing may effectively determine the appropriate chemotherapy regimen for advanced ICC

Development of autoimmune hepatitis type 1 after pulsed methylprednisolone therapy for multiple sclerosis: A case report

A 43-year-old woman with multiple sclerosis (MS) was treated with pulsed methylprednisolone and interferon β at a hospital. Four weeks after initiating treatment, liver dysfunction occurred and she was referred and admitted to our hospital. Clinical and laboratory findings were consistent with and fulfilled the criteria for drug-induced hepatitis, but not for autoimmune hepatitis (AIH). She was successfully treated with corticosteroids. As ataxia developed after 1 year, she was treated with pulsed methylprednisolone for 3 d, then readmitted to our hospital when liver dysfunction occurred. Clinical and laboratory findings led to the diagnosis of AIH. To the best of our knowledge, this is the second case of AIH developed after pulsed methylprednisolone for MS

Evaluation of nail fold capillaroscopy findings in patients with primary biliary cirrhosis

AIM: Some patients with primary biliary cirrhosis (PBC) experience Raynaud's phenomenon. The objective of this study was to clarify the relationships between nail fold capillaroscopy findings and clinical presentations of PBC. METHODS: A total of 70 patients with PBC and 57 patients with non-PBC liver diseases, including 44 patients with chronic viral hepatic disease, eight with autoimmune hepatitis and five with non-alcoholic fatty liver disease, were included in this study. Nail fold capillaroscopy findings were classified as normal or abnormal and were further graded as mild, moderate or severe, and the relationships between frequency of abnormal blood vessel and their clinical presentations were examined. RESULTS: The frequency of abnormal nail fold capillaroscopy findings was significantly higher in PBC patients (54.3%) than in patients with non-PBC liver disease (13.8%) (P < 0.01). These abnormal findings observed in PBC patients were graded as mild in 15 patients, moderate in 18 patients and severe in five patients. Significantly more PBC patients with abnormal capillaroscopy findings (19/38, 50%) were positive for anticentromere antibody than were those with normal capillaroscopy findings (3/32, 9.4%) (P < 0.01). CONCLUSION: PBC patients had significantly higher frequency of abnormal nail fold capillaroscopy findings than did patients with non-PBC liver disease

Possible association of cytotoxic T lymphocyte antigen-4 genetic polymorphism with liver damage of primary biliary cirrhosis in Japan

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an important inhibitor of T-lymphocyte response. Polymorphisms in the CTLA-4 gene have been reported to be associated with numerous autoimmune diseases. The aim of this study was to determine whether polymorphisms of CTLA-4 exon 1 (+49) genes are associated with susceptibility and clinicolaboratory findings of primary biliary cirrhosis (PBC) in the Japanease population. Blood samples were obtained from 45 patients (6 men and 39 women, aged 23-56 years) with PBC and 73 healthy controls (48 men and 25 women, aged 22-72 years). CTLA-4 exon 1 (+49) polymorphism was defined using a polymerase chain reaction-restriction fragment length polymorphism with Bst71I restriction enzyme. The genotype frequencies of A/A, A/G, and G/G in 45 patients with PBC were 11% (5 patients), 44% (20 patients), and 44% (20 patients), respectively. There was no significant difference between frequencies in PBC patients and healthy controls. PBC patients with G/G genotype had significantly higher serum levels of ALT, GGT, and IgM than those in patients with A/A or A/G genotype. In conclusion, CTLA-4 gene polymorphisms are not associated with susceptibility of PBC in Japan; however, G/G genotype may be associated with liver damage

Expression of human glucocorticoid receptor beta of peripheral blood mononuclear cells in patients with severe autoimmune hepatitis

We evaluated the expression of human glucocorticoid receptor beta (hGRbeta) in patients with severe autoimmune hepatitis (AIH). The subjects were 27 patients with AIH, including 6 with severe type (prothrombin time [PT] 40%). Total RNA extracted from peripheral blood mononuclear cells (PBMCs) was reversed using reverse transcriptase. The resultant complementary DNA was amplified by reverse transcription polymerase chain reaction (RT-PCR) using specific primers for hGR alpha and beta. The six patients with severe AIH were female; three presented fulminant hepatic failure with hepatic encephalopathy. In all patients with AIH, hGR a was detected. The incidence of hGR beta expression in patients with non-severe type was 42.9% (9/21) ; it was 100% (6/6) in those with severe type. The positive ratio was significantly higher in severe-type patients. These results suggest that hGR beta expression in PBMCs is a novel predictor of AIH severity

Clinicolaboratory characteristics of Japanese patients with primary biliary cirrhosis-autoimmune hepatitis overlap

To clarify the clinicolaboratory characteristics of patients with primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap, we analyzed their clinicolaboratory findings and compared them with those of patients with AIH or PBC retrospectively. We analyzed the laboratory findings of 177 patients that diagnosed 103 PBC and 74 AIH patients at our department during the period from January 1990 to April 2005. Of 103 PBC patients with a diagnosis of PBC, we identified 10 cases (9.7%) of PBC-AIH overlap (2 male, 8 female; mean age 56.5 years). PBC preceded AIH in 2 patients, and both diseases occurred simultaneously in the other 8 patients. There is no patients AIH preceded PBC. Positive frequency of anti-smooth muscle antibody (ASMA), IgG and IgM levels were significantly higher in patients with overlap than in those with AIH or PBC. Ursodeoxychoric acid (UDCA) was administered to all 10 patients initially, and later an immunosuppressant, prednisolone or azathioprine, was added in 6 patients. Two of the 10 patients died of liver failure 5 and 12 years after diagnosis, respectively. Both patients had been treated by either prednisolone or UDCA alone. We conclude that in patients with PBC-AIH overlap, the clinical characteristics of both PBC and AIH exist in an enhanced manner

Autoantibodies by line immunoassay in patients with primary biliary cirrhosis

Objectives: We attempted to measure multiple autoantibodies simultaneously using line immunoassay (LIA) in patients with primary biliary cirrhosis (PBC) with or without anti-mitochondrial antibody (AMA) and patients with PBC-autoimmune hepatitis (AIH) overlap, and we examined the clinical significance of measuring these autoantibodies. Methods: The study population consisted of 80 patients with PBC (including 12 AMA-negative patients), 16 patients with PBC-AIH overlap and 40 patients with AIH as controls. Nine antibodies (AMA-M2, M2-3E, Sp100, PML, gp210, Ro-52, LKM-1, LC-1 and SLA/LP) were detected by LIA, and AMA-M2 and anti-centromere antibody (ACA) were detected by ELISA. We examined the relationship between these autoantibodies and clinical findings. Results: The positive prevalence of each autoantibody and ACA in the PBC group, as determined by LIA, was as follows: 13.8% for anti-Sp100, 8.7% for anti-PML, 40% for anti-gp210 and 27.5% for anti-Ro-52 antibodies and 32.5% for ACA. In the PBC-AIH overlap group, the prevalence of anti-gp210 antibody (68.7%) and that of anti-Ro-52 antibody (81.2%) were significantly higher than those in the PBC and AIH groups. Only a few patients were positive for 2 or more autoantibodies. Nine patients were determined to be negative for all autoantibodies by LIA, of whom 7 were positive for ACA. Patients positive for anti-gp210 antibody included more patients classified as stage 4 on histology than did the negative group. Those positive for ACA included more patents with varices than did the negative group. Conclusion: LIA can measure multiple autoantibodies simultaneously and thus is considered useful in diagnosing PBC and PBC-AIH overlap. In addition, ACA is a useful marker for identifying AMA-negative PBC

A case of peripheral T-cell lymphoma presenting with acute liver failure

A 68-year-old woman was evaluated by her primary physician for swelling and pain in the right neck. Treatment with antibiotics failed to achieve any improvement. Two weeks later, she was hospitalized to the gastroenterology service because of liver dysfunction and pneumonia. Disseminated intravascular coagulation (DIC) was diagnosed, and protease inhibitor and steroid pulse therapy were started. She was transferred to our department for further evaluation the following day. Bone marrow examination revealed hemophagocytosis and infiltration of CD3-positive cells. Multiple masses were identified in the liver. Her prothrombin time was 35.7% of the standard value 17 days from disease onset, despite improvement of DIC. She was diagnosed with acute liver failure based on the Japanese diagnostic criteria. Her general condition worsened quickly, which prevented use of chemotherapy, and she died after a total course of 19 days. Autopsy revealed atypical lymphocytes in the liver. The diagnosis was peripheral T-cell lymphoma