Michihiko Shibata

Methotrexate-related Primary Hepatic Lymphoma in a Patient with Rheumatoid Arthritis

A 56-year-old woman with rheumatoid arthritis treated with methotrexate (MTX) was admitted to our hospital due to multiple liver tumors. Contrast-enhanced computed tomography (CT) revealed multiple hypovascular masses, and 18F-fluorodeoxyglucose positron emission tomography CT showed diffuse abnormal accumulation in the liver only. We therefore made a diagnosis of MTX-related primary hepatic lymphoma (MTX-PHL) exhibiting features of diffuse large B-cell lymphoma. Although MTX has been reported to increase the risk of lymphoproliferative disorders, MTX-PHL has not been reported previously. The present case is the first case in which MTX appears to have been involved in the development of PHL.

Late diagnosed Wilson disease with hepatic and neurological manifestations.

A 50‐year‐old woman was referred to our hospital due to liver dysfunction and progressive neurological symptoms. She had previously been diagnosed with nonalcoholic steatohepatitis (NASH). Ursodeoxycholic acid (UDCA) had effectively normalized her serum aminotransferase levels, however, she presented with loss of balance, dysarthria and difficulty in handwriting. Autoantibodies and hepatitis virus markers were negative. Serum ceruloplasmin and copper levels were noted to be 9 mg/dL and 32 µg/dL, respectively. The 24‐h urinary copper excretion was 331.8 µg/day. Kayser‐Fleischer ring was demonstrated. Histological examination of the liver revealed inflammatory infiltrate and fibrosis, and the hepatic copper concentration was 444.4 µg/g dry weight. We diagnosed her as having Wilson disease and started treatment with trientine. Immuohistochemistry for keratin 8 and p62 demonstrated Mallory‐Denk bodies. Many of the p62‐expressing cells were positive for 4‐Hydroxy‐2‐nonenal (HNE). Few Ki‐67‐positive hepatocytes were present in the liver. Wilson disease is one of the causes of NASH and UDCA may be a supportive therapeutic agent for Wilson disease. Cell proliferation is suppressed under copper‐loaded conditions and this phenomenon may be associated with the clinical course of Wilson disease.

Bullous Pemphigoid Associated with the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin in a Patient with Liver Cirrhosis Complicated with Rapidly Progressive Hepatocellular Carcinoma

A 78-year-old man presented with cutaneous blisters of the limbs and abdominal distension. He had been treated for various diseases, including liver cirrhosis. He had begun receiving sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, for diabetes mellitus three years before the hospitalization. A skin biopsy demonstrated bullous pemphigoid. Ultrasonography (US) revealed multiple liver tumors, although he had been receiving regular US studies. We stopped sitagliptin and started insulin and corticosteroids. However, his renal dysfunction progressed, and he died 14 days after the hospitalization. We should therefore be careful of various complications, including bullous pemphigoid and progression of tumors, when using DPP-4 inhibitors.

Hepatic peribiliary cysts with rapidly progressive refractory obstructive jaundice and esophageal varices.

A 54-year-old man with decompensated alcoholic liver cirrhosis presented with acute cholangitis. Although no localized lesions were detected in the liver on contrast-enhanced computed tomography and no risky varices were noted on endoscopy, hepatic peribiliary cysts (HPBCs) developed along the intrahepatic portal vein in the course of only 40 days. Moreover, esophageal varices with the red color sign grew rapidly during the same period, and the patient ultimately died due to rupture. HPBC formation is a rare complication of liver disease, including cirrhosis. Although HPBCs are generally harmless, on rare occasions they may induce the rapid progression of esophageal varices.

Churg–Strauss syndrome manifesting as cholestasis and diagnosed by liver biopsy

A 56‐year‐old woman was referred to our hospital due to fever and cholestatic liver dysfunction. Her eosinophil count was normal and she had no abdominal pain or neurological manifestations. We performed a liver biopsy and found fibrinoid necrosis of the hepatic artery with granulomatous reaction and eosinophilic infiltration in the portal area in the liver. Later, sensory abnormalities of the arms and legs appeared and the eosinophil count increased. Serum immunoglobulin E and immunoglobulin G4 were elevated and rheumatoid factor was strongly positive. Endoscopic retrograde cholangiopancreatography revealed no abnormality of the bile duct and pancreatic duct. We made a diagnosis of Churg–Strauss syndrome and began corticosteroid treatment. Fever and liver function immediately improved. In the present patient, Churg–Strauss syndrome manifested first in the liver, before hypereosinophilia and neural manifestations. We believe that Churg–Strauss syndrome is an autoimmune liver disease, and it is important to recognize that the liver may be involved in Churg–Strauss syndrome.

Reactivation of Occult Hepatitis B Virus Infection 27 Months after the End of Chemotherapy Including Rituximab for Malignant Lymphoma

A 68-year-old man with occult hepatitis B virus (HBV) infection was diagnosed with malignant lymphoma and achieved complete remission after treatment with a chemotherapy regimen including rituximab for 5 months. Entecavir (ETV) was also used during and after chemotherapy and was ended at 14 months after chemotherapy. However, reactivation of HBV was observed in blood tests, which showed not only elevation of HBV-DNA but also HBsAg and HBeAg, at 27 months after the end of chemotherapy. After restarting ETV, the HBV-DNA levels immediately subsided. In addition, anti-HBs became and remained positive at 31 months after chemotherapy. ETV was re-discontinued at 36 months after chemotherapy.

Severe Alcoholic Hepatitis Effectively Treated with Vitamin E as an Add-on to Corticosteroids

A 49-year-old woman with a history of heavy alcohol drinking was admitted to our hospital due to jaundice and abdominal distention. A blood test showed leukophilia, mild hypoalbuminemia, hyperbilirubinemia, hepatobiliary injury and coagulopathy. Image studies showed an extremely enlarged fatty liver and splenomegaly. The Japan alcoholic hepatitis score and Maddreys discriminant function were 10 and 54 points, respectively. We diagnosed her with severe alcoholic hepatitis and treated her with corticosteroids, but her liver function did not improve. We therefore administered the vitamin E product tochopheryl acetate (150 mg/day) as an add-on therapy, after which her leukophilia, liver enzymes and coagulopathy improved immediately.

Prediction of Disseminated Intravascular Coagulation by Liver Function Tests in Patients with Japanese Spotted Fever

Objective Cases of Japanese spotted fever (JSF) are sometimes complicated by disseminated intravascular coagulation (DIC) with an abnormal liver function, resulting in unfavorable outcomes. The aim of the present study was to clarify the correlation between liver function test results and DIC scores. Methods Twenty patients diagnosed with JSF between April 2010 and April 2014 were enrolled. Age, gender, disturbance of consciousness, body temperature, pulse rate, presence of diffuse erythema, eschar and swelling of lymph nodes, laboratory test results at the time of initial presentation such as blood cell count, C-reactive protein, liver function, renal function and blood coagulation and fibrinolysis, maximum Japanese Association for Acute Medicine (JAAM) DIC score during the course of JSF, treatment and the prognosis were retrospectively reviewed. Results The median age of the patients (8 men, 12 women) was 68.3 years. There were significant differences in the alkaline phosphatase (ALP) and rothrombin time international normalized ratio (PT-INR) between the DIC and non-DIC groups using Mann-Whitneys U test. A multiple logistic regression analysis showed that the ALP and blood urea nitrogen (BUN) levels at the time of initial presentation were independent predictors of the occurrence of DIC. Conclusion We should pay special attention to JSF patients showing high levels of ALP at the initial presentation, since such patients may have a higher likelihood of developing DIC over the course of JSF and unfavorable outcomes than those with lower levels.

A Young Adult Patient with Nonalcoholic Steatohepatitis Developed Severe Gastroesophageal Varices Associated with Severe Obesity and Diabetes Mellitus

Obesity is a major contributor to insulin resistance and nonalcoholic fatty liver disease, which is the most common cause of chronic liver diseases. Nonalcoholic steatohepatitis (NASH) can progress to liver cirrhosis and end-stage liver diseases. Some cases already show severe liver fibrosis at the time of diagnosis. We present the case of a 44-year-old male with overt obesity who was admitted with hematemesis due to the rupture of gastric varices. We diagnosed him with NASH with severe liver fibrosis. This case shows that we should be concerned about the progression of liver fibrosis due to NASH associated with severe obesity even in young patients.

Spontaneous Regression of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus

An 83-year-old man underwent transcatheter arterial chemoembolization (TACE) for a 20-mm hepatocellular carcinoma (HCC) in Couinaud’s segment 4. Computed tomography (CT) 4 months after TACE showed tumor thrombus in the portal vein in addition to diffuse metastases and arterioportal shunts in the left lobe. Although we performed the best supportive care, the tumor thrombus in the portal vein and tumors in the left lobe had completely disappeared on CT 16 months after the TACE. Rapidly grown portal vein tumor thrombus and arterioportal shunt might be the causes of spontaneous regression of HCC, probably associated with tumor hypoxia.