Eosinophilic enteritis accompanied by cytomegalovirus disease: a case report.

BACKGROUND: Eosinophilic enteritis is a chronic inflammatory disorder of the intestinal tract that is characterized by eosinophil infiltration. Cytomegalovirus (CMV), a common virus, has a broad infectivity range. CMV is retained in the host body after infection. Impairment of host immune defences may reactivate the latent CMV, leading to symptoms of overt disease. CASE PRESENTATION: A Japanese female in her 70 s was admitted to a hospital due to diarrhoea and then transferred to our hospital. Laboratory data showed hypoalbuminemia. Computed tomography (CT) revealed oedema of the small intestine. Lower gastrointestinal endoscopy revealed oedema of the submucosa, without any remarkable changes in the mucosa of the terminal ileum. Histological examination of the terminal ileum revealed infiltration of > 20 eosinophils per high-power field (HPF). These findings aided in diagnosing eosinophilic enteritis. We administered methylprednisolone (500 mg/day) for three days, followed by tapering prednisolone. However, the patient's general condition and hypoalbuminemia failed to improve. Immunoglobulin (Ig) G- CMV and IgM-CMV tests were positive. CMV antigenemia was extremely high. Therefore, we administered ganciclovir intravenously, which improved the patient's condition. Furthermore, azathioprine was administered to taper and discontinue prednisolone without relapse of eosinophilic enteritis. This treatment helped stabilize the patient's condition for approximately four years. CONCLUSION: We present a case of eosinophilic enteritis accompanied by CMV disease during prednisolone treatment. The patient's condition improved after administration of ganciclovir. Azathioprine aided in discontinuing prednisolone and stabilizing the patient's condition for approximately four years.

Spontaneous Regression of Hepatocellular Carcinoma due to Disruption of the Feeding Artery.

We present an unusual case of spontaneous regression of hepatocellular carcinoma (HCC). A 77-year-old man with alcoholic liver cirrhosis presented with a 50-mm tumor in the Couinaud's segment 8 (S8) of the liver, a 15-mm tumor in the S8-7 and 10-mm tumors in the other segments (S4, S6). The tumors were diagnosed as HCC by typical imaging findings and elevated serum alpha-fetoprotein (AFP, 1,825.0 ng/ml) and protein induced by vitamin K absence II (PIVKA II, 3,043 mAU/ml). One month later, AFP and PIVKA II decreased to 51.1 ng/ml and 411 mAU/ml, respectively, and the 50-mm tumor in the S8 became small and completely necrotic on angiography and computed tomography arteriography without any treatment. On the other hand, the 15-mm tumor in the S8-7 decreased in size to 10 mm and received blood supply from the right posterior superior arteries (A7). The other 10-mm tumors remained. Ischemia of the tumors due to disruption of the feeding artery (A8) might have induced tumor regression in the present case.

The natural history of a hepatic angiosarcoma that was difficult to differentiate from cavernous hemangioma.

A 69-year old man came to our hospital complaining of abdominal pain. Contrast-enhanced computed tomography (CT) showed a 65-mm ruptured mass in Couinaud segment 5 of the liver. The mass was treated with emergent transcatheter arterial embolization (TAE), followed by partial hepatectomy. Microscopically, the mass was determined to be an angiosarcoma. Six months previously, enhanced CT had shown a 15-mm mass diagnosed as a cavernous hemangioma in the same region of the liver. Even when the enhancement pattern of a small hepatic mass resembles that of hemangioma, the mass should be reassessed within several months to exclude a diagnosis of hepatic angiosarcoma.

[CT enterography with polyethylene glycol electrolyte solution for diagnosis of Crohn's disease].

This study aimed to assess the diagnostic usefulness of CT enterography (CTE) in Crohn's disease in Japanese patients. A total of 32 cases with bowel symptoms underwent CT enterography with polyethylene glycol electrolyte solution as oral contrast medium, among which 18 were clinically diagnosed as Crohn's disease and 14 were not: ulcerative colitis 1, Beçhet disease 1, simple ulcer 1, inflammatory bowel disease without definite diagnosis 5 and bowel symptoms of unknown origin 6. The incidence of bowel wall thickening, mural hyperenhancement, "the comb sign", mesenteric lymph nodes swelling, and stenosis were significantly higher in Crohn's disease than in other disease. Moreover, uneven bowel wall thickening and unilateral mural hyperenhancement on CTE were characteristic features of Crohn's disease, which our original quantitative evaluation with imaging analysis could support. Consequently, CTE is useful in Japanese patients with Crohn's disease.

Limited benefit of biochemical response to combination therapy for patients with recurrent hepatitis C after living-donor liver transplantation.

BACKGROUND: Effective management of patients with recurrent hepatitis C after liver transplantation has not been established. In this study, we tested the significance of biochemical response (BR) as well as sustained virological response (SVR) to combination therapy with interferon alpha-2b and ribavirin for recurrent hepatitis C after living-donor liver transplantation. METHODS: Forty patients received therapy and formed 3 groups by response: SVR (n=14, 35%) and BR (n=14, 35%), defined when serum alanine aminotransferase normalized during therapy in non-SVR patients, and no response (NR; n=12, 30%). Histological changes of these groups after the combination therapy were investigated. RESULTS: Activity grade of liver histology improved significantly in patients with an SVR at 1 and at 2-4 years after the initiation of treatment, showing difference from the BR and NR groups in which the activity was not improved by interferon therapy. Fibrosis deteriorated significantly in both the BR and the NR groups at two to four years. The rates of patients whose fibrosis stage deteriorated to stage F2 or more were significantly greater in the BR and NR groups than in the SVR group. Fibrosis decreased or remained stable in five of eight patients (63%) with an SVR at two to four years, whereas it increased in 12 of 15 patients (80%) with a BR or NR. CONCLUSIONS: Patients with an SVR showed histological improvement, but the benefit of a BR for non-SVR patients to improve the activity grade or to inhibit the progression of fibrosis was limited.

Clinical outcomes of living donor liver transplantation for hepatitis C virus (HCV)-positive patients.

BACKGROUND: Whether hepatitis C virus recurrence occurs earlier and with greater severity for living donor liver transplantation (LDLT) than for deceased donor liver transplantation (DDLT) has recently become a subject of debate. METHODS: We retrospectively evaluated clinical outcomes for a cohort of 91 HCV-positive patients who underwent LDLT at Kyoto University with a median follow-up period of 25 months. RESULTS: Overall 5-year patient survival for HCV patients was similar to that for non-HCV patients (n=209) who underwent right-lobe LDLT at our institute (69% vs. 71%). Survival rate of patients without HCC (n=34) tended to be better than that of patients with HCC (n=57) (82% vs. 60%, P=0.069). According to annual liver biopsy, rate of fibrosis progression to stage 2 or more (representing significant fibrosis) was 39% at 2 years after LDLT. Univariate analysis showed that female recipient and male donor represented significant risk factors for significant fibrosis. Progression to severe recurrence (defined as the presence of liver cirrhosis (F4) in a liver biopsy and/or the development of clinical decompensation) was observed in five patients. CONCLUSIONS: Postoperative patient survival was similar for HCV-positive and -negative recipients in our adult LDLT series. Rates of progression to severe disease due to HCV recurrence seemed comparable between our LDLT recipients and DDLT recipients described in the literature. Although longer-term follow-up is required, our results suggest that LDLT can produce acceptable outcomes also for patients suffering from HCV-related cirrhosis.

Hepatitis B virus infection in lymphatic tissues in inactive hepatitis B carriers.

BACKGROUND/AIMS: Hepatitis B virus (HBV) infection in extrahepatic tissues is controversial. To clarify whether episomal HBV can infect nonhepatic tissues, we investigated the molecular forms of HBV in the lymphatic cells of inactive HBV carriers who lacked viremia, thus avoiding contamination with HBV genomes originating from the viral particles present in the serum. METHODS: We assessed HBV genome, replicative forms, and viral integrants in the liver, serum, peripheral blood mononuclear cells (PBMC), and lymph nodes of 21 inactive HBV carriers who tested positive for antibodies against the HBV core antigen (anti-HBc). RESULTS: Of the 21 anti-HBc positive individuals, HBV-DNA was detected in liver samples of 15 (71.4%), in the lymph nodes of 11 (52.4%), and in PBMC of three (14.3%). However, none of the detected HBV genomes from lymphatic tissues included the replicative forms of HBV. In one case, integrated HBV was present in the lymphatic tissues and the host-viral junction was present in the intronic sequences of chromosome 17. CONCLUSIONS: These data suggest that human lymphatic tissues cannot support viral replication in anti-HBc positive inactive HBV carriers, while retaining the viral genome as an integrated form.

Whole-blood counting immunoassay as a short-turnaround test for detection of hepatitis B surface antigen, anti-hepatitis C virus antibodies, and anti-Treponema pallidum antibodies.

Whole-blood samples were used for a counting immunoassay (CIA) with the aim of developing a short- turnaround test. After optimization of the CIA, hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibodies (anti-HCV), and anti-Treponema pallidum antibodies (anti-TP) were detected as efficiently as by an enzyme immunoassay (EIA) with serum samples. The correlations between whole-blood CIA and serum EIA were 99.8, 97.1, and 99.4% for HBsAg, anti-HCV, and anti-TP, respectively. Whole-blood CIA may be of value when rapid screening of many samples is required.

Lens culinaris agglutinin-A-reactive alpha-fetoprotein as a marker for liver atrophy in fulminant hepatic failure.

Liver atrophy is frequently found at autopsy of patients with fulminant hepatic failure (FHF). Imaging studies in patients with FHF demonstrate that estimation of total liver volume correlates with prognosis. In this study, in order to determine serum markers for evaluating liver atrophy, we measured the weight of whole livers resected from 31 transplant recipients with FHF, and assessed the relation between the liver weights and several prognostic markers. The level of liver atrophy was evaluated by calculating the ratio of the removed whole liver weight to the body weight of each recipient, and 16 major variables including several serological markers were analyzed among those recipients. We found that the serum Lens culinaris agglutinin-A-reactive alpha-fetoprotein (AFP-L3) levels were significantly higher in patients with FHF than in those with other liver diseases. In FHF patients, the serum AFP-L3 level at the onset of encephalopathy was significantly higher in cases with mild atrophy than in those with severe atrophy (P<0.05). Notably, the residual liver volume was significantly correlated with the serum AFP-L3 level (Pearson's correlation coefficient=0.63), but not with AFP. In conclusion, AFP-L3 is a possible serum marker for evaluating liver atrophy and/or liver regeneration in patients with FHF.

Liver targeting of human interferon-beta with pullulan based on metal coordination.

Although interferon (IFN)-beta is widely used for the elimination of hepatitis C virus in patients with chronic liver disease, its clinical efficacy is unsatisfactory. Targeting IFN-beta to the liver might enhance its efficacy without increasing its side effects. The objective of the present study was to target IFN-beta to the liver to enhance its biological activity and reduce its side effects. A chelating residue, diethylenetriaminepentaacetic acid (DTPA), was introduced to pullulan, a water-soluble polysaccharide with a high affinity to the liver (DTPA-pullulan) and natural human IFN-beta was coordinately conjugated with the DTPA-pullulan by mixing in an aqueous solution containing zinc ions (Zn(2+)). Intravenous injection of the IFN-beta-DTPA-pullulan conjugate with Zn(2+) coordination into mice enhanced induction of an antiviral enzyme, 2',5'-oligoadenylate synthetase (2-5AS), specifically in the liver to a significantly greater extent than free natural IFN-beta. The enhanced 2-5AS level in the liver depended on the molar mixing ratio of IFN-beta, DTPA residue of the DTPA-pullulan, and Zn(2+). Moreover, the duration of the liver 2-5AS induction by the IFN-beta-DTPA-pullulan conjugate was longer than that by free natural IFN-beta. Thus, human IFN-beta-DTPA-pullulan conjugate appears to be applicable for clinical use, which is promising for treatment of patients with chronic hepatitis C.