OBJECTIVE: We evaluated the usefulness of contrast-enhanced harmonic gray scale sonography with a newly developed sonographic contrast medium as a means of guidance for percutaneous ablation therapy of hepatocellular carcinoma lesions not detected by conventional sonography. METHODS: We examined 85 patients with 108 hepatocellular carcinoma lesions that were identified as hypervascular by multidetector-row computed tomography by using contrast-enhanced harmonic gray scale sonography after injection of Sonazoid (GE Healthcare, Oslo, Norway), a lipid-stabilized suspension of a perfluorobutane gas microbubble contrast agent. We scanned the whole liver by this modality at a low mechanical index in the late phase to detect lesions not detected by conventional sonography and then scanned the lesions again by this modality at a high mechanical index to visualize tumor vessels and enhancement. We also performed percutaneous ablation therapy guided by this modality to treat viable hepatocellular carcinoma lesions that could not be detected by conventional sonography. RESULTS: Conventional sonography identified 90 (83%) of 108 hepatocellular carcinoma lesions; 15 (14%) additional viable lesions not detected by conventional sonography were detected in the late phase of contrast-enhanced harmonic gray scale sonography at a low mechanical index, and tumor vessels and enhancement were observed in the late phase at a high mechanical index. Contrast-enhanced harmonic gray scale sonography diagnosed 105 (97%) of the 108 viable hepatocellular carcinoma lesions, and 14 (93%) of the 15 lesions not detected by conventional sonography were successfully treated by percutaneous ablation therapy guided by this modality. CONCLUSIONS: Contrast-enhanced harmonic gray scale sonography is useful for guidance of percutaneous ablation therapy of hepatocellular carcinoma lesions not detected by conventional sonography.
AIM: Aplastic anaemia following hepatitis may develop in as many as 1 of 3 patients with non-A, non-B and non-C hepatitis. Several causative factors have been discussed, such as viral infections and autoimmunity. Here we describe the natural history of this condition in 7 children and investigate possible hepatitis-causing agents. METHODS: We reviewed the medical records, bone marrow and liver biopsies of 7 children with severe hepatitis, with or without liver failure, who subsequently had developed aplastic anaemia. RESULTS: The median time from onset of hepatic symptoms until diagnosed onset of aplasia was 54 days. No associated viral infections could be identified. On liver biopsy, a majority had lobular inflammation but lacked signs of autoimmune hepatitis, findings compatible with a viral aetiology. Three of 6 children had low reticulocyte counts already at onset of hepatitis. All, but one patient is alive at median follow-up of 8 years. CONCLUSION: The unknown pathogenetic mechanism appears to target liver and bone marrow simultaneously, because half of the children concomitantly had low reticulocyte counts and severe liver failure.
Advanced glycation end products (AGE) are present in amyloid deposits in beta2-microglobulin amyloidosis, and it has been postulated that glycation of beta2-microglobulin may be involved in fibril formation. The aim of this paper was to ascertain whether AGE occur in amyloid deposits in familial amyloidotic polyneuropathy (FAP).
Department of Medicine, Umeå University Hospital and First Department of Internal Medicine, Kumamoto University School of Medicine.
The presence of AGE was sought immunohistochemically and biochemically in amyloid-rich tissues from patients with FAP.
Biopsy specimens from nine patients and 10 controls were used for the immunohistochemical analysis. For amyloid preparation, vitreous samples from three FAP patients were used.
Immunohistochemical studies using a polyclonal anti-AGE antibody revealed positive immunoreactivity in intestinal materials, but the pattern of reactivity was unevenly distributed; it was often present in the border of amyloid deposits, or surrounding them. Non-amyloid associated immunoreactivity was also observed in a few regions of the specimens, although the AGE-positive structures were situated in areas containing amyloid deposits. Western blotting of purified amyloid from the vitreous body of FAP patients revealed a significant association of AGE with amyloid fibrils.
The immunoreactivity for the AGE antibody suggests that AGE may be involved in fibril formation in FAP.
We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins.
OBJECTIVE: To investigate signs of liver disease, and biochemical and immunological markers in blood donors with isolated GBV-C/HGV viremia. METHODS: Eighteen donors with isolated GBV-C/HGV viremia were followed up 3-5 years after initial identification. Testing for GBV-C/HGV RNA, GBV-C/HGV-E2 antibodies and a range of biochemical and immunological tests was performed. Thirteen donors consented to liver biopsy. RESULTS: Twelve donors remained GBV-C/HGV viremic at follow-up. Five donors had developed E2 antibodies. Liver biopsies revealed mild portal inflammatory lesions in 6/11 individuals with persistent viremia, and steatosis in 10/13 biopsied donors. CONCLUSION: Steatosis and mild portal inflammatory lesions were found in liver biopsies from several blood donors with isolated GBV-C/HGV viremia.
Autoimmune hepatitis (AIH) in childhood is a progressive chronic inflammatory liver disease. The aim of this study was to compare the clinical and biochemical characteristics of 33 paediatric patients diagnosed as having AIH with earlier described cohorts, and to examine the effect of early treatment strategies on the course of disease.
A population-based cohort of patients from January 1993 to September 2009 was identified prospectively, and the patient data were collected by a retrospective examination of the files.
Twenty-nine patients had type 1 AIH, 2 had type 2, and 2 could not be categorised. Among the 33 children, 16 (48.5%) were girls and 17 (51.5%) were boys. Twenty-three (69.7%) of the patients had symptoms at presentation indistinguishable from acute viral hepatitis, but in 16 (69.6%) of those the liver biopsy showed cirrhosis. Twenty (60.6%) patients were treated with prednisolone and azathioprine at the time of remission, whereas 8 (24.2%) were treated with prednisolone. One (3%) patient did not experience remission during the observation period.
The patients in our study appeared similar to previously published cohorts, although a female predominance was not observed. Our data suggest that early treatment including both prednisolone and azathioprine could be more effective than prednisolone alone, even if randomised controlled paediatric studies comparing these 2 different treatment regimens are needed.
PURPOSE: To assess the value of mangafodipir trisodium-enhanced MR imaging for characterization of hepatocellular lesions. MATERIALS AND METHODS: Magnetic resonance images of 41 patients with 48 histopathologically proven hepatocellular lesions (20 cases of focal nodular hyperplasia [FNH], 4 adenomas, 15 hepatocellular carcinomas [HCCs], 7 regenerative nodules, and 2 others) were retrospectively studied. Magnetic resonance imaging was performed on a 1.5-T unit (Vision, Siemens, Erlangen, Germany; ACS-NT, Philips, Best, The Netherlands) using T2-weighted, fat-saturation, turbo spin echo imaging and T1-weighted gradient echo imaging before and 20 minutes after infusion of 5 micromol/kg mangafodipir (Amersham Health, Oslo, Norway). Qualitative analysis by 4 blinded independent readers included assessment of unenhanced images and, in a second step, assessment of unenhanced and contrast-enhanced images together. Lesions were classified as benign or malignant using a 5-point scale, and readers made a specific diagnosis. RESULTS: For characterization of hepatocellular lesions, mangafodipir-enhanced imaging was significantly superior to unenhanced imaging (P
Chronic evolution after acute hepatitis B virus infection. During a 13 months period 1977-1978 a total of 129 cases of acute viral hepatitis type B occurred among patients who were admitted with hepatitis to Roslagstull, Hospital, Stockholm, Sweden. Less than 1% progressed to chronicity. Prevalence of Delta superinfection was studied among 60 patients with chronic hepatitis B. Nineteen (32%) were anti-delta positive. The majority of the positive patients were either non-European immigrants or addicts, both 9/19 (47%). Infections with the delta agent was found to have occurred in Stockholm already in the early 1970s. Rate of HBeAg clearance during chronic HBV was studied among 36 HBeAg positive patients. Seroconversion to anti-HBe was noted in 17 patients (47%), whereas HBeAg persisted in 19 during a mean follow-up period of 53 months. The spontaneous annual HBeAg seroconversion rate was 11%. HBeAg clearance occurred as frequently among homosexual men as among patients in other categories. However, 12/14 homosexual men were HBeAg positive after 2 years follow-up, compared with 1/13 drug addicts. Thus, homosexual men seemed to require a longer time for HBeAg seroconversion than i.v. drug addicts. HBV-DNA in serum, a strong indicator of viral particles and infectivity was analysed among patients with HBeAg seroconversion, initial HBeAg negativity and/or delta superinfection. HBV-DNA was found in 75-80% of our HBeAg positive patients. A correlation between chronic liver disease and presence of HBV-DNA in serum was also found. Thus, HBV DNA was found in 63% of patients with CAH or CAH/CI as compared with only 39% of patients with CPH. Delta infected patients had HBV-DNA more often than those without hepatitis D infection. Seven delta infected, anti-HBe positive, patients were still HBV-DNA positive five to eight years later. Therefore delta infected anti-HBe positive patients can be infectious for prolonged periods. Histological outcome. 63% (12/19) anti-delta positive patients were classified as CAH with or without cirrhosis as against 39% (16/41) of the anti-delta negative patients. Eleven of 15 homosexual men (73%) had histological findings classified as CAH or CAH/CI. None of them were superinfected with HDV. Thus homosexual men developed severe hepatic lesions without being delta infected. In contrast 78% (7/9) i.v. drug addicts with CAH were delta infected. A numerical scoring system was applied and compared with conventional morphological classification of liver histology to assess the histological outcome of 42 patients with repetitive liver biopsies.
Alcoholic fatty liver disease comprises alcoholic pure steatosis and alcoholic steatohepatitis. These diseases are prevalent, but their prognostic outcome is uncertain, particularly regarding the impact of hepatic inflammation. The paucity of data based on liver biopsy diagnoses contributes to this uncertainty.
To examine the cirrhosis and mortality risks of Danish men and women with biopsy-verified alcoholic pure steatosis or steatohepatitis.
In this registry-based historical cohort study we combined liver biopsy diagnoses with hospital discharge diagnoses from nationwide healthcare registries to identify all Danish citizens with alcoholic pure steatosis (N = 136) or alcoholic steatohepatitis (N = 58) during 1997-2008. We enrolled a reference cohort of 100 gender- and age-matched persons from the general population for each patient and compared cirrhosis and mortality risks through 2010.
The 5-year cirrhosis risks were 6.9% (95% CI: 3.4-12.2%) for patients with alcoholic pure steatosis and 16.0% (95% CI: 7.8-26.8%) for patients with alcoholic steatohepatitis, their 5-year mortality risks were 16.7% (95% CI: 11.3-24.2%) and 25.1% (95% CI: 15.7-38.9%), respectively. Patients with steatohepatitis had a higher liver-related mortality than patients with pure steatosis. In the reference cohort, the 5-year cirrhosis and mortality risks were 0.3% and 4.3%, respectively.
Patients with alcoholic fatty liver disease had markedly increased cirrhosis and mortality risks compared with a matched reference cohort. The cirrhosis risk was more than twice as high for the patients with steatohepatitis than for those with pure steatosis; and was higher for women than for men.
to study the clinical and morphological manifestations of portal gastropathy in patients with liver cirrhosis (LC).
One hundred and sixty-nine patients with Child-Pugh Classes B and C CL and 150 patients with gastritis and peptic ulcer disease without LC were examined. All the patients underwent fibrogastroscopy and morphological study of the gastric mucosa (GM). Morphological and serological studies detected Helicobacter pylori in all the patients.
The endoscopic signs of portal gastropathy were found in 46.7-50.9% of the patients with LC; dilated capillaries and microbleedings in the GM were recorded in 73.9-83.7%. Ulcerative and erosive defects of the gastroduodenal area were identified in 31.9% of the patients with CL and these were accompanied by nemorrhages in 50% of cases. In patients with ulcers and erosions, the diameter of capillaries in different gastric portions was 23-56% larger than that in patients without these abnormalities. There was a significant direct correlation between the presence of H. pylori IgG and the morphological signs of portal gastropathy in the antrum.
An association was found between the signs of portal gastropathy and the presence of ulcerative and erosive defects in the gastroduodenal area in patients with LC.