Per Christoffersen

Hepatic effects of dietary weight loss in morbidly obese subjects

This prospective study was carried out in order to evaluate the influence on liver morphology and function of a very-low-calorie formula diet. Fourty-one morbidly obese, non-alcoholic subjects had liver biopsy performed before and after a median weight loss of 34 kg. Fatty change improved (p less than 0.001), but 24% of the patients developed slight portal inflammation (p = 0.039) or slight portal fibrosis (p = 0.063). Patients developing portal fibrosis had a higher degree of fatty change at entry (p = 0.029), a more pronounced reduction of fatty change (p = 0.014) and a faster weight loss (p = 0.026). Liver biochemistry, which was of no individual diagnostic value, improved. It is concluded that morbidly obese subjects with a high degree of hepatic fatty change are at risk of developing portal inflammation and fibrosis when undergoing very fast dietary weight reductions.

Quantification of liver fat using magnetic resonance spectroscopy.

Localized proton MR spectroscopy using stimulated echoes was used to quantify the liver fat concentration in patients with various degrees of fatty liver due to alcohol abuse. Ten patients underwent a liver biopsy followed by chemical triglyceride estimation of the fatty content. A statistically significant correlation was found between the fat concentration measured in the liver biopsies, and the concentration calculated from the spectroscopic experiments (r = 0.9, p < .001). Quantitative assessment of liver fat concentrations using localized spectroscopy is superior to methods based on differences in relaxation times, and can be used to estimate the fat concentration over the full range of fat content in contrast to the spectroscopic imaging methods. Localized spectroscopy may replace liver biopsy in the diagnosis of diffuse fatty infiltrations, and can be used for follow-up, due to its noninvasive nature.

Serum YKL-40 is increased in patients with hepatic fibrosis

BACKGROUND/AIMS YKL-40, a mammalian member of the chitinase family, is a lectin that binds heparin and chitin. The function of YKL-40 is unknown, but it may function in tissue remodelling. The aims of this study were to assess the level of circulating YKL-40 in patients with various kinds and degree of chronic liver disease and its possible relation to liver fibrosis. METHODS Serum YKL-40 levels were determined by radioimmunoassay in 129 patients with suspected liver disease and related to histological findings and immunohistochemical staining of YKL-40 in a liver biopsy taken simultaneously with the blood sample. RESULTS The median serum YKL-40 was highest in patients with alcoholic cirrhosis (532 microg/l), in particular in patients with additional alcoholic hepatitis (740 microg/l). Patients with alcoholic cirrhosis, post-hepatitic cirrhosis (425 microg/l) and non-cirrhotic fibrosis (330 microg/l) had significantly higher serum YKL-40 than normal subjects (102 microg/l), patients with fatty liver (195 microg/l) or patients with viral hepatitis without fibrosis (174 microg/l). Serum YKL-40 was significantly (p<0.001) related to the degree of liver fibrosis with the highest levels in patients with moderate (466 microg/l) to severe (676 microg/l) fibrosis. Serum YKL-40 was also increased (p=0.018) in patients with slight fibrosis (270 microg/l) compared to patients without fibrosis. Immunohistochemical analysis demonstrated positive staining for YKL-40 antigen in areas with fibrosis, particularly areas with active fibrogenesis. YKL-40 staining was never found in hepatocytes. CONCLUSIONS Our study indicates that the increased serum YKL-40 in patients with liver disease of various degree and aetiology seems to reflect fibrosis and fibrogenesis.

Incidence and meaning of persistence of Australia antigen in patients with acute viral hepatitis: development of chronic hepatitis.

Abstract In a prospective study for occurrence and persistence of Australia antigen, 253 consecutively admitted patients with biopsy-verified acute viral hepatitis were examined. Australia antigen was detected in serum specimens from 112 of the patients (44 per cent). In 88 of these 112, the antigen was transitorily detectable for one to 13 weeks (average, 4 1/2 weeks). Australia antigen persisted for more than 13 weeks in 11 of the 253 patients (4.3 per cent), in all of whom clinical and biochemical signs of chronic hepatitis developed. In 10 of these patients the chronic hepatitis was verified by repeated liver biopsies. Chronic aggressive hepatitis developed in eight patients, and chronic persistent hepatitis in two. Thus, 4 to 5 per cent of the patients with acute viral hepatitis admitted to Copenhagen hospitals have persistence of Australia antigen for several months; in this group, chronic hepatitis is apt to develop.

Final results of a long-term, clinical follow-up in fatty liver patients

Objective. There is increasing focus on non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to conduct a long-term clinical follow-up of patients with biopsy-confirmed fatty liver without inflammation or significant fibrosis (pure fatty liver), to analyse for potential risk factors at the time of index liver biopsy important for survival and the development of cirrhosis and to describe the causes of death. Material and methods. Patients were linked through their personal identification number to the Danish National Registry of Patients and the Register of Causes of Death. All admissions, discharge diagnoses and causes of death during follow-up were collected. All surviving patients were invited to a clinical follow-up. Results. The follow-up period was 20.4 and 21.0 years, respectively, for the NAFLD and alcoholic fatty liver disease (AFLD) groups. Two NAFLD patients (1.2%) developed cirrhosis during the follow-up period versus 54 (22%) AFLD patients. Sixty-four percent of 178 surviving patients out of an original cohort of 417 patients attended the clinical follow-up. In NAFLD patients, none of the risk factors studied was significant in relation to the risk of death. Patients with AFLD died primarily from cirrhosis and other alcohol-related disorders, whereas in patients with NAFLD the main causes of death were cardiovascular disease and cancer. Conclusions. For patients with pure non-alcoholic fatty liver, survival was good and independent of the histological, clinical and biochemical characteristics at the time of biopsy; the main causes of death were cardiovascular disease and cancer.

Early alcoholic liver injury: Activation of lipocytes in acinar zone 3 and correlation to degree of collagen formation in the disse space

Acinar zone 3 areas in liver biopsy specimens from 23 alcoholics and 47 non-alcoholics were investigated by light microscopy and transmission electron microscopy to asses fibrosis in the perisinusoidal space and to evaluate the role of the lipocytes. Quantitative analysis by light microscopy on toluidine blue-stained sections showed a significant reduction in number of lipocytes--median values of 2.7 and 1.2 lipocytes per 100 hepatocytes in biopsies from chronic alcoholics showing no or varying degrees of zone 3 fibrosis, respectively, as compared to 3.6 lipocytes per 100 hepatocytes in non-alcoholic livers. By transmission electron microscopy, the reduction in number of lipocytes was related to a corresponding increase in number of cells rich in rough endoplasmic reticulum and microfilaments (activated lipocytes). The occurrence of activated cells was significantly correlated to fibrosis of the perisinusoidal space. Activation of lipocytes and collagenization of the perisinusoidal space appeared before light microscopic evidence of fibrosis and were topographically not related to Mallory bodies or alcoholic hepatitis.

Abnormal bile duct epithelium in chronic aggressive hepatitis and cirrhosis: A review of morphology and clinical, biochemical, and immunologic features

Abstract This paper describes the so-called abnormal bile duct epithelium seen in chronic aggressive hepatitis and cirrhosis as well as associated histologic changes. The epithelial changes are characteristic and easily recognized when one is familiar with them. The changes affect the bile ducts of medium size that are centrally located in the connective tissue. This type of abnormal bile duct epithelium differs from other previously described types of abnormal epithelium in bile ducts of the same size. The bile duct changes are probably of viral origin, possibly with a superimposed immunologic component. Patients with chronic aggressive hepatitis with abnormal bile duct epithelium develop cirrhosis more quickly and more frequently than do similar patients without it.

Prolonged bone marrow T1-relaxation in acute leukaemia. In vivo tissue characterization by magnetic resonance imaging

In vivo tissue characterization by measurement of T1- and T2-relaxation processes is one of the greatest potentials of magnetic resonance imaging (MRI). This may be especially useful in the evaluation of bone marrow disorders as the MRI-signal from bone marrow is not influenced by the overlying osseous tissue. Nine patients with acute leukaemia, one patient with myelodysplastic syndrome, and ten normal volunteers were included in the study. The T1- and T2-relaxation processes were measured in the lumbar spine bone marrow using a wholebody superconductive MR-scanner operating at 1.5 Tesla. In the patients MRI was done at the time of diagnosis and during follow-up of chemotherapy and related to bone marrow biopsies taken within three days of the MRI. At the time of diagnosis T1-relaxation time was increased two to three times in the patients (range 0.7-3.0 sec.) compared to the controls (range 0.38-0.60 sec.). No significant difference was seen in the T2-relaxation process. In relation to chemotherapy T1 decreased towards the normal range in the patients who obtained complete remission, whereas T1 remained prolonged in the patients who did not respond successfully to the treatment. The results indicate that MRI may be a non-invasive clinically useful tool in the evaluation of acute leukaemia especially as a follow-up control of chemotherapy.

Zinc depletion in alcoholic liver diseases.

Liver and serum zinc concentrations were investigated in 24 patients with alcoholic liver diseases, 22 patients with non-alcoholic liver diseases, and in 36 control subjects. The liver samples were obtained by percutaneous liver biopsies, and the ratio of hepatocytes to fibrous connective tissue was estimated. The liver zinc concentration was expressed in relation to the amount of hepatocytes, and the serum zinc concentration was calculated in relation to total, albumin-, and alpha 2-macroglobulin-bound serum zinc. The results show that the liver zinc concentration was decreased in patients with alcoholic liver diseases (P < 0.01), in contrast to in patients with non-alcoholic liver diseases. Albumin-bound serum zinc was decreased in both groups (P < 0.001). The results indicate that alcoholic liver damage is associated with zinc deficiency.

The nature and the occurrence of birefringent material in different organs in fatal drug addiction

Insoluble birefringent tablet filler materials commonly found in tablets used in solution by drug addicts as intravenous injections were investigated microscopically. The following filler materials were investigated: talc, potato- and maize-starch, microcrystalline cellulose, magnesium stearate and siliciumoxid. The morphological characteristics of the different materials are described. Tissue sections (lung, liver, spleen, heart, bone-marrow, kidney, lymph-nodes and endocrine glands) from 33 consecutive fatality cases of intravenous drug addicts autopsied at the University Institute of Forensic Medicine in Copenhagen were studied with special reference to the occurrence and nature of birefringent material. Birefringent material was most often demonstrated in lung tissue (94%), followed by spleen (76%), liver (55%), lymph-nodes (portal: 39%) and bone-marrow (24%). The material was always localized intracellularly. Granulomatous reaction was only seen in the lungs. Except for one case, talc was the only foreign material seen in other organs than the lungs, undoubtedly due to its smaller size. The presence of insoluble foreign material in lung tissue of drug addicts indicates a habit of intravenous administration and the amount of the material indicates whether the addict usually injects tablets or only does so occasionally. The presence of birefringent material in the organs have only rarely any obvious clinical implications.