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Biomedical subjects

P Christoffersen

Publications and source records attributed to P Christoffersen.

At least 19 recordsLinked to original sources

Long term prognosis of fatty liver: risk of chronic liver disease and death.

BACKGROUND AND AIMS: Fatty liver is a common histological finding in human liver biopsy specimens. It affects 10-24% of the general population and is believed to be a marker of risk of later chronic liver disease. The present study examined the risk of development of cirrhotic liver disease and the risk of death in a cohort diagnosed with pure fatty liver without inflammation. METHODS: A total of 215 patients who had a liver biopsy performed during the period 1976-1987 were included in the study. The population consisted of 109 non-alcoholic and 106 alcoholic fatty liver patients. Median follow up time was 16.7 (0.2-21.9) years in the non-alcoholic and 9.2 (0.6-23.1) years in the alcoholic group. Systematic data collection was carried out by review of all medical records. All members of the study cohort were linked through their unique personal identification number to the National Registry of Patients and the nationwide Registry of Causes of Death, and all admissions, discharge diagnoses, and causes of death were obtained. RESULTS: In the non-alcoholic fatty liver group, one patient developed cirrhosis during the follow up period compared with 22 patients in the alcoholic group. Survival estimates were significantly (p<0.01) different between the two groups, for men as well as for women, with a higher death rate in the alcoholic fatty liver group. Survival estimates in the non-alcoholic fatty liver group were not different from the Danish population. CONCLUSIONS: This study revealed that patients with type 1 non-alcoholic fatty liver disease have a benign clinical course without excess mortality.

Adult↗

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.

Adipokines↗

Distribution of liver haemosiderin iron in 187 patients with various types of hepatic diseases.

The purpose of this study was to evaluate the distribution of haemosiderin iron in various regions of the liver (central, intermediary and peripheral hepatocytes, Kupffer cells, portal macrophages and bile duct epithelial cells) in 174 patients with different hepatic diseases (alcoholic cirrhosis (n = 49), alcoholic steatosis (n = 60), non-alcoholic cirrhosis (n = 16), acute hepatitis (n = 20), clinically overt untreated hereditary haemochromatosis (n = 3), miscellaneous disorders (n = 26)), and in 13 subjects with a normal liver biopsy. Furthermore, the relationship between liver haemosiderin iron, biochemical iron status markers and biochemical liver tests was investigated. In haemochromatosis iron was consistently present in all examined regions of the liver, and in 43% of patients with alcoholic liver disease haemosiderin was present in at least one region of the liver lobule. In 65% of patients with acute hepatitis, haemosiderin was present in macrophages and Kupffer cells. In other hepatic diseases and in normal livers, haemosiderin was rarely seen. Regression analyses showed a correlation between iron status markers in most patients, except in those with high serum aspartate aminotransferase levels. In conclusion, haemosiderin iron is distributed in a typical pattern in haemochromatosis, alcoholic liver disease and acute hepatitis. Both histochemical liver iron and serum ferritin are of value as indirect markers of liver iron stores in patients with moderate hepatocellular damage.

Adolescent↗

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.

Adult↗

Relationships among serum iron status markers, chemical and histochemical liver iron content in 117 patients with alcoholic and non-alcoholic hepatic disease.

Histochemical and chemical liver iron and iron status markers (serum (S-) ferritin, transferrin saturation) were determined in 109 patients with various types of liver disease (71 alcoholic, 38 non-alcoholic disease) and 8 normal subjects. In the series as a whole there was a significant correlation between histochemical hepatocyte iron and chemical iron (rho = 0.48, p = 0.0001). Of the iron status markers, only S-ferritin showed clinically significant correlations with histochemical liver iron (rho = 0.54, p = 0.0001) and chemical liver iron (r = 0.45, p = 0.0001) (log vs. log values). The highest correlation was found between S-ferritin and the product of chemical iron x ASAT (r = 0.61, p = 0.0001) (log vs. log values). None of the normal livers had stainable hepatocyte iron; median chemical iron content was 15 mumol/g dry weight (range 8-25). The entire group of alcoholics had a median liver iron content of 21 mumol/g; all patients had a hepatic iron index (hepatic iron/age) of under 1.4. In alcoholic liver disease, median chemical liver iron content was 15 mumol/g (range 3-36) in 35 subjects with grade 0 hepatocyte iron; 24 mumol/g (range 6-90) in 25 subjects with grade 1 + 2 hepatocyte iron; 30 mumol/g (range 14-74) in 11 subjects with grade 3 + 4 hepatocyte iron. Among subjects with alcoholic liver disease and normal liver iron (< 26 mumol/g), 39% had stainable hepatocyte iron vs. 70% in subjects with increased liver iron (> or = 26 mumol/g). The corresponding figures in subjects with non-alcoholic liver disease were 13% and 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cerebral atrophy in AIDS: a stereological study.

Stereological estimates of mean volumes, surface areas, and cortical thicknesses were obtained on formalin-fixed brains from 19 men with AIDS and 19 controls. Volumes of neocortex, white matter, central brain nuclei, ventricles and archicortex were estimated using point counting and Cavalieri's unbiased principle for volume estimation. In AIDS, the mean volume of neocortex was reduced by 11%, and that of the central brain nuclei by 18%. Mean ventricular volume was increased by 55%. Mean neocortical thickness was reduced by 12%. The mean volume of white matter was reduced by 13%. The findings in 6 clinically demented AIDS patients were not statistically different from the rest of the group.

AIDS Dementia Complex↗

Relation between bone marrow hemosiderin iron, serum iron status markers, and chemical and histochemical liver iron content in 82 patients with alcoholic and nonalcoholic hepatic disease.

Bone marrow hemosiderin iron was assessed in 48 patients with alcoholic, and in 34 patients with nonalcoholic liver disease (53 men, 29 women, median age 55 years, range 18-84) and correlated to serum (S)-iron status markers (iron, transferrin, ferritin), as well as to histochemical hepatocyte iron and chemical liver iron content. In a control group of 53 healthy subjects (23 men, 30 women, median age 28 years, range 18-90) marrow hemosiderin iron and iron status markers were evaluated as well. Among liver patients, the marrow iron grade was higher in men than in women (p = 0.03). Correlations were found between marrow iron and histochemical liver iron (rho = 0.38, p = 0.0001) as well as chemical liver iron (rho = 0.33, p = 0.01). Marrow iron was correlated to S-ferritin (rho = 0.53, p = 0.0001), mean red cell volume (rho = 0.34, p = 0.003), and S-transferrin (rho = -0.24, p = 0.02). Alcoholics had a higher marrow iron grade than nonalcoholics (p = 0.001) and controls (p = 0.0001). Among controls, the marrow iron grade was likewise higher in men than in women (p = 0.01). Correlations were found between marrow iron and ferritin (rho = 0.64, p = 0.0001), transferrin saturation (rho = 0.56, p = 0.001), transferrin (rho = 0.53, p = 0.001), S-iron (rho = 0.37, p = 0.01), and hemoglobin in women (rho = 0.38, p = 0.05). The results indicate that alcoholics either have increased marrow hemosiderin iron stores, or display a redistribution of iron in reticuloendothelial cells from soluble ferritin-bound iron to insoluble hemosiderin iron. Among patients with absent marrow hemosiderin iron, 81% had absent hepatocyte hemosiderin iron as well. Among patients with absent hepatocyte hemosiderin iron, 23% had absent and 77% normal or increased marrow hemosiderin iron. Therefore, in patients with iron depletion, assessment of marrow hemosiderin iron yields more relevant information of iron status than assessment of hepatocyte hemosiderin iron.

Adolescent↗

Deposition of C3, the terminal complement complex and vitronectin in primary biliary cirrhosis and primary sclerosing cholangitis.

Characteristics of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are bile duct destruction and portal inflammation. Increased levels of circulating complement activation products are also present. This raises the possibility of involvement of complement-dependent cytotoxic mechanisms in the pathogenesis. Therefore, we investigated liver biopsy specimens from 21 patients with PBC, six patients with PSC and six controls for complement deposits by immunohistochemistry using polyclonal and monoclonal antibodies against C3d, the terminal complement complex (TCC) and vitronectin (S-protein). We found C3d, TCC and vitronectin deposits only in the portal tracts. C3d and TCC were present in the walls of the hepatic arteries and in the connective tissue stroma but never around the bile ducts. We found vitronectin deposits throughout the connective tissue, often independent of the TCC deposits. When vitronectin and TCC were co-localized, the staining patterns were inverse; that is, intense staining for TCC accompanied weak staining for vitronectin and vice versa. Occasionally complete dissociation between TCC and vitronectin staining was observed. Deposits of TCC and vitronectin showed a focal distribution leaving many portal tracts free of TCC. Our results question whether complement-dependent cytotoxic mechanisms take part in the bile duct destruction in PBC and PSC.

Adult↗

Identification of patients with hereditary haemochromatosis by magnetic resonance imaging and spectroscopic relaxation time measurements.

A total of 4302 healthy blood donors were screened for elevated serum ferritin and transferrin saturation. Fifteen had increased serum ferritin at a follow-up examination. Five relatives of these donors also entered the study. Eleven patients had elevated liver iron concentrations, while five had normal liver iron concentrations. The R2 relaxation rate in the liver was first measured with a conventional multi-spin-echo imaging sequence, and then by a volume-selective spectroscopic multi-spin-echo sequence, in order to achieve a minimum echo time of 4 msec. No correlation was found between the relaxation rate R2 and the liver iron concentration, when R2 was calculated from the imaging data. Multi-exponential transverse relaxation could be resolved when the spectroscopic sequence was used. A strong correlation between the initial slope of the relaxation curve and the liver iron concentration was found (r = 0.90, p < 0.001). Signal intensity ratios between liver and muscle were calculated from the first three echoes in the multi-echo imaging sequence, and from a gradient echo sequence. A strong correlation between the logarithm of the signal intensity ratios and the liver iron concentration was found. Although both spectroscopic T2 relaxation time measurements and signal intensity ratios could be used to quantify liver iron concentration, the gradient echo imaging seemed to be the best choice. Gradient echo imaging could be performed during a single breath hold, so motion artifacts could be avoided. The accuracy of liver iron concentration estimates from signal intensity ratios in the gradient echo images was about 35%.

Biopsy↗

Longitudinal study of influence of Helicobacter pylori on current risk of duodenal ulcer relapse. The Hvidovre Ulcer Project Group.

Seventy-four patients with duodenal ulcer were followed up longitudinally for 2 years after initial ulcer healing. Endoscopy including biopsy of the antral mucosa was performed every 3rd month and whenever clinical symptoms of relapse occurred. The presence of Helicobacter pylori in the biopsy specimens was scored as 0 (none), 1 (sporadic occurrence), 2 (clusters), and 3 (numerous bacteria found diffusely in the mucus layer). The incidence rates of ulcer relapse per patient-month, grouped in accordance with these scores, were (with 95% confidence intervals) 0.073 (0.048-0.111), 0.083 (0.052-0.133), 0.123 (0.096-0.157), and 0.069 (0.041-0.116), respectively. No significant differences in incidence rates across H. pylori scores were observed when taking into account the observation period after healing of the first ulcer, number of ulcer recurrence (1st, 2nd, 3rd), sex, age, smoking habits, peak acid output, time of healing of the preceding ulcer, treatment of the present ulcer (cimetidine, antacids, or no treatment), or type and degree of gastritis. Thus, although H. pylori is prevalent in patients with duodenal ulcer disease, the present study indicates that H. pylori does not have a substantial note in the precipitation of active duodenal ulcer.

Adult↗

The pattern of fibrosis in the acinar zone 3 areas in early alcoholic liver disease.

The degree of fibrosis and the pattern of collagen distribution in the acinar zone 3, as well as the thickness of the terminal hepatic vein walls (THV) were analyzed in 48 consecutive liver needle biopsies from 48 alcoholics with preserved liver architecture. The fibrosis occurred to more or less the same degree in the whole circumference of each THV. A positive correlation was found between the degrees of perisinusoidal/pericellular fibrosis (PSF) and the occurrence of incomplete or complete septa. The thickness of THV walls (TTHV) varied from 1.0-12.5 microns with a median of 3.9 microns. No relationship was found between TTHV and PSF. The results were compared to similar data obtained in liver biopsies from 117 non-alcoholics with normal morphology or slight non-specific changes. No significant difference concerning TTHV and THV diameter was found between alcoholic and non-alcoholic patients. The results suggest that the initial liver fibrosis in alcoholics is slightly asymmetrical distributed in each acinar zone 3 area. With progression, the fibrosis tends to be more uniformly distributed and septa appear, eventually linking THV with portal tracts. Apparently, thickening of the THV walls does not occur in early alcoholic liver disease.

Adolescent↗

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.

Adult↗

The spectrum of alcohol induced liver disease. Histological features.

Alcohol may induce a variety of changes in the liver. None of the features are diagnostic, but some are relatively specific. Usually the simultaneous occurrence of one or more non-specific lesions in combination with other more specific changes leads to the correct diagnosis of alcoholic liver disease.

Fatty Liver, Alcoholic↗

A reappraisal of Poulsen's disease (hepatic zone 1 sinusoidal dilatation).

The possible cause and pathogenesis of this disease are reviewed. The condition is rare, and there are only few reports which throw some light on this remarkable morphology. It is hypothesized that metabolic zonation in the functional liver acinus may be the basis of these changes, but lack of experimental and clinical studies still makes it enigmatic.

Contraceptives, Oral↗

[The therapeutic needs and possibilities of persons in detention assessed immediately after release].

Immediately before release, all detainees in Slagelse were assessed with the object of providing relevant therapeutic offers on the basis of the established therapeutic system. This investigation comprised 24 placements in detention of 20 individuals. The persons who had been placed in detention were mainly young single men with unstable employment histories. 33% were placed in detention in order to protect themselves because they were unable to take care of themselves on account of alcohol intoxication. These should rather have been observed by health staff. 67% were placed in detention because they were committing a breach of the place. It was obvious that there was a great need for supportive measures and treatment of addiction but only two out of 20 desired a therapeutic offer. These two were already in touch with the therapeutic system. Three persons considered that they were in an acute crisis. On the basis of assessment of the personalities of the persons in detention and their lack of motivation to commence a therapeutic programme, it is concluded that the existing therapeutic system could not provide further measures as regards long-term treatment. In this investigation one individual was placed in detention three times. For him detention had the nature of a "social braking function", which must be criticised.

Adult↗

[The long-term therapeutic needs of persons in detention].

With the object of describing the long-term therapeutic needs and possibilities for persons in detention all of the persons placed in detention in Slagelse og Korsør during a period of six months were offered transport to a clinic for the treatment of alcoholism or a psychiatric department after release with the object of reestablishing an individual therapeutic course. Two out of the 105 persons placed in detention who were offered follow-up treatment were interested in the offer. No therapeutic projects were initiated. The police collected some social information about the persons in detention. This information confirmed that the persons placed in detention were mainly young single men and that 47% of these had previously been in detention. As it did not prove possible to illustrate the therapeutic needs and possibilities for persons in detention adequately, the investigation will be continued with an altered design, see the following article.

Adult↗

Prolonged T1 in patients with liver cirrhosis: an in vivo MRI study.

Fifteen patients with liver cirrhosis and two control groups were examined. The first control group consisted of 7 healthy volunteers, and the second group of 17 patients with nonfocal liver diseases. The T1 and T2 relaxation times were calculated from signal intensities read out from a region of interest centrally located in the liver. T1 relaxation time was longer in the patients with liver cirrhosis than in the two reference groups. Ten patients had a liver biopsy taken prior to the MRI study. No correlation was found between histopathology and the measured relaxation times.

Humans↗