Transjugular intrahepatic portosystemic shunt for the treatment of portal hypertension secondary to non-cirrhotic perisinusoidal hepatic fibrosis

Non-cirrhotic perisinusoidal hepatic fibrosis is a process of imprecise pathogenesis involving collagenization of the space of Disse. Exposure to chemicals, auto-immunity, thrombophilia and/or infections are suspected primary agents. Here, we present the case of a patient who developed severe portal hypertension with histological features suggesting a non-cirrhotic perisinusoidal hepatic fibrosis. A 52-year-old man was hospitalized for oesophageal variceal haemorrhage. Liver cirrhosis or portal vein thrombosis were absent as attested by laboratory tests, duplex sonography, computed tomography scan and histological examination of a liver biopsy specimen. Presinusoidal portal hypertension was suggested by a normal wedge-free hepatic vein gradient. Only electron microscopy examination of a liver biopsy specimen could disclose perisinusoidal fibrosis. This was most probably secondary to a combined chemotherapy received 4 years earlier for non-Hodgkin large-cell lymphoma. As variceal ligation failed to control oesophageal varices while liver function tests were normal, a transjugular intrahepatic portosystemic shunt (TIPS) was performed. This dramatically improved the signs of portal hypertension. This case illustrates the use of TIPS in the treatment of portal hypertension secondary to non-cirrhotic perisinusoidal fibrosis.     

Serum aminoterminal type III procollagen peptide and the 7S domain of type IV collagen in patients with alcohol abuse. Relation to ultrastructural fibrosis in the acinar zone 3 and to serum hyaluronan

Serum concentrations of the aminoterminal propeptide of type III procollagen and of the 7S domain of type IV collagen, presumed to reflect fibrotic activity in liver tissue, and of the glycosamonoglycan hyaluronan, were obtained from 40 alcohol abusers, at the time of liver biopsy. The serological results were related to morphological findings in liver tissue, i.e. no fibrosis, fibrosis without cirrhosis, micronodular cirrhosis and macronodular cirrhosis, and to ultrastructural indications of perisinusoidal fibrosis in the acinar zone 3. All patients with fibrosis and cirrhosis on light microscopy had elevated serum levels of the type III procollagen peptide as well as of the 7S domain of type IV collagen. However, due to a considerable overlap between the groups, no relations could be demonstrated to the severity of the fibrosis, supporting the assumption that these serological markers reflect the current fibrotic activity and not the amount of fibrotic tissue previously deposited. Among patients without fibrosis on light microscopy, a relation between the propeptide levels and ultrastructural perisinusoidal zone 3 fibrosis was observed, suggesting that type III procollagen peptide may be valuable in detecting very early liver fibrosis. A positive correlation was demonstrated between the serum concentrations of type III procollagen peptide and hyaluronan. As hyaluronan is degraded in the liver endothelial cells, it is suggested that the liver is involved, not only in the synthesis, but also in the degradation of the propeptide.     

Hepatic fibrosis in patients with idiopathic thrombocytopenic purpura

Three patients showing all the symptoms of idiopathic thrombocytopenic purpura underwent a splenectomy. A wedge liver biopsy revealed hepatic fibrosis around central veins and an increased perisinusoidal network on Sirius red staining. Fibrosis was moderate or mild. Liver histology was otherwise normal, as were liver function tests. Hepatic fibrosis could not be attributed to any known causes. Electron microscopy showed numerous Kupffer cells with intense phagocytic activity, and perisinusoidal cells with some of the characteristics of fibro/myofibroblasts. The mechanisms of fibrosis remain unknown but could be attributed, by analogy to agnogenic myeloid metaplasia, to the massive destruction of platelets liberating PDGF and to increased activation of macrophages.     

Development from simple steatosis to liver cirrhosis and hepatocellular carcinoma: a 27-year follow-up case

Nonalcoholic fatty liver disease (NAFLD) is classified as nonalcoholic steatohepatitis (NASH) or simple steatosis (SS) according to histological findings. It is well recognized that NASH may develop into cirrhosis and hepatocellular carcinoma (HCC), both with unfavorable prognoses. Although the outlook of SS is reported to be better than that of NASH, the long-term prognosis of SS remains unclear. Here, we report the case of a patient who was diagnosed as having SS by a first liver biopsy, and later developed into cirrhosis and HCC over a period of 27 years. In 1980, a 42-year-old Japanese man was admitted because of abnormal liver function tests. He had no history of alcohol intake and was negative for hepatitis virus markers and autoantibodies. A liver biopsy specimen showed macrovesicular steatosis without ballooned hepatocytes, Mallory hyaline, lobular inflammation, or perisinusoidal/perivenular fibrosis, confirming the diagnosis of SS. The patient’s serum aminotransferase levels did not normalize despite repeated dietary instruction, and in 2001, liver histology demonstrated cirrhosis with mild steatosis and hepatocyte ballooning, leading to the diagnosis of NASH-related cirrhosis. HCC appeared in 2007. Overall, this patient progressed to cirrhosis and HCC in 20 and 27 years, respectively, following initial diagnosis. Platelet counts and degree of steatosis, as assessed by periodic ultrasonography, were seen to gradually reduce with progression of fibrosis. This case demonstrates that even a diagnosis of SS does not guarantee non-progression to cirrhosis and HCC, and careful follow-up is needed not only in patients with NASH, but also in those with SS.     

慢性乙型肝炎肝窦及窦周隙的病变与肝纤维化的关系

目的 探讨慢性乙型肝炎肝窦及窦周隙内病变及其与肝纤维化的关系。方法 采用ＨＥ。特殊染色及免疫组织化学染色法,用光镜观察肝组织病理分级诊断为Ｇ１－Ｇ４和活动性肝硬化（ＡＬＣ）各３０例,慢性重型肝炎（ＣＳＨ）１０例的肝活检组织中各成分的分布。设正常肝５例和肝硬化（ＬＣ）１０例作对照,结果 肝窦及窦周隙病理改变有塌陷、扩张、阻塞及狭窄、平滑肌肌动蛋白分布演变尤具特征性。ＣＩＶ、ＦＮ和ＬＮ三种成分在肝窦沉     

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.     

Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions

OBJECTIVE: Steatohepatitis is a morphological pattern of liver injury that may be seen in alcoholic or nonalcoholic liver disease. This pattern may occur with obesity, diabetes, the use of certain drugs, or the cause may be idiopathic. The well-recognized histopathological features of nonalcoholic steatohepatitis (NASH) include hepatocellular steatosis and ballooning, mixed acute and chronic lobular inflammation, and zone 3 perisinusoidal fibrosis. Currently, there are no systems for grading necroinflammatory activity or for staging fibrosis as exist for various other forms of chronic liver disease. The purpose of this study was to develop such a grading and staging system and was based on review of liver biopsies from 51 patients with nonalcoholic steatohepatitis from Saint Louis University Health Sciences Center. METHODS: For determination of grade, 10 histological variables of activity were initially analyzed; an overall impression of mild, moderate, and severe was made and the variables considered to be most significant were used to develop the necroinflammatory grade. RESULTS: The histological lesions considered to be significant were: steatosis, ballooning, and intra-acinar and portal inflammation. A staging score was developed to reflect both location and extent of fibrosis. The fibrosis score was derived from the extent of zone 3 perisinusoidal fibrosis with possible additional portal/periportal fibrosis and architectural remodeling. Fibrosis stages are as follows: Stage 1, zone 3 perisinusoidal fibrosis; Stage 2, as above with portal fibrosis; Stage 3, as above with bridging fibrosis; and Stage 4, cirrhosis. CONCLUSION: We propose a grading and staging system that reflects the unique histological features of nonalcoholic steatohepatitis.     

Serum aminoterminal type III procollagen peptide and the 7S domain of type IV collagen in patients with alcohol abuse Relation to ultrastructural fibrosis in the acinar zone 3 and to serum hyaluronan

ABSTRACT— Serum concentrations of the aminoterminal propeptide of type III procollagen and of the 7S domain of type IV collagen, presumed to reflect fibrotic activity in liver tissue, and of the glycosamonoglycan hyaluronan, were obtained from 40 alcohol abusers, at the time of liver biopsy. The serological results were related to morphological findings in liver tissue, i.e. no fibrosis, fibrosis without cirrhosis, micronodular cirrhosis and macronodular cirrhosis, and to ultrastructural indications of perisinusoidal fibrosis in the acinar zone 3. All patients with fibrosis and cirrhosis on light microscopy had elevated serum levels of the type III procollagen peptide as well as of the 7S domain of type IV collagen. However, due to a considerable overlap between the groups, no relations could be demonstrated to the severity of the fibrosis, supporting the assumption that these serological markers reflect the current fibrotic activity and not the amount of fibrotic tissue previously deposited. Among patients without fibrosis on light microscopy, a relation between the propeptide levels and ultrastructural perisinusoidal zone 3 fibrosis was observed, suggesting that type III procollagen peptide may be valuable in detecting very early liver fibrosis. A positive correlation was demonstrated between the serum concentrations of type III procollagen peptide and hyaluronan. As hyaluronan is degraded in the liver endothelial cells, it is suggested that the liver is involved, not only in the synthesis, but also in the degradation of the propeptide.     

Nonsyndromatic paucity of interlobular bile ducts: light and electron microscopic evaluation of sequential liver biopsies in early childhood

Liver biopsies and/or autopsy specimens from 17 children (ages 1 week to 5 years) with nonsyndromatic paucity of the interlobular bile ducts were studied by light and electron microscopy. Initial biopsies were obtained before 90 days of age from all patients, and two or more specimens were available from nine. No specific underlying condition was found in nine infants. The remaining cases were associated with Down's syndrome (n = 2), hypopituitarism (n = 2), cystic fibrosis (n = 1), alpha 1-antitrypsin deficiency (n = 1), cytomegalovirus (n = 1) and Ivemark syndrome (n = 1). Before 90 days of age, portal changes included duct paucity and fibrosis. Lobular changes were nonspecific, consisting of cholestasis, giant cell transformation, extramedullary hematopoiesis and perisinusoidal fibrosis. Duct paucity, portal fibrosis and perisinusoidal fibrosis persisted after 90 days. Cholestasis was mild or no longer apparent. Portal changes before 90 days of age appear to be sufficiently distinctive to microscopically distinguish nonsyndromatic from syndromatic paucity. Electron microscopic findings suggest that paucity in nonsyndromatic patients may result from a primary ductal insult: ultrastructural studies revealed bile duct destruction characterized by undulation and breaks in the basal lamina and infiltration of the epithelium by lymphocytes. Bile canalicular dilatation with blunting of microvilli and electron-dense material in the lumen, predominantly seen before 90 days, also reinforces the hypothesis of a primary ductal defect.     

Digital quantification of fibrosis in liver biopsy sections: description of a new method by Photoshop software

BACKGROUND: The precise quantification of fibrous tissue in liver biopsy sections is extremely important in the classification, diagnosis and grading of chronic liver disease, as well as in evaluating the response to antifibrotic therapy. Because the recently described methods of digital image analysis of fibrosis in liver biopsy sections have major flaws, including the use of out-dated techniques in image processing, inadequate precision and inability to detect and quantify perisinusoidal fibrosis, we developed a new technique in computerized image analysis of liver biopsy sections based on Adobe Photoshop software. METHODS: We prepared an experimental model of liver fibrosis involving treatment of rats with oral CCl4 for 6 weeks. After staining liver sections with Masson's trichrome, a series of computer operations were performed including (i) reconstitution of seamless widefield images from a number of acquired fields of liver sections; (ii) image size and solution adjustment; (iii) color correction; (iv) digital selection of a specified color range representing all fibrous tissue in the image and; (v) extraction and calculation. RESULTS: This technique is fully computerized with no manual interference at any step, and thus could be very reliable for objectively quantifying any pattern of fibrosis in liver biopsy sections and in assessing the response to antifibrotic therapy. It could also be a valuable tool in the precise assessment of antifibrotic therapy to other tissue regardless of the pattern of tissue or fibrosis.     

Alcoholic liver injury in baboons: transformation of lipocytes to transitional cells

Ultrastructure of the lipocytes (the main perisinusoidal cells) and their alterations in the progression of hepatic fibrosis were studied in liver biopsy specimens of baboons pair-fed with diets containing alcohol, or isocaloric carbohydrate, for up to 112 mo. In control baboons, 97% of the cells in the Disse space were lipocytes characterized by a volume density of lipid droplets occupying greater than 20% of the cell volume and by the presence of microfilament bundles with associated dense bodies and pinocytic vesicles. Intercellular junctions of the adherens type were present between lipocytes and hepatocytes. After alcohol consumption, the number of lipocytes (as assessed by light microscopy) was significantly decreased in fatty livers and at various stages of hepatic fibrosis; this was associated with a decreased hepatic vitamin A content. In baboons fed alcohol, only 48% of cells were lipocytes, whereas 52% were transitional cells defined by a volume of lipid droplets less than 20% of the cell. Like the lipocytes, transitional cells exhibited microfilament bundles, dense bodies, and pinocytic vesicles, and were attached to the hepatocytes by cell junctions. The rough endoplasmic reticulum in transitional cells was conspicuous and had an area significantly greater than that in lipocytes of controls and alcohol-fed animals (69% and 37%, respectively). There was a significant correlation between the percentage of transitional cells as well as the area of their rough endoplasmic reticulum and the degree of hepatic fibrosis. Thus, in baboons fed alcohol, the progression of hepatic fibrosis is associated with transformation of lipocytes to transitional cells characterized by a depletion of lipid droplets and a hypertrophy of the rough endoplasmic reticulum; these transitional cells may play a role in promoting hepatic fibrosis in alcoholic liver injury.     

Unusual cause of ascites: the POEMS syndrome

A 39-year-old woman presented with polyneuropathy, hepatomegaly, splenomegaly, endocrinopathy, monoclonal protein and skin changes, several of the many clinical features of the recently described POEMS syndrome. In addition, she had a Castleman's disease (angiofollicular lymph node hyperplasia). In this case ascites was a main presenting feature. Thus, the POEMS syndrome must be added to the list of rare causes of ascites. Electron microscopy of the liver showed perisinusoidal fibrosis.     

Alpha-smooth muscle actin-positive stromal cells in cholangiocarcinomas, hepatocellular carcinomas and metastatic liver carcinomas

Aims/Methods: In the human liver, α-smooth muscle actin (ASMA) is present in smooth muscle of the vasculature, perisinusoidal cell (Ito cells), and myofibroblasts derived from perisinusoidal cells. In this study, we investigated ASMA-positive stromal cells and their relation to tumor fibrosis in 50 cholangiocarcinomas, 30 hepatocellular carcinomas, and 57 metastatic liver carcinomas.Results: Tumor fibrosis was much more extensive in cholangiocarcinomas and metastatic liver carcinomas than in metastatic liver carcinomas. ASMA immunoreactivity was prominent in the sinusoids surrounding cancer nodules and in the cancerous stroma, not in sinusoids remote from cancer nodules. ASMA-positive stromal cells were divisible into peritumoral ASMA-positive perisinusoidal cells and intratumoral ASMA-positive stromal cells. Both types of ASMA-positive cells were abundant in cholangiocarcinomas and metastatic liver carcinomas, but much more scanty in hepatocellular carcinomas. The number of both types showed a significant positive correlation with the degree of tumor fibrosis. The peritumoral ASMA-positive perisinusoidal cells were frequently in direct continuity with intratumoral ASMA-positive stromal cells in cholangiocarcinomas and metastatic liver carcinomas.Conclusions: These findings show that ASMA-positive stromal cells are related to tumor fibrosis in liver malignancies. Although direct evidence is lacking, the data suggest that, in cholangiocarcinomas and metastatic liver carcinomas, peritumoral ASMA-positive perisinusoidal cells transform into activated perisinusoidal cells (myofibroblasts), are incorporated into the tumor (intratumoral ASMA-positive stromal cells), and produce extracellular matrix proteins, that lead to tumor fibrosis. The scantly ASMA-positive cells in hepatocellular carcinomas may in part be responsible for the small amount of fibrosis in this tumor.     

实验性脂肪肝肝纤维化组织中弹性蛋白表达的研究

目的探讨弹性蛋白表达与脂肪肝肝纤维化的关系。方法分别建立高脂饮食、低脂酒精饮食、高脂酒精饮食和四氯化碳大鼠实验性脂肪肝肝纤维化模型,用免疫组织化学方法观察造模肝组织中弹性蛋白的表达。结果低脂饮食组、高脂饮食组和低脂饮食酒精组未见弹性蛋白的表达;高脂饮食酒精组有部分表达,而四氯化碳组均见弹性蛋白的表达;窦周肝细胞表达强度明显高于肝细胞。结论在肝纤维化的发展过程中,弹性蛋白的表达见于肝纤维化后期,与肝纤维化程度相关,可反映肝纤维化的病程;窦周肝细胞（主要是肝星状细胞）在肝纤维化进程中起十分重要的作用。     

Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH): diagnosis and clinical course

Non-alcoholic fatty liver disease (NAFLD) is a frequent syndrome encompassing fatty liver alone and steatohepatitis (NASH). Often asymptomatic, the suspicion arises because of abnormal aminotransferases or a bright liver on abdominal ultrasound. It should be suspected during evaluation of associated conditions as obesity, diabetes or dyslipidaemia. The diagnostic evaluation must exclude other potential causes of liver disease and may include a liver biopsy, the only method able to confirm features of necroinflammation and fibrosis that define NASH and its prognostic implications. Indeed, the presence of necroinflammation has been associated with a significant risk of progression to cirrhosis and eventually hepatocellular carcinoma. Age >45 years, obesity and diabetes have also been associated with an increased risk of liver fibrosis and progression to cirrhosis. Given the high prevalence of NAFLD, general measures of life-style changes, focusing on exercise, diet, and total alcohol abstinence, should be implemented before a liver biopsy is considered.     

Sampling variability of liver biopsy in nonalcoholic fatty liver disease

BACKGROUND & AIMS: In nonalcoholic fatty liver disease (NAFLD), the distinction between steatosis and steatohepatitis (NASH) and the assessment of the severity of the disease rely on liver histology alone. The aim of this study was to assess the sampling error of liver biopsy and its impact on the diagnosis and staging of NASH. METHODS: Fifty-one patients with NAFLD underwent percutaneous liver biopsy with 2 samples collected. The agreement between paired biopsy specimens was assessed by the percentage of discordant results and by the kappa reliability test. RESULTS: No features displayed high agreement; substantial agreement was only seen for steatosis grade; moderate agreement for hepatocyte ballooning and perisinusoidal fibrosis; fair agreement for Mallory bodies; acidophilic bodies and lobular inflammation displayed only slight agreement. Overall, the discordance rate for the presence of hepatocyte ballooning was 18%, and ballooning would have been missed in 24% of patients had only 1 biopsy been performed. The negative predictive value of a single biopsy for the diagnosis of NASH was at best 0.74. Discordance of 1 stage or more was 41%. Six of 17 patients with bridging fibrosis (35%) on 1 sample had only mild or no fibrosis on the other and therefore could have been under staged with only 1 biopsy. Intraobserver variability was systematically lower than sampling variability and therefore could not account for most of the sampling error. CONCLUSIONS: Histologic lesions of NASH are unevenly distributed throughout the liver parenchyma; therefore, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies.     

Morbid obesity, nonalcoholic fatty liver disease, and weight loss surgery

OBJECTIVE: This study examines the impact of biliopancreatic diversion, a malabsorptive variant of gastric bypass, on liver histology. METHODS: Liver samples were collected from 689 severely obese (BMI 47 +/- 9 kg m(2)) patients undergoing biliopancreatic diversion. Exclusion criteria included: history of hepatitis, exposure to hepatotoxic medications, prior weight loss surgery, and alcohol consumption greater than 100 grams per week. One group of 14 patients had cirrhosis in their initial biopsy. Eleven of those 14 patients underwent multiple biopsies to monitor their liver disease. A second group of 104 patients had re-operations and a second liver biopsy. A hepatopathologist conducted blind evaluations of all biopsy specimens looking for steatosis and fibrosis. RESULTS: All patients lost weight and showed improvement in their metabolic syndrome. Of the 104 patients undergoing re-operation with a second liver biopsy, 28 showed a decrease in severe fibrosis, while 42 patients developed mild fibrosis. On average, this group lost 38 +/- 18 kg over 41 +/- 25 post-surgical months. A sub-group analysis revealed an association between increased fibrosis and post-operative low serum albumin, diarrhea, pre-operative alcohol consumption, and menopausal status. The eleven patients with cirrhosis in their initial biopsy showed a reduction in their fibrosis grade (mean fibrosis grade from 5 to 3) during nine years of follow-up care. CONCLUSION: These findings indicate that significant weight loss after biliopancreatic diversion can improve liver histology in patients with advanced fibrosis.     

Systemic and splanchnic hemodynamic changes in patients with hepatic schistosomiasis

Abstract: Although hepatic schistosomiasis is a common cause of portal hypertension, only a few hemodynamic studies, in humans, have been published on this subject. The aim of this study was to determine the systemic and splanchnic hemodynamic changes in hepatic schistosomiasis and to evaluate the influence of liver fibrosis on these changes. A retrospective analysis of a series of 13 patients with hepatic schistosomiasis who had undergone hemodynamic studies was performed. Portal or perisinusoidal fibrosis was present at liver biopsy in 8 patients. The control group included 22 patients with chronic hepatitis and normal hepatic venous pressure gradients. Patients with schistosomiasis exhibited high cardiac index (4.11±1.15 1 · min^-1 · m^-2 vs 2.99±0.85 1 · min^-1 · m^-2; p<0.05) and low systemic vascular resistance (1039±316 dyn · s · cm^-5 vs 1334±336 dyn · cm^-5; p<0.05). The hepatic venous pressure gradient and hepatic blood flow were normal. Azygos blood flow was markedly increased (0.90±0.66 1 · min^-1 vs 0.13±0.04 1 · min^-1; p<0.05). Hemodynamic values were not significantly different between patients with liver fibrosis and those without fibrosis at liver biopsy. In conclusion, patients with hepatic schistosomiasis had a hyperkinetic systemic and splanchnic circulation. In patients with esophageal varices, a normal hepatic venous pressure gradient confirmed presinusoidal portal hypertension. The presence of portal or perisinusoidal fibrosis did not influence hyperdynamic splanchnic state.     

Association of idiopathic hepatic sinusoidal dilatation with the immunological features of the antiphospholipid syndrome

BACKGROUND: Isolated sinusoidal dilatation is an uncommon hepatic lesion and the cause is largely unknown. OBJECTIVE: To investigate whether prothrombotic disorders or perisinusoidal cell changes could be involved in pure idiopathic hepatic sinusoidal dilatation (HSD). METHODS: Evaluation for associated conditions, prothrombotic disorders, and studies of hepatic perisinusoidal cell activation in consecutive patients, seen between 1993 and 2002, with isolated sinusoidal dilatation unrelated to outflow block, sinusoidal infiltration, or hepatic granulomas. RESULTS: Among 11 patients, associated conditions were prothrombotic disorders (n = 5) and oral contraceptive use (n = 3). Prothrombotic disorders were polycythemia vera (n = 1) and anticardiolipin antibodies combined with lupus anticoagulant (n = 4). No genetic thrombophilia factor was found. Of four patients with lupus anticoagulant, three had antinuclear factors and high serum levels of anticardiolipin antibodies at repeated testing. There was no evidence of intrahepatic or extrahepatic thrombosis in any of the patients. Sinusoidal dilatation was marked in six of 11 patients (54%), including two patients with antiphospholipid antibodies. Activated perisinusoidal cells were only found around markedly dilated sinusoids. CONCLUSION: Idiopathic pure HSD is frequently associated with the immunological features of the antiphospholipid syndrome. Therefore, finding pure HSD in a liver biopsy specimen should prompt the search for antiphospholipid antibodies.     

Choline fails to prevent liver fibrosis in ethanol-fed baboons but causes toxicity

To determine how choline supplementation affects the liver and whether it can protect against ethanol-induced liver injury, baboons were fed either normal or choline-supplemented diets, each with or without ethanol. Eighteen baboons were pair-fed for 3 to 4 years liquid diets with 50% of total energy as ethanol or isocaloric carbohydrate; ten animals were given our regular diets, whereas in eight the choline content was increased 5-fold. Six additional animals were fed individually with the control diets (with or without additional choline). With both ethanol-containing diets, ethanol intake was comparable and resulted in hepatic steatosis and striking mitochondrial lesions, with increases in serum bilirubin and SGOT, SGPT and glutamate dehydrogenase activities. In addition, of the five animals fed alcohol with the regular diet, one progressed to incomplete cirrhosis and two others developed perivenular and associated perisinusoidal fibrosis. Similarly, in the four baboons fed alcohol with choline supplementation, incomplete cirrhosis developed in one and perivenular fibrosis in two. Collagen deposition was demonstrated by immunoperoxidase with a specific antibody against procollagen Type III. These animals also displayed proliferation of myofibroblasts in the perivenular area and transformation of fat-storing cells to transitional cells in the perisinusoidal space, with associated enhanced collagen fiber deposition. Thus, in baboons, choline supplementation failed to prevent alcohol-induced steatosis and fibrosis. All parameters remained normal in the eight baboons fed the regular control diet. However, in the choline-supplemented controls, serum bilirubin, SGOT and glutamate dehydrogenase activities increased moderately and serum albumin decreased. Occasional fat droplets appeared in hepatocytes with mitochondrial changes (enlargement and alterations of the cristae) and an abundance of "myelin" figures in the cytoplasm, indicating that choline supplementation exerts moderate hepatotoxicity.