Vitamin A toxicity in a physical culturist patient: a case report and review of the literature

Excessive intake of vitamin A may produce acute or chronic toxicity. Vitamin A can be consumed in foods, fortified products and supplements. We present a case of a young physical culturist man who was referred to our Unit because of chronic liver disease of unknown origin. The patient had a history of increased vitamin A intake from natural source with the addition of high dose of vitamin A supplements with the purpose of improving his muscular development. Our patient showed chronic liver disease with severe fibrosis, signs of portal hypertension and marked hyperplasia of Ito cells. In conclusion, chronic vitamin A toxicity may produce severe liver damage and should be recognized in the differential diagnosis of chronic liver diseases.     

Effect of abnormal liver function on vitamin E status and supplementation in adults with cystic fibrosis.

Patients with cystic fibrosis tend to have reduced serum concentrations of vitamin E and are therefore at risk of developing the neurological complications associated with vitamin E deficiency. Improved survival in cystic fibrosis has resulted in an increasing number of older patients who may develop hepatobiliary complications which may further impair the absorption of vitamin E. In this study the vitamin E status and results of supplementation with oral vitamin E were compared in adult patients with and without evidence of liver involvement as assessed by routine liver function tests. The serum vitamin E concentrations were reduced below normal in 24 of 25 patients. The mean serum vitamin E concentration was significantly lower (p less than 0.05) in those patients with abnormal liver function. When vitamin E status was assessed as the serum vitamin E/cholesterol ratio, however, there was no significant difference between those patients with normal and abnormal liver function. After supplementation with oral vitamin E, either 10 mg/kg/day for one month or 200 mg/day (equivalent to 3.4 to 4.4 mg/kg/day) for up to three months, there was no significant difference in the vitamin E status between the two groups. The results of this study indicate that in general, patients with cystic fibrosis and abnormal liver function do not require increased supplements of vitamin E compared with those with normal liver function.     

Diagnostic accuracy of apparent diffusion coefficient values combined with γ-glutamyl transpeptidase-to-platelet ratio parameters for predicting hepatitis B-related fibrosis

ObjectivesThe accuracy of non-invasive liver fibrosis diagnosis based on the apparent diffusion coefficient (ADC) value combined with the γ-glutamyl transpeptidase-to-platelet ratio (GPR) model to predict the stage of hepatitis B-related fibrosis has not been reported. This study aimed to evaluate the diagnostic efficacy of ADC value combined with GPR for liver fibrosis grading.MethodsThe data of 180 patients with chronic hepatitis B (CHB) diagnosed by liver biopsy were analyzed. The ADC value, GPR, and their combination were assessed in different cirrhosis stages using receiver operating characteristic curve analysis to evaluate their value in diagnosing liver fibrosis.ResultsWe observed that liver fibrosis stages were inversely associated with ADC values (r=?0.691, P<0.001), and positively associated with GPR (r=0.502, P<0.001). The area under the curve for diagnostic efficacy of ADC values, GPR, and their combination for F≥2 liver fibrosis was 0.831, 0.749, and 0.858, respectively, and for F≥3 was 0.872, 0.771, and 0.903, respectively. The diagnostic cutoffs of the combination for each stage were -7.07, -12.21 and -37.75, respectively.ConclusionsThe combined diagnostic tool of ADC and GPR may improve the accuracy of hepatitis B-related liver fibrosis diagnosis, especially for F≥3.     

Hepatic hyper-vitaminosis A: importance of retinyl ester level determination

We report the case of a 32-year-old man with portal hypertension without cirrhosis due to chronic vitamin A intoxication. Portal hypertension revealed by oesophageal varice rupture progressively worsened and ascites occurred 5 years after the patient stopped vitamin A intake. Initially, serum retinyl palmitate concentration was increased whereas serum retinol concentration was normal. There was no hepatic fibrosis on light microscopic examination of liver biopsy specimens. Five years after the patient stopped excessive vitamin A intake, serum retinol and retinol-binding protein concentrations were below the normal range even though there was an increased hepatic retinyl ester content. This was attributed to the late development of peri-sinusoidal fibrosis. This case mainly shows the importance of retinyl ester level determination: serum retinyl palmitate should be measured immediately after intoxication and hepatic retinyl esters should be measured initially and particularly later. Indeed, later serum and hepatic retinol levels in chronic hyper-vitaminosis A may be normal and lead to under-estimation of liver vitamin A overload.     

Apolipoprotein AI and alcoholic liver disease

A prospective study of apolipoprotein AI has been undertaken in 581 alcoholic patients and in 100 controls in order to describe the changes of apolipoprotein AI according to the different stages of the alcoholic liver disease, to correlate the changes to serum liver tests and to estimate its diagnosis and prognostic value. Results showed that apolipoprotein AI concentration is highly related to the degree of liver injury, reaching a maximum in patients with steatosis (229 +/- 90 mg per dl), beginning to decrease in patients with fibrosis (188 +/- 88 mg per dl) and reaching a minimum in patients with severe cirrhosis (91 +/- 46 mg per dl). Apolipoprotein AI had an independent and discriminative value for the diagnosis of fibrosis (p less than 0.001) vs. steatosis and for the diagnosis of cirrhotic vs. noncirrhotic fibrosis (p less than 0.001) or vs. acute alcoholic hepatitis without cirrhosis (p less than 0.001). Cirrhotic patients with apolipoprotein AI less than 100 mg per dl had a lower survival rate at 1 year (62 +/- 7%) than patients with greater value (80 +/- 6%; p less than 0.05), but this prognostic value disappeared in multivariate analysis when other known prognostic factors were taken into account.     

Wernicke encephalopathy in a patient after liver transplantation: A case report

Wernicke encephalopathy(WE) is an acute neurological disorder resulting from vitamin B1 deficiency, which is common in chronic alcoholism and is rare in acute liver failure. So far, there are 2 cases of WE reported after liver transplantation. Here, we report a case of a 45-year-old nonalcoholic male patient who developed psychiatric and neurological disturbance 15 d after receiving orthotopic liver transplantation because of hepatitis B-related cirrhosis and portal hypertension. Brain magnetic resonance imaging(MRI) showed symmetric high-signal intensities in the periaqueductal area. The patient was diagnosed with WE and given intravenous high-dose vitamin B1 immediately. His neurological disturbance resolved in 7 d after receiving the vitamin B1. Brain MRI after 5 mo showed nearly complete recovery. Most WE cases may be misdiagnosed in patients after liver transplantation, and we should pay more attention to its onset.     

High,but not low,dietary retinoids aggravate manifestation of rat liver fibrosis

BACKGROUND: Although there is strong implication that retinoids regulate Ito cell proliferation and collagen synthesis, results from in vivo studies on the relationship between vitamin A and liver fibrosis are conflicting. The present study focuses on the role of vitamin A in carbon tetrachloride (CCl4)-induced fibrosis by chronic feeding of rats with either a vitamin A-supplemented or -depleted diet. METHODS AND RESULTS: In animals with high dietary hepatic retinoid levels, liver fibrosis was more pronounced and was associated with an increased CCl4-toxicity resulting in high mortality (73%). Enhanced liver fibrosis was confirmed by in vivo fluorescence microscopic determination of both collagen deposits (7.4 +/- 1.1 vs 3.9 +/- 0.3% in high vitamin A diet-fed and standard diet-fed fibrotic animals, respectively; P < 0.05) and rarefication of sinusoids (1.5 +/- 0.2 vs 2.4 +/- 0.2 sinusoids/200 microm in high vitamin A diet-fed and standard diet-fed fibrotic animals, respectively; P < 0.05). It was further associated with decreased bile flow and increased parenchymal cell damage. CCl4 reduced hepatic retinoid levels in high vitamin A diet-fed animals, but restored hepatic retinoid levels in animals fed with a vitamin A-deficient diet, implying major interference of vitamin A metabolism with hepatotoxic agents such as CCl4. Low vitamin A feeding did not modulate liver fibrogenesis and caused no mortality. CONCLUSIONS: These results show that the vitamin A status of the liver plays an important role in liver fibrogenesis. While dietary vitamin A shortage does not promote liver fibrogenesis, high levels of vitamin A have the potential to increase systemic and hepatic toxicity of CCl4. Thus, the narrow therapeutic window for nutritional vitamin A substitution must take into account that liver fibrotic patients may display enhanced susceptibility to the adverse effects of vitamin A.     

The value and significance of 25(OH) and 1,25(OH) vitamin D serum levels in adult coeliac patients: A review of the literature

Within the wide spectrum of symptoms and alteration of systems that characterizes CeD, several studies indicate a low-level of vitamin D, therefore recent guidelines suggest its evaluation at the time of diagnosis. This review examines the data from existing studies in which vitamin D has been assessed in CeD patients. Our review indicates that most of the studies on vitamin D in adult CeD report a 25 (OH) vitamin D deficiency at diagnosis that disappears when the patient goes on a gluten-free diet, independently of any supplementation. Instead, when the calcitriol, the active 1,25 (OH) vitamin D form, was evaluated, it resulted in the normal range at the time of CeD diagnosis. A strict and lifelong gluten-free diet can help recover vitamin D level without any supplementation.     

Hepatitis B-related polyarteritis nodosa presenting necrotizing vasculitis in the hepatobiliary system successfully treated with lamivudine, plasmapheresis and glucocorticoid

A 64-year-old man was admitted for alithiasic cholecystitis. Necrotizing vasculitis was detected in a gallbladder obtained at the cholecystectomy. Slight elevation of transaminases, HBe antigens and hepatitis B-DNA (HBV-DNA) were detected in the patient. Intrahepatic necrotizing vasculitis was also detected in the liver biopsy specimen, and he also suffered from peripheral neuropathy of suddenly onset. Based on the diagnosis of hepatitis B-related polyarteritis nodosa, lamivudine was initially administered, followed by plasmapheresis and glucocorticoid steroid therapy. These treatments brought satisfactory improvement of polyarteritis nodosa without exacerbation of liver function.     

Hepatic hydrothorax associated with vitamin a toxicity

We report the first case of an adult presenting with respiratory symptoms caused by hepatic hydrothorax secondary to vitamin A intoxication. The patient was a 52-year-old woman who presented to the hospital with progressive dyspnea. Evaluation demonstrated mild elevation of her liver function tests, ascites, and a right pleural effusion. The patient consumed a variety of vitamins, including vitamin A. Her estimated vitamin A intake was at least 162,300,000 international units (IU) during 18 years. She dramatically escalated her dose the year before admission for a total acute dose of 98,550,000 IU, with a daily intake of 270,000 IU. The recommended daily allowance is 4,000 IU. A transjugular liver biopsy revealed histopathologic changes consistent with vitamin A toxicity: hypertrophy and hyperplasia of hepatic stellate cells, focal pericellular fibrosis, mild perivenular fibrosis, and minimal, predominantly microvesicular steatosis. Despite the absence of cirrhosis, pressure readings demonstrated portal hypertension. During her hospitalization, the patient's symptoms and biochemical profile improved. As the large and generally unregulated United States dietary supplement industry continues to grow, it is increasingly likely that individuals will present with the signs and symptoms of vitamin excess rather than vitamin deficiency. Physicians need to remain alert to the varied presentations and toxic manifestations of excessive vitamin use.     

慢性乙肝病毒感染者血清血管内皮生长因子的研究

目的:检测慢性乙型肝炎病毒感染患者血清中血管内皮生长因子(VEGF)的水平,探讨其临床意义.方法:采用双抗体夹心ELISA法对50例肝细胞癌、40例乙型肝炎肝硬化、36例乙型肝炎肝纤维化、40例慢性乙型肝炎患者血清中VEGF进行检测,并以43例健康者作为对照.同时采用全自动生化分析仪检测所有人员的肝功能常规指标.结果:慢性乙型肝炎、肝纤维化、肝硬化、肝细胞癌组患者血清VEGF浓度明显高于正常对照组(P＜0.01,P＜0.05,P＜0.05,P＜0.05),同时四组患者之间比较,差异均有统计学意义(P＜0.05).四组患者血清VEGF水平与肝功能指标AST、ALT无相关性,与GGT成正相关(r=0.337,P＜0.05).结论:VEGF与慢性乙型肝炎病毒感染者病情密切相关,可作为病情发展动态监测的指标.VEGF与GGT联合检测,可显著提高肝细胞癌的检出率.     

Hepatic Osteodystrophy after Liver Transplantation in a Patient with Primary Biliary Cirrhosis

A patient is presented who developed hepatic osteodystrophy after orthotopic liver transplantation in association with persistently low serum 25-hydroxyvitamin D levels. After successful liver transplantation there was a delay in the return to normal of the serum 25-hydroxyvitamin D levels until oral supplementation with vitamin D was instituted. This case emphasizes the need for effective treatment of hepatic osteodystrophy with vitamin D especially in patients considered for transplantation.     

Vitamin E dietary supplementation protects against carbon tetrachloride-induced chronic liver damage and cirrhosis.

Previous studies have shown that alpha-tocopherol (vitamin E) pretreatment of experimental animals can protect against acute liver necrosis induced by carbon tetrachloride. In this study we investigated whether the increase of vitamin E liver content by dietary supplementation influences chronic liver damage and cirrhosis induced by carbon tetrachloride in the rat. Our data indicate that vitamin E supplementation did not interfere with the growth rate of the animals and increased about threefold the liver's content of the vitamin. Vitamin E supplementation significantly reduced oxidative liver damage, but it was not effective in protecting against development of fatty liver and did not interfere with metabolic activation of carbon tetrachloride. Moreover, vitamin E-fed animals showed incomplete but significant prevention of liver necrosis and cirrhosis induced by carbon tetrachloride. This has been shown by means of histological examination, analysis of serum parameters and biochemical evaluation of collagen content. These results show that an increased liver content of vitamin E can afford a significant degree of protection against carbon tetrachloride-induced chronic liver damage and cirrhosis.     

Effects of dietary supplementation with vitamin E and selenium on rat hepatic stellate cell apoptosis

AIM: To evaluate the effects of dietary supplementation with vitamin E and selenium on proliferation and apoptosis of hepatic stellate cells (HSCs), in acute liver injury induced by CCl4, and to explore their role in the recovery from hepatic fibrosis phase. METHODS: An acute liver damage model of rats was established by intraperitoneal injection of carbon tetrachloride (0.3 mL/100 g body weight) twice a week, then the rats were killed at 6, 24, 48, and 72 h after the first and third injection, respectively. A liver fibrosis model was established by the same injection for 8 wk. Then three rats were killed at 3, 7,14, and 28 d after the last injection, respectively. The rats from the intervention group were fed with chow supplemented with vitamin E (250 mg/kg) and selenium (0.2 mg/kg), and the rats in the normal control group and pathological group were given standard chow. Livers were harvested and stained with hematoxylin and eosin, Sirius red. Activated HSCs were determined by α-smooth muscle actin immunohistochemistry staining. Apoptotic HSCs were determined by dual staining with the terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL) and α-smooth muscle actin immunohistochemistry. Serum alanine aminotransferase and aspartate aminotransferase were also analyzed. RESULTS: In the acute liver damage model, the degree of liver injury was more serious in the pathological group than in the intervention group. At each time point, the number of activated HSCs was less in the intervention group than in the pathological group, while the number of apoptotic HSCs was more in the intervention group than in the pathological group. In the liver fibrosis model, the degree of liver fibrosis was more serious in the pathological group than in the intervention group. At each time point, the number of activated HSCs was less in the intervention group than in the pathological group, and the number of apoptotic HSCs was more in the intervention group than in the pathological group. CONCLUSION: Vitamin E and selenium supplementation at the given level can inhibit CCl4-induced activation and proliferation of HSCs and promote the apoptosis of activated HSCs in acute damage phase. Vitamin E and selenium can also effectively decrease the degree of hepatic fibrosis and promote the recovery process.     

Differential relationship of vitamin A and E levels in methylnitrosourea-induced Sprague-Dawley rats following prolonged feeding of fatty diets enriched with the vitamins

Summary Prolonged supplementation of vitamins A and E (2500 IU and 11.3 IU/rat daily) in 10.3% and 21.6% fatty diets administered to methylnitrosourea-induced Sprague-Dawley rats caused alterations in plasma and liver levels of both vitamins as well as of the total lipids. Liver vitamin A levels increased steadily (more than four-fold) until termination of the experiment, whereas plasma vitamin A levels only showed a minor increase at the end of the study in comparison to rats fed a standard diet. Liver vitamin E levels initially showed no difference from those of rats treated with a standard diet, and were decreased at the end of the experiment, whereas the respective plasma levels were increased throughout the study, only showing a decrease relative to initial values at termination of the experiment. Plasma total lipids increased with age and following supplementation of the vitamins in the high-fat diet, whereas liver total lipids were influenced less by aging than by the fat and vitamin contents of the respective diets. The observed alterations were, however, not related to significant chemopreventive activity of the vitamins A and E contained in high-fat diets.Dedicated to Professor Dr. Dietrich Schmähl on the occasion of his 65th birthday     

Overview of studies of the vitamin D/vitamin D receptor system in the development of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in the world. NAFLD is known to be associated with obesity, type 2 diabetes, metabolic syndrome and increased cardiovascular events: for these reasons, it is becoming a global public health problem and represents an important challenge in terms of prevention and treatment. The mechanisms behind the pathogenesis of NAFLD are multiple and have not yet been completely unraveled; consequently, at moment there are not effective treatments. In the past few years a large body of evidence has been assembled that attributes an important role in hepatic aberrant fat accumulation,inflammation and fibrosis, to the vitamin D/vitamin D receptor(VD/VDR) axis,showing a strong association between hypovitaminosis D and the diagnosis of NAFLD. However, the data currently available, including clinical trials with VD supplementation, still provides a contrasting picture. The purpose of this editorial is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to VD/VDR. Based on recent data from literature, we focused in particular on the hypothesis that VDR itself, independently from its traditional ligand VD, may have a crucial function in promoting hepatic fat accumulation.This might also offer new possibilities for future innovative therapeutic approaches in the management of NAFLD.     

Antioxidant levels in peripheral blood, disease activity and fibrotic stage in chronic hepatitis C.

BACKGROUND: This study addressed the suggested association between levels of the antioxidants glutathione (GSH), vitamin C and vitamin E in peripheral blood and the histological activity and fibrosis stage in chronic hepatitis C (CHC). We then determined whether regular antioxidant supplementation influenced these antioxidant levels or disease severity. METHODS: Clinical, biochemical, histological and demographic data were collected from 247 CHC patients at the time of liver biopsy. Whole blood total GSH, plasma vitamin C and E were assessed by high-performance liquid chromatography. Statistical analyses were performed to test for associations between the variables and to identify independent predictors for hepatic necroinflammatory and fibrosis scores. RESULTS: GSH and vitamin C, but not vitamin E correlated with both portal/periportal activity (r = -0.19, P = 0.004; r = -0.19, P = 0.009 respectively) and fibrosis stage (r = -0.18, P = 0.007; r = -0.18, P = 0.009 respectively). GSH was an independent negative predictor of portal/periportal inflammation (P = 0.02) and fibrosis (P = 0.01). Vitamin C was an independent negative predictor of fibrosis stage (P = 0.02). Antioxidant intake was associated with higher vitamin C (P < 0.0001) and vitamin E (P = 0.005) levels, but not GSH. CONCLUSIONS: Whole blood GSH and plasma vitamin C are negatively associated with hepatic portal/periportal inflammation and fibrosis stage in CHC. Controlled intervention studies with vitamin C and agents that boost endogenous GSH levels are warranted.     

CT图像自动识别系统诊断肝炎肝硬化的研究

目的探讨肝炎肝硬化早期诊断方法。方法基于肝脏CT平扫图像，采用计算机图像自动识别及测量技术．计算乙型肝炎患者肝叶比例，通过统计对照数据库中的历史数据，对早期肝硬化做出诊断。结果肝硬化组与乙型肝炎组比较，本系统L1／L2和R1／L1比值均有显著性差异（P〈0．05）；建立判别方程：D=1．650LI／L 2＋0．509R1／L1-5．019；确定判别的临界值为0．0795；D〉0．0795为肝硬化，D〈0．0795为乙型肝炎；判别效果分析（回代），结果诊断肝硬化的正确率为68．42％，诊断乙型肝炎或判断为无肝硬化的正确率为89．8％。结论可以利用肝脏各叶的比例变化来预测和早期诊断肝炎肝硬化。     

Role of hepatic vitamin A and lipocyte distribution in experimental hepatic fibrosis

ABSTRACT— Lipocytes are the major site of hepatic vitamin A storage, and they have been demonstrated to lose their vitamin A content in the process of hepatic fibrosis. To investigate the relationship between hepatic vitamin A content and the degree of hepatic fibrosis, we measured levels of retinyl palmitate and retinol in the CCl₄-induced fibrotic liver using high-performance liquid chromatography. We estimated hepatic collagen content using a spectrophotometric analysis with sirius red, and also by measuring hydroxyproline levels. Lipocytes were detected by an immunoperoxidase method with anti-desmin antibody, and were counted morphometrically through a Texture Analyzing System. A significant negative correlation was observed between the level of retinyl palmitate and collagen content (r = –0.64) as well as the hydroxyproline level (r = –0.69) in the CCl₄-induced fibrotic liver. In the process of fibrosis, hepatic retinol levels were elevated in association with a decrease in retinyl palmitate. In particular in the early stage of fibrosis, lipocytes increased remarkably in number in fibrotic areas in spite of a decrease in total hepatic vitamin A. The present study suggests that an increase in hepatic retinol as well as a decrease in retinyl palmitate may facilitate the process of hepatic fibrosis produced by lipocytes.     

Performance of Acoustic Radiation Force Impulse imaging for the staging of liver fibrosis: a pooled meta-analysis

Acoustic Radiation Force Impulse (ARFI) imaging is a novel ultrasound-based elastography method that is integrated in a conventional ultrasound machine enabling the exact localization of measurement site. It might present an alternative method to transient elastography for the noninvasive assessment of liver fibrosis. At present, studies with small patient population have shown promising results. A systematic review and meta-analysis of pooled patient data were performed to evaluate the overall performance of ARFI for the staging of liver fibrosis. Literature databases were searched up to 10/2010. The authors of the original publication were contacted, and the original patient data were requested. A meta-analysis was performed using a random effect meta-analytic method for diagnostic tests. In addition, available data comparing ARFI with FibroScan with the DeLong test were evaluated. Literature search yielded nine full-paper publications evaluating ARFI while using liver biopsy as reference method. Original patient data were available from eight studies including 518 patients. The mean diagnostic accuracy of ARFI expressed as areas under ROC curves (AUROC) was 0.87 for the diagnosis of significant fibrosis (F ≥ 2), 0.91 for the diagnosis of severe fibrosis (F ≥ 3), and 0.93 for the diagnosis of cirrhosis. ARFI can be performed with good diagnostic accuracy for the noninvasive staging of liver fibrosis.