Diagnosis of hepatic glycogenosis in poorly controlled type 1 diabetes mellitus

Hepatic glycogenosis (HG) in type 1 diabetes is a underrecognized complication. Mauriac firstly described the syndrome characterized by hepatomegaly with altered liver enzymes, growth impairment, delay puberty and Cushingoid features, during childhood. HG in adulthood is characterized by the liver disorder (with circulating aminotransferase increase) in the presence of poor glycemic control (elevation of glycated hemoglobin, HbA1c levels). The advances in the comprehension of the metabolic pathways driving to the hepatic glycogen deposition point out the role of glucose transporters and insulin mediated activations of glucokinase and glycogen synthase, with inhibition of glucose-6-phosphatase. The differential diagnosis of HG consists in the exclusion of causes of liver damage (infectious, metabolic, obstructive and autoimmune disease). The imaging study (ultrasonography and/or radiological examinations) gives information about the liver alterations (hepatomegaly), but the diagnosis needs to be confirmed by the liver biopsy. The main treatment of HG is the amelioration of glycemic control that is usually accompanied by the reversal of the liver disorder. In selected cases, more aggressive treatment options (transplantation) have been successfully reported.     

Glycogenic hepatopathy: A narrative review

Glycogenic hepatopathy(GH) is a rare complication of the poorly controlled diabetes mellitus characterized by the transient liver dysfunction with elevated liver enzymes and associated hepatomegaly caused by the reversible accumulation of excess glycogen in the hepatocytes. It is predominantly seen in patients with longstanding type 1 diabetes mellitus and rarely reported in association with type 2 diabetes mellitus. Although it was first observed in the pediatric population, since then, it has been reported in adolescents and adults with or without ketoacidosis. The association of GH with hyperglycemia in diabetes has not been well established. One of the essential elements in the pathophysiology of development of GH is the wide fluctuation in both glucose and insulin levels. GH and non-alcoholic fatty liver disease(NAFLD) are clinically indistinguishable, and latter is more prevalent in diabetic patients and can progress to advanced liver disease and cirrhosis. Gradient dual-echo MRI can distinguish GH from NAFLD; however, GH can reliably be diagnosed only by liver biopsy. Adequate glycemic control can result in complete remission of clinical, laboratory and histological abnormalities. There has been a recent report of varying degree of liver fibrosis identified in patients with GH. Future studies are required to understand the biochemical defects underlying GH, noninvasive, rapid diagnostic tests for GH, and to assess the consequence of the fibrosis identified as severe fibrosis may progress to cirrhosis. Awareness of this entity in the medical community including specialists is low. Here we briefly reviewed the English literature on pathogenesis involved, recent progress in the evaluation, differential diagnosis, and management.     

Ultrasonic patterns of tumors of the liver

This study deals with the ultrasonic analysis of tumors of the liver and involves 85 cases of anatomically confirmed neoplasms. We shall describe four specific patterns of cancer: the large, highly echogenic nodule, anechoic nodules surrounded by a band of echoes, which correspond to necrotic, metastatic nuclei; the indistinct, transonic region within in echogenic parenchyma, often found in cancers observed in the course of cirrhosis; the large, entirely homogeneous hepatomegaly, which is the normal pattern of primary cancers, but which can be mistaken for a fluid collection. We consider that accurate information about these patterns may lead to a more reliable and precise diagnosis.     

Ultrasonography in primary hepatic tumors in early childhood

Ultrasonography was useful in preoperative investigation of primary hepatic tumors in nine children, aged 4 weeks to 4 years. In all patients, the hepatic origin and the solid or mixed echogenic nature of the tumor was determined. In two children (one with hemangioendothelioma, one with cystic mesenchymoma) the ultrasonographic findings were even more specific when correlated with angiography and/or histology. Ultrasonography in children with hepatomegaly should be performed as a screening procedure before angiography, to determine if enlargement of the liver is of tumorous origin. For follow-up, ultrasonography should be preferred over radionuclide imaging because it does not require the use of ionizing energy.     

Patients with severe schistosomiasis mansoni in Ituri Province,Democratic Republic of the Congo

Background::Severe hepatosplenic complications arise in patients with chronic Schistosoma mansoni infection after heavy exposure to disease agents in end...     

High-density CT of muscle and liver may allow early diagnosis of childhood-onset Pompe disease

Pompe disease is classified into infantile-, childhood- and adult-onset forms based on onset age and the degree of organ involvement. Differing from the infantile-onset form which is characterized by marked organ involvement, the childhood-onset form usually presents with muscle weakness and elevation of serum creatine kinase (CK), mimicking those of progressive muscular dystrophy. We report our successful early diagnosis and initiation of enzyme replacement therapy (ERT) in a young girl with childhood-onset Pompe disease before the development of skeletal muscle symptoms. She was referred to our hospital at the age of 2 years 4 months because of hyperCKemia detected incidentally. She was active and lacked developmental delay and muscle weakness; however, hepatomegaly was noted. The combination of high-density changes in the liver and skeletal muscle on computed tomography (CT) images was suggestive of glycogen storage disorder, especially childhood-onset Pompe disease. Low alpha-glucosidase (GAA) activity on dried blood spots facilitated the diagnostic process, and genetic analysis of GAA allowed a definitive diagnosis, without performing muscle biopsy. We promptly started ERT at the age of 2 years 6 months. After 1 year, she still had not developed any skeletal muscle symptoms, and serum CK level was almost normal. Since the efficacy of ERT is thought to depend on the extent of muscle damage at its commencement, we expect that ERT may have prevented the manifestation of skeletal muscle involvement in this patient.     

Development of an updated PBPK model for trichloroethylene and metabolites in mice, and its application to discern the role of oxidative metabolism in TCE-induced hepatomegaly

Trichloroethylene (TCE) is a lipophilic solvent rapidly absorbed and metabolized via oxidation and conjugation to a variety of metabolites that cause toxicity to several internal targets. Increases in liver weight (hepatomegaly) have been reported to occur quickly in rodents after TCE exposure, with liver tumor induction reported in mice after long-term exposure. An integrated dataset for gavage and inhalation TCE exposure and oral data for exposure to two of its oxidative metabolites (TCA and DCA) was used, in combination with an updated and more accurate physiologically-based pharmacokinetic (PBPK) model, to examine the question as to whether the presence of TCA in the liver is responsible for TCE-induced hepatomegaly in mice. The updated PBPK model was used to help discern the quantitative contribution of metabolites to this effect. The update of the model was based on a detailed evaluation of predictions from previously published models and additional preliminary analyses based on gas uptake inhalation data in mice. The parameters of the updated model were calibrated using Bayesian methods with an expanded pharmacokinetic database consisting of oral, inhalation, and iv studies of TCE administration as well as studies of TCE metabolites in mice. The dose-response relationships for hepatomegaly derived from the multi-study database showed that the proportionality of dose to response for TCE- and DCA-induced hepatomegaly is not observed for administered doses of TCA in the studied range. The updated PBPK model was used to make a quantitative comparison of internal dose of metabolized and administered TCA. While the internal dose of TCA predicted by modeling of TCE exposure (i.e., mg TCA/kg-d) showed a linear relationship with hepatomegaly, the slope of the relationship was much greater than that for directly administered TCA. Thus, the degree of hepatomegaly induced per unit of TCA produced through TCE oxidation is greater than that expected per unit of TCA administered directly, which is inconsistent with the hypothesis that TCA alone accounts for TCE-induced hepatomegaly. In addition, TCE-induced hepatomegaly showed a much more consistent relationship with PBPK model predictions of total oxidative metabolism than with predictions of TCE area-under-the-curve in blood, consistent with toxicity being induced by oxidative metabolites rather than the parent compound. Therefore, these results strongly suggest that oxidative metabolites in addition to TCA are necessary contributors to TCE-induced liver weight changes in mice.     

以肝损害为主的肝豆状核变性23例临床特征分析

目的提高对以肝损害为主的肝豆状核变性患者临床特点的认识,减少误诊。方法对23例以肝损害为主的肝豆状核变性的临床表现、实验室检查结果以及入院诊断进行回顾性分析。结果23例（100％）患者均有不同程度的血清转氨酶（ALT、AST）和（或）总胆红素（TB）升高;17例（73．9％）患者有肝病临床表现,仅有2例合并神经系统症状;分别有23例（100％）和21例（91．3％）患者有血清铜蓝蛋白降低和尿铜增加;13例（56．5％）患者角膜K-F环阳性;首诊误诊率达43．5％,最常见的误诊疾病为病毒性肝炎和肝硬化;2例患者死亡。结论以肝损害为主的肝豆状核变性临床误诊率高,血清铜蓝蛋白、尿铜、血清铜以及角膜K-F环联合检测能提高诊断的准确率。     

False Positive Immunoglobulin M Antibody to Cytomegalovirus in Child with Infectious Mononucleosis Caused by Epstein-Barr Virus Infection

A 16-month-old boy was admitted because of cough that had lasted for 10 days. The patient showed severe hepatomegaly incidentally, and dual positivity of Immunoglobulin (Ig) M to Epstein-Barr virus (EBV) viral capsid antigen (VCA) and cytomegalovirus (CMV). On the basis of seroconversion to Epstein-Barr nuclear antigen (EBNA) Ig G positivity and reduced CMV Ig M titer with persistently negative CMV Ig G, a definite diagnosis of EBV-induced infectious mononucleosis was established 1 year 2 month later.     

Assessment of abdominal involvement of adult T-cell leukemia/lymphoma by ultrasonography: comparison among four clinical types.

Adult T-cell leukemia/lymphoma (ATLL) is an HTLV-I associated lymphoid malignancy frequently seen in Japan. Abdominal involvement in 40 patients with ATLL were assessed by ultrasonography and the findings seen in four clinical types, acute, chronic, lymphoma and smoldering, were compared. Splenomegaly was frequently found in the cases of acute and lymphoma types, and the sizes of the spleens measured by ultrasonography correlated well with the disease activity. Hepatomegaly was also found more frequently in acute and lymphoma types, and hepatosplenomegaly was proved to be due to the infiltration by ATL cells. Nodular lesions in spleen and liver and abdominal lymph node swelling were also found frequently in the lymphoma type but rarely in the other types. Ascites, pleural effusion, and pericardial effusion were found in the active stage of acute and lymphoma types. Ultransonography also could detect findings associated with therapies. Thus, ultrasonography studies were found to be very useful for assessing the clinical classification, examining various pathological conditions associated with ATLL, and monitoring the disease activity.