Irisin expression and FNDC5 (rs3480) gene polymorphism in type 2 diabetic patients with and without CAD.

BACKGROUND: Irisin was found to correlate with coronary artery disease (CAD) in diabetic patients. This study investigated the association of irisin and FNDC5 (SNP rs3480) with the presence and severity of CAD in T2DM. METHODS: This cross-sectional study included 100 patients with T2DM divided into two groups, DM group (n = 50), including patients without CAD and CAD group (n = 50), including those confirmed to have CAD by coronary angiography. Irisin was measured. SNP rs3480 genotyping of FNDC5 was done. RESULTS: Irisin levels were significantly lower in the CAD group (p < 0.001). The CAD group had significantly higher HbA1c and lower HDL (p < 0.001). Patients with controlled DM had significantly higher irisin levels (p < 0.001). single nucleotide polymorphism (SNP) rs3480 was not associated with irisin levels, and the FNDC5 rs3480 AA reference allele was significantly associated with significant CAD. CONCLUSION: Irisin appears to be protective against developing CAD in diabetic patients. Irisin level was an independent predictor of significant CAD in diabetic patients combined with the FNDC5 rs3480 genotype. CLINICAL TRIAL REGISTRATION NUMBER: NCT04957823.

Acute liver failure: an uncommon complication of commonly used medication.

The incidence of drug-related acute liver failure is approximately 14 per 100,000 populations. Drug-induced liver injury may take place through a variety of mechanism. Withdrawal of the offending agent may result in complete recovery. Clindamycin is known to cause mild derangement of liver function; however, acute liver injury causing severe derangement of liver function associated with encephalopathy is uncommon.

Benign afebrile convulsions in the course of mild acute gastroenteritis: a study of 28 patients and a literature review.

OBJECTIVES: Since the description of afebrile convulsions in the course of mild acute gastroenteritis (AGE) in 1982 by Morooka in Japan, there have been few reports of further cases outside Asia. The aim of this study was to share our casuistry--from a non-Asian country. METHODS: This is a retrospective study of identified cases in our center from January 2002 to December 2007. RESULTS: A total of 28 patients were studied. All were previously healthy patients who experienced convulsions with mild AGE without dehydration and with normal blood analysis. The mean age was 17.25 months (range, 6-48 months), with 93% younger than 24 months. Seizures were generalized tonic-clonic (61%), followed by generalized tonic (31%), and hypotonic (5.2%), with 2 (2.6%) partial. Only 8 patients (28.6%) presented one convulsion, and in 13 patients (46%), the seizures were in clusters from 3 to 6. Eleven patients (39%) presented 2 different types of convulsion. The duration of the crises ranged from 30 seconds to 10 minutes, and all of them occurred within 24 hours of the first. Electroencephalograms, obtained for all patients, were normal. Rotavirus was the main infectious agent in the AGEs, found in 11 patients with 22 determinations. In one patient, Salmonella serotype Enteritidis was isolated. All of the patients developed favorably, with no sequelae or epilepsy during the follow-up period. CONCLUSIONS: Afebrile convulsion in the course of mild gastroenteritis exists in our environment. It is a banal symptom in the course of the disease with good prognosis. Recognition of this fact may help avoid needless explorations and treatment in patients of this kind.

The Unusual Suspect: A Case of Non-occlusive Mesenteric Ischemia in a Patient With Cirrhosis.

Acute mesenteric ischemia has a variety of etiologies. Non-occulusive mesenteric ischemia accounts for 20-30% of patients with acute mesenteric ischemia. We describe a case of non-occulusive jejunal ischemia leading to infarction that occurred in a patient with cirrhosis and no previous history of cardiovascular disease.

Resolution of hereditary hemorrhagic telangiectasia and anemia with prolonged alpha-interferon therapy for chronic hepatitis C.

Hereditary hemorrhagic telangiectasia is a group of autosomal dominant disorders, characterized by telangiectases that develop in the skin, mucous membranes, and visceral organs. Currently, there is no satisfactory treatment of hereditary hemorrhagic telangiectasia. Interferon has never been used for the treatment of hereditary hemorrhagic telangiectasia. In this case, we report disappearance of hereditary hemorrhagic telangiectasia lesions after 12 months of treatment with interferon-alpha for chronic hepatitis C. Further studies are warranted to evaluate its role and potential use in the treatment of hereditary hemorrhagic telangiectasia.

Role of fresh frozen plasma infusion in correction of coagulopathy of chronic liver disease: a dual phase study.

OBJECTIVE: Fresh frozen plasma infusions are commonly used to correct the prolonged prothrombin time in patients with advanced chronic liver disease. The aim of this study was to establish how frequently this treatment is effective in correcting this coagulopathy. METHODS: A split retrospective-prospective study design was employed. In the retrospective series, 80 patients were identified with prolongation of the prothrombin time who received fresh frozen plasma infusions. In the prospective arm, 20 patients were included. All patients had confirmed chronic liver disease and showed no response to vitamin K injections. None of the patients had evidence of disseminated intravascular coagulation. The indications for infusion of fresh frozen plasma, number of units administered, complications, and percentage of patients who corrected their prothrombin time to less than 3 s longer than control time were recorded. RESULTS: The majority of patients (75%) received 2-4 units of fresh frozen plasma. The mean prothrombin time was numerically improved by the infusion of 2-6 units of fresh frozen plasma. However, using correction to less than 3 s longer than control time as an endpoint, only 12.5% of the retrospective and 10% of the prospective study groups respectively had correction of their coagulopathy. Only one complication of infusion of plasma was noted during the course of the study. CONCLUSIONS: Our results reiterate previous observations made more than 45 yr ago, that fresh frozen plasma infusions using the number of units commonly employed in clinical practice infrequently correct the coagulopathy of patients with chronic liver disease. Higher volumes (6 or more units) may be more effective but are rarely employed.

Steatohepatitis in obese individuals.

Nonalcoholic steatohepatitis (NASH), which is the most severe histological form of nonalcoholic fatty liver disease (NAFLD), is emerging as the most common clinically important form of liver disease in developed countries. Although its prevalence is 3% in the general population, this increases to 20-40% in obese patients. Since NASH is associated with obesity, prevalence has been predicted to increase along with the arsent epidemic of obesity and type II diabetes mellitus. The importance of this observation comes from the fact that NASH is a progressive fibrotic disease, in which cirrhosis and liver-related death occur in 25% and 10% in these patients respectively over a 10-year period. This is of particular concern given the increasing recognition of NASH in children. Treatment consists of treating obesity and its co-morbidities; diabetes and hyperlipidemia. Nascent studies suggest that a number of pharmacological therapies may be effective, but all remain unproven at present. Histological and laboratory improvement occurs with a 10% decrease in body weight. Bariatric surgery is indicated in selected patients.A greater understanding of the pathophysiological progression of NASH in obese patients must be obtained in order to develop more focused and improved therapy.

Connective tissue diseases and the liver.

Connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren's syndrome, and scleroderma are systemic disorders that may have an autoimmune basis. The system manifestations vary, and there is frequent overlap among the syndromes. Liver involvement in patients with connective tissue diseases has been well documented but is generally considered rare. Although advanced liver disease with cirrhosis and liver failure is rare in patients with connective tissue diseases, clinical and biochemical evidence of associated liver abnormalities is common. Previous treatment with potentially hepatotoxic drugs or coincident viral hepatitis has usually been implicated as the main causes of liver disease in patients with connective tissue diseases. However, even after careful exclusion of these etiologies, the question remains whether to classify the patient as having a primary liver disease with associated autoimmune, clinical, and laboratory features or as having liver disease as a manifestation of generalized connective tissue disease. The main example of this pathogenetic dilemma is autoimmune hepatitis and SLE-associated hepatitis, which have been regarded as two different entities, although they have features in common of autoimmune syndromes. Several clinical and histopathologic features have been used to discriminate autoimmune hepatitis from SLE, a relevant diagnostic exercise because complications and therapy are quite different. Although hepatic steatosis and abnormal results on biochemical liver function tests are the most common hepatic abnormalities associated with connective tissue diseases, other less frequent abnormalities have been noted, such as nodular regenerative hyperplasia, portal vein obliteration and portal hypertension, features of primary biliary cirrhosis, and rarely portal fibrosis with abnormal lobular architecture. Vascular disorders of the liver also have been described, such as Budd-Chiari syndrome. Histologic assessment may reveal a variety of subclinical liver diseases. The aim of this contribution is to review the current published data regarding liver involvement in connective tissue diseases.

Diabetes mellitus, obesity, and hepatic steatosis.

Nonalcoholic fatty liver disease is emerging as the most common liver disease in North America. The histological spectrum of nonalcoholic fatty liver disease ranges from fatty liver alone to steatohepatitis and to the most serious form--nonalcoholic steatohepatitis (NASH). An increasing body of evidence suggests that NASH is associated with the development of progressive fibrosis and eventually cirrhosis in approximately 20% of cases. These data emphasize the need to develop effective therapy for the treatment of NASH. Cases occur most commonly in obese middle age women with diabetes. However, NASH may also occur in children and normal weight men with normal glucose and lipid metabolism. The pathophysiology involves 2 steps. The first is insulin resistance, which causes steatosis. The second is oxidative stress, which produces lipid peroxidation and activates inflammatory cytokines resulting in NASH. Liver biopsy provides prognostic information and identifies NASH patients who may benefit from therapy. Treatment consists of managing the comorbidities: obesity, diabetes, and hyperlipidemia. Nascent clinical trials suggest that a number of therapies may be beneficial. These include anti-oxidants such as vitamin E and betaine, bile acid therapy with ursodeoxycholic acid, and improved insulin sensitivity with metformin. Another potential therapeutic strategy is the reduction of inflammatory cytokines.

The liver in other (nondiabetic) endocrine disorders.

The liver has a major role in the proper maintenance of intermediate metabolism and endocrine homeostasis. It contains enzymes that are essential for hormonal biotransformation and the regulation of numerous metabolic reactions, which control hormone metabolism. The liver also manufactures several proteins, which carry circulating hormones to their effector sites. The endocrine system exerts tight control of the metabolic reactions within the liver, which also can be disturbed by endocrine disorders. These types of interactions and the effects of the exogenous hormones and the drugs that are used as treatment for hormonal disorders are discussed.