Marek Hartleb

Serum chemerin and vaspin in non-alcoholic fatty liver disease.

Abstract Objective. Chemerin and vaspin are new adipokines which may modulate inflammatory response and insulin sensitivity in non-alcoholic fatty liver disease (NAFLD). The aims of this study were to assess: (1) circulating levels of chemerin and vaspin and their association with liver histology and markers of liver injury in NAFLD patients; and (2) the relationship between the analyzed adipokines and insulin resistance. Material and methods. A total of 41 NAFLD patients with body mass index (BMI) 30.4 ± 3.3 kg/m2 [20 with non-alcoholic steatohepatitis (NASH) and BMI 30.3 ± 3.3 kg/m2 and 21 with simple steatosis/uncertain NASH (SS/UN) and BMI 30.5 ± 3.4 kg/m2] and 10 healthy volunteers with BMI 24.0 ± 2.9 kg/m2 were included in the study. Results. Serum chemerin concentration was significantly higher in NAFLD patients compared to healthy volunteers (p = 0.009). Serum chemerin was significantly higher in patients with NASH compared to patients with SS/UN (p = 0.009). The homeostasis model assessment for insulin resistance (HOMA-IR) value was higher in patients with NASH than in patients with SS/UN (p = 0.01). Serum chemerin and HOMA-IR were positively associated with NAFLD activity score (r = 0.40, p = 0.02; and r = 0.43, p = 0.008, respectively). Serum chemerin was associated with hepatocyte ballooning degeneration (r = 0.37; p = 0.03), total cholesterol (r = 0.45; p = 0.008) and diastolic blood pressure (r = 0.41; p = 0.02). HOMA-IR was related to fibrosis stage (r = 0.51; p = 0.001) and inflammatory activity grade in portal tracts (r = 0.40; p = 0.01). Serum vaspin correlated with hepatocyte ballooning degeneration (r = 0.31; p = 0.04), alanine aminotransferase and aspartate aminotransferase (r = 0.33, p = 0.03; and r = 0.32, p = 0.04, respectively) and diastolic blood pressure (r = 0.39, p = 0.01). Conclusions. This study shows for the first time that chemerin and vaspin serum concentrations are altered in patients with NAFLD. The analyzed adipokines appear to play a pivotal role in the pathogenesis of NAFLD, not only as regulators of insulin sensitivity, but also as mediators of the inflammatory process.

Nodular regenerative hyperplasia: Evolving concepts on underdiagnosed cause of portal hypertension

Nodular regenerative hyperplasia (NRH) is a rare liver condition characterized by a widespread benign transformation of the hepatic parenchyma into small regenerative nodules. NRH may lead to the development of non-cirrhotic portal hypertension. There are no published systematic population studies on NRH and our current knowledge is limited to case reports and case series. NRH may develop via autoimmune, hematological, infectious, neoplastic, or drug-related causes. The disease is usually asymptomatic, slowly or non-progressive unless complications of portal hypertension develop. Accurate diagnosis is made by histopathology, which demonstrates diffuse micronodular transformation without fibrous septa. Lack of perinuclear collagen tissue distinguishes NRH from typical regenerative nodules in the cirrhotic liver. While the initial treatment is to address the underlying disease, ultimately the therapy is directed to the management of portal hypertension. The prognosis of NRH depends on both the severity of the underlying illness and the prevention of secondary complications of portal hypertension. In this review we detail the epidemiology, pathogenesis, diagnosis, management, and prognosis of NRH.

Kidneys in chronic liver diseases

Acute kidney injury (AKI), defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL, occurs in about 20% of patients hospitalized for decompensating liver cirrhosis. Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state, reduced effective blood volume and stimulation of vasoconstrictor hormones. The most common causes of AKI in cirrhosis are pre-renal azotemia, hepatorenal syndrome and acute tubular necrosis. Differential diagnosis is based on analysis of circumstances of AKI development, natriuresis, urine osmolality, response to withdrawal of diuretics and volume repletion, and rarely on renal biopsy. Chronic glomerulonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients. AKI is one of the last events in the natural history of chronic liver disease, therefore, such patients should have an expedited referral for liver transplantation. Hepatorenal syndrome (HRS) is initiated by progressive portal hypertension, and may be prematurely triggered by bacterial infections, nonbacterial systemic inflammatory reactions, excessive diuresis, gastrointestinal hemorrhage, diarrhea or nephrotoxic agents. Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy. The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion, which is effective in about 50% of patients. The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt, renal vasoprotection or systems of artificial liver support.

Coagulopathy in liver diseases

Liver cirrhosis is associated with number of hematological complications and coagulation disturbances. In view of various haemostatic abnormalities it is surprising that many patients do not bleed spontaneously. Severe coagulopathy of liver disease is more frequently seen in acute liver failure, but still remains important complication of liver cirrhosis and chronic liver failure. Decreased production of blood coagulation factors by the liver plays a key role in altered haemostasis in liver diseases. Altered fragile balance of blood coagulation proteins and infection are associated with both worsening coagulopathy and bleeding risk. Additional haemostatic abnormalities in patients with severe liver diseases are thrombocytopenia, chronic disseminated intravascular coagulation, accelerated fibrinolysis, hypofibrinogenemia and dysfibrinogenemia. In this review we discuss a complicated issue of multiple coagulopathies in patients with advanced liver dysfunction.

Validation of the BARD scoring system in Polish patients with nonalcoholic fatty liver disease (NAFLD)

AbtractBackgroundNonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver diseases, ranging from pure steatosis to nonalcoholic steatohepatitis (NASH), and eventually to liver cirrhosis with its complications. Identifying advanced fibrosis in patients is crucial to evaluating prognosis and possible therapeutic intervention. A novel, simple, and highly accurate scoring system called BARD, which identifies patients with NAFLD and without significant fibrosis, has been recently introduced and validated in North America..The aim of this study is to validate the BARD scoring system in a Polish cohort with NAFLD.MethodsA group of 104 Caucasians with biopsy-proven NAFLD were included in this study. Fibrosis in liver biopsies was evaluated according to the Histological Scoring System for Nonalcoholic Fatty Liver Disease. The BARD scoring system was assessed according to Harrison et al.: BMI ≥ 28 = 1 point, AST/ALT ratio (AAR) ≥ 0.8 = 2 points, type 2 diabetes mellitus = 1point.ResultsAge over 50 and AAR over 0.8 showed, respectively, a moderate and strong association with advanced fibrosis. A BARD score of 2-4 points was associated with F3 or F4 stages of fibrosis with an odds ratio of 17.333 (95% Cl; 3,639 - 82.558) and negative predictive value of 97%.ConclusionOur results demonstrate that the BARD scoring system has value in the non-invasive diagnosis of advanced fibrosis in NAFLD patients. The vast majority of patients with NAFLD would avoid liver biopsy if BARD was broadly introduced into the clinic.

Serum adipokines in inflammatory bowel disease

AIM To investigate serum adipokine levels in inflammatory bowel disease (IBD) patients before treatment and after achieving clinical remission. METHODS Serum concentrations of six adipokines (tissue growth factor-β1, adiponectin, leptin, chemerin, resistin, and visfatin) were studied in 40 subjects with active IBD [24 subjects with Crohns disease (CD) and in 16 subjects with ulcerative colitis (UC)] before and after three months of therapy with corticosteroids and/or azathioprine. Clinical diagnoses were based on ileocolonoscopy, computed tomography or magnetic resonance enterography and histological examination of mucosal biopsies sampled during endoscopy. Serum levels of adipokines were assessed by an indirect enzyme-linked immunosorbent assay. The control group was comprised of 16 age- and sex-matched healthy volunteers. RESULTS Baseline leptin concentrations were significantly decreased in both types of IBD compared to controls (8.0 ± 9.1 in CD and 8.6 ± 6.3 in UC vs 16.5 ± 10.1 ng/mL in controls; P < 0.05), and significantly increased after treatment only in subjects with CD (14.9 ± 15.1 ng/mL; P < 0.05). Baseline serum resistin concentrations were significantly higher in CD (19.3 ± 12.5 ng/mL; P < 0.05) and UC subjects (23.2 ± 11.0 ng/mL; P < 0.05) than in healthy controls (10.7 ± 1.1 ng/mL). Treatment induced a decrease in the serum resistin concentration only in UC subjects (14.5 ± 4.0 ng/mL; P < 0.05). Baseline serum concentrations of visfatin were significantly higher in subjects with CD (23.2 ± 3.2 ng/mL; P < 0.05) and UC (18.8 ± 5.3 ng/mL; P < 0.05) than in healthy controls (14.1 ± 5.3 ng/mL). Treatment induced a decrease in the serum visfatin concentrations only in CD subjects (20.4 ± 4.8 ng/mL; P < 0.05). Serum levels of adiponectin, chemerin and tissue growth factor-β1 did not differ between CD and UC subjects compared to healthy controls and also were not altered by anti-inflammatory therapy. Clinical indices of IBD activity did not correlate with adipokine levels. CONCLUSION IBD modulates serum adipokine levels by increasing resistin and visfatin release and suppressing leptin production.

Procalcitonin and macrophage inflammatory protein-1 beta (MIP-1β) in serum and peritoneal fluid of patients with decompensated cirrhosis and spontaneous bacterial peritonitis.

PURPOSE Spontaneous bacterial peritonitis (SBP) is the most frequent infection in patients with cirrhosis causing significant mortality which requires rapid recognition for effective antibiotic therapy, whereas ascitic fluid cultures are frequently negative. The aim of this study was to evaluate the SBP diagnostic efficacy of procalcitonin (PCT) and macrophage inflammatory protein-1 beta (MIP-1β) measured in serum and peritoneal fluid. MATERIAL/METHODS Thirty-two participants with liver cirrhosis and ascites were included into the study (11 females and 21 males, mean age 49.5 ± 11.9 years). The peritoneal fluid and venous blood were collected for routine laboratory examinations and measurements of PCT and MIP-1β. Patients were divided into two groups according to the ascitic absolute polymorphonuclear leukocytes count (≥250 mm(-3) and <250 mm(-3)). RESULTS Ascites was sterile in 22 participants and SBP was diagnosed in 10 patients. Serum and ascitic levels of PCT and MIP-1β did not correlate with clinical and routine laboratory parameters. MIP-1β in the ascitic fluid was significantly higher in patients with SBP (213 ± 279 pg/ml vs. 66.3 ± 49.8 pg/ml; p=0.01). The sensitivity and specificity for diagnosis of SBP with ascitic MIP-1β were 80% and 72.7%, respectively (cut-off value 69.4 pg/ml) with AUROC 0.77 (95%CI 0.58-0.96). Serum levels of MIP-1β showed lower diagnostic yield. Serum and ascitic PCT levels were not different in patients with and without SBP. CONCLUSIONS MIP-1β concentration in ascitic fluid may distinguish patients with and without SBP with satisfactory sensitivity and specificity. Chemokines should be further explored for diagnostic use.

Liver injury induced by high-dose methylprednisolone therapy: a case report and brief review of the literature.

Corticosteroids are used widely to treat many types of disease. In general, these drugs are considered safe for the liver; however, recent reports have demonstrated that high-dose methylprednisolone (MT) may cause severe liver injury. Here, we report a case of a 24-year-old female who was given pulsed MT therapy for multiple sclerosis. MT induced icteric hepatitis and impaired liver synthetic function. Hepatotoxicity developed several weeks after drug exposure, and the causal association with MT was confirmed by unintentional rechallenge test. A brief review of the literature on corticosteroid-induced hepatotoxicity is presented.

Severe dilated cardiomyopathy as a consequence of Ecstasy intake

Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure with a prevalence of 1:2500. There are several primary and secondary etiologic factors, including gene mutations, infection agents, particularly viruses, toxins, autoimmune, and systemic disorders, and pheochromocytoma, neuromuscular, metabolic, mitochondrial, and nutritional disorders. However, a precise diagnosis can be reached only in no more than 50% of all cases. Herein, we report a rare case of hepatic damage and severe DCM as a consequence of relatively popular socially used narcotic-Ecstasy (3,4-methylenedioxy-N-methylamphetamine [MDMA]).

Neuroendocrine neoplasms of the small intestine and the appendix — management guidelines (recommended by the Polish Network of Neuroendocrine Tumours)

We present revised Polish guidelines regarding the management of patients harbouring neuroendocrine neoplasms (NENs) of the small intestine and appendix. The small intestine, especially the ileum, is the most common origin of these neoplasms. Most of them are well differentiated with slow growth. Rarely, they are less differentiated, growing fast with a poor prognosis. Since symptoms can be atypical, the diagnosis is often accidental. Typical symptoms of carcinoid syndrome occur in less than 10% of patients. The most useful laboratory marker is chromogranin A; 5-hydroxyindoleacetic acid is helpful in the monitoring of carcinoid syndrome. Ultrasound, computed tomography, magnetic resonance imaging, colonoscopy, video capsule endoscopy, balloon enteroscopy and somatostatin receptors scintigraphy are used in the visualisation. A histological report is crucial for the proper diagnostics and therapy of NENs, and it has been extensively described. The treatment of choice is surgery, either radical or palliative. Somatostatin analogues are crucial in the pharmacological treatment of the hormonally active and non-active small intestine NENs and NENs of the appendix. Radioisotope therapy is possible in patients with a good expression of somatostatin receptors. Chemotherapy is not effective in general. Everolimus therapy can be applied in patients with generalised NENs of the small intestine in progression and where there has been a failure or an inability to use other treatment options. Finally, we make recommendations regarding the monitoring of patients with NENs of the small intestine and appendix.