Relationship of 24-hour ambulatory blood pressure and heart rate with markers of hepatic function in cirrhotic patients

<p>Abstract</p> <p>Background</p> <p>There is evidence that in cirrhotic patients, certain hemodynamic parameters, such as blood pressure and heart rate, are related to the severity of liver disease. This study investigated whether non-invasive 24-hour ambulatory blood pressure and heart rate are more closely associated with markers of liver disease severity than conventional office measurements.</p> <p>Methods</p> <p>Ambulatory patients with cirrhosis underwent office blood pressure and heart rate measurements, 24-hour ambulatory blood pressure monitoring and blood laboratory tests.</p> <p>Results</p> <p>Fifty-one patients (32 men, mean age 57.4 ± 11.3 years) completed the study. Twenty six patients had compensated liver cirrhosis (group A) and 25 patients had more advanced liver disease (group B). Group A and B patients differed significantly both in ambulatory asleep diastolic blood pressure (p < 0.05) and office diastolic blood pressure (p < 0.01), which were lower in more advanced liver disease. Office blood pressure and heart rate correlations were similar to or even stronger than ambulatory ones. Ambulatory blood pressure and heart rate awake-asleep variation (dipping) showed a relatively flat pattern as markers of liver dysfunction were deteriorating. The strongest correlations were found with both ambulatory and office heart rate, which increased as indicators of severity of liver disease were worsening.</p> <p>Conclusions</p> <p>Heart rate seems to be a more reliable marker of ongoing liver dysfunction than blood pressure. Evaluation of blood pressure and heart rate with 24-hour ambulatory measurement does not seem to offer more information than conventional office measurements.</p

11β-HSD1 plays a critical role in trabecular bone loss associated with systemic glucocorticoid therapy

Background: Despite their efficacy in the treatment of chronic inflammation, the prolonged application of therapeutic glucocorticoids (GCs) is limited by significant systemic side effects including glucocorticoid-induced osteoporosis (GIOP). 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates GCs in vivo, regulating tissue-specific exposure to active GC. We aimed to determine the contribution of 11β-HSD1 to GIOP. Methods: Wild type (WT) and 11β-HSD1 knockout (KO) mice were treated with corticosterone (100 μg/ml, 0.66% ethanol) or vehicle (0.66% ethanol) in drinking water over 4 weeks (six animals per group). Bone parameters were assessed by micro-CT, sub-micron absorption tomography and serum markers of bone metabolism. Osteoblast and osteoclast gene expression was assessed by quantitative RT-PCR. Results: Wild type mice receiving corticosterone developed marked trabecular bone loss with reduced bone volume to tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N). Histomorphometric analysis revealed a dramatic reduction in osteoblast numbers. This was matched by a significant reduction in the serum marker of osteoblast bone formation P1NP and gene expression of the osteoblast markers Alp and Bglap. In contrast, 11β-HSD1 KO mice receiving corticosterone demonstrated almost complete protection from trabecular bone loss, with partial protection from the decrease in osteoblast numbers and markers of bone formation relative to WT counterparts receiving corticosterone. Conclusions: This study demonstrates that 11β-HSD1 plays a critical role in GIOP, mediating GC suppression of anabolic bone formation and reduced bone volume secondary to a decrease in osteoblast numbers. This raises the intriguing possibility that therapeutic inhibitors of 11β-HSD1 may be effective in preventing GIOP in patients receiving therapeutic steroids

Management of Hepatitis C Antiviral Therapy Adverse Effects

Hepatitis C is one of the leading causes of liver disease in the United States, affecting more than 4 million individuals. The current treatment regimen involves pegylated interferon in combination with ribavirin. Although antiviral treatment has been associated with a greater than 50% sustained viral response rate, the adverse effects have proven to be detrimental to quality of life and therapy adherence, and consequently lead to lower sustained viral response rates. This article identifies the most frequently described complications associated with pegylated interferon and ribavirin. The active management of these complications is discussed, including both preventive and empiric treatments

A Switch in Hepatic Cortisol Metabolism across the Spectrum of Non Alcoholic Fatty Liver Disease

Context: Non alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of liver disease ranging from reversible hepatic steatosis, to non alcoholic steato-hepatitis (NASH) and cirrhosis. The potential role of glucocorticoids (GC) in the pathogenesis of NAFLD is highlighted in patients with GC excess, Cushing's syndrome, who develop central adiposity, insulin resistance and in 20% of cases, NAFLD. Although in most cases of NAFLD, circulating cortisol levels are normal, hepatic cortisol availability is controlled by enzymes that regenerate cortisol (F) from inactive cortisone (E) (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1), or inactivate cortisol through A-ring metabolism (5α- and 5β-reductase, 5αR and 5βR). Objective and Methods: In vitro studies defined 11β-HSD1 expression in normal and NASH liver samples. We then characterised hepatic cortisol metabolism in 16 patients with histologically proven NAFLD compared to 32 obese controls using gas chromatographic analysis of 24 hour urine collection and plasma cortisol generation profile following oral cortisone. Results: In patients with steatosis 5αR activity was increased, with a decrease in hepatic 11β-HSD1 activity. Total cortisol metabolites were increased in this group consistent with increased GC production rate. In contrast, in patients with NASH, 11β-HSD1 activity was increased both in comparison to patients with steatosis, and controls. Endorsing these findings, 11β-HSD1 mRNA and immunostaining was markedly increased in NASH patients in peri septal hepatocytes and within CD68 positive macrophages within inflamed cirrhotic septa. Conclusion: Patients with hepatic steatosis have increased clearance and decreased hepatic regeneration of cortisol and we propose that this may represent a protective mechanism to decrease local GC availability to preserve hepatic metabolic phenotype. With progression to NASH, increased 11β-HSD1 activity and consequent cortisol regeneration may serve to limit hepatic inflammation

Flour contamination as a source of lead intoxication

Case Report: A 43-year-old man was hospitalized became of severe anemia and recurrent bouts of abdominal pain over 20 days. There was no known occupational exposure to toxins. Concomitantly, the patient&apos;s father complained of having the same symptoms. Familial lead poisoning was diagnosed when all 6 family members tested had high blood leads (31-64 μg/dL). Results: Following detailed examination of the potential sources common to all members of the household, the cause of poisoning was determined to be corn flour containing 38.7 mg/g lead. Physicians are reminded to consider lead poisoning in the differential diagnosis of individuals with unexplained symptoms, particularly those of abdominal discomfort and anemia

Relationship of 24-hour ambulatory blood pressure and heart rate with markers of hepatic function in cirrhotic patients

Background: There is evidence that in cirrhotic patients, certain hemodynamic parameters, such as blood pressure and heart rate, are related to the severity of liver disease. This study investigated whether non-invasive 24-hour ambulatory blood pressure and heart rate are more closely associated with markers of liver disease severity than conventional office measurements. Methods: Ambulatory patients with cirrhosis underwent office blood pressure and heart rate measurements, 24-hour ambulatory blood pressure monitoring and blood laboratory tests. Results: Fifty-one patients (32 men, mean age 57.4 +/- 11.3 years) completed the study. Twenty six patients had compensated liver cirrhosis (group A) and 25 patients had more advanced liver disease (group B). Group A and B patients differed significantly both in ambulatory asleep diastolic blood pressure (p &lt; 0.05) and office diastolic blood pressure (p &lt; 0.01), which were lower in more advanced liver disease. Office blood pressure and heart rate correlations were similar to or even stronger than ambulatory ones. Ambulatory blood pressure and heart rate awake-asleep variation (dipping) showed a relatively flat pattern as markers of liver dysfunction were deteriorating. The strongest correlations were found with both ambulatory and office heart rate, which increased as indicators of severity of liver disease were worsening. Conclusions: Heart rate seems to be a more reliable marker of ongoing liver dysfunction than blood pressure. Evaluation of blood pressure and heart rate with 24-hour ambulatory measurement does not seem to offer more information than conventional office measurements