Hepatic Sarcoidosis Presenting as Portal Hypertension and Liver Cirrhosis: Case Report and Review of the Literature

Systemic sarcoidosis is a disease of unknown etiology, with the liver being the third most commonly affected organ. Most cases of hepatic sarcoidosis are not clinically apparent, but a few can progress to liver cirrhosis, portal hypertension and ultimately liver failure. The diagnosis of hepatic sarcoidosis is difficult, considering that no single laboratory test or radiographic finding can definitively diagnose this systemic disease. Diagnosis of hepatic sarcoidosis relies heavily on histopathologic evaluation of two or more organs, a diagnostic modality that is invasive and may not be applicable to all patients. The treatment of hepatic sarcoidosis is challenging, with no large randomized controlled trials done to date. Physicians must be aware of the complications of hepatic sarcoidosis, and must include the same in the differential diagnosis of liver cirrhosis. We present a case of hepatic sarcoidosis complicated by portal hypertension and liver cirrhosis

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

Factors linked to severe thrombocytopenia during antiviral therapy in patients with chronic hepatitis c and pretreatment low platelet counts

<p>Abstract</p> <p>Background</p> <p>Baseline low platelet count (< 150,000/μL) increases the risk of on-treatment severe thrombocytopenia (platelet count < 50,000/μL) in patients with chronic hepatitis C (CHC) undergoing antiviral therapy, which may interrupt treatment. The purpose of this study was to identify risk factors for severe thrombocytopenia during treatment for CHC in patients with baseline thrombocytopenia.</p> <p>Methods</p> <p>Medical records were reviewed for 125 patients with CHC treated with antiviral therapy according to the standard of care, with regular follow-up examinations. Early platelet decline was defined as platelet decrease during the first 2 weeks of therapy.</p> <p>Results</p> <p>Severe thrombocytopenia developed in 12.8% of patients with baseline thrombocytopenia, and predicted a higher therapeutic dropout rate. Multivariate analysis revealed baseline platelet count < 100,000/μL and rapid early platelet decline (> 30% decline in the first 2 weeks) were significantly associated with severe thrombocytopenia (<it>P </it>< 0.001 and 0.003, odds ratios, 179.22 and 45.74, respectively). In these patients, baseline PLT ≥ 100,000/μL and lack of rapid early platelet decline predicted absence of severe thrombocytopenia (negative predictive values were 95.1% and 96.6%, respectively). In contrast, baseline platelet count < 100,000/μL combined with rapid early platelet decline predicted severe thrombocytopenia (positive predictive value was 100%).</p> <p>Conclusions</p> <p>For patients with CHC on antiviral therapy, baseline platelet counts < 100,000/μL and rapid early platelet decline can identify patients at high risk of developing on-treatment severe thrombocytopenia.</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

POLYMYOSITIS ASSOCIATED WITH PRIMARY BILIARY-CIRRHOSIS

The coexistence of polymyositis (PM) and primary biliary cirrhosis (PBC) is rare; only nine cases have been described in English literature. We report a case of a 46-year- old woman presenting with these two autoimmune diseases. The diagnosis of PM was based on the symmetrical, proximal limb muscle weakness, elevated muscle enzymes and was confirmed with the electromyography and muscle biopsy, The diagnosis of PBC was based on the increased serum levels of alkaline phosphatase, gamma glutamyltransferase, IgM immunoglobulin, the presence of antimitochondrial antibodies and diagnostic liver biopsy

Q fever endocarditis masquerading as Mixed cryoglobulinemia type II. A case report and review of the literature

Background: The clinical manifestations of Q fever endocarditis are protean in nature. Mixed cryoglobulinemia type II is rarely a facet of the presenting clinical manifestations of Q fever endocarditis. Case presentation: We report a case of a 65- year- old pensioner with such an association and review the literature. As transesophageal echocardiograms are usually normal and blood cultures are usually negative in Q fever endocarditis, many of the manifestations ( fever, rash, glomerulonephritis/ evidence of renal disease, low serum C4 complement component, presence of mixed type II cryoglobulin, constitutional symptoms as arthralgias and fatigue) can be attributed to Mixed cryoglobulinemia type II per se. The use of Classic Duke Endocarditis Service criteria does not always suffice for the diagnosis of Q fever. Conclusion: The application of the modified criteria proposed by Fournier et al for the improvement of the diagnosis of Q fever endocarditis will help to reach the diagnosis earlier and thus reduce the high mortality of the disease. We would like to stress the importance of ruling out the diagnosis of Q fever endocarditis in cases of mixed type II cryoglobulinemia