Digital image analysis of liver collagen predicts clinical outcome of recurrent hepatitis C virus 1 year after liver transplantation.

Clinical outcomes of recurrent hepatitis C virus after liver transplantation are difficult to predict. We evaluated collagen proportionate area (CPA), a quantitative histological index, at 1 year with respect to the first episode of clinical decompensation. Patients with biopsies at 1 year after liver transplantation were evaluated by Ishak stage/grade, and biopsy samples stained with Sirius red for digital image analysis were evaluated for CPA. Cox regression was used to evaluate variables associated with first appearance of clinical decompensation. Receiver operating characteristic (ROC) curves were also used. A total of 135 patients with median follow-up of 76 months were evaluated. At 1 year, median CPA was 4.6% (0.2%-36%) and Ishak stage was 0-2 in 101 patients, 3-4 in 23 patients, and 5-6 in 11 patients. Decompensation occurred in 26 (19.3%) at a median of 61 months (15-138). Univariately, CPA, tacrolimus monotherapy, and Ishak stage/grade at 1 year were associated with decompensation; upon multivariate analysis, only CPA was associated with decompensation (P = 0.010; Exp(B) = 1.169; 95%CI, 1.037-1.317). Area under the ROC curve was 0.97 (95%CI, 0.94-0.99). A cutoff value of 6% of CPA had 82% sensitivity and 95% specificity for decompensation. In the 89 patients with hepatic venous pressure gradient (HVPG) measurement, similar results were obtained. When both cutoffs of CPA > 6% and HVPG ≥ 6 mm Hg were used, all patients decompensated. Thus, CPA at 1-year biopsy after liver transplantation was highly predictive of clinical outcome in patients infected with hepatitis C virus who underwent transplantation, better than Ishak stage or HVPG.

Multiple myeloma presenting with an acute bacterial infection.

Increased susceptibility to bacterial infections is a common manifestation of multiple myeloma (MM), arising mainly from a defect in humoral immunity and is associated with major morbidity and mortality. The propensity to infection is increased in the first months after the initial diagnosis and in patients with renal dysfunction. Gram-positive infections, mainly pneumonia from Streptococcus pneumoniae, occur more frequently in patients with untreated disease while Gram-negative infections, mainly of the urinary tract, are more common after chemotherapy. However, an acute bacterial infection is rarely reported as the first manifestation of underlying MM. In this review, we analysed data from 17 such cases reported between 1978 and 2008. Median age was 65.5 years and most patients were females; monoclonal paraprotein was IgG in 92%. In contrast to diagnosed treated or untreated MM, musculoskeletal infections predominated in these early cases (47%) followed by pneumonia (29%). In particular, septic arthritis, mainly of the knee, was the most common infectious complication (35%). Streptococcus pneumoniae was isolated in two-thirds of infections and bacteremia was common (80%). In this early phase, immunodeficiency arised from a decreased synthesis of polyclonal immunoglobulins. White blood cell counts were frequently normal, particularly in musculoskeletal infections. Renal impairment occurred in 67% and correlated with increasing monoclonal paraprotein levels. The outcome was favorable in most cases (79%). MM should be considered in previously asymptomatic middle-aged patients who present with a major acute bacterial infection, without an apparent predisposing factor. In particular, suspicion should be high in cases of septic arthritis and pneumococcaemia.

Akinetic mutism followed by a manic reaction on introduction of steroid replacement for Addison's disease.

Neuropsychiatric changes during exogenous corticosteroid administration are well-recognized. However, reports of neuropsychiatric reactions to corticosteroid replacement for Addison's disease are distinctively rare. We report on a patient with primary adrenocortical insufficiency, initially presenting with depressive symptoms, who developed akinetic mutism followed by acute manic illness shortly after the initiation of steroid replacement. Both disorders occurred with physiological doses of hydrocortisone and resolved spontaneously. The pathogenesis of the above neuropsychiatric reactions is discussed in the context of glucocorticoid receptor-related brain effects of glucocorticoids. In addition, this report points to the need for accurate psychiatric assessment of patients with Addison's disease upon introduction of replacement therapy.

Multiple brown tumors of the ribs simulating malignancy.

Bone disease associated with primary hyperparathyroidism, known as osteitis fibrosa cystica, is now very rarely encountered, since the parathyroid disorder is most often diagnosed at the early stage of asymptomatic hypercalcemia. Here, we report the case of a patient with multiple pleural-based masses and hypercalcemia, which led to the presumptive diagnosis of malignancy. However, histological and laboratory data were consistent with the development of brown tumors of the ribs due to underlying severe hyperparathyroidism.

A case of insulin edema with inappropriate hyperaldosteronism.

Edema of variable severity is an uncommon complication of insulin treatment. Increased sodium reabsorption, transient proteinuria and hypoalbuminemia are the most frequently reported laboratory disorders at the time of edema formation. This case report describes a 44-yr-old man with a 4-month history of anorexia, polyuria, polydipsia and weight loss of 25 kg who presented with diabetic ketoacidosis. On admission, there were no clinical or laboratory signs of volume depletion. Following insulin treatment he developed marked insulin edema and a cluster of abnormalities, including decreased sodium excretion, hypokalemia, hypouricemia, proteinuria, hypoalbuminemia and anemia. The diagnostic work-up showed the presence of high renin and aldosterone values despite the absence of evident hypovolemia and no evidence of gastrointestinal, cardiovascular, renal, thyroid, hepatic or other endocrine disorder. Complement values were normal; autonomic neuropathy and venoocclusive intraabdominal lesions were excluded and no other drugs except insulin were administered. Initiation of spironolactone was associated with prompt resolution of the edema and gradual correction of the laboratory abnormalities. Our findings show that hyperaldosteronism may occur in patients with insulin edema, even in the absence of volume depletion, contributing to the development of increased sodium reabsorption and of other laboratory disorders.

Isolated ACTH deficiency associated with Crohn's disease.

We report a case of a 37-yr-old man with a 11-yr history of Crohn's disease (CD), who presented with mucous diarrheas of 1-week duration and a 3-month history of anorexia, increasing fatigue and weight loss of 7 kg. The patient was treated with sulfasalazine 3 g/day until 2 weeks prior to the present admission, when he reduced the dose to half as he considered the drug responsible for his symptoms. Despite aggressive iv rehydration and resolution of diarrheas with an increase in sulfasalazine dose, the patient remained hemodynamically unstable, while laboratory results showed anemia, hypoglycemia, hypertransaminasemia and hyponatremia with marked natriuresis. Thyroid function tests were consistent with primary hypothyroidism, without evidence of autoimmunity. Further laboratory investigation revealed a low basal cortisol and undetectable ACTH with preserved secretory responses of the other trophic pituitary hormones, establishing the diagnosis of isolated ACTH deficiency. Hydrocortisone replacement treatment induced a clinical and laboratory improvement. The autoimmune basis of isolated ACTH deficiency is discussed in association with the presumed contribution of immunologic reactions in the pathogenesis of CD. However more evidence is needed before isolated ACTH deficiency is added to the list of extraintestinal manifestations of CD.