Polycystic ovary syndrome and severe nonalcoholic steatohepatitis: beneficial effect of modest weight loss and exercise on liver biopsy findings.

OBJECTIVE: To report a case of biopsy-documented nonalcoholic steatohepatitis (NASH), which improved appreciably through moderate exercise and weight loss in a young woman with polycystic ovary syndrome (PCOS) and insulin resistance. METHODS: We present a detailed case report, including laboratory and pathologic findings. In addition, we review the recent literature regarding the association of insulin resistance with NASH and PCOS. RESULTS: A 24-year-old woman was referred to the Duke Gastroenterology Clinic for evaluation of long-term high serum aminotransferase levels. She also reported a history of chronically irregular menses, infertility, and hirsutism and was diagnosed with PCOS. Subsequent glucose tolerance testing suggested the presence of insulin resistance. Liver biopsy findings were consistent with severe nonalcoholic steatohepatitis. Under the supervision of her physician and an exercise physiologist, the patient initiated a diet and exercise program that resulted in an 11.5% weight loss during approximately 8 months and yielded normalization of her aminotransferase levels. A repeat liver biopsy done 13 months after the initial biopsy revealed a substantial decrease in steatosis and a reduction in inflammation. CONCLUSION: Women with PCOS and insulin resistance have an increased risk of developing many of the consequences of the dysmetabolic syndrome, including type 2 diabetes, hypertension, and hyperlipidemia. This case report suggests that fatty liver and NASH may be other important diseases to identify in such women. It also demonstrates the improvement in this condition with moderate exercise and weight loss.

Treatment of TIPS/biliary fistula-related endotipsitis with a covered stent.

"Infective endotipsitis" describes a recurrent bacteremia or fungemia in patients with a transjugular intrahepatic portosystemic shunt (TIPS) in place and no other identifiable source of infection. The present report describes a patient who developed polymicrobial endotipsitis 6 years after TIPS creation. Blood cultures remained positive for polymicrobial growth despite long courses of antibiotic therapy. Communication between the TIPS and an infected biliary tree, precipitated by cholecystitis, was ultimately recognized. The biliary/TIPS fistula was closed with a polytetrafluoroethylene-covered stent. The patient remains asymptomatic and follow-up blood cultures remain negative with a low dose of oral antibiotics 2 years after the procedure.

Utility of thiopurine methyltransferase genotyping and phenotyping, and measurement of azathioprine metabolites in the management of patients with autoimmune hepatitis.

BACKGROUND/AIMS: Azathioprine is a key drug in the management of autoimmune hepatitis (AIH), with effects mediated via conversion to 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP), the latter controlled by thiopurine methyltransferase (TPMT). Our aims were to evaluate the role of TPMT genotyping and phenotyping and to examine 6-TG and 6-MMP metabolite levels in patients with AIH. METHODS: TPMT genotyping and phenotyping was performed on 86 patients with AIH, and metabolites evaluated in assessable patients. RESULTS: Eighty-six patients with AIH received azathioprine; 22 developed toxicity and 4/22 were heterozygous for TPMT alleles. Cirrhosis was more common amongst patients who developed toxicity (12/22 (54.5%) versus 19/64 (29.6%), P=0.043). Patients who required persistent prednisone at equivalent azathioprine doses had a higher mean fibrosis stage (P=0.044). TPMT activity, but not metabolites, was lower in patients with stage III/IV fibrosis versus stage I/II fibrosis (30+/-1.92 versus 35.2+/-1.93, P=0.044). Azathioprine dose significantly correlated with measured 6-TG levels (r=0.409, P<0.0001) and 6-MMP levels (r=0.387, P<0.001). CONCLUSIONS: Advanced fibrosis but not TPMT genotype or activity predicts azathioprine toxicity in AIH. Overlap in 6-TG and 6-MMP metabolite levels is noted whether or not steroid therapy is used to maintain remission.

Ischemic colitis: a clinical review.

Ischemic colitis is the most common form of intestinal ischemia. It manifests as a spectrum of injury from transient self-limited ischemia involving the mucosa and submucosa to acute fulminant ischemia with transmural infarction that may progress to necrosis and death. Although there are a variety of causes, the most common mechanism is an acute, self-limited compromise in intestinal blood flow. Patients typically have mild abdominal pain and tenderness over the involved segment of bowel. There is usually passage of blood mixed with stool, but hemodynamically significant bleeding is unusual. Although computed tomography may have suggestive findings, colonoscopy is the procedure of choice for diagnosis. Supportive care with intravenous fluids, optimization of hemodynamic status, avoidance of vasoconstrictive drugs, bowel rest, and empiric antibiotics will produce clinical improvement within 1 to 2 days in most patients. Twenty percent of patients will have development of peritonitis or may deteriorate despite conservative management and will require surgery.

Acute intestinal ischemia and infarction.

Acute intestinal ischemia is a gastrointestinal emergency resulting from a sudden decrement in intestinal blood flow. It may occur as a consequence of mesenteric vascular occlusion and/or hypoperfusion and may involve the small intestine or colon. Bowel infarction, sepsis, and death may result, making prompt diagnosis and management imperative. Acute mesenteric ischemia generally stems from interruption of blood flow within the superior mesenteric artery or vein, and leads to small intestinal hypoperfusion and infarction. It carries with it a mortality rate of approximately 70%, but improved survival may be achieved as a result of early diagnostic consideration, undelayed angiography, and surgical intervention, when appropriate. Acute colonic ischemia occurs typically as a result of a transient mismatch between intestinal blood flow and the metabolic demands of the colon. Although infarction may occur, colonic ischemia is often a reversible condition with mortality rates considerably lower than those witnessed in acute mesenteric ischemia. This article reviews the pathophysiology, clinical features, diagnostic, and therapeutic options applicable to patients with acute intestinal ischemia.