Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is now recognized as part of the metabolic syndrome, and is specifically related to obesity and insulin resistance. Lifestyle modification is advocated for the treatment of NAFLD, but few studies have evaluated its impact on liver histology. The purpose of this study was to investigate which, if any, specific diet and exercise recommendations are associated with histopathologic changes. METHODS: A total of 56 participants were randomly assigned to 1 of 4 lifestyle modification subgroups for 6 months: standard care, low-fat diet and moderate exercise, moderate-fat/low-processed-carbohydrate diet and moderate exercise, or moderate exercise only. All subjects had biopsy-proven NAFLD, to include nonalcoholic steatohepatitis (NASH), and received a repeat 6-month biopsy to detect histopathologic changes. Other measures included blood assay of liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase), fasting glucose, serum insulin, lipid panel, body weight, dietary intake, fat mass, and fitness level. RESULTS: Among the 41 participants who completed the study (88% with NASH), a significant change was found in pre- to post-NAFLD activity score in the group as a whole (p < 0.001) with no difference detected between subgroups (p = 0.31). Our results confirm that lifestyle modification is effective in improving NAFLD and NASH. CONCLUSIONS: Regardless of intervention group, lifestyle modification improved liver histology, as verified by repeat biopsy, after a 6-month intervention. This study reinforces the importance of lifestyle modification as the primary treatment strategy for patients with NAFLD.

Gastroduodenal Cryptococcus in an AIDS Patient Presenting With Melena.

Gastrointestinal cryptococcosis is extremely rare with only a few case reports found in the literature and involvement primarily identified post-mortem. This is a case of 54-year-old man with a 20-year history of poorly controlled human immunodeficiency virus presented with constitutional symptoms along with melena. Diagnostic work up with esophagogastroduodenoscopy showed 4 irregular ulcers in the stomach notable for red-pigmented lesions within the ulcers, erythematous mucosa in the antrum and patchy friable mucosa in the duodenum. H&E staining and Mucicarmine staining showed findings consistent with C. neoformans. Blood culture and cerebrospinal fluid studies also revealed C. neoformans. Cryptococcus neoformans is an AIDS defining illness that most commonly presents as meningoencephalitis and pneumonitis. Key management principles includes: induction of antifungal therapy followed by consolidation and maintenance; management of elevated intracranial pressure and immune reconstitution inflammatory syndrome. Although the organism can infect nearly all organs, gastrointestinal involvement is rarely described. Our case highlights the fact that gastrointestinal C. neoformans infection can be associated with upper gastrointestinal symptoms and may be the initial presentation of disseminated cryptococcosis.

Rosiglitazone versus rosiglitazone and metformin versus rosiglitazone and losartan in the treatment of nonalcoholic steatohepatitis in humans: a 12-month randomized, prospective, open- label trial.

UNLABELLED: Medication combinations that improve the efficacy of thiazolidinediones or ameliorate weight-gain side effects of therapy represent an attractive potential treatment for (NASH). The aim of this randomized, open-label trial was to assess the efficacy of rosiglitazone and metformin in combination versus rosiglitazone and losartan, compared to rosiglitazone alone, after 48 weeks of therapy. A total of 137 subjects with biopsy-proven NASH were enrolled and randomly assigned to receive either 4 mg twice-daily of rosiglitazone, 4 mg of rosiglitazone and 500 mg of metformin twice-daily, or 4 mg of rosiglitazone twice-daily and 50 mg of losartan once-daily for 48 weeks. Patients were screened for other etiologies of chronic liver disease, including daily alcohol intake in excess of 20 g. Repeat liver biopsy was performed after 48 weeks of therapy and reviewed in a blinded fashion by a single expert hepatopathologist. The primary aim of the study was to assess for differences between treatment groups in the improvement of steatosis, hepatocellular inflammation, and fibrosis. In total, 108 subjects completed the trial. Primary outcome revealed no significant difference between treatment groups in all histologic parameters (steatosis, P = 0.137; hepatocellular inflammation, P = 0.320; fibrosis, P = 0.229). Overall improvement in steatosis, hepatocellular inflammation, ballooning degeneration, and fibrosis was observed (P ≤ 0.001). Serum aminotransferases were reduced in all three groups (P < 0.001 within treatment, P > 0.05 between groups). Metformin did not significantly mitigate weight gain (P = 0.051). CONCLUSIONS: Forty-eight weeks of combination therapy with rosiglitazone and metformin or rosiglitazone and losartan confers no greater benefit than rosiglitazone alone with respect to histopathology.

Drug-induced liver injury caused by the histrelin (Vantus) subcutaneous implant.

Drug-induced liver injury (DILI) is the leading cause of acute hepatic failure in the United States. Up to 13% of acute liver failure cases occur due to drugs other than acetaminophen. This clinical diagnosis, made after other causes of liver injury have been excluded, requires establishing a causal relationship between drug exposure and liver injury. The case of a patient with liver injury following a subcutaneous histrelin (Vantus) implant as therapy for advanced prostate cancer is presented.

Secondary tumors and tumorlike lesions of the peritoneal cavity: imaging features with pathologic correlation.

Tumors and tumorlike lesions that secondarily involve the mesothelial or submesothelial layers of the peritoneum are a diverse group of disorders that range in biologic behavior from benign to highly malignant. The anatomy of peritoneal ligaments and mesenteries and the normal circulation of peritoneal fluid dictate location and distribution of these diseases within the peritoneal cavity. Peritoneal carcinomatosis is the most common secondary tumor to affect the peritoneal cavity. When it arises from carcinomas of the gastrointestinal tract or ovary, the prognosis is grave. However, when low-grade mucinous adenocarcinoma of the appendix spreads to the peritoneal cavity, the consequence is typically pseudomyxoma peritonei, which is a clinical syndrome, characterized by recurrent and recalcitrant voluminous mucinous ascites due to surface growth on the peritoneum without significant invasion of underlying tissues. Carcinomas from elsewhere in the body, as well as lymphomas and sarcomas, may also produce diffuse peritoneal metastasis. Granulomatous peritonitis is the consequence of disseminated infection such as tuberculosis or histoplasmosis, foreign materials, or rupture of a tumor or hollow viscus. Finally, a group of benign miscellaneous conditions that range from common disorders such as endometriosis and splenosis to very rare conditions such as gliomatosis peritonei and melanosis may also affect the peritoneum diffusely. Secondary tumors and tumorlike lesions of the peritoneum have overlapping imaging features when compared with each other and primary peritoneal tumors. Knowledge of peritoneal anatomy, normal fluid circulation within the peritoneal cavity, and clinical and pathologic features of secondary peritoneal lesions is essential for identification of these lesions.

From the archives of the AFIP: primary peritoneal tumors: imaging features with pathologic correlation.

Primary peritoneal tumors are uncommon lesions that arise from the mesothelial or submesothelial layers of the peritoneum. Primary malignant mesothelioma, multicystic mesothelioma, primary peritoneal serous carcinoma, leiomyomatosis peritonealis disseminata, and desmoplastic small round cell tumor are the most prominent of these rare lesions. Primary malignant mesothelioma is a highly aggressive malignancy that occurs most commonly in older men and that has a strong association with high levels of asbestos exposure. It manifests most often as diffuse sheetlike or nodular thickening of the peritoneal surfaces, but it may occasionally be a localized mass. Multicystic mesothelioma occurs most frequently in women and has benign or indolent biologic behavior in the majority of patients. It is a multilocular cystic mass that arises from the pelvic peritoneal surfaces. Primary peritoneal serous carcinoma occurs almost exclusively in women. It is histologically identical to ovarian serous carcinoma and may be indistinguishable from metastatic ovarian carcinoma at imaging studies. Leiomyomatosis peritonealis disseminata is a rare, benign proliferative process that also occurs exclusively in women and is characterized by multiple smooth muscle nodules throughout the peritoneum. Desmoplastic small round cell tumor is a highly aggressive malignancy of unknown origin that occurs most often in the peritoneal cavity of young men. This unusual group of tumors is linked together by a common site of origin and imaging manifestations that mimic those of peritoneal carcinomatosis. Knowledge of the spectrum of imaging findings in this group of primary peritoneal tumors, along with their clinical and pathologic characteristics, is important in the evaluation of patients with diffuse peritoneal disease.