The HELLP syndrome: Clinical issues and management. A Review

<p>Abstract</p> <p>Background</p> <p>The HELLP syndrome is a serious complication in pregnancy characterized by haemolysis, elevated liver enzymes and low platelet count occurring in 0.5 to 0.9% of all pregnancies and in 10–20% of cases with severe preeclampsia. The present review highlights occurrence, diagnosis, complications, surveillance, corticosteroid treatment, mode of delivery and risk of recurrence.</p> <p>Methods</p> <p>Clinical reports and reviews published between 2000 and 2008 were screened using Pub Med and Cochrane databases.</p> <p>Results and conclusion</p> <p>About 70% of the cases develop before delivery, the majority between the 27th and 37th gestational weeks; the remainder within 48 hours after delivery. The HELLP syndrome may be complete or incomplete. In the Tennessee Classification System diagnostic criteria for HELLP are haemolysis with increased LDH (> 600 U/L), AST (≥ 70 U/L), and platelets < 100·10⁹/L. The Mississippi Triple-class HELLP System further classifies the disorder by the nadir platelet counts. The syndrome is a progressive condition and serious complications are frequent. Conservative treatment (≥ 48 hours) is controversial but may be considered in selected cases < 34 weeks' gestation. Delivery is indicated if the HELLP syndrome occurs after the 34th gestational week or the foetal and/or maternal conditions deteriorate. Vaginal delivery is preferable. If the cervix is unfavourable, it is reasonable to induce cervical ripening and then labour. In gestational ages between 24 and 34 weeks most authors prefer a single course of corticosteroid therapy for foetal lung maturation, either 2 doses of 12 mg betamethasone 24 hours apart or 6 mg or dexamethasone 12 hours apart before delivery. Standard corticosteroid treatment is, however, of uncertain clinical value in the maternal HELLP syndrome. High-dose treatment and repeated doses should be avoided for fear of long-term adverse effects on the foetal brain. Before 34 weeks' gestation, delivery should be performed if the maternal condition worsens or signs of intrauterine foetal distress occur. Blood pressure should be kept below 155/105 mmHg. Close surveillance of the mother should be continued for at least 48 hours after delivery.</p

COMBINATION THERAPY OF METFORMIN AND CALORIC RESTRICTION IN THE TREATMENT OF TYPE 2 DIABETES AND NAFLD IN OLETF RATS

Melissa A. Linden1,4, Kristi T. Lopez1,2, Justin A. Fletcher1,4, Grace M. Meers1,2, Sameer Siddique1, 2, E. MatthewMorris1,2, M. Harold Laughlin, FACSM5, James R. Sowers1,3, John P. Thyfault, FACSM1,2,4, Jamal A. Ibdah1,2,4,andR. Scott Rector1,2,4; 1Research Service-Harry S Truman Memorial Veterans Medical Center, Columbia, Missouri and Departments of Internal Medicine-2Division of Gastroenterology and Hepatology, Internal Medicine-3Division of Endocrinology, 4Nutrition and Exercise Physiology, and 5Biomedical Sciences, University of Missouri; Columbia, MO Weight loss remains a cornerstone therapy in the treatment for nonalcoholic fatty liver disease (NAFLD). In addition, limited literature suggests that metformin can effectively lower liver enzymes in type 2 diabetics. However, the efficacy of metformin therapy when taken in combination with weight loss on NAFLD outcomes remains largely unexamined. PURPOSE: Here, we sought to determine the therapeutic effects of metformin, caloric restriction, and the combination on type 2 diabetes and NAFLD outcomes in hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. METHODS: We randomly assigned OLETF rats (age 20 weeks; n=6-8/group) to ad libitum fed (AL), metformin (300 mg/kg/d; Met), daily caloric restriction (70% of AL fed; CR), or combination CR+Met groups for 12 weeks of treatment. RESULTS: Met therapy lowered body weight and body fat compared with AL, but to a lesser extent than CR and CR+Met (p\u3c0.05). All three therapies improved fasting insulin, glucose, and/or HbA1c levels, but only the combination of CR+Met improved post-challenge glucose tolerance. Met, CR, and CR+Met reduced hepatic triglycerides by 40%, 70%, and 60% (p\u3c0.05 between Met and CR/CR+Met groups), respectively compared with AL rats, and although there was no additive effects of CR+Met on lowering hepatic steatosis beyond CR alone, the combination resulted in further attenuation in serum alanine aminotransferase (ALT) levels. Met alone failed to alter hepatic de novo lipogenesis proteins fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and stearoyl-CoA desaturase-1 (SCD-1), or hepatic mitochondrial activity assessed with palmitate oxidation and β-hydroxy-acyl-CoA dehydrogenase (β-HAD) activity; whereas, CR alone reduced FAS, ACC and SCD-1 protein content, and increased complete palmitate oxidation and β-HAD activity. Furthermore, the combination therapy resulted in further reductions in ACC and SCD-1 protein content compared with CR alone. CONCLUSIONS: Caloric restriction appears to be a more effective therapy than metformin alone in the treatment of NAFLD in the obese, hyperphagic OLETF rat. However, the combination of caloric restriction + metformin offered greater benefits in improving glycemic control, reducing markers of liver injury, and suppressing markers of hepatic de novo lipogenesis than either therapy alone. This work was partially supported by NIH grants HL-36088 (MHL), DK-088940 (JPT), HL73101-07 (JRS), HL107910-03 (JRS), and T32 AR-048523 (JAF and EMM) and by VA Grant VHA-CDA2 IK2BX001299-01 (RSR) and VA Merit System 0018 (JRS)