Therapeutic Options in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease, an entity that includes nonalcoholic steatohepatitis, is typically a benign, indolent condition. However, in a subset of patients, the clinical course may progress to advanced cirrhosis, end-stage liver disease, or hepatocellular carcinoma. Unfortunately, the pathogenesis, natural history, and potential therapies for these disorders remain poorly understood. Identifying patients who should be targeted for potential treatment remains difficult. Liver biopsy should be considered to assess the degree of hepatic inflammation and fibrosis, because physical examination findings, biochemical parameters, and the results of radiographic studies have been shown to correlate poorly with the severity of steatohepatitis and fibrosis. Although there is some evidence suggesting that obesity, diabetes mellitus, older age, and perhaps an aspartate transaminase:alanine aminotransaminase ratio higher than 1 may be predictors of more advanced fibrosis, histology remains the gold standard. Most patients with simple hepatic steatosis appear to follow a benign course and probably do not require aggressive therapy. Conversely, patients with steatohepatitis with extensive inflammation and fibrosis are the patients who are most likely to benefit from effective therapies. The most commonly recommended treatment is weight loss. Existing data suggest that rapid weight loss may promote hepatic inflammation and fibrosis; therefore, gradual weight loss should be recommended. Large, randomized, controlled trials evaluating the long-term histologic impact and clinical outcomes of weight loss strategies are lacking. Potentially promising pharmacologic therapies include insulin-sensitizing oral hypoglycemic agents such as metformin and the thiazolidenediols, antihyperlipidemic agents such as gemfibrozil or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, vitamin E and other antioxidants, ursodeoxycholic acid, and betaine. As with weight loss, data regarding the efficacy of these pharmacologic options are limited. In addition, there are no widely accepted guidelines to help direct the clinician in the optimal use of these agents in patients with nonalcoholic fatty liver diseases.

Laparoscopic adjustable gastric banding: a prospective comparison of two commonly used bands.

BACKGROUND: Surgery for morbid obesity has increased since the introduction of the adjustable gastric bands (AGB), which can be placed laparoscopically. There are two AGB in wide use: the Swedish Adjustable Gastric Band (SAGB, Obtech), and the Lap-Band (Inamed Health). We present the results of a comparative study between the 2 AGB. METHODS: 101 patients with a minimal follow-up of 6 months were included. 49 patients received a Swedish Adjustable Gastric Band (SAGB), and the remaining 52 received the Lap-Band (LB). Postoperative weight loss and complications were compared at set intervals of 3 months in the first postoperative year, and 6 months in the years following. RESULTS: Mean follow-up was 9.9 months for the SAGB and 7.2 months for the LB. All but 5 procedures were performed laparoscopically. Mean operating-time was 102 minutes for the SAGB and 86 minutes for the LB. No significant difference in complications was noted between the 2 AGB. 1 SAGB was repositioned and 2 were removed, compared to 2 repositions and 2 removals of the LB. We excluded 5 patients with leakage of a SAGB due to technical failure. Mean preoperative weight kg/BMI of the SAGB patients was 133/45.3; in the LB patients 138/46.4. Mean weight loss at 6 months was 28 kg with the SAGB and 30 kg with the LB, and mean weight loss at 1 year 36 kg and 38 kg respectively. After 2 years, weight loss was 46 kg and 42 kg respectively. CONCLUSION: There was no significant difference in postoperative weight loss and complications between the SAGB and the LB.

Weight change, survival time and cause of death in Dutch elderly.

Weight change, subsequent survival time and cause of death are reported from the Dutch Longitudinal Study among the Elderly. Data consist of a national sample of persons aged 65-99 years. Six hundred and fifty-eight subjects were examined in the baseline years 1955-1957 and were re-examined 5 years later. Vital status and cause of death were ascertained for 604 of these subjects through 1983. Those subjects who experienced a decline in body mass index (BMI, kg/m(2)) during the period of observation, were likely to be in poorer health and have a shorter survival time than those subjects with stable weight, regardless of initial BMI. Weight gain was associated with shorter survival time only in the age group 65-74 and in those with heart disease. weight loss, on the other hand, was most likely to result in decreased survival time among those ultimately dying of stroke, pneumonia/influenza or heart disease. As such, weight loss may be an indicator of the severity of disease. The noted associations remained, even when those surviving less than two years were omitted from the analyses. Thus, in longer survivors, weight loss may be associated with decreased vitality and decreased ability to survive once a disease becomes apparent.

Effect of significant intermediate-term weight loss on serum leptin levels and body composition in severely obese subjects.

BACKGROUND: Leptin, produced by adipose tissue, signals body fat content to the hypothalamus. Serum leptin levels (SLL), elevated in obese humans, decrease with weight loss. This study investigated the reduction of SLL and fat mass following restrictive bariatric surgery. METHODS: Obese subjects (body mass index [BMI] >35 kg/m2, n=154) undergoing gastric banding (weight-reduced subjects) were investigated for SLL and body composition before surgery and for 2 years after. Overweight subjects matched for fat mass and gender (fat mass-matched overweight controls, n=194) and subjects who had never been obese (normal weight controls, n=158) were studied for comparison. RESULTS: SLL were highest in weight-reduced subjects and decreased with weight loss (P <0.001), remaining elevated compared with normal weight controls (P <0.001) but lower than fat mass-matched overweight controls (women: P <0.04). At 2 years, SLL normalized for fat mass (allowing comparison between various levels of adiposity) were lower in weight-reduced subjects compared with fat mass-matched overweight controls (women: P =0.003), yet were similar for weight-reduced subjects at 2 years compared with normal weight controls despite 14 kg greater fat mass. Relative lean mass of extremities in weight-reduced subjects increased with weight loss (P <0.001). CONCLUSION: SLL decreased after considerable weight loss more than could be accounted for by fat mass or BMI reduction alone. This disproportionate decrease in SLL might point to a mechanism that evolved as adaptation to starvation during times of famine. Thus, post-obese subjects may be at risk of weight-regain due to disproportionately low SLL and increased appetite via the leptin-melanocortin pathway.

Use of nonprescription weight loss products: results from a multistate survey.

CONTEXT: Lifestyle changes to lose weight can be difficult; hence, both prescription and nonprescription diet products are appealing. Usage patterns of the nonprescription products phenylpropanolamine (PPA) and ephedra are of particular interest because of recent safety concerns. OBJECTIVE: To estimate the prevalence of overall and specific nonprescription weight loss product use by demographic characteristics, prescription diet pill use, diabetic status, and lifestyle choices. DESIGN AND SETTING: The Behavioral Risk Factor Surveillance System, a random-digit telephone survey conducted in 1998 in 5 states: Florida, Iowa, Michigan, West Virginia, and Wisconsin. PARTICIPANTS: Population-based sample of 14 679 noninstitutionalized adults 18 years or older. MAIN OUTCOME MEASURES: Prevalence of nonprescription weight loss product use in 1996-1998. RESULTS: Seven percent reported overall nonprescription weight loss product use, 2% reported PPA use, and 1% reported ephedra product use. Overall use was especially common among young obese women (28.4%). Moreover, 7.9% of normal-weight women reported use. There was no difference in nonprescription weight loss product use by daily consumption of fruits and vegetables; however, more users than nonusers reported being physically active (for those who exercised >/=30 minutes 5 times per week, odds ratio, 1.5; 95% confidence interval, 1.2-2.0). Among prescription weight loss product users, 33.8% also took nonprescription product. CONCLUSIONS: With increasing rates of obesity, nonprescription product use is likely to increase. Clinicians should know about their patients' use of both prescription and nonprescription weight loss products.

Heterosis and recombination effects on pig reproductive traits.

The objective was to estimate breed, heterosis, and recombination effects on pig reproductive traits in two different four-breed composite populations. Breeds included Yorkshire, Landrace, Large White, and Chester White in Exp. 1 and Duroc, Hampshire, Pietrain, and Spot in Exp. 2. Data were recorded on purebred pigs, two-breed cross pigs, and pigs from generations F1 through F6, where F1 pigs were the first generation of a four-breed cross. Litter traits were considered a trait of the gilt. There were 868 first parity litters in Exp. 1 and 865 in Exp. 2. Direct heterosis significantly increased sow weight at 110 d of gestation and litter weight at 14 and 28 d (weaning) in both experiments. Direct heterosis significantly increased number of nipples, weight at puberty, lactation weight loss, litter size, and litter birth weight in Exp. 2. Gestation length in Exp. 1 and age at puberty in Exp. 1 and Exp. 2 were significantly decreased by direct heterosis. Maternal heterosis significantly increased age at puberty in Exp. 2 and decreased sow weight at 110 d of gestation in Exp. 1. Recombination significantly increased sow weight at 110 d of gestation and tended to increase total number born and litter birth weight in Exp. 1. Recombination significantly decreased age at puberty in Exp. 2. Litter heterosis significantly increased number of pigs at 14 and 28 d; litter weights at birth, 14, and 28 d; and tended to increase lactation weight loss in Exp. 1. Litter heterosis decreased litter size in Exp. 2. Maternal heterosis and recombination effects had a sampling correlation of -0.97 in Exp. 1 and -0.91 in Exp. 2 for number of fully formed pigs. Therefore, maternal heterosis and recombination effects were summed, and their net effect was tested. This net effect tended to increase number of nipples, lactation weight loss, and litter birth weight and significantly increased number of fully formed pigs in Exp. 1. Direct, maternal, and litter heterosis and recombination effects significantly influenced reproductive traits.

The LM Proring Band and left approach in laparoscopic vertical banded gastroplasty: preliminary results in 44 cases.

BACKGROUND: Morbid obesity is one of the most important social and medical issues in Western countries. Many authors have adopted a minimally invasive approach to reproduce current bariatric operations. The aim of this study is to present a personal technique for laparoscopic vertical banded gastroplasty (LVBG) and the preliminary results of 44 patients. METHODS: Patients fulfilled the indications for bariatric surgery and were followed prospectively. LVBG was performed in patients who refused laparoscopic banding because of port placement and adjustment, or in patients with hiatus hernia, with or without gastroesophageal reflux disease. The technique performed consisted of a laparoscopic Mason modified-MacLean gastroplasty using only 4 ports. The circular stapler was introduced in the left anterior axillary line subcostally using the same working port as the Endo-GIA stapler. A new device, a non-adjustable silicone ring, was placed as the collar around the lower end of the gastric pouch. RESULTS: The 44 patients underwent a satisfactory LVBG with no conversions to open surgery. Mean operative time was 80 minutes (range 45-180), hospital stay was 4 days, and all 44 operations had an uneventful postoperative course. There were 40 women and 4 men, with mean age 42.5 years (24-59). Preoperative mean weight was 118.7 kg (84.5-184), with mean BMI 44.5 (35.6-60.1). 27 of the 44 patients were selected for analysis of weight loss, selection criteria being a sufficient amount of data (> 2 weight losses separated by at least 2 months). For these 27 patients, mean age 41.9 (26-59), preoperative weight 119.3 kg (95-145) and mean BMI 44.6 (38.3-53.6), weight loss data were fitted with an exponential growth function, using a quasi-Newton fit algorithm. The fitted coefficient was used to calculate % excess weight loss and BMI. Mean weight loss at 1, 3, 6 and 12 months was 9.2 kg (4.4-17.2), 24.5 kg (11.0-35.9), 29 kg (12.6-53.6), and 36.5 kg (12.8-66.5) respectively. CONCLUSION: LVBG has given good results thus far and may be selected as a restrictive procedure. weight loss and resolution of comorbidities occurred, and a considerable increase in self-confidence and quality of life were reported.

Lipid peroxides in obese patients and effects of weight loss with Orlistat ( Xenical ) on lipid peroxides levels.

OBJECTIVE: obesity is a well-known risk factor of atherosclerosis. Recent studies showed that obesity is associated with enhanced lipid peroxidation. The aim of this study is to investigate the effect of weight reduction with Orlistat ( Xenical ) treatment on lipid peroxidation levels. We assessed lipid peroxidation by measuring the concentration of plasma malondialdehyde (MDA). DESIGN: A randomized, controlled, open-label 6-month study. SUBJECTS: In total, 36 obese (body mass index (BMI) >30 kg/m2) and 11 healthy age-matched control subjects were enrolled in the study. MEASUREMENTS: Fasting glucose, triglyceride, total cholesterol, HDL cholesterol and LDL cholesterol and MDA levels were measured in both groups. Obese subjects received Orlistat ( Xenical ), 120 mg three times daily together with hypocaloric diet. After 6 months of treatment laboratory tests were repeated. RESULTS: MDA levels were significantly higher in obese patients than the control group (P<0.0001). After 6 months of treatment in obese subjects, the mean weight of the patients decreased by 6.8 kg, the BMI by 3.2 kg/m2. Plasma MDA levels were significantly reduced by weight loss from 2+/-0.77 to 0.89+/-0.41 nmol/ml (P<0.001). BMI correlated with MDA levels at baseline (r=0.6, P<0.0001). Changes in BMI was positively associated with plasma MDA level reduction (r=0.36, P<0.05). CONCLUSION: These results indicate that obesity is associated with increases in endogenous lipid peroxides. Our data show that the indicator of lipid peroxidation-MDA-falls markedly in association with weight loss with Orlistat ( Xenical ). The demonstration of decreased free radical generation has important implications for oxidative mechanism underlying obesity-associated disorders.