Bariatric Surgery and Liver Disease: General Considerations and Role of the Gut–Liver Axis

Weight loss is a therapeutic solution for many metabolic disorders, such as obesity and its complications. Bariatric surgery aims to achieve lasting weight loss in all patients who have failed after multiple dietary attempts. Among its many benefits, it has been associated with the regression of non-alcoholic fatty liver disease (NAFLD), which is often associated with obesity, with evidence of substantial improvement in tissue inflammation and fibrosis. These benefits are mediated not only by weight loss, but also by favorable changes in systemic inflammation and in the composition of the gut microbiota. Changes in microbial metabolites such as short-chain fatty acids (SCFAs), capable of acting as endocrine mediators, and bile acids (BAs) as well as modifications of the gut-brain axis, are among the involved mechanisms. However, not all bariatric surgeries show beneficial effects on the liver; those leading to malabsorption can cause liver failure or a marked worsening of fibrosis and the development of cirrhosis. Nevertheless, there are still many unclear aspects, including the extent of the benefits and the magnitude of the risks of bariatric surgery in cirrhotic patients. In addition, the usefulness and the safety of these procedures in patients who are candidates to or who have undergone liver transplant need solid supporting evidence. This paper aims to review literature data on the use of bariatric surgery in the setting of chronic liver disease.     

Impact of Obesity in Kidney Diseases

The clinical consequences of obesity on the kidneys, with or without metabolic abnormalities, involve both renal function and structures. The mechanisms linking obesity and renal damage are well understood, including several effector mechanisms with interconnected pathways. Higher prevalence of urinary albumin excretion, sub-nephrotic syndrome, nephrolithiasis, increased risk of developing CKD, and progression to ESKD have been identified as being associated with obesity and having a relevant clinical impact. Moreover, renal replacement therapy and kidney transplantation are also influenced by obesity. Losing weight is key in limiting the impact that obesity produces on the kidneys by reducing albuminuria/proteinuria, declining rate of eGFR deterioration, delaying the development of CKD and ESKD, and improving the outcome of a renal transplant. Weight reduction may also contribute to appropriate control of cardiometabolic risk factors such as hypertension, metabolic syndrome, diabetes, and dyslipidemia which may be protective not only in renal damage but also cardiovascular disease. Lifestyle changes, some drugs, and bariatric surgery have demonstrated the benefits.     

Bariatric surgery outcomes following organ transplantation: A review study

Weight gain is a frequent postoperative complication following a solid organ transplant which can be solved by bariatric surgery. The outcomes of bariatric surgery among patients with an organ transplant history are always a challengeable subject for surgeons and surgery candidates. In this review article, we aim to investigate the existence literature about the rates of morbidity and mortality, frequent complications in terms of graft function, remission in diabetes, hypertension, pulmonary and cardiovascular disorders, hepatic and renal functions, and immunosuppressive stability, as well as the safety of bariatric surgery among patients.     

Treating the obese patient. Suggestions for primary care practice

Obesity is a major health problem in America. Weight loss is associated with improvements in obesity-related health complications, but patients and practitioners are frequently disappointed by the long-term results of weight control efforts. Recent research has yielded new findings concerning the causes of obesity, as well as new goals for obesity treatment. Traditionally, the goal of therapy has been reduction to ideal weight. Several scientific bodies, however, now recommend a more modest 5% to 15% reduction in initial weight. Current options for weight loss include behavioral or pharmacological management provided during primary care visits, self-help and commercial programs, hospital-based interventions, and bariatric surgery. Regardless of the approach selected, long-term care usually is required to facilitate the maintenance of weight loss.     

Pretransplant obesity: a weighty issue affecting transplant candidacy and outcomes.

Because of the global increase in prevalence of obesity, many more overweight and obese individuals are undergoing evaluation for transplantation than in the past. Although obesity seems to provide a survival benefit in dialysis patients, obesity has traditionally been considered a contraindication for transplantation of most organs. It is theorized that obesity will contribute to worse transplant outcomes, including lower rates of graft and patient survival and higher rates of delayed graft function and infection. This review evaluates the available literature evaluating outcomes of obese patients with end-stage organ failure who undergo transplantation. Obesity seems to be associated with increased rates of wound infection after transplantation. However, other adverse transplant outcomes related to obesity seem to be dependent on the type of organ being transplanted and the degree of obesity. For example, a body mass index (BMI) of 30 kg/m(2) may reduce short-term survival in lung transplant recipients; however, obesity does not seem to confer an adverse effect on short- or long-term survival in liver transplant patients until a much higher BMI is reached (such as 35 or 40 kg/m(2)). Each transplant center must determine weight guidelines and criteria for identifying the level of obesity as a contraindication for transplantation. This must be based on organ type, each center's transplant and complication statistics, and available donor pools. Guidelines must also consider the morbidity and mortality risks of the obese patient with organ failure who does not receive a transplant.     

Combination of Caloric Restriction and a Mixed Training Protocol as an Effective Strategy to Counteract the Deleterious Effects in Trabecular Bone Microarchitecture Caused by a Diet-Induced Obesity in Sprague Dawley Rats

The association of obesity with changes in bone mass is not clear. Obese individuals tend to have an increased bone mineral density, but other studies have shown that obesity is a major risk factor for fractures. The mechanisms of bone response during a weight loss therapy as well as the possible osteoprotective effect of exercise should be analyzed. The aim of this study was to test the effects of a weight-loss program based on the combination of caloric restriction and/or a mixed training protocol on different parameters of bone morphology and functionality in a DIO rat model. Three stages were established over a 21-week period (obesity induction 0–12 w, weight loss intervention 12–15 w, weight maintenance intervention 15–21 w) in 88 male Sprague Dawley rats. Bone microarchitecture, total mineral and elemental composition, and bone metabolism parameters were assessed. Weight loss interventions were associated to healthy changes in body composition, decreasing body fat and increasing lean body mass. On the other hand, obesity was related to a higher content of bone resorption and inflammatory markers, which was decreased by the weight control interventions. Caloric restriction led to marked changes in trabecular microarchitecture, with a significant decrease in total volume but no changes in bone volume (BV). In addition, the intervention diet caused an increase in trabeculae number and a decrease in trabecular spacing. The training protocol increased the pore diameter and reversed the changes in cortical porosity and density of BV induced by the high protein diet at diaphysis level. Regarding the weight-maintenance stage, diminished SMI values indicate the presence of more plate-like spongiosa in sedentary and exercise groups. In conclusion, the lifestyle interventions of caloric restriction and mixed training protocol implemented as weight loss strategies have been effective to counteract some of the deleterious effects caused by a dietary induction of obesity, specifically in trabecular bone morphometric parameters as well as bone mineral content.     

Weight gain and cardiovascular risk after organ transplantation

Organ transplantation has become a common and effective approach to the management of patients with organ failure. The improvement in long-term survival has resulted in the emergence of cardiovascular disease as the primary cause of death in renal transplant patients and a significant complication in other organ recipients. A number of factors explain this trend, including a high incidence of hypertension, posttransplant diabetes, hyperlipidemia, and obesity-risk factors that are mediated by direct effects of immunosuppressive medications. Weight gain posttransplant affects approximately 50% of patients and represents a significant problem because of the potential synergism between obesity and immunosuppressive medication-induced effects on cardiovascular disease risk factor development. This review discusses the incidence and implications of cardiovascular disease risk factors in organ transplant recipients, strategies for clinical management, and future research directions.     

Composition (lean and fat tissue) of weight changes in adult Danes

BACKGROUND: Weight loss may be associated with unfavorable changes in body composition not compensated for by subsequent weight gain. OBJECTIVE: We examined the composition of weight change in relation to obesity, previous weight changes, weight-loss attempts, and physical activity. DESIGN: Part of the Danish MONICA (Monitoring Trends in Cardiovascular Disease) project, this was a longitudinal population study of changes in weight and body composition, with examinations in 1982-1983, 1987-1988, and 1993-1994. A total of 1236 men and 1200 women aged 35, 45, 55, or 65 y in 1987-1988 participated. Changes in fat and fat-free mass were measured by bioelectrical impedance. RESULTS: Before adjustment for age-related changes, fat-free mass made up 41% of weight lost and 24% of weight gained in men. In women, loss of fat-free mass (35%) was more than double that of gains (15%). After adjustment, the fractions of weight gained as fat-free mass were not significantly different from the fractions lost. These fractions were independent of age, obesity, and weight changes in the previous 5 y; successful weight-loss attempts; and physical activity. Independent of age and degree of obesity, weight changes were associated with greater changes in fat-free mass in men than in women. CONCLUSIONS: These data do not support the theory that weight loss or weight cycling may lead to an unfavorable body composition, nor do they provide a biological explanation for why long-term weight loss is often unsuccessful. However, the metabolic and health consequences of weight change may differ in men and women.     

Factors Associated with Health-Related Quality of Life Among Overweight and Obese Korean Women

Health-related quality of life (HRQOL) tends to be lower among individuals who are overweight and obese than those of normal weight, and women may be more vulnerable to lower HRQOL associated with obesity than men. Identifying factors associated with HRQOL may be crucial for improving HRQOL for overweight/obese women. We aimed to determine the factors associated with obesity-specific HRQOL among overweight/obese Korean women. A cross-sectional study was conducted with 125 women aged 20–64 years, who comprised a baseline sample in the Community-based Heart and Weight Management Trial. The data were collected from September 2010 to November 2011. The Weight Efficacy Lifestyle, Beck Depression Inventory-II, Interpersonal Social Evaluation List, and Impact of Weight on Quality of Life (IWQOL)–Lite scales were used to measure self-efficacy for weight control, depressive symptoms, social support, and HRQOL, respectively. Increased body mass index, lower self-efficacy for weight control, and higher levels of depressive symptoms were significantly associated with greater impairment in total IWQOL in the regression models. However, social support was not significantly associated with IWQOL. Along with weight loss strategies, other strategies for improving self-efficacy and alleviating depressive symptoms may be essential for improving HRQOL among overweight and obese women.     

Measuring Social Support for Weight Loss in an Internet Weight Loss Community

Although overweight and obese individuals are turning to Internet communities for social support for weight loss, there is no validated online instrument for measuring the subjective social support experiences of participants in these communities. The authors' objective was to determine whether an online version of a validated paper questionnaire, the Weight Management Support Inventory, is appropriate for measuring social support among members of Internet weight loss communities. The authors administered the paper and online versions of the questionnaire in random, counterbalanced fashion to 199 members of a large Internet weight loss community. Scores for the paper and online versions were comparable in between-subjects and within-subjects comparisons. Convergent validity is suggested by the finding that participants who posted messages on Internet forums several times per day reported more social support than those who posted less frequently. However, the instrumental (tangible) support items did not load significantly on the instrumental support factor, suggesting that instrumental support is not relevant to the social support exchanged among participants in these communities. The authors conclude that the online, modified Weight Management Support Inventory, without items for instrumental support, is an appropriate instrument for measuring social support for weight loss among members of Internet weight loss communities.     

Measuring social support for weight loss in an internet weight loss community

Although overweight and obese individuals are turning to Internet communities for social support for weight loss, there is no validated online instrument for measuring the subjective social support experiences of participants in these communities. The authors' objective was to determine whether an online version of a validated paper questionnaire, the Weight Management Support Inventory, is appropriate for measuring social support among members of Internet weight loss communities. The authors administered the paper and online versions of the questionnaire in random, counterbalanced fashion to 199 members of a large Internet weight loss community. Scores for the paper and online versions were comparable in between-subjects and within-subjects comparisons. Convergent validity is suggested by the finding that participants who posted messages on Internet forums several times per day reported more social support than those who posted less frequently. However, the instrumental (tangible) support items did not load significantly on the instrumental support factor, suggesting that instrumental support is not relevant to the social support exchanged among participants in these communities. The authors conclude that the online, modified Weight Management Support Inventory, without items for instrumental support, is an appropriate instrument for measuring social support for weight loss among members of Internet weight loss communities.     

An initial evaluation of a commercial weight loss program: short-term effects on weight, eating behavior, and mood

OBJECTIVE: This paper describes an initial, 4-week evaluation of a commercial weight loss program. RESEARCH METHODS AND PROCEDURES: Respondents (n = 985) to newspaper advertisements in two metropolitan areas were assigned to 4 weeks of either the Weight Watchers program or to a Self-Help condition. Weight loss, psychological vitality, and eating behavior were evaluated before and after the 4-week intervention. RESULTS: Weight Watchers participants showed greater improvements than Self-Help participants on all measures; weight losses averaged 1.87 and 0.77 kg, respectively. The superior outcomes shown by Weight Watchers participants on measures of vitality and eating behavior were still evident when extent of weight loss was controlled. Weight losses across different sites, incomes, and levels of obesity were similar. DISCUSSION: Although the present study's intervention and outcome assessments were short-term, the promising results obtained suggest that longer term studies should be undertaken.     

Nutrition assessment and support of organ transplant recipients

Timely nutrition assessment and intervention in organ transplant recipients may improve outcomes surrounding transplantation. A pretransplant nutrition assessment should include a variety of parameters including physical assessment, history, anthropometric measurements, and laboratory tests. Malnutrition compromises posttransplant survival; prolonged waiting times worsen outcomes when patients are already malnourished. Severe obesity may decrease graft function and survival in kidney transplant recipients. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by organ failure. Enteral tube feeding is indicated for patients with functional gastrointestinal tracts who are not eating adequately. Parenteral nutrition is rarely needed pretransplant except in cases of intestinal failure. When determining pretransplant nutrient requirements, nutritional status, weight, age, gender, metabolic state, stage and type of organ failure, malabsorption, induced losses, goals, and comorbid conditions must be considered. During the acute posttransplant phase, adequate nutrition is required to help prevent infection, promote wound healing, support metabolic demands, replenish lost stores, and perhaps mediate the immune response. Nutrient recommendations reflect posttransplant metabolic changes. The appropriateness of posttransplant nutrition support depends on the prevalence of malnutrition among patients with a specific type of organ failure and the benefits when nutrition support is given. Organ transplantation complications including rejection, infection, wound healing, renal insufficiency, hyperglycemia, and surgical complications require specific nutritional requirements and therapies. Many potential applications of nutrition in the pre- and posttransplant phases exist and require further study.     

Treatment of obesity-associated hypertension.

Many obese people are hypertensive either because of obesity-associated hypertension or because the two conditions coexist. Weight loss is recommended for all obese hypertensives as some patients benefit by concomitant reductions of arterial pressure and/or decreased requirements for antihypertensive drugs. Since obesity-associated hypertension cannot be diagnosed as a separate entity, available evidence was reviewed to determine the antihypertensive effectiveness of weight loss and effects of weight loss on antihypertensive drug requirements. Generally speaking, patients with mild hypertension appear to respond better to weight reduction than those with moderate and severe hypertension. However, a substantial percentage of patients with mild hypertension may be unresponsive. Weight loss also seems to have potential for lessening requirements for antihypertensive drug therapy. Beneficial effects for both blood pressure and drug requirements are due to weight loss and not caloric restriction, per se. Mechanisms of the beneficial effects are related to consequences of weight loss and appear to involve decreased cardiac output and blood volume. The issue of salt sensitivity of obesity-associated hypertension is unresolved.     

Central obesity is common in renal transplant recipients and is associated with increased prevalence of cardiovascular risk factors

Aim: Obesity following renal transplantation is common and may be associated with cardiovascular disease. We sought to investigate the prevalence of central obesity in renal transplant recipients (RTR) and its association with cardiovascular risk factors. Methods: Weight, height, body mass index (BMI), waist and hip circumference, and biochemical cardiovascular risk factors were prospectively measured in 199 RTR, and were compared against published data from the Australian general population. Results: When obesity was defined by BMI, there was no difference between RTR and the Australian population irrespective of age. Significantly more female RTR had central obesity (defined as waist circumference ≥90 cm for men and ≥80 cm for women) when compared with the general population, and this was apparent at a younger age. In younger women (<45 years), 76% of RTR had central obesity compared with 17% of women from the general population (P < 0.0001). This trend was also seen in older female RTR. Younger male RTR (<45 years) had a greater prevalence of central obesity than aged‐matched men in the general population (66% vs 44%, respectively, P < 0.001). This trend was not seen in older male RTR. Centrally obese RTR gained significantly more weight post transplant than those who were lean (9.5 kg vs 2.4 kg, respectively, P < 0.0001), and were more likely to have a history of childhood obesity (P = 0.04). On multivariate analysis, central obesity was independently associated with weight gain post transplant (P < 0.001), a history of hyperlipidaemia (P = 0.01) and a history of hypertension (P = 0.02). Conclusion: Central obesity is a common problem for all RTR, particularly women and men aged below 45 years. Measures of central obesity should be used for RTR in clinical practice. BMI is not a suitable measure to determine central obesity. Central obesity is associated with cardiovascular risk factors, and further studies targeting multidisciplinary lifestyle interventions are recommended.     

Prevention of Type 2 Diabetes through Lifestyle Modification: Is There a Role for Higher-Protein Diets?

Type 2 diabetes (T2D) incidence is increasing worldwide, driven by a rapidly changing environment and lifestyle and increasing rates of overweight and obesity. Prevention of diabetes is key and is most likely achieved through prevention of weight gain and/or successful long-term weight loss maintenance. Weight loss is readily achievable but there is considerable challenge in maintaining that weight loss over the long term. Lower-fat carbohydrate-based diets are widely used for T2D prevention. This is supported primarily by 3 successful long-term interventions, the US Diabetes Prevention Program, the Finnish Diabetes Prevention Study, and the Chinese Da Qing Study, but evidence is building in support of novel higher-protein (>20% of energy) diets for successful weight loss maintenance and prevention of T2D. Higher-protein diets have the advantage of having relatively low energy density, aiding longer-term appetite suppression, and preserving lean body mass, all central to successful weight loss and prevention of weight regain. Here, we review the carbohydrate-based intervention trials and present mechanistic evidence in support of increased dietary protein for weight loss maintenance and a possible novel role in prevention of dysglycemia and T2D.     

Combining weight-loss counseling with the weight watchers plan for obese breast cancer survivors

OBJECTIVE: The objective was to develop effective weight-loss methods for women who have had breast cancer, because obesity may result in an adverse prognosis. RESEARCH METHODS AND PROCEDURES: This randomized pilot study tested an individualized approach toward weight loss in obese women who have had a diagnosis of breast cancer. An individualized approach was applied either alone or combined with the commercial Weight Watchers program. Forty-eight women (body mass index of 30 to 44 kg/m(2)) were enrolled. RESULTS: Weight change after 12 months of intervention was as follows (mean +/- SD): 0.85 +/- 6.0 kg in the control group, -2.6 +/- 5.9 kg in the Weight Watchers group, -8.0 +/- 5.5 kg in the individualized group, and -9.4 +/- 8.6 kg in the comprehensive group that used both individualized counseling and Weight Watchers. Weight loss relative to control was statistically significant in the comprehensive group 3, 6, and 12 months after randomization, whereas weight loss in the individualized group was significant only at 12 months. Weight loss of 10% or more of initial body weight was observed in 6 of 10 women in the comprehensive group at 12 months. In the comprehensive and Weight Watchers-only groups, weight loss was significantly related to frequency of attendance at Weight Watchers meetings, and attendance was more frequent in the comprehensive group. DISCUSSION: These data indicate that the most weight loss was achieved when the counseling approach combined both Weight Watchers and individualized contacts. This was effective even though most of the individualized contacts were by telephone.     

A practical approach to tuberculosis diagnosis and treatment in liver transplant recipients in a low-prevalence area

Solid organ transplant candidates/recipients are at risk of mycobacterial infections. Although guidelines on the management of latent tuberculosis infection and active tuberculosis are available for solid organ transplant recipients, limited guidance focuses on end-stage liver disease or liver transplant recipients who require management in a referral center. Therapeutic challenges arise from direct antituberculosis drug-related hepatotoxicity, and substantial metabolic interactions between immunosuppressive and antituberculosis drugs. Another issue is the optimal timing of therapy with regards to the time of transplantation. This review focuses on the importance of tuberculosis screening with immunological tests, challenges in the diagnosis, management, and treatment of latent tuberculosis infection and active tuberculosis, as well as risk assessment for active tuberculosis in the critical peri-liver transplantation period. We detail therapeutic adjustments required for the management of antituberculosis drugs in latent tuberculosis infection and active tuberculosis, particularly when concomitantly using rifampicin and immunosuppressive drugs.     

The Impact Once-Weekly Semaglutide 2.4 mg Will Have on Clinical Practice: A Focus on the STEP Trials

Obesity is a complex and chronic disease that raises the risk of various complications. Substantial reduction in body weight improves these risk factors. Lifestyle changes, including physical activity, reduced caloric ingestion, and behavioral therapy, have been the principal pillars in the management of obesity. In recent years, pharmacologic interventions have improved remarkably. The Semaglutide Treatment Effect in People with Obesity (STEP) program is a collection of phase-III trials geared toward exploring the utility of once-weekly 2.4 mg semaglutide administered subcutaneously as a pharmacologic agent for patients with obesity. All the STEP studies included diet and exercise interventions but at different intensities. This review paper aims to explore the impact of the behavioral programs on the effect of semaglutide 2.4 mg on weight loss. The results of the STEP trials supported the efficacy of high-dose, once-weekly 2.4 mg semaglutide on body weight reduction among patients with obesity with/without diabetes mellitus. Semaglutide was associated with more gastrointestinal-related side effects compared to placebo but was generally safe and well tolerated. In all the STEP studies, despite the varying intestines of the behavioral programs, weight loss was very similar. For the first time, there may be a suggestion that these behavioral programs might not increase weight reduction beyond the effect of semaglutide. Nevertheless, the importance of nutritional support during substantial weight loss with pharmacotherapy needs to be re-evaluated.