Incorporating Weight Loss Medications Into Hepatology Practice for Nonalcoholic Steatohepatitis

Abstract

There is an urgent need for practical approaches to patients with nonalcoholic steatohepatitis (NASH). Total body weight loss (TBWL) is an important approach, as its effects are amplified in the liver, with 10% TBWL resulting in a 50% loss of liver triglycerides and improvement in all aspects of NASH histology. Lifestyle changes are the first step in addressing TBWL, but uncommonly result in the range required to improve liver histology in NASH (7%-10%). Weight loss medications (WLMs) are an effective additional tool because they can provide TBWL in the 7%-10% range, have a well-characterized clinical profile, have clear guidelines, and meet approved criteria for their use (body mass index greater than 27 kg/m 2 ) for most NASH patients. Use of WLMs requires shared decision making with the patient, which hepatologists, due to their understanding of the natural history of NASH, are uniquely positioned to provide. WLMs do present the challenge of incorporating new medications into the hepatology clinic, but this will be necessary with all medications to manage NASH. WLMs provide a practical intervention that can be incorporated into hepatology clinics and can be offered to most NASH patients. NASH-specific medicines in clinical trials offer partial histological responses, and TBWL will likely enhance this. Conclusion: WLMs provide the hepatologist with effective and welcome clinical intervention beyond the diagnosis and staging of NASH and provide patients with a sense of empowerment about the treatment of their liver disease. (Hepatology 2019;70:1443-1456). N onalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, and its severe phenotype nonalcoholic steatohepatitis (NASH) results in a significant liver disease burden due to the development of cirrhosis and hepatocellular carcinoma. NASH presents a major management challenge and is an active area of clinical research. The development of insulin resistance plays a central role in NASH pathogenesis, and modest weight loss improves insulin sensitivity with improvement in NASH. Fortunately, weight loss of 4%-5% of total body weight (TBW) results in improved steatosis, and loss of 7%-10% of TBW has demonstrated improvement in inflammation and even fibrosis. (1) Consistent with these data, guidelines by the American Association for the Study of Liver Diseases recommend weight loss-directed lifestyle intervention in all patients with NASH, and bariatric surgery in those meeting the conventional criteria for surgery. However, this leaves major gaps in management, as lifestyle interventions typically only result in more than 5% weight loss in approximately 12% of patients. (2) Bariatric surgery is effective in improving liver histology in NASH through a combination of weight loss and hormonal changes

Clinical impact of sexual dimorphism in non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH)

“…The main strategy to treat NAFLD focuses on the control of underlying risk factors like diabetes, hyperlipidaemia, obesity and other comorbidities. Since no effective pharmacological treatment for NAFLD/NASH has been approved, the lifestyle changes, consisting of balanced diet and physical activity represent the cornerstone of intervention for NAFLD treatment 132 …”

“…Since no effective pharmacological treatment for NAFLD/NASH has been approved, the lifestyle changes, consisting of balanced diet and physical activity represent the cornerstone of intervention for NAFLD treatment. 132 Recent studies have reported that a 6-to 12-month widespread lifestyle modification, based on reduced energy intake and increased physical activity, leads to improvement in liver enzymes and metabolic parameters, and reduced steatosis and necroinflammation, including ballooning and fibrosi. The most recent European and American guidelines recommend that lifestyle interventions should be included as part of the clinical care of all NAFLD patients, regardless of the stage of disease.…”

Gender-specific prevalence of metabolic-associated fatty liver disease among government employees in Tianjin, China: a cross-sectional study

“…31 32 Other scholars have also associated the rising obesity rate with the simultaneous rise in the prevalence of MAFLD. 18 33 34 However, a growing body of literature has pointed out that weight loss can prevent MAFLD from progressing to more serious fatty hepatitis and liver cirrhosis, or even completely reverse the condition, [35][36][37] which has attracted our attention. Combining our outcomes with the results of the aforementioned studies, we have concluded that new strategies are necessary to effectively curb the further spread of MAFLD.…”

<p>A Review Of Current And Upcoming Treatment Modalities In Non-Alcoholic Fatty Liver Disease And Non-Alcoholic Steatohepatitis</p>

“…An aspect of weight loss that has yet to be widely studied in NAFLD patients is the effects of pharmacologic weight loss agents in the reduction of liver fat content. These drugs can help patients lose 7–10% of their total body weight, fitting well with the amount of weight loss shown needed to improve liver histology in NASH 26,27. One of the criteria to be placed on pharmacologic weight loss agents includes a BMI of greater than 27, a criterion in which 85% of the NASH patients qualify.…”