Should nasogastric enteral feeding become a standard escalation to reverse malnutrition in liver transplant candidates?

Chapman et al. recently published an open-label randomized controlled trial (1) assessing the value of nasogastric enteral feeding (NGF) using a nasogastric tube in malnourished patients aged over 18 years awaiting liver transplantation. Inclusion criteria were a diagnosis of severe malnutrition [as determined by subjective global assessment (SGA) class C (2)] with low muscle strength [hand grip strength (HGS) values below normative values]. In this single-center study, 55 patients (58% male, median age ~59 years) with advanced liver dysfunction (>75% with Model for End Stage Liver Disease (MELD) ≥20 and Child-Pugh C) were randomized. Alcohol-related liver disease was the leading etiology (>40%). Compared to the control group receiving standard high-energy, high-protein (HEHP) dietary counseling alone, the intervention group—which received the same counseling supplemented with overnight NGF—showed a significant improvement in the primary outcome, namely muscle function. This was assessed using HGS, with a median group difference of 3.6 kg [95% confidence interval (CI): 1.7 to 5.2; P<0.001] within 63 [interquartile range (IQR), 34.5–127.0] days of follow-up in the NGF group. Several secondary anthropometric outcomes, such as mid-upper arm circumference and triceps skinfold thickness, also improved significantly in the NGF group. A trend toward increased dry weight was also observed (P=0.06).

Malnutrition and sarcopenia are major yet common concerns in patients awaiting liver transplantation. Indeed, they are associated with increased mortality in patients with severe end-stage cirrhosis. In patients who have undergone transplantation, poor nutritional status prior to transplant has been suggested to also impact early outcomes, resulting in higher morbidity. Malnutrition is difficult to assess in this population partly because commonly used indicators such as serum albumin and anthropometric measures are often confounded in the setting of cirrhosis (3). Moreover, standard dietary counseling alone has repeatedly failed to improve nutritional intake or reverse malnutrition in this population. Key barriers include poor adherence, often driven by the unpalatability of high-protein supplements, compounded by poor appetite, early satiety, taste alterations, and various other functional symptoms directly related to liver disease—particularly the development of ascites and hepatic encephalopathy (4).

In Chapman et al.’s (1) study, muscle function—as measured by HGS—was appropriately selected as the primary endpoint, as it is a core component of frailty in liver transplant candidates and an independent predictor of waitlist mortality (5). HGS has limitations, such as inter-device and protocol variability, and the influence of confounders such as age, sex, and comorbidities—particularly in patients with cirrhosis (6). More importantly, HGS is sensitive to patient motivation and submaximal effort, which can raise concerns in an open-label design and a population of patients with encephalopathy (7). Nevertheless, HGS demonstrates excellent test-retest reliability, even in patients with musculoskeletal, neurologic, or systemic conditions, and remains a strong predictor of functional limitations and adverse health outcomes (8). Chapman et al.’s (1) study, by definition, includes patients with low HGS values, hence with pre-sarcopenia, as per the revised EWGSOP2 criteria (9). In line with these criteria (9), the assessments of muscle mass [computed tomography (CT) or magnetic resonance imaging (MRI)-based] and physical performance [e.g., gait speed, the Short Physical Performance Battery (SPPB), and the Timed-Up and Go (TUG) test] would have confirmed the presence of sarcopenia and severe sarcopenia possibly strengthening the findings by demonstrating an anatomical improvement of muscle quantity (e.g., skeletal muscle index) and quality (e.g., intramuscular fat content via muscle attenuation) (10). The latter remain relevant and promising endpoints—particularly in the liver transplant community, where imaging-based measurements are widely adopted (4,11).

Beyond meeting its primary objective on muscle function, Chapman et al.’s trial (1) raises several important considerations. One of the most compelling findings was the achievement of optimal protein and energy intake in the NGF group without diminishing patients’ spontaneous oral intake [group differences in energy intake +1,285 kcal (95% CI: 860–1,677) and in protein intake +51 g (95% CI: 32–71) (both P<0.001)], therefore addressing the primary challenge in re-nourishing these patients efficiently. The correlation data reported between NGF duration, muscle function and anthropometric improvements are encouraging despite being of moderate magnitude, and suggest a dose–response effect. Based on their results, Chapman et al. (1) endorse a minimum of 4-week NGF duration, while the optimal timing and duration remain to be determined. Moreover, the authors used night-time NGF, which plays a crucial role in ensuring patients’ comfort and quality of life, and deserves particular emphasis given the extended duration of enteral feeding. In addition, the improved immune function in the NGF group, as measured using QuantiFERON-Monitor, supports NGF intervention to mitigate peri-transplant infection risk. Yet, these results did not translate into better post-transplant outcomes, likely due to the small sample size of the study design, as reported by the authors in the limitations. There is, in fact, little doubt that improving muscle function would benefit patients regarding both the post-transplant course and long-term outcomes. However, the study falls short of definitively establishing NGF’s safety—a key limitation to the widespread adoption of this approach. The short follow-up and small sample size limit the ability to detect less frequent but serious adverse events in this high-risk population (most had ascites or encephalopathy). In clinical practice, NGF presents several challenges, including limited patient acceptance and adherence. Since this study did not report clear data on patient compliance, it remains difficult to determine whether NGF could be implemented in daily practice. Furthermore, risks such as aspiration, gastrointestinal bleeding, refeeding syndrome, and worsened electrolyte imbalances or hepatic encephalopathy—particularly in individuals with impaired renal function—require close monitoring and add to the already complex care of these patients (12).

These considerations encourage refining the selection of the enlisted candidate population for NGF. Chapman et al. (1) used SGA to identify malnourished patients; after screening, 17.3% had MELD >16, severe malnutrition (SGA class C), and pre-sarcopenia (2). However, studies assessing sarcopenia in patients with cirrhosis report higher prevalence rates—ranging from 22% to 70% (13). Since SGA incorporates parameters heavily influenced by liver disease and its complications, its performance in this population is debatable (13). This reinforces the potential value of systematic CT-based screening for sarcopenia in patients with cirrhosis to identify frail and malnourished profiles (13,14). Moreover, the trial’s generalizability is limited by the exclusion of patients at risk for variceal bleeding—a group that constitutes a significant proportion of the transplant waiting list. This inherently narrows the applicability of NGF to a select subset of candidates. Notably, esophageal varices are no longer considered a contraindication for enteral feeding or nasogastric tube placement in the most recent guidelines, except during an active bleeding episode (15). NGF could therefore have been initiated in this population after a short safety delay of a few days following a bleeding event. Another notable limitation is the high rate of non-inclusion among eligible patients during the study period (42%), raising concerns about feasibility and potential selection bias. For instance, patients with refractory ascites, who often have a low MELD score, were excluded from the present study, even though they are frequently frail and have sarcopenia. It would be valuable to understand the specific barriers to enrollment—particularly whether NGF acceptance played a role. Lastly, the marked difference in follow-up duration between the NGF and control groups [63.0 (IQR, 34.5–127.0) vs. 112.5 (IQR, 74.75–206.25) days; P=0.03] may suggest faster access to transplantation in the NGF group, especially when associated with a reduced waitlist mortality; it warrants consideration regarding potential selection bias.

Altogether, the study by Chapman et al. (1) significantly elevates the level of evidence supporting the use of NGF in malnourished patients awaiting liver transplantation. NGF transformative effect on muscle function—likely driven by optimized energy and protein intake—provides compelling support for a more proactive approach to managing sarcopenia and malnutrition in this vulnerable population. Future research should focus on clarifying the appropriate and specific indicators of malnutrition in the cirrhotic population, which would guide systematic NGF escalation as well as its optimal duration while ensuring its safety.

Acknowledgments

None.

Footnote

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