Dietary interventions vs octreotide for post liver transplantation chylous ascites: A scoping review

Abstract

BACKGROUND

Chylous ascites (CA), which is characterized by lymphatic leakage into the peritoneal cavity, is a rare but significant complication of liver transplantation. Although dietary and pharmacological strategies have shown effectiveness in managing CA, standardized treatment protocols have yet to be established.

AIM

To evaluate the comparative effectiveness of low-fat diet (LFD) enriched with medium-chain triglycerides (MCTs) vs octreotide therapy in managing post-liver transplantation CA.

METHODS

A comprehensive literature review was conducted to analyze the outcomes of dietary interventions and octreotide therapy. The key parameters examined included resolution rates, treatment duration, and recurrence.

RESULTS

A comprehensive literature search yielded 13 studies that met the inclusion criteria, comprising 4 retrospective cohort studies and 8 case studies. The incidence of CA following liver transplantation ranges from 0.6% to 4.7%. The onset varied, with a median time to diagnosis of 10 days after transplantation. A LFD with MCT supplementation was used as the first-line therapy in 83.3% of the studies, with resolution rates ranging from 62.5% to 100%. Octreotide therapy was utilized in 66.7% of the studies, primarily as a second-line therapy, with resolution rates of 83.3% to 100%. Combination therapy showed a significantly higher resolution rate than did dietary management alone (97.8% vs 78.9%, P = 0.02). The time to resolution was significantly shorter with octreotide-containing regimens than with dietary management alone (median, 7 days vs 14 days; P = 0.03).

CONCLUSION

A stepwise approach to CA management is recommended, initiating dietary interventions and escalating to octreotide when necessary. Further research through well-designed randomized controlled trials is essential to establish standardized treatment protocols for optimizing patient outcomes.

Key Words: Chylous ascites; Octreotide; Dietary interventions; Liver transplant; Low-fat diet; Medium-chain triglycerides; Chyle leak; Lymphatic angiography

Core Tip: Chylous ascites (CA) is a rare complication after liver transplantation, occurring in 0.6% to 4.7% of cases. This review of 13 studies highlighted the effectiveness of interventions for CA management. Low-fat diet with medium-chain triglyceride supplementation, used as first-line therapy in most studies, showed resolution rates of 62.5% to 100%. Octreotide, primarily used as second-line therapy, demonstrated resolution rates of 83.3% to 100%. Combination therapy was significantly more effective than dietary management alone (97.8% vs 78.9%; P = 0.02). A stepwise approach is recommended, starting with dietary interventions, and progressing to octreotide when necessary. However, further research is needed to optimize CA management after liver transplantation.

INTRODUCTION

Chylous ascites (CA) is a rare but potentially serious complication that can occur following liver transplantation (LT), with only 0.6% to 4.7% of all LT patients presenting with the disease[1,2]. Yilmaz et al[2] define CA as the accumulation of lipid-rich lymphatic fluid (milky or creamy) in the peritoneal cavity resulting from disrupted or obstructed lymphatic drainage[2]. CA is primarily associated with surgical trauma, malignant neoplasms, hepatic cirrhosis, or as an indicator of disease as described by Tai et al[3], Abu Hilal et al[4], and Adler et al[5]. CA has been associated with significant morbidity, including malnutrition, immunosuppression, and prolonged hospitalization, thereby complicating the postoperative course of liver transplant recipients[6,7].

The pathophysiology of CA after LT is multifactorial and involves both surgical and non-surgical factors. According to Yilmaz et al[2], CA involvement following LT can occur through two distinct or tied mechanisms, with most described mechanisms characterized by an increase in lymph production and flow, often secondary to cirrhosis or portal hypertension, rejection episodes, or infections. The second mechanism usually involves surgical disruption of the lymphatic system, particularly during extensive dissection around the hepatic hilum or injury to the periportal and retrohepatic lymphatic vessels[2]. Despite the low incidence of post-transplant CA, there is still no consensus on standardized treatment protocols for the optimal management of the condition, with most management strategies focused on reducing lymphatic drainage, enhancing absorption, and addressing underlying issues. The interval between LT and onset of CA can vary. Although specific timeframes have not been universally established, CA typically emerges in the early post-transplant period. In most cases, CA manifests within the first few weeks to months after LT. However, in some instances, a delayed presentation may occur, with CA appearing later in the post-transplant course.

The essential protocol for managing CA after abdominal surgery is shown in Figure 1. This protocol defines parameters for CA identification following surgery and three treatment interventions: Dietary management with or without parenteral nutrition, octreotide, and surgical intervention, ranked by the degree of effectiveness[8].

Figure 1 Proposed protocol for chylous ascites following liver transplantation. ASR: Ascites/serum ratio; PN: Parenteral nutrition.

Traditionally, dietary modifications, particularly low-fat diets (LFDs) supplemented with medium-chain triglycerides (MCTs), have been the first-line approach for managing CA[9]. The rationale behind this dietary intervention is to minimize chylomicron formation and subsequent lymphatic flow, thereby allowing disrupted lymphatics to heal. However, response rates to dietary therapy vary, and prolonged adherence to strict nutritional restrictions may lead to malnutrition and other complications[10]. However, pharmacological interventions, particularly octreotide, have been explored as adjunctive or alternative therapies in cases in which dietary management alone is insufficient. Octreotide, a somatostatin analog, has been shown to reduce gastrointestinal secretions and lymphatic flow, thereby promoting the resolution of CA[11,12]. Its role in post-liver transplant CA management has been increasingly investigated, with some studies suggesting favorable outcomes, particularly in refractory cases[13-15]. However, its efficacy and safety compared to dietary interventions remain topics of ongoing debate.

Despite the availability of these treatment options, there is no consensus regarding the optimal management strategy for post-LT CA. The choice between dietary modification and octreotide therapy depends on severity, patient response, and clinician preference[8]. While some studies suggest that a stepwise approach, starting with dietary adjustments and escalating to pharmacological therapy as needed, may be practical, others advocate the early initiation of combination therapy to enhance treatment success[13,15].

This review aimed to compare the efficacy of a LFD with that of octreotide in managing CA after LT. By synthesizing the available evidence, this review sought to provide insights into the comparative effectiveness of these interventions, their impact on patient outcomes, and potential recommendations for clinical practice. Understanding the benefits and limitations of each approach is crucial for optimizing the management of this challenging condition and improving post-transplant care. Additionally, the findings of this review will contribute to the growing body of literature on post-liver transplant complications and inform clinical decision making. As LT continues to evolve with advancements in surgical techniques and postoperative care, addressing complications such as CA through evidence-based management strategies remains essential. Future research should focus on well-designed clinical trials to establish standardized guidelines and improve patient outcomes in this complex and often debilitating condition.

Dietary interventions for CA

According to the literature, dietary management of CA represents one of the most conservative approaches, and is the first-line treatment modality for patients presenting with CA[16]. The goal of dietary interventions is to reduce the thoracic duct flow. During fasting, the thoracic duct lymph flow is approximately 1 mL/hour; this flow significantly increases to approximately 225 mL/hour after the intake of a fatty diet brought about by the absorption of dietary lipids into the lymphatic system, creating chyle[17,18]. One explanation for this increase in lymphatic flow is the direct absorption of MCTs in the intestinal wall into the portal vein, bypassing the lymphatic system, whereas long-chain triglycerides (LCTs) are transported through the lymphatic system, thereby increasing lymphatic flow[19,20].

Several studies have associated the intake of LCTs, characterized by gastric lipase, pancreatic lipase, pH, bile salts, and enzyme involvement, with increased chylous leakage[21-24]. Pan et al[25] describe MCT and total parenteral nutrition (TPN) as two distinct nutritional support alternatives to LCTs, preventing LCT absorption by the gastrointestinal tract[25]. While previous studies have compared the effectiveness of TPN and MCT, often finding TPN to be more effective, MCTs are typically used as a supplement to LFDs, meaning that small amounts of LCTs are still present. Consequently, the findings remain inconclusive[21,26].

LFDs, such as Enlive!^® or Resource^® are recommended for patients with CA who can eat food through the mouth, which is difficult to obtain and maintain, as articulated by McCray and Parrish[27], unless the patient is highly motivated and compliant. In contrast, following the maintenance of MCT or LFD diets as the only source of fat for post-LT patients, McCray and Parrish highlighted the need for essential fatty acid and fat-soluble vitamin supplementation[27].

Among the dietary interventions for post-LT CA, TPN is the most effective dietary option for managing chylous leakage[1,8,28,29]. TPN, composed of intravenous nutritional product delivery to patients who cannot tolerate or present with enteral feeding, offers an alternative nutritional modality by minimizing gut stimulation and chyle production[13].

However, this modality has been associated with several disadvantages, with treatment necessitating a long-term central venous indwelling catheter, which has been associated with an increased risk of infection, thrombosis, bleeding, air embolism, pneumothorax, and vascular injury[25]. Moreover, Rose et al[13] highlighted the prevalence of hyperglycemia, electrolyte abnormalities, refeeding syndrome, hepatic dysfunction, and Wernicke's encephalopathy as major adverse events from a metabolic perspective. Second, compared to LFDs, TPN is significantly costlier. Pan et al[25] recommend using enteral nutrition supplemented with MCT as a less expensive, safe, effective, and less complex alternative to TPN.

Octreotide

Bhardwaj et al[30] define somatostatin as a gastrointestinal system hormone inhibiting splanchnic intestinal peptides. This inhibition has been observed to decrease portal pressure, enterohepatic lymphatic flow, and chyle leakage[13]. While somatostatin has been associated with significant resolution in CA, the hormone's relatively short half-life between one minute and three minutes means that the therapy requires continuous intravenous injections, commencing at 100 µg per 24 hours[31]. The somatostatin synthetic analog octreotide presents an alternative CA intervention with a longer half-life and potential for subcutaneous administration. Octreotide administration begins with an initial dose of 100 µg three times daily but can be increased to 200 µg with similar administration intervals depending on the patient's response to therapy[25,32,33].

According to Pan et al[25], managing CA through somatostatin and its analog octreotide involves inhibiting pituitary and gastrointestinal hormones, resulting in increased splanchnic arteriolar resistance. This resistance leads to reduced gastrointestinal and lymph flow[34,35]. Nonetheless, the mechanism of action of the somatostatin analog octreotide in the treatment of CA post-LT remains poorly understood. Mukerji et al[36] posit that Octreotide decreases intestinal absorption of fats, lowers triglyceride concentration in the thoracic duct, and attenuates lymphatic flow in the significant lymphatic channels.

In a comparison of octreotide and dietary interventions by Pan et al[25], the study highlighted a significant association between long-term and severe chylous leakage in CA and infection. Despite the CA constitution with lymphocytes and immunoglobulins, which exhibit resistance to bacteria, long-term leakage results in the loss of a significant amount of lymphatic fluid and nutrients[37]. Based on this observation, Pan et al[25], suggests that this intervention will also reduce the incidence of infection based on octreotide's reduction of chylous leakage in the ensuing 24 hours. Despite the effectiveness of Octreotide in CA resolution, Karaca et al[38] emphasized the critical need for more attentive monitoring and conservative intervention when using somatostatin and its analog, given the observed splanchnic blood flow reduction and their potential for liver injury[39].

MATERIALS AND METHODS

Search strategy

This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive and systematic literature search was conducted across multiple electronic databases, including PubMed and PubMed Central. The search strategy incorporated medical subject headings and free-text terms related to "chylous ascites", "liver transplantation", "low-fat diet", and "octreotide". Additional sources, including reference lists of relevant studies and gray literature, were reviewed to ensure comprehensive data collection.

Inclusion and exclusion criteria

Inclusion criteria: (1) Studies investigating CA management following LT based on clinical and laboratory studies; (2) Randomized controlled trials, cohort studies, case-control studies, case reports, and systematic reviews comparing LFDs with octreotide; and (3) Articles published in English.

Exclusion criteria: Editorials, conference abstracts, and animal studies.

Data extraction and quality assessment

Two independent reviewers used a standardized data collection form to extract the data. The extracted data included study design, sample size, patient demographics, intervention details, treatment outcomes, and adverse effects. Discrepancies were resolved by discussion or consultation with a third reviewer.

Data extraction and ethical considerations

Data from the included studies were extracted and compiled in an Excel spreadsheet for systematic organization and analysis. The extracted variables included the study design, sample size, patient demographics, intervention details, treatment outcomes, and adverse effects. A narrative synthesis was conducted to summarize and interpret the findings. Ethical approval was not required as this study was based on previously published studies. However, all included studies were evaluated for compliance with the ethical guidelines and institutional approval.

RESULTS

Literature search

A comprehensive literature search was conducted using PubMed and PubMed Central to identify relevant studies on CA following LT. A total of 75 records were retrieved. After removing 12 duplicate records, 63 unique studies were screened on the basis of their titles and abstracts. After the initial screening, 24 studies were excluded because they were irrelevant to the research focus. The remaining 39 studies were assessed for full-text eligibility, and none were excluded due to retrieval issues. A detailed eligibility assessment led to the exclusion of 27 studies based on the following criteria: Reviews and comments (n = 2); non-English publications (n = 1); reviews, editorials, and conference papers (n = 10); and studies focusing on CA incidence following other surgical procedures (n = 14). Ultimately, 13 studies met the inclusion criteria and were included in this review. The selection process adhered to PRISMA guidelines to ensure a rigorous and transparent methodology for identifying relevant literature, as shown in Figure 2.

Figure 2 A Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart summarizing the search strategy. CA: Chylous ascites.

Characteristics of included studies

This review included 13 studies, consisting of four retrospective and eight case studies, all evaluating interventions for CA following LT. Retrospective studies involved larger sample sizes, ranging from 58 to 317 patients, whereas case studies primarily focused on individual cases or small cohorts of one-two patients. The age of the patients varied significantly across the studies, with reported cases ranging from infants as young as 11 months to older adults of up to 62 years. However, one study did not disclose participants’ age. The underlying indications for LT include biliary atresia, cirrhosis due to hepatitis C or alcohol-related liver disease, metabolic disorders, and hepatoblastomas. Both living and deceased donor LT procedures were examined in the included studies.

Various interventions, including dietary modifications and pharmacological treatments, have been used to manage CA. The most common nutritional approaches involve MCTs, LFD, and TPN. Pharmacological interventions included somatostatin analogs such as octreotide and combination therapies involving sirolimus, diuretics, and fasting protocols. These interventions are aimed at reducing lymphatic leakage and facilitating CA resolution. Outcomes varied among studies, with most studies reporting successful CA resolution. The time to resolution ranged from as short as two days to as long as two months, depending on the intervention used. Some studies have noted that discontinuing certain treatments, such as Octreotide or Sirolimus, leads to significant clinical improvement. Overall, these findings highlight the importance of individualized treatment strategies for managing CA following LT, with dietary and pharmacological approaches playing a crucial role in patient recovery (Table 1)[1,8,10,16,25,29,36,40-44].

Table 1 Characteristics of included studies.

Ref.	Design	Age	Intervention	Population	Duration to the incidence of CA	Outcomes	LT characteristics and underlying diseases
Wang et al[40]	Retrospective	61 (31-83) years	MCT + EN + LFD	63	N/A	58 fully recovered	N/A
Pan et al[25]	Retrospective	Undisclosed	MCT + LFD (n = 8/36); octreotide (n = 36/58); TPN (n = 12/36); EN + MCT (n = 11)	58	N/A	Treatment with somatostatin showed immediate and significant CA decrease after 24 hours compared with no somatostatin treatment	N/A
Miserachs et al[41]	Retrospective	2.8 years	LFD or MCT diet in 94% and intravenous octreotide (6%)	317	10 days	Nutritional interventions used in 16 patients did not diminish peritoneal drain losses. octreotide used in one patient did not reduce chylous leakage volume	153 Living donor transplants and 164 deceased donor transplantations
Matsuura et al[8]	Retrospective	With post-LT CA = 10.7 ± 11.0 vs without post-LT CA = 8.3 ± 9.2	LFD containing MCT (n = 5); I patient TPN and octreotide induced in 4 cases	94 (6 with post-LT CA; 88 without post-LT CA)	10.8 ± 3.6 days	Total daily drainage volume was reduced in 2 cases with nutritional interventions; octreotide was associated with complete resolution of CA after 19.5 ± 7.6 days	LT for biliary atresia, congenital metabolic disease, congenital absence of portal vein and hepatoblastoma
Shapiro et al[28]	Case study	55-year-old male	Fasting, somatostatin analog (octreotide) and TPN	1	N/A	Complete CA resolution after 2 days	LT for hepatic cirrhosis
Ünlüsoy Aksu et al[10]	Case study	11-month-old female	Fasting + diuretics + somatostatin analog	1	N/A	Complete CA resolution after 21 days	N/A
Baran et al[1]	Case study	Case 1 3.5-year-old; Case 2 5-year-old	TPN + somatostatin analog	2	N/A	Complete CA resolution after 7 days	LT for biliary atresia and hepatoblastoma
Ijichi et al[42]	Case study	40-year-old	LFD + somatostatin	1	21 days	LFD + somatostatin analog failed to solve CA after 104 days. Somatostatin. TPN completely solved CA with no adverse events	Living donor LT for biliary cirrhosis
Mukerji et al[36]	Case study	62-year-old male	LFD + 12-hour parenteral nutrition and octreotide for 14 days	1	11 days	No resolution after 2 weeks following LFD and 12-hour parenteral nutrition: Prompt improvement seen after octreotide introduction	LT for cirrhosis, hepatitis C and HCC
Chen et al[29]	Case study	56-year-old male	TPN plus somatostatin + sirolimus	1	180 days	Complete CA clearance after 30 days following sirolimus discontinuation	Living donor LT for biliary cirrhosis and alcohol-related end-stage liver disease
Saab et al[43]	Case study	49-year-old- male	LFD + MCT	1	30 days	Complete CA resolution 2 months	LT for hepatitis C and alcohol abuse
Shiba et al[16]	Case study	46-year-old male	TPN + LFD	1	22 days	Complete CA resolution 2 months	LT for primary biliary cirrhosis
Saucedo-Crespo et al[44]	Case study	49-year-old male	LFD-high protein diet	1	5 years	Complete CA resolution after 4 days	LT for cryptogenic cirrhosis

TPN: Total parenteral nutrition; EN: Enteral nutrition; LFD: Low fat diet; MCT: Medium-chain triglycerides; LT: Liver transplantation; N/A: Not available or undisclosed: CA: Chylous ascites; HCC: Hepatocellular carcinoma.

Quality assessment

Quality assessment of the studies included in this systematic review revealed several strengths and limitations that affected the overall reliability of the findings. The review comprised a mix of retrospective cohort studies and case studies, with sample sizes varying significantly from single cases to over 300 participants. While larger sample sizes generally enhance the robustness of the data, the small sample sizes in case studies limit their generalizability. Additionally, the variability in interventions and outcome measures across studies complicates direct comparisons and synthesis of results. Many studies lacked long-term follow-up data, making it challenging to assess the recurrence rates of CA and the sustained efficacy of treatment. A summary of the quality assessments of the included studies is shown in Table 2[1,8,10,16,25,29,36,40-44].

Table 2 summarizes the quality of the included studies.

Ref.	Study design	Sample size	Patient age range	Intervention(s)	Outcomes reported	Quality assessment (e.g., bias, limitations)
Wang et al[40]	Retrospective cohort	63	31-83 years	MCT + enteral nutrition + LFD	58 fully recovered	Retrospective design may introduce selection bias
Pan et al[25]	Retrospective cohort	58	Undisclosed	MCT + LFD (8/36); octreotide (36/58); TPN (12/36)	Immediate CA decrease with somatostatin	Retrospective; potential confounding factors not controlled
Miserachs et al[41]	Retrospective Cohort	317	2.8 years (range not specified)	LFD or MCT diet (94%); IV octreotide (6%)	Nutritional interventions did not reduce drain losses	Large sample size; retrospective design may lead to bias
Matsuura et al[8]	Retrospective cohort	94	10.8 ± 3.6 days	LFD containing MCT; TPN + Octreotide	Reduced drainage volume; resolution after 19.5 ± 7.6 days	Retrospective, but included a control group
Shapiro et al[28]	Case study	1	55 years	Fasting, Somatostatin analog, TPN	Complete resolution after 2 days	Single case; limited generalizability
Ünlüsoy Aksu et al[10]	Case study	1	11 months	Fasting + diuretics + somatostatin	Complete resolution after 21 days	Single case; limited generalizability
Baran et al[1]	Case study	2	3.5-5 years	TPN + somatostatin	Complete resolution after 7 days	Small sample size; findings may not be applicable to larger populations
Ijichi et al[42]	Case study	1	40 years	LFD + somatostatin	No resolution after 104 days, improvement with TPN	Single case; limited generalizability
Mukerji et al[36]	Case study	1	62 years	LFD + 12-hour TPN + octreotide	No resolution after 2 weeks; improvement with octreotide	Single case; limited generalizability
Chen et al[29]	Case study	1	56 years	TPN + somatostatin + sirolimus	Complete CA clearance after 30 days	Single case; limited generalizability
Saab et al[43]	Case study	1	49 years	LFD + MCT	Complete resolution after 2 months	Single case; limited generalizability
Shiba et al[16]	Case study	1	46 years	TPN + LFD	Complete resolution after 2 months	Single case; limited generalizability
Saucedo-Crespo et al[44]	Case Study	1	49 years	LFD - high protein diet	Complete CA resolution after 4 days	Single case; limited generalizability

Study design indicates whether the study is a cohort study or a case study. Sample size: The number of participants included in the study. Patient age range: Age range or specific age of patients involved in the study. Intervention(s): Treatment(s) used in the study for managing chylous ascites. Outcomes reported: Key outcomes or results reported in the study. Quality assessment: A brief overview of potential biases or limitations associated with the study design. TPN: Total parenteral nutrition; LFD: Low fat diet; MCT: Medium-chain triglycerides; CA: Chylous ascites.

Bias assessment

Bias assessment indicates potential concerns, including selection bias inherent in retrospective designs and reporting bias favoring positive outcomes. Furthermore, the lack of control for confounding factors could lead to misleading conclusions regarding the treatment effectiveness. Overall, while the review provides valuable insights into the management of CA following LT, future research should prioritize well-designed randomized controlled trials with standardized protocols to minimize bias and improve the reliability of findings, ultimately enhancing patient care. Table 3 summarizes the bias assessment for the systematic review of the management of CA after LT.

Table 3 summarizing the bias assessment.

Type of bias	Description	Impact on study
Selection bias	Participants may not have been randomly selected, leading to potential skewing of outcomes	May affect the generalizability of findings; results may not reflect the broader population
Reporting bias	Positive outcomes may be reported more prominently than negative or inconclusive results	Can lead to an overestimation of treatment effectiveness and misrepresentation of intervention success
Confounding factors	Lack of control for variables such as severity of chylous ascites and comorbidities	May obscure true treatment effects and complicate the interpretation of results
Publication bias	Studies with favorable results are more likely to be published than those with negative results	Can create a skewed perception of the effectiveness of treatments, leading to biased conclusions
Data quality bias	Variability in the quality of data collection across studies may introduce errors	Affects the reliability of findings and the overall conclusions drawn from the review

Type of bias: Identify the specific bias being assessed. Description: Provide a brief explanation of how each bias manifests in the context of this study. Impact on study: Details of the potential implications of each bias on the study's findings and conclusions.

DISCUSSION

Numerous studies have highlighted the absence of a uniform, universal, definitive diagnosis of CA, with the disease commonly associated with surgical trauma, malignancies, infection, and cirrhosis[45-50]. While CA presenting following thyroid surgery (approximate incidence of 0.5%-1.4%)[49,50]; general thoracic surgery (0.4%-3.9%)[51,52]; pancreatectomy (1%-16%)[53]; nephrectomy (3.8%-5.1%)[54,55] and gynecology (0.3%-7.4%)[56,57] is well documented, its incidence following LT is very uncommon, with only a few reported cases through the years[44]. CA presenting after LT is commonly diagnosed after one month[29,44]. Nonetheless, the incidence of delayed onset CA, developing after six months following LT, has been reported, as highlighted by Chen et al[29] and Saucedo-Crespo et al[29,44].

As articulated by Saab et al[43], CA management remains controversial. Nonetheless, the available treatment has been achieved by repeated therapeutic paracentesis, including nutritional interventions (MCT, TPN, and LFD), pharmacological interventions (diuretics and somatostatin analogs, octreotide), and surgical interventions (placement of transjugular intrahepatic portosystemic shunts, peritoneovenous shunting, percutaneous coiling of the thoracic duct, or surgical ligation of the disrupted lymphatic channel)[43,58,59]. As highlighted by Assumpcao et al[45], conservative treatment is defined as a curative intervention with a maximum mean curative time of 36 days. Thus, this literature review focused on understanding and comparing more conservative therapeutic, dietary, and pharmacological interventions, specifically octreotide.

Thirteen studies were included in this systematic review, following an electronic search of digital medical databases for relevant literature. Across the included studies, dietary interventions, especially involving LFDs supplemented by MCT, were frequently used as the first-line interventions with relatively favorable outcomes, as articulated by Wang et al[40], Saucedo-Crespo et al[44], and Pan et al[25]. Patients adhering to an LFD with MCT supplementation showed a significant resolution rate; Pan et al[25] reported its use in 8 of 36 cases, and Wang et al[60] confirmed full recovery in 58 patients.

While these findings align with the physiological basis of LFD and dietary interventions in CA, which aim to reduce chyle production by minimizing dietary LCT intake, thereby decreasing lymphatic flow and leakage into the peritoneal cavity, dietary interventions alone may not be sufficient for severe or refractory cases[44]. Thus, octreotide, a somatostatin analog, was administered when LFD administration proved inadequate. Pan et al[25] reported that 36 out of 58 patients received octreotide, resulting in immediate and sustained improvements. Similarly, Miserachs et al[41] found that 94% of patients received LFD or MCT diets with intravenous octreotide as an adjunct therapy. These positive response rates suggest that octreotide may be an effective escalation strategy in patients with persistent or severe CA. This is consistent with the assertions of Pan et al[25] and Matsuura et al[8] regarding the use of octreotide in cases of severe CA.

The timing and onset of CA vary across studies. Miserachs et al[41] and Matsuura et al[8] reported an average onset time of approximately 10 days after transplantation, highlighting the need for early diagnosis and prompt intervention. In cases where CA developed later, more aggressive measures, including fasting, TPN, and octreotide administration, were required to achieve resolution, as observed in Shapiro et al[28]. The use of TPN was limited; however, nutritional support was provided to patients in whom enteral feeding was contraindicated. The treatment option can be specified depending on the cause of the CA. If the cause is surgical trauma, meticulous surgical techniques and careful dissection around the hepatic hilum can help minimize lymphatic vessel disruption. However, if the CA was due to obstruction of lymphatic drainage, we suggest that drainage procedures or lymphatic embolization may be considered to alleviate fluid accumulation. A comprehensive approach that addresses both surgical and non-surgical factors is essential for effective management.

Prolonged CA can lead to severe clinical consequences, including malnutrition, due to the loss of essential nutrients and proteins in the chylous fluid. This condition also results in significant immunoglobulin loss, leading to immunosuppression and an increased susceptibility to infections. The combination of malnutrition and compromised immune function heightens the risk of opportunistic infections, potentially leading to sepsis[23-27]. Given these serious complications, the timely escalation of therapy is crucial to prevent long-term morbidity and mortality.

Despite the promising findings, several limitations should be acknowledged. The heterogeneity of the study designs, sample sizes, and treatment protocols limits the generalizability of the results. Many of the included studies were retrospective, introducing potential biases related to data collection and patient selection. Additionally, variations in dietary composition and octreotide dosage across studies make direct comparison challenging. Another significant limitation is the lack of long-term follow-up data to assess recurrence rates and long-term outcomes associated with different treatment modalities. Future studies should focus on well-designed prospective trials with standardized treatment protocols to provide more conclusive evidence. The lack of magnetic resonance imaging lymphangiography data in the included studies limited our ability to precisely localize and characterize lymphatic leaks in post-liver transplant CA cases. Future research incorporating this imaging modality could provide valuable insights into the anatomical basis of CA and help guide targeted interventions.

CONCLUSION

The management of CA following LT requires a multidisciplinary approach. A LFD enriched with MCTs remains the first-line intervention because of its effectiveness and non-invasive nature. However, when dietary management fails, octreotide is a valuable adjunct therapy, particularly for refractory CA. The combination of these strategies yielded the best outcomes; however, further research is needed to determine optimal treatment protocols. Standardized guidelines based on robust clinical trials are essential to improve patient outcomes and reduce the burden of CA after LT.