Pathogenesis and treatment of parenteral nutrition-associated liver disease

BACKGROUND: Parenteral nutrition-associated liver disease (PNALD) has been common in patients who require long-term parenteral nutrition. PNALD develops in 40%-60% of infants on long-term parenteral nutrition compared with 15%-40% of adults on home parenteral nutrition for intestinal failure. The pathogenesis of PNALD is multifactorial and remains unclear There is no specific treatment. Management strategies for its prevention and treatment depend on an understanding of many risk factors. This review aims to provide an update on the pathogenesis and treatment of this disease. DATA SOURCES: A literature search was performed on the MEDLINE and Web of Science databases for articles published up to October 2011, using the keywords: parenteral nutrition associated liver disease, intestinal failure associated liver disease lipid emulsions and fish oil. The available data reported in the relevant literatures were analyzed. RESULTS: The literature search provided a huge amount of evidence about the pathogenesis and management strategies on PNALD. Currently, lack of enteral feeding, extended duration of parenteral nutrition, recurrent sepsis, and nutrient deficiency or excess may play important roles in the pathogenesis of PNALD. Recent studies found that phytosterols present as contaminants in soy-based lipid emulsions, are also an important factor in the pathogenesis. Moreover, the treatment of PNALD is discussed. CONCLUSIONS: The use of lipid emulsions, phytosterols in particular, is associated with PNALD. Management strategies for the prevention and treatment of PNALD include consideration of early enteral feeding, the use of specialized lipid emulsions such as fish oil emulsions, and isolated small bowel or combined liver and small bowel transplantation. A greater understanding of the pathogenesis of PNALD has led to promising interventions to prevent and treat this condition. Future work should aim to better understand the mechanisms of PNALD and the long-term outcomes of its treatment.

Fish oil-containing lipid emulsions prevention on parenteral nutrition-associated cholestasis in very low birth weight infants:a meta-analysis

Background The effect of fish oil-containing lipid emulsions on preventing parenteral nutrition-associated cholestasis(PNAC)in very low birth weight(VLBW)infants is not known.Thus,we conducted a meta-analysis to identify any preven-tion effect.Methods PubMed,EMBASE,and CENTRAL were searched up to 26 January 2021 for studies related to the preventive effect of fish oil-containing lipid emulsions and fish oil-free lipid emulsions on cholestasis in VLBW infants.Revman 5.3 was used to synthesize the results.A fixed-effect model was used to summarize the data when the heterogeneity was non-significant(I2<50%),and a random-effects model was used when the heterogeneity was significant(I2>50%).Results Of 728 articles,11 randomized controlled trials met the inclusion criteria.The meta-analysis indicated that fish oil-containing lipid emulsion reduced the occurrence of PNAC significantly with risk ratio(RR)=0.53,95%confidence interval(CI)0.36-0.80,P=0.002.The heterogeneity was non-significant with I2=23%.Subgroup analysis based on par-enteral nutrition duration and median birth weight was performed.The synthesis results for patients with parenteral nutri-tion duration exceeding 14 days revealed I2=35%(P=0.15)and pooled RR=0.47,95%CI 0.30-0.73,P=0.0008;and for patients with duration less than 14 days revealed I2=0%(P=0.72)and pooled RR=1.14,95%CI 0.39-3.35,P=0.81.The synthesis for patients with birth weight more than 1000 g revealed I2=0%(P=0.41)and pooled RR=0.55,95%CI 0.26-1.18,P=0.12;and for patients with birth weight below 1000 g revealed I2=44%(P=0.11)and pooled RR=0.53,95%CI 0.33-0.85,P=0.009.Conclusions The fish oil-containing lipid emulsion can reduce the occurrence of PNAC in VLBW infants based on the avail-able original randomized controlled trial studies,especially for patients with parenteral nutrition duration exceeding 14 days and extremely low birth weight infants.Future studies should be performed before a definitive conclusion can be established.

Fish oil-based lipid emulsion:current updates on a promising novel therapy for the management of parenteral nutrition-associated liver disease

Intestinal failure is characterized by loss of enteral function to absorb necessary nutrients and water to sustain life.Parenteral nutrition(PN)is a lifesaving therapeutic modality for patients with intestinal failure.Lifelong PN is also needed for patients who have short bowel syndrome due to extensive resection or a dysmotility disorder with malabsorption.However,prolonged PN is associated with short-term and long-term complications.Parenteral nutrition-associated liver disease(PNALD)is one of the long-termcomplications associated with the use of an intravenous lipid emulsion to prevent essential fatty acid deficiency in these patients.PNALD affects 30–60%of the adult population on long-term PN.Further,PNALD is one of the indications for isolated liver or combined liver and intestinal transplantation.There is no consensus on how to manage PNALD,but fish oil-based lipid emulsion(FOBLE)has been suggested to play an important role both in its prevention and reversal.There is significant improvement in liver function in those who received FOBLE as lipid supplement compared with those who received soy-based lipid emulsion.Studies have also demonstrated that FOBLE reverses hepatic steatosis and reduces markers of inflammation in patients on long-term PN.Future prospective studies with larger sample sizes are needed to further strengthen the positive role of FOBLE in PNALD.