Effect of a 12-week nutritional intervention in the food intake of patients on the waiting list for liver transplantation: A secondary analysis of a randomized controlled trial.

BACKGROUND: Inadequate food intake contributes to malnutrition in patients with cirrhosis on the waiting list for liver transplantation (LTx). OBJECTIVE: To evaluate food intake during 12 weeks of nutritional follow-up and assess factors independently associated with the difference between energy and protein intake in LTx patients. METHODS: A secondary analysis of data from a randomized controlled trial that evaluated the effects of Beta-Hydroxy-Beta-Methylbutyrate (HMB) supplementation and nutritional intervention in patients on a liver transplant waiting list. Dietary guidelines for patients with cirrhosis were used to prescribe the nutritional plan (35 kcal/kg; 1.5 g/kg dry weight for protein) and to evaluate the nutritional goals (30 kcal/kg; 1.2 g/kg dry weight for protein; late evening snack) and nutritional counseling dietary follow-ups were performed in each evaluation. Food intake was assessed in six moments: Baseline, week 0 (W0), week 2 (W2), week 4 (W4), week 8 (W8), and week 12 (W12). RESULTS: Forty-seven patients (55.0 ± 10.6y; 72.3% male) were evaluated. Only 25.5% (n = 12) of patients achieved nutritional goals at the end of the study. The mean energy intake at Baseline was 1782 ± 784 kcal (27.6 ± 13.2 kcal/kg) without difference between moments. The protein intake increased between W0 [63.4 ± 29.8g; 0.8(0.2-2.2 g/kg)] and W8 [72.0 ± 28.0g; 1.0(0.4-2.6 g/kg); p = 0.03; p = 0.03, respectively]. The consumption of cholesterol, calcium, phosphorus, magnesium, iron, and niacin increased (p < 0.05), as well as the consumption of legumes; roots and tubers; dairy; and meat, poultry and fish groups through time (p < 0.05). The percentage of patients that consumed a late evening snack rised from 40.4% (Baseline) to 76.6% (W8) (p < 0.001). The presence of ascites, nourished patients, frailty index classification, short physical performance battery score, systemic symptoms, and emotional function in the Quality of Life Test were independently associated with the energy intake difference between W12 and Baseline (p < 0.05). Diabetes mellitus, patients with moderately malnourishment, poor performance, fatigue, systemic symptoms, and emotional function in the Quality of Life Test were independently associated with the difference in protein intake between W12 and Baseline (p < 0.05). CONCLUSION: Patients on the liver transplant waiting list showed slight food intake improvement during the follow-up, but few met nutritional guidelines. Various clinical and nutritional factors independently affected energy and protein intake from W12 to Baseline.

Human Umbilical Cord Blood-Derived Mesenchymal Stem Cell Transplantation for Patients with Decompensated Liver Cirrhosis.

BACKGROUND OR PURPOSE: Although human umbilical cord blood-derived mesenchymal stem cell transplantation (HUCB-MSCT) resulted in a good short-term therapeutic effect on patients with decompensated liver cirrhosis (DLC), the long-term survival remained unclear. This study aimed to evaluate the impact of HUCB-MSCT on long-term outcomes in patients with DLC. METHODS: This retrospective cohort study included hospitalized patients with decompensated cirrhosis in Liuzhou Hospital of Traditional Chinese Medicine between November 2010 and February 2013. The primary outcome was overall survival (OS). The secondary outcomes were 3-year and 5-year survival rates and the occurrence rate of hepatocellular carcinoma (HCC). RESULTS: A total of 201 subjects were enrolled, including 36 patients who underwent HUCB-MSCT (SCT group) and 165 patients who did not (non-SCT group). After PSM (1:2), there were 36 patients in the SCT group and 72 patients in non-SCT group. The 3-year and 5-year survival rates of the two groups were 83.3% vs. 61.8% and 63.9% vs. 43.6%, and median OS time was 92.50 and 50.80 months, respectively. HUCB-MSCT treatment was found to be an independent beneficial factor for patient OS (hazard ratio = 0.47; 95% CI: 0.29-0.76; P = 0.002). There was no significant difference in the occurrence rate of HCC between the two groups (P = 0.410). DISCUSSION OR CONCLUSIONS: HUCB-MSCT may improve long-term OS without increasing the occurrence of HCC in patients with DLC. TRIAL REGISTRATION: The Chinese Clinical Trial Registry (ChiCTR2100047550).

Research Progress in Chinese Medicine Preparations for Promoting Blood Circulation and Removing Blood Stasis for Cirrhotic Patients with Portal Vein Thrombosis Following Splenectomy.

This article presented an overview of the therapeutic effects of Chinese medicine (CM) preparations for promoting blood circulation and removing blood stasis for patients with portal vein thrombosis (PVT) after splenectomy. Based on published clinical researches of CM preparations for PVT after splenectomy in patients with cirrhotic portal hypertension (CPH), this paper evaluated the incidence of PVT, and explored potential active components and mechanisms of CM preparations. Safflower Yellow Injection, Danshen Injection () Danhong Injection (), and Compound Danshen Dropping Pill () achieved good curative effect alone or combined with anticoagulant therapy. In addition, Compound Biejia Ruangan Tablet () and Anluo Huaxian Pill () can also significantly improve the hemodynamic disorders of portal vein system in patients with cirrhosis. Considering the role of CM preparations in ameliorating the incidence of PVT after splenectomy in patients with CPH, we suggested that future research should provide more attention to CM alone or CM combined with anticoagulant for cirrhosis with PVT.

Recommendations and Guidance on Nutritional Supplementation in the Liver Transplant Setting.

Malnutrition is a frequent complication in patients with cirrhosis and liver transplant (LT) candidates. It is highly related to sarcopenia, and their implications in morbidity and mortality go beyond the waiting list period throughout the post-LT. However, there are no specific interventions defined by guidelines regarding the kind or the timing of the nutritional intervention to improve LT outcomes. Results from studies developed in the LT setting and evaluating their impact on the LT candidates or recipients are discussed in this review, and new research lines are presented.

Nutrition Support in Liver Transplantation and Postoperative Recovery: The Effects of Vitamin D Level and Vitamin D Supplementation in Liver Transplantation.

Vitamin D plays an important role in the arena of liver transplantation. In addition to affecting skeletal health significantly, it also clinically exerts immune-modulatory properties. Vitamin D deficiency is one of the nutritional issues in the perioperative period of liver transplantation (LT). Although vitamin D deficiency is known to contribute to higher incidences of acute cellular rejection (ACR) and graft failure in other solid organ transplantation, such as kidneys and lungs, its role in LT is not well understood. The aim of this study was to investigate the clinical implication of vitamin D deficiency in LT. LT outcomes were reviewed in a retrospective cohort of 528 recipients during 2014-2019. In the pre-transplant period, 55% of patients were vitamin-D-deficient. The serum vitamin D level was correlated with the model for end-stage liver disease (MELD-Na) score. Vitamin D deficiency in the post-transplant period was associated with lower survival after LT, and the post-transplant supplementation of vitamin D was associated with a lower risk of ACR. The optimal vitamin D status and vitamin D supplementation in the post-transplant period may prolong survival and reduce ACR incidence.

Protective effects of coffee consumption following liver transplantation for hepatocellular carcinoma in cirrhosis.

BACKGROUND: Increasing evidence suggests that coffee consumption might protect against hepatocellular carcinoma (HCC) and liver cirrhosis-associated death risk. Caffeine is a natural antagonist to extracellular adenosine and exhibits experimental tumoricidal activity. AIM: To evaluate if coffee consumption has beneficial effects on HCC recurrence after orthotopic liver transplantation (OLT). METHODS: Coffee consumption of patients before and after OLT for HCC was assessed and correlated with HCC recurrence. HepG2 cells were analysed for proliferation and metastasis potential after treatment with adenosine, in the presence or absence of adenosine receptor antagonists. Expression of adenosine receptors was determined, and known adenosine-mediated cancer pathways inclusive of MAPK and NF-kappa B were tested. RESULTS: Ninety patients underwent OLT for HCC. Sixteen (17.8%) patients experienced HCC recurrence after median time of 11.5 months (range 1-40.5). For overall survival postoperative coffee intake emerged as major factor of hazard reduction in a multivariate analysis (HR = 0.2936, 95% CI = 0.12-0.71, P = 0.006). Those with such postoperative coffee intake (≥3 cups per day) had a longer overall survival than those who consumed less or no coffee: M = 11.0 years, SD = 0.52 years vs. M = 7.48 years, SD = 0.76 years = 4.7, P = 0.029). CONCLUSIONS: Coffee consumption is associated with a decreased risk of HCC recurrence and provides for increased survival following OLT. We suggest that these results might be, at least in part, associated with the antagonist activity of caffeine on adenosine-A2AR mediated growth-promoting effects on HCC cells.

Liver Cirrhosis From Chronic Hypervitaminosis A Resulting in Liver Transplantation: A Case Report.

Herein we report a case of liver dysfunction caused by consumption of vitamin A supplements leading to liver transplantation. The patient was a 48-year-old male with a medical history of congenital ichthyosiform erythroderma in treatment with vitamin A until 12 years of age, at which point he discontinued the supplements because he had developed ascites. Liver cirrhosis was diagnosed as secondary to hypervitaminosis A on the basis of histologic examination of liver biopsy and the absence of other potential causes of chronic liver disease. Despite interruption of administration of vitamin A, the patient continued to deteriorate over the years, with development of portal hypertension signs. His medical conditions were aggravated with the development of hepatic insufficiency manifested by refractory ascites, renal insufficiency, and severe encephalopathy and he underwent orthotopic liver transplantation, followed by disappearance of all signs of portal hypertension. This case highlights the need to take a careful history of consumption of vitamin A when evaluating a patient with liver failure.

Use of Iodized Oil and Gelatin Sponge Embolization in Splenic Artery Coiling Reduces Bleeding from Laparoscopic Splenectomy for Cirrhotic Portal Hypertension Patients with Complicating Hypersplenic Splenomegaly: A Comparative Study.

OBJECTIVE: Laparoscopic splenectomy (LS) is relatively contraindicated in cirrhotic portal hypertension (CPH) patients with complicating hypersplenic splenomegaly (HS). This study aimed to evaluate the effectiveness and safety of incorporation of iodized oil and gelatin sponge embolization to conventional splenic artery embolization (cSAE) with coiling in CPH/HS patients undergoing LS. PATIENTS AND METHODS: Between April 2012 and March 2014, eligible CPH/HS patients (n = 56) were assigned to preoperative modified SAE (mSAE) with LS (mSAE+LS group, n = 16), cSAE with LS (cSAE+LS group, n = 20) or LS alone (LS group, n = 20). Main outcome measures included frequency of conversion to laparotomy, operative time, intraoperative bleeding, and transfusion. RESULTS: The three groups had similar baseline characteristics (all P > .05). mSAE and cSAE similarly decreased LS conversion frequency (mSAE+LS versus cSAE+LS versus LS, 0.0% versus 10.0% versus 30.0%, P = .030) and operative time (155 ± 23 minutes versus 170 ± 26 minutes versus 221 ± 42 minutes, P < .001) compared with LS alone. mSAE significantly reduced bleeding (178 ± 22 mL versus 250 ± 27 mL versus 328 ± 67 mL, P < .001) compared with cSAE and LS alone. The three groups had similar postoperative recovery times and surgical morbidities (all P > .05). CONCLUSIONS: In CPH/HS patients, preoperative SAE reduced LS conversion frequency and reduced operative time compared with LS alone, while mSAE further decreased volume of blood loss.

Análisis de los resultados a largo plazo del trasplante hepático de donante vivo en adulto / Analysis of the long-term results of living donor liver transplantation in adults

Introducción: El trasplante hepático de donante vivo (THDV) es una alternativa al trasplante convencional dados sus excelentes resultados. El objetivo de este trabajo es la evaluación de los resultados a largo plazo en los receptores de THDV. Métodos: Cien receptores consecutivos de THDV del Hospital Clínic de Barcelona desde marzo de 2000 hasta octubre de 2015. La indicación principal de trasplante fue hepatopatía terminal (58%) seguido de hepatocarcinoma (41%). Los injertos consistieron en un 95% del hígado derecho del donante y en un 5% del izquierdo. Resultados: Tras una mediana de seguimiento de 65,5 meses, la supervivencia global a uno, 3 y 5 años de los pacientes y de los injertos fue del 93%, 80% y 74% y del 90%, 76% y 71% respectivamente, con una tasa de retrasplante global del 9%. La complicación a largo plazo más frecuente fue una estenosis biliar (40%), con un tiempo medio de aparición de 13,5±12 meses, que comportó repetidos ingresos y una media de 1,9±2 abordajes endoscópicos y 3,5±3 abordajes radiológicos por paciente. El tratamiento definitivo fue dilatación radiológica en un 40% de los casos, intervención quirúrgica en un 22,5% y retrasplante en un 7,5%. Conclusiones: Dados los resultados a largo plazo, el THDV se confirma como una alternativa al trasplante convencional. Sin embargo, la alta tasa de complicaciones biliares tardías conlleva repetidos ingresos y tratamientos invasivos que, si bien no comprometen la supervivencia, pueden afectar la calidad de vida del paciente (AU)

Introduction: Living donor liver transplantation (LDLT) is an alternative to conventional transplantation given its excellent results. The aim of this study is to evaluate long-term outcomes in LDLT recipients. Methods: 100 consecutive THDV recipients from the Hospital Clínic of Barcelona from March 2000 to October 2015 were included. The main indication for transplantation was end-stage liver disease (58%) followed by hepatocellular carcinoma (41%). 95% of grafts consisted of the right liver of the donor and the 5% of the left liver. Results: After a median follow-up of 65.5 months, patient and graft survival at 1, 3, and 5 years was 93%, 80% and 74% and 90%, 76%, and 71%, respectively. The overall re-transplant rate was 9%. The most common long-term complication was biliary stenosis (40%) with an average time of onset of 13.5±12 months, with repeated admissions and an average of 1.9±2 endoscopic procedures and 3.5±3 Radiological procedures per patient. The definitive treatment was radiological dilation in 40% of cases, surgical intervention in 22.5% and re-transplantation in 7.5%. Conclusions: Given the long-term results, LDLT is confirmed as an alternative to conventional transplantation. However, the high rate of late biliary complications involves repeated admissions and invasive treatments that, while not compromising survival, can affect the patient's quality of life (AU)

Liver transplantation from a deceased donor with ß-thalassemia intermedia is not contraindicated: A case report.

The use of extended criteria donors who might have previously been deemed unsuitable is an option to increase the organ supply for transplantation. This report presents a pediatric case of a successful liver transplantation from a donor with ß-thalassemia intermedia. A patient, 6-year-old female, with a diagnosis of cryptogenic liver cirrhosis underwent deceased donor liver transplantation from a thalassemic donor. Extreme hyperferritinemia was detected shortly after transplantation. The most probable cause of hyperferritinemia was iron overload secondary to transplantation of a hemosiderotic liver. Hepatocellular injury due to acute graft rejection might have contributed to elevated ferritin levels by causing release of stored iron from the hemosiderotic liver graft. Iron chelation and phlebotomy therapies were started simultaneously in the early postoperative period to avoid iron-related organ toxicity and transplant failure. Follow-up with monthly phlebotomies after discharge yielded a favorable outcome with normal transplant functions. Thalassemia intermedia patients can be candidates of liver donors to decrease pretransplant waitlist mortality. After transplantation of a hemosiderotic liver, it is important to monitor the recipient in terms of iron overload and toxicity. Early attempts to lower iron burden including chelation therapy and/or phlebotomy should be considered to avoid organ toxicity and transplant failure.

n-3 fatty acid-based parenteral nutrition improves postoperative recovery for cirrhotic patients with liver cancer: A randomized controlled clinical trial.

BACKGROUND & AIMS: A new lipid emulsion enriched in n-3 fatty acid has been reported to prevent hepatic inflammation in patients following major surgery. However, the role of n-3 fatty acid-based parenteral nutrition for postoperative patients with cirrhosis-related liver cancer is unclear. We investigated the safety and efficacy of n-3 fatty acid-based parenteral nutrition for cirrhotic patients with liver cancer followed hepatectomy. METHODS: A prospective randomized controlled clinical trial (Registered under ClinicalTrials.gov Identifier no. NCT02321202) was conducted for cirrhotic patients with liver cancer that underwent hepatectomy between March 2010 and September 2013 in our institution. We compared isonitrogenous total parenteral nutrition with 20% Structolipid and 10% n-3 fatty acid (Omegaven, Fresenius-Kabi, Germany) (treatment group) to Structolipid alone (control group) for five days postoperatively, in the absence of enteral nutrition. RESULTS: We enrolled 320 patients, and 312 (97.5%) were included in analysis (155 in the control group and 157 in the treatment group). There was a significant reduction of morbidity and mortality in the treatment group, when compared with the control group (total complications 78 [50.32%] vs. 46 [29.30%]; P < 0.001, total infective complications, 30 [19.35%] vs. 15 [9.55%]; P = 0.014), overall mortality (5 [3.23%] vs. 1 [0.64%]; P = 0.210), and hospital stay (12.56 ± 3.21 d vs. 10.17 ± 3.15 d; P = 0.018). CONCLUSIONS: We found that addition of n-3 fatty acid-based parenteral nutrition significantly improved postoperative recovery for cirrhotic patients with liver cancer following hepatectomy, with a significant reduction in overall mortality and length of hospital stay.

Effects of branched-chain amino acid supplementation after radiofrequency ablation for hepatocellular carcinoma: A randomized trial.

OBJECTIVE: Maintenance of liver function is important for better outcomes after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). The aim of this study was to examine the effects of oral branched-chain amino acid (BCAA) supplementation on liver function, intrahepatic recurrence rate, and incidence of complications after RFA for HCC. METHODS: Patients with cirrhosis who underwent RFA were enrolled between August 2009 and April 2012, randomized to oral supplementation with Aminoleban EN (BCAA group) or diet alone (control group), and followed to determine changes in serum parameters and health status. Patients in the BCAA group were instructed to ingest a packet of Aminoleban EN twice daily. Levels of physical and mental stress were assessed using the Short Form-8 health survey. Oral BCAA and dietary interventions were initiated 2 wk before local therapy, and contrast-enhanced computed tomography was performed every 3 mo to assess recurrence. RESULTS: We evaluated 25 patients in the BCAA group and 26 in the control group. The median follow-up period was 3.9 y (736-1818 d). There were no significant differences between the two groups in basal characteristics. Complications were less frequent in the BCAA group (P = 0.03). Event-free survival was significantly higher in the BCAA group, whereas the intrahepatic recurrence rate was significantly lower (P = 0.04 and 0.036, respectively). A significant improvement in the Short Form-8 mental component score was observed in the BCAA group only (P < 0.01). CONCLUSION: Aminoleban EN may be beneficial for cirrhotic patients after RFA to relieve mental stress and reduce the risks for intrahepatic recurrence and complications.

Prevalence of fat-soluble vitamin (A, D, and E) and zinc deficiency in patients with cirrhosis being assessed for liver transplantation.

PURPOSE: To evaluate the prevalence of fat-soluble vitamin (A, D, and E) and zinc deficiency in patients with cirrhosis being assessed for liver transplantation and the correlations between vitamin deficiencies, nutritional markers, and severity of liver disease. METHODS: This is a single centre retrospective study. Serum vitamin A, D, E, and zinc levels were collected in adult patients being assessed for liver transplantation between January and July 2012. Patient and liver disease demographics, nutritional markers, Child-Pugh score, and MELD-Na score were collected. Fisher's exact test and multiple variable logistic regression was used for statistical analysis. RESULTS: A total of 109 adult patients were assessed for liver transplantation during the 6-month period. The mean patient age was 54 ± 10 years and 66% were males. Mean BMI was 27 ± 6 kg/m2, pre-albumin was 0.10 ± 0.07 g/L, albumin was 33 ± 6 g/L, total bilirubin was 48 ± 61 mmol/L, MELD-Na score was 16 ± 5 (range 6-33), and 15% had hepatocellular carcinoma. The Child-Pugh score was A in 29%, B in 54%, and C in 17%. The causes of liver disease were hepatitis C in 36%, alcohol in 20%, non-alcoholic fatty liver disease in 17%, and other in 27%. The mean vitamin A level was 0.88 ± 0.86 umol/L, D was 69 ± 52 nmol/L, E was 24 ± 17 umol/L, and zinc was 477 ± 145 ug/L. Vitamin A deficiency was prevalent in 77%, D in 63%, E in 37%, and zinc in 84%. On multiple variable analysis, low albumin (OR = 0.78, 95% CI = 0.65-0.94, p = 0.0069) was a predictor of vitamin A deficiency ; cholestatic liver enzyme elevation (OR = 3.53, 95%CI = 1.40-8.89, p = 0.0073) and low albumin (OR = 0.83, 95%CI = 0.73-0.94, p = 0.0032) were predictors of vitamin D deficiency ; low albumin (OR = 0.85, 95% CI = 0.74-0.97, p = 0.015) was a predictor of vitamin E deficiency ; and age (OR = 0.83, 95% CI = 0.72-0.96, p = 0.012), low albumin (OR = 0.59, 95% CI = 0.42-0.84, p = 0.0036), and high MELD-Na (1.43, 95% CI = 1.05-1.94, p = 0.021) were predictors of zinc deficiency. Vitamin A (p = 0.0034), D (p = 0.020), E (p = 0.012), and zinc (p<0.001) deficiency correlated with a higher Child-Pugh. CONCLUSION: Low albumin was a recurrent predictor of fat-soluble vitamin (A, D, and E) and zinc deficiency while other predictors varied depending on the vitamin or mineral. Further studies need to be conducted on fat-soluble vitamin and zinc supplementation in deficient patients with cirrhosis to assess clinical outcomes.

Coffee consumption protects against progression in liver cirrhosis and increases long-term survival after liver transplantation.

BACKGROUND: Therapeutic options to treat progression of end-stage liver disease (ESLD) or improve long-term survival after liver transplantation remain scarce. We investigated the impact of coffee consumption under these conditions. METHODS: We recorded coffee consumption habits of 379 patients with ESLD awaiting liver transplantation and 260 patients after liver transplantation. Survival was analyzed based on coffee intake. RESULTS: One hundred ninety-five patients with ESLD consumed coffee on a daily basis, while 184 patients did not. Actuarial survival was impaired (P = 0.041) in non-coffee drinkers (40.4 ± 4.3 months, 95% confidence interval [CI]: 32.0-48.9) compared with coffee drinkers (54.9 ± 5.5 months, 95% CI: 44.0-65.7). In subgroup analysis, the survival of patients with alcoholic liver disease (ALD; P = 0.020) and primary sclerosing cholangitis (PSC; P = 0.017) was increased with coffee intake while unaffected in patients with chronic viral hepatitis (P = 0.517) or other liver disease entities (P = 0.652). Multivariate analysis showed that coffee consumption of PSC and ALD patients retained as an independent risk factor (odds ratio [OR]: 1.94; 95% CI: 1.15-3.28; P = 0.013) along with MELD score (OR: 1.13; 95% CI: 1.09-1.17; P = 0.000). Following liver transplantation, long-term survival was longer in coffee drinkers (coffee: 61.8 ± 2.0 months, 95% CI: 57.9-65.8) than non-drinkers (52.3 ± 3.5 months, 95% CI: 45.4-59.3; P = 0.001). CONCLUSIONS: Coffee consumption delayed disease progression in ALD and PSC patients with ESLD and increased long-term survival after liver transplantation. We conclude that regular coffee intake might be recommended for these patients.

The prescription of medical cannabis by a transitional pain service to wean a patient with complex pain from opioid use following liver transplantation: a case report.

PURPOSE: The purpose of this case report is to describe a patient with a preoperative complex pain syndrome who underwent liver transplantation and was able to reduce his opioid consumption significantly following the initiation of treatment with medical cannabis. CLINICAL FEATURES: A 57-yr-old male with a history of hepatitis C cirrhosis underwent liver transplantation. Preoperatively, he was taking hydromorphone 2-8 mg⋅day(-1) for chronic abdominal pain. Postoperatively, he was given intravenous patient-controlled analgesia through which he received hydromorphone 30 mg⋅day(-1). Our multidisciplinary Transitional Pain Service was involved with managing his moderate to severe acute postsurgical pain in hospital and continued with weaning him from opioid medications after discharge. It was difficult to wean the patient from opioids, and he was subsequently given medical cannabis at six weeks postoperatively with remarkable effect. By the fifth postoperative month, his use of opioids had tapered to 6 mg⋅day(-1) of hydromorphone, and his functional status was excellent on this regimen. CONCLUSION: Reductions in opioid consumption were achieved with the administration of medical cannabis in a patient with acute postoperative pain superimposed on a chronic pain syndrome and receiving high doses of opioids. Concurrent benefits of initiating medical cannabis may include improvements in pain profile and functional status along with reductions in opioid-related side effects. This highlights the potential for medical cannabis as an adjunct medication for weaning patients from opioid use.

EFFECTIVENESS AND OUTCOMES OF CURRENT PRACTICE IN TREATING VITAMIN D DEFICIENCY IN PATIENTS LISTED FOR LIVER TRANSPLANTATION.

OBJECTIVE: Vitamin D deficiency is prevalent in cirrhotic patients awaiting liver transplantation (LT). Optimal vitamin D management for these patients remains undefined. We sought to determine the effectiveness of our practice in addressing vitamin D deficiency in LT patients. METHODS: This retrospective study included 127 patients who received a first LT between July 2010 and July 2011. Outcomes measured included readmission rates, fractures, and functional status post-LT. 25-Hydroxyvitamin D (25-OH D) deficiency was stratified as: mild (20-30 ng/mL), moderate (15-19.9 ng/mL), and severe (<15 ng/mL). We estimated the amount of vitamin D supplementation required for each patient. RESULTS: At LT evaluation, 107 patients (84%) had vitamin D deficiency, and 74% remained vitamin D deficient at LT. Only 62% received vitamin D supplementation pre-LT. Moderate and severe deficiencies were less common at LT and rare 4 months post-LT. There was an association between improvement in vitamin D deficiency category at LT and increased vitamin D (>400,000 IU total) supplementation (P = .004). We found no association between vitamin D deficiency at LT and functional status, fractures, or readmissions post-LT. Patients receiving induction immunosuppressant therapy with basiliximab had a significantly greater degree of worsening in bone mineral density (BMD) post-LT. CONCLUSION: Moderate-to-severe vitamin D deficiency was very prevalent in a cohort of patients undergoing evaluation for LT. Deficiency was improved with increased vitamin D replacement therapy. Vitamin D deficiency at LT was not associated with worse bone or functional outcomes post-LT. The influence of basiliximab on bone health post-LT requires further evaluation.

The natural history of cirrhosis from parenteral nutrition-associated liver disease after resolution of cholestasis with parenteral fish oil therapy.

OBJECTIVE: To determine the natural history of cirrhosis from parenteral nutrition-associated liver disease (PNALD) after resolution of cholestasis with fish oil (FO) therapy. BACKGROUND: Historically, cirrhosis from PNALD resulted in end-stage liver disease, often requiring transplantation for survival. With FO therapy, most children now experience resolution of cholestasis and rarely progress to end-stage liver disease. However, outcomes for cirrhosis after resolution of cholestasis are unknown and patients continue to be considered for liver/multivisceral transplantation. METHODS: Prospectively collected data were reviewed for children with cirrhosis because of PNALD who had resolution of cholestasis after treatment with FO from 2004 to 2012. Outcomes evaluated included need for liver/multivisceral transplantation, mortality, and the clinical progression of liver disease. RESULTS: Fifty-one patients with cirrhosis from PNALD were identified, with 76% demonstrating resolution of cholestasis after FO therapy. The mean direct bilirubin decreased from 6.4 ± 4 mg/dL to 0.2 ± 0.1 mg/dL (P < 0.001) 12 months after resolution of cholestasis, with a mean time to resolution of 74 days. None of the patients required transplantation or died from end-stage liver disease. Pediatric End-Stage Liver Disease scores decreased from 16 ± 4.6 to -1.2 ± 4.6, 12 months after resolution of cholestasis (P < 0.001). In children who remained PN-dependent, the Pediatric End-Stage Liver Disease score remained normal throughout the follow-up period. CONCLUSIONS: Cirrhosis from PNALD may be stable rather than progressive once cholestasis resolves with FO therapy. Furthermore, these patients may not require transplantation and show no clinical evidence of liver disease progression, even when persistently PN-dependent.

Liver collagen in cirrhosis correlates with portal hypertension and liver dysfunction.

Liver collagen proportionate area (CPA) assessed by computer-assisted digital image analysis has been proposed as an accurate and objective histological variable for subclassifying cirrhosis. The study aimed to examine the relationship between CPA and relevant clinical parameters in cirrhotic patients and to evaluate the sampling variability for CPA. The study included 48 consecutive liver transplantation patients with established cirrhosis. Hepatic venous pressure gradient (HVPG) and serum markers of liver failure were determined prior to transplantation. CPA was assessed in the explanted livers. In 20 of the livers, CPA was measured in more than one tissue sample. CPA showed significant correlations with HVPG and with various surrogate markers of hepatic dysfunction including albumin, bilirubin, INR, MELD score and Child-Pugh score. CPA reliably discriminated HVPG ≥10 mmHg, termed 'clinically significant portal hypertension' (area under receiver operator curve: 0.923, p < 0.001; odds ratio: 1.209, p = 0.003). CPA measured on tissue blocks showed no significant sampling variability (p > 0.5). In conclusion, the study correlated portal hypertension and hepatic dysfunction with the amount of collagen in cirrhotic livers. The findings support the presumption of CPA as a useful histological marker for subclassifying cirrhosis and as a helpful supplement to the qualitative description of hepatic architectural changes in routine pathology.

Plasma fatty acid lipidome is associated with cirrhosis prognosis and graft damage in liver transplantation.

BACKGROUND: Knowledge regarding the plasma fatty acid (FA) pattern in patients with liver cirrhosis is fragmentary. OBJECTIVE: We evaluated plasma FA lipidome and its association with the prognosis of cirrhosis and severity of liver graft damage after transplantation. DESIGN: In this observational study, plasma FA lipidome was investigated in 51 cirrhotic patients before liver transplantation and in 90 age- and sex-matched healthy control subjects. In addition, we studied ischemia-reperfusion damage in the liver of 38 patients for whom a graft biopsy was available at transplantation. With the use of logistic regression, we modeled the presence of cirrhosis, the dichotomized model for end-stage liver disease score below and above the median, and the presence of severe liver graft ischemia-reperfusion damage. RESULTS: The FA pattern was markedly altered in cirrhotic patients, who showed, compared with healthy controls, higher monounsaturated FAs, lower n-6 and n-3 polyunsaturated FAs, and undetectable cerotic acid. Plasma di-homo-γ-linolenic acid was independently associated with the presence of cirrhosis (OR: 0.026; 95% CI: 0.004, 0.196; P < 0.0001), severity of its prognosis (OR: 0.041; 95% CI:0.005, 0.376; P = 0.006), postreperfusion graft hepatocellular necrosis (OR: 0.921; 95% CI: 0.851, 0.997; P = 0.043), and sinusoidal congestion (OR: 0.954; 95% CI: 0.912, 0.998; P = 0.039). Associations of di-homo-γ-linolenic acid with the presence of cirrhosis and severity of its prognosis were confirmed also after false discovery rate correction. CONCLUSIONS: Cerotic and di-homo-γ-linolenic acids may serve as markers of disease and prognosis in liver cirrhosis. Dietary supplementation with di-homo-γ-linolenic acid could be a reasonable interventional strategy to delay disease progression in liver cirrhosis.