Late-evening snack with branched-chain amino acids improves liver function after radiofrequency ablation for hepatocellular carcinoma

Aim: This prospective study was designed to examine whether consumption of a branched‐chain amino acid (BCAA)‐enriched nutrient mixture as a late‐evening snack (LES) helps maintain and/or improve liver functioning in liver cirrhosis (LC) patients who have undergone radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). Methods: An equal number (10) of 30 LC patients who had undergone RFA for HCC was randomly assigned to a standard diet group (control) group, a morning BCAA (M‐BCAA) administration group, or a LES with BCAA (LES‐BCAA) administration group. Liver function testing was performed and Child–Pugh scores (CPS) calculated for each group to assess the improvement at 1, 4 and 12 weeks post‐RFA. Results: Compared to the control and M‐BCAA groups, the LES‐BCAA group experienced a rapid and significant improvement in albumin and total serum bilirubin levels and in CPS that began during the initial post‐RFA period. These results indicate that LES with BCAA supplementation significantly improved the CPS of the LES‐BCAA group at 4 and 12 weeks post‐RFA. Although no patients experienced serious adverse effects, two patients who had been diagnosed with diabetes mellitus before undergoing RFA required blood sugar management to improve glycemic control and one subject withdrew due to supplement‐induced vomiting. Conclusion: LES with BCAA supplementation significantly and rapidly improves liver functioning and CPS in LC patients who have undergone RFA for HCC. Control of blood sugar levels is necessary when calorie‐containing BCAA is administrated to LC patients with impaired glucose tolerance.     

Clinical significance of therapy using branched‐chain amino acid granules in patients with liver cirrhosis and hepatocellular carcinoma

The liver is the major organ for the metabolism of protein, fat and carbohydrate. A nutritional approach is required in the treatment of cirrhosis, which is frequently complicated with protein–energy malnutrition. Several advanced treatment approaches for hepatocellular carcinoma (HCC) have been established in the past decade. HCC is often complicated by cirrhosis, so treatment of the underlying liver diseases is also necessary to improve the prognosis. Branched‐chain amino acid (BCAA) granules were developed originally for the treatment of hypoalbuminemia associated with decompensated cirrhosis. However, subsequent studies found various other pharmacological actions of this agent. We review the clinical significance of therapy using BCAA granules in patients receiving different treatment approaches for cirrhosis and HCC based on the published work as well as our own data.     

Effect of a late evening snack using branched‐chain amino acid‐enriched nutrients in patients undergoing hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

Aim: A late evening snack (LES) is recommended for protein‐energy malnutrition in patients with liver cirrhosis. This study investigated energy metabolism in cirrhotic patients with hepatocellular carcinoma (HCC) and the effects of LES using a branched‐chain amino acid (BCAA)‐enriched nutrient in cirrhotic patients with advanced HCC undergoing hepatic arterial infusion chemotherapy (HAIC). Methods: Energy metabolism was measured using indirect calorimetry for 10 cirrhotic patients without HCC and 36 patients with various stages of HCC. Next, in 23 cirrhotic patients with advanced HCC undergoing HAIC, 13 patients received LES (LES group), and 10 patients received ordinary food (control group). Changes in energy metabolism and glucose tolerance were examined using indirect calorimetry and 75‐g oral glucose tolerance test (OGTT) before and after 1 cycle of treatment. Results: Non‐protein respiratory quotient (npRQ) was significantly lower in patients with advanced HCC than in cirrhotic patients without HCC, or in patients with early‐stage HCC. In cirrhotic patients with advanced HCC undergoing HAIC, npRQ, BCAA/tyrosine ratio (BTR), and prealbumin and ALT levels were significantly improved in the LES group, but not in controls. In addition, area under the concentration curve for glucose (AUC glucose) tended to be improved in the LES group. Conclusions: LES using BCAA‐enriched nutrients appears to improve energy metabolism and glucose tolerance in cirrhotic patients with advanced HCC undergoing HAIC.     

Effects of branched-chain amino acids-enriched nutrient support for patients undergoing liver resection for hepatocellular carcinoma

Background and Aims: Most patients with hepatocellular carcinoma (HCC) have underlying liver cirrhosis that is frequently associated with a state of protein energy malnutrition. The aim of this study was to evaluate the clinical benefit of perioperative supplementation of a branched‐chain amino acid–enriched nutrient‐mixture for patients undergoing liver resection for HCC. Methods: A total of 112 patients with HCC who underwent hepatic resection were enrolled in this study. These patients were divided into two groups: 40 patients received perioperative supplementation of branched‐chain amino acid–enriched nutrient‐mixture (AEN group) and 72 patients did not (control group). Laboratory data, postoperative complications, duration of hospitalization, and survival were assessed for each group and compared. Results: The overall incidence of postoperative complications was lower in the AEN group (17.5%) than in the control group (44.4%) (P = 0.01). Among the postoperative complications, surgical site infection and bile leakage was observed in 5% of patients in the AEN group and in 15.3% and 12.5% of patients in the control group, respectively. Ascites appeared after the surgery in 7.5% of patients in the AEN group and in 16.7% of patients in the control group. The duration of hospitalization was significantly shorter in the AEN group was than in the control group (P < 0.05). Conclusions: This study strongly suggests that perioperative supplementation of a branched‐chain amino acid–enriched nutrient‐mixture is clinically beneficial in reducing the morbidity associated with postoperative complications and in shortening the duration of hospitalization of patients with chronic liver disease who undergo liver resection for HCC.     

Effect of an oral branched chain amino acid‐enriched snack in cirrhotic patients with sleep disturbance

Aim: Sleep is closely related to physical and mental health. Sleep disturbance is reported in patients without encephalopathy. We examined the relationship among cirrhotic symptoms, laboratory data and sleep disturbances. Next, we examined the influence of a branched chain amino acid (BCAA) supplement on sleep disturbance in cirrhotic patients. Methods: We investigated a total of 21 patients at Nagasaki University Hospital from January to June 2009. We constructed questionnaire items for the evaluation of cirrhotic symptoms. The items, as major symptoms of cirrhotic patients, were as follows: hand tremor, appetite loss, muscle cramp of foot, fatigue, decreased strength, anxiety, abdominal fullness, abdominal pain and a feeling of low energy. We used the Epworth Sleepiness Scale (ESS) for the evaluation of daytime hypersomnolence. Energy supplementation with a BCAA snack was performed as a late evening snack (LES). All patients were assessed at the time of entry into the study, and at 4 and 8 weeks. Results: It was found that BCAA snack, taken p.o. as an LES, improved the ESS for cirrhotic patients without encephalopathy. This beneficial result was recognized in the short term, 4 weeks after beginning of treatment. This study demonstrated the utility of BCAA supplementation for cirrhotic patients with sleep disturbance. However, the cirrhotic symptom‐related score was positively relation with the Child–Pugh score at the time of patient entry, and we were unable to identify the item that related to ESS. Conclusion: A BCAA snack is a useful drug for cirrhotic patients who do not have any overt encephalopathy, but who suffered from sleep disturbance.     

Tolerance of radiofrequency ablation by patients of hepatocellular carcinoma

Background

Radiofrequency ablation (RFA) is currently an effective method for ablation of hepatocellular carcinoma (HCC). Early reports have indicated that RFA is safe and virtually free from major complications. Unlike partial hepatectomy for HCC on patients with cirrhosis, there are no data on the safety limit of RFA. However, information is vital for selection of appropriate patients for the procedure. In this study, we analyzed results from use of RFA on HCC patients and determined the lower limit of liver function with which HCC patients can tolerate RFA.

Method

Preoperative variables of 310 patients who underwent RFA for HCC were analyzed to identify the risk factors in RFA intolerance in terms of morbidity associated with stress-induced complications.

Results

Thirty-nine (12.6%) patients developed intolerance of RFA. Postoperative morbidity was mainly because of intractable ascites (n = 13), hyperbilirubinemia (n = 10), massive pleural effusion (n = 7), and other complications (n = 14). Multivariate analysis revealed that serum albumin level (P = 0.001), serum bilirubin level (P = 0.000), tumor number (P = 0.002), and RFA duration (P = 0.017) all played a role in this issue.

Conclusions

Simple data such as serum bilirubin, serum albumin level, and tumor number can be used to predict HCC patients’ tolerance of RFA. Avoidance of excessive RFA time and careful monitoring of patients at risk are important means of reducing the postoperative morbidity rate.     

Effects of late evening snack including branched‐chain amino acid on the function of hepatic parenchymal cells in patients with liver cirrhosis

Aim: A late evening snack (LES) improves protein‐energy malnutrition due to overnight starvation and the catabolic state in patients with liver cirrhosis. Our aim was to examine whether LES including a branched‐chain amino acid (BCAA) could maintain hepatic reserve and the function of hepatic parenchymal cells in patients with liver cirrhosis, including those in the early stage of disease. Methods: Seventeen patients with liver cirrhosis received LES with a BCAA‐enriched nutrient mixture. During the study period, each patient was instructed on energy and protein intake. Indicators of liver function measured at 6 months included maximum asialoscintigraphic removal (Rmax: indicator of total liver receptors), asialoscintigraphic imaging grade, serum albumin, ammonia, tyrosine and BTR (molar ratio of branched‐chain amino acids to tyrosine). Results: Serum albumin levels, BTR and tyrosine levels of the 17 patients were significantly improved after nutrient treatment. In patients with Rmax of 0.2 or higher, serum albumin level and tyrosine level were significantly improved. Conclusion: LES with BCAA‐enriched nutrient therapy can improve protein malnutrition in patients with liver cirrhosis, and is more useful in the early stages of liver cirrhosis in improving hepatic parenchymal cell mass.     

Laparoscopic repair of iatrogenic diaphragmatic hernia following radiofrequency ablation for hepatocellular carcinoma

Radiofrequency ablation (RFA) is commonly used for treating unresectable hepatic malignancies. Some commonly associated complications of RFA include fever, symptomatic pleural effusion, abscess, hepatoma and hepatic insufficiency. Here, we report a case of diaphragmatic hernia in a patient following RFA for hepatic malignancy with cirrhosis.     

Utility of contrast-enhanced ultrasonography with Sonazoid in radiofrequency ablation for hepatocellular carcinoma

Background and Aims: Kupffer imaging in contrast‐enhanced ultrasonography (CEUS) with Sonazoid, which lasts for 60 min or longer, may be useful in ultrasound‐guided percutaneous tumor ablation. The utility of Sonazoid in radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) was investigated in this study. Methods: We analyzed a total of 716 HCC nodules that were detected on dynamic computed tomography in 316 patients. Detectability of these nodules was compared between CEUS and conventional ultrasonography. The effectiveness in the treatment was assessed by comparing the mean numbers of treatment sessions of RFA in patients treated with CEUS and that in historical controls matched for tumor and background conditions. Results: Detectability of tumor nodule was 83.5% in conventional ultrasonography and 93.2% in CEUS (P = 0.04). Sixty‐nine nodules in 52 patients were additionally detected with CEUS. The number of additionally detected tumor nodules was positively correlated with serum albumin level (P = 0.016). The number of RFA sessions was 1.33 ± 0.45 with CEUS as compared to 1.49 ± 0.76 in the historical controls (P = 0.0019). Conclusions: CEUS with Sonazoid is useful for HCC detection in patients with a well‐conserved liver function reservoir. The decrease in RFA session numbers indicated the utility of Sonazoid in RFA treatment of HCC.     

Neutrophil-to-lymphocyte ratio associated with mortality in early hepatocellular carcinoma patients after radiofrequency ablation

Background and Aim: Increasing evidence correlates the presence of systemic inflammation with poor survival in patients with hepatocellular carcinoma (HCC). We studied whether peripheral blood neutrophil‐to‐lymphocyte ratio (NLR), a marker of systemic inflammatory response, would be a useful predictor for outcome in patients with early HCC undergoing radiofrequency ablation (RFA). Methods: A total of 158 patients with early HCC underwent RFA. Potential prognostic factors such as age, gender, tumoral characteristics, Child‐Turcotte‐Pugh (CTP) class and NLR were analyzed. The study endpoints were overall survival (OS) and new recurrence. Results: We modeled NLR as a continuous explanatory variable in regression analyses. Multivariate analysis revealed that tumor size (P = 0.005) and high baseline NLR (P = 0.001) were independent explanatory variables associated with unfavorable OS. Regarding new recurrence, multivariate analysis showed that CTP class B (P = 0.002), α‐fetoprotein > 400 ng/mL (P = 0.030), tumor size (P = 0.002) and tumor multiplicity (P = 0.013) were found to be worse prognosticators, but not baseline NLR. In a subset analysis of 140 patients whose post‐RFA NLR data at first follow‐up visit were available, multivariate analysis revealed that high post‐RFA NLR was identified as an independent covariate, not only for OS (P = 0.006), but for new recurrence (P = 0.010) as well. Conclusions: High baseline NLR was associated with worse OS for patients with early HCC; post‐RFA NLR predicted not only OS, but also tumor recurrence.