Experimental Characteristics of Patients with Newly Diagnosed Multiple Myeloma.

Background: Multiple myeloma (MM), a malignant plasma cell proliferative disease, makes up to 1% of all cancers and somewhat exceeds 10% of all hematological cancers. Since it affects many organs, the signs and symptoms of myeloma vary greatly. This investigation was carried out to identify the clinical and laboratory characteristics of MM. Method: From January 1, 2014, to June 30, 2020, 169 in-patients who received a MM diagnosis for the first time at China-Japan Friendship Hospital in Beijing had their medical information examined. Results: Among 169 newly diagnosed patients, the median age was 60 years (26-84 years). Seven patients were younger than 40 years, and 16.0% (27/169) were 70 years or older. 40.8% (69/169) had IgG M-protein and 27.2% (46/169) had IgA. 84% (142/169) of patients were in the Durie Salmon stage 3. The major sign and symptoms at diagnosis were fatigue (100/169, 59.2%), bone pain (96/169, 56.8%), and weight loss (34/169, 20.1%). Anemia was present initially in 94.0% (159/169), high erythrocyte sedimentation rate in 92.7% (101/109), and thrombocytopenia in 26.6% (45/169). Similarly, hypercalcemia, renal insufficiency, and hypoalbuminemia were observed in 19.3% (31/161), 27.8%, and 75.7% respectively. Immunoparesis was found in 94% (110/117) of IgG, IgA, or IgM patients, and in 87% (33/38) of light chain myeloma patients. A localized band was found in 78.3% (123/157) of patients upon serum protein electrophoresis while monoclonal protein was detected by immunofixation in 91.5% (139/152) of patients. 4.1% (7/169) of the patients had non-secretory myeloma. The prevalence of light chain myeloma was 22.5% (38/169), and these individuals were more likely than other myeloma patients to have renal insufficiency (50% versus 21%, P < .05). In 84.8% of patients, the bone marrow had 10% or more plasma cells. Conclusion: The notable features that can be concluded from this study are the early onset of myeloma in the Chinese population and an advanced disease stage at the time of diagnosis with most of them accompanying anemia, hypoalbuminemia, and immunoparesis.

Hypovitaminosis D Is Prevalent in Patients With Renal AL Amyloidosis and Associated With Renal Outcome.

Introduction: Vitamin D deficiency is common, but no data have been reported on vitamin D levels in light chain (AL) amyloidosis. Patients and Methods: In this exploratory study, stored serum samples from 173 patients with newly diagnosed AL amyloidosis were analyzed for vitamin studies which included 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2D] and vitamin D binding protein (DBP). Measurements were made by liquid chromatography-tandem mass spectrometry. Kidney survival and overall survival (OS) were assessed in association to vitamin D status. Results: Cardiac and kidney involvement occurred in 69% and 63% of patients, respectively. 25(OH)D deficiency (<20 ng/mL) was seen in 56.6% of the patients and was notably found among patients with heavy proteinuria (96%), hypoalbuminemia (84.3%) and morbidly obese patients (68.3%). Heavy proteinuria (>5 gr/24-h) and vitamin D supplementation were independent predictors of 25(OH)D level on nominal multivariate regression analysis. 1,25(0H)2D deficiency was noted in 37.6% of patients and was independently associated with low eGFR and hypoalbuminemia. Progression to ESRD occurred in 23.7% of evaluable patients. Patients who progressed to ESRD had lower serum 25(OH)D and 1,25(OH)2D levels compared to those who did not progress to ESRD. On a multivariate analysis, severe 25(OH)D deficiency was an independent predictor of progression to ESRD as was renal stage, while 1,25(OH)2D deficiency was not. Conclusions: Hypovitaminosis D is common in AL amyloidosis, particularly among patients with heavy proteinuria. Severe 25(OH)D deficiency at time of diagnosis predicts progression to ESRD.

A 6-Month clinical practice pilot study of sucroferric oxyhydroxide on nutritional status in patients on peritoneal dialysis.

BACKGROUND: Hyperphosphatemia is common in patients on peritoneal dialysis (PD). Restricting dietary phosphorus often leads to a decrease in protein intake, which may result in hypoalbuminemia. The high pill burden of phosphate binders may also contribute to compromised appetite and dietary intake. Hypoalbuminemia is associated with an increased risk of morbidity and mortality in PD patients. The goal of this study was to determine if sucroferric oxyhydroxide improves albumin and self-reported measures of appetite in PD patients. METHODS: We performed a prospective, open-label, 6-month, pilot study of 17 adult PD patients from the Denver Metro Area. Patients had to use automated peritoneal dialysis for ≥ 3 months, have a serum albumin ≤ 3.8 g/dL, and have serum phosphate ≥ 5.5 mg/dL or ≤ 5.5 mg/dL on a binder other than SO. SO was titrated to a goal serum phosphate of < 5.5 mg/dL. The primary outcome was change in serum phosphate, albumin, and phosphorus-attuned albumin (defined as albumin divided by phosphorus) over 6 months. RESULTS: The mean (SD) age and dialysis vintage was 55 ± 13 years and 3.8 ± 2.7 years, respectively. Participants' serum phosphate significantly decreased with fewer phosphate binder pills/day after switching to SO. There was no change in serum albumin, appetite, or dietary intake. However, participants had significant improvements in phosphorus-attuned albumin. CONCLUSION: The transition to SO improved phosphorus control, phosphorus-attuned albumin, and pill burden. There were no significant changes in self-reported appetite or dietary intake during the study. These findings suggest that PD patients maintained nutritional status with SO therapy. TRIAL REGISTRATION: First registered at ClinicalTrials.gov ( NCT04046263 ) on 06/08/2019.

Hypoalbuminemia and not undernutrition predicts high-dose methotrexate-induced nephrotoxicity in children with acute lymphoblastic leukemia in resource-constrained centers.

BACKGROUND: The standard practice to mitigate high-dose methotrexate (HD-MTX)-induced nephrotoxicity (HMN) in acute lymphoblastic leukemia (ALL) is to monitor levels until serum MTX falls below a predefined threshold. It is not feasible in most resource-constrained centers. Literature on the various factors affecting HMN in these centers is limited, retrospective, and heterogeneous. Though hypoalbuminemia has been postulated as a risk factor for HMN, the relationship of undernutrition with HMN has not been studied. PROCEDURE: This prospective observational study consecutively enrolled children < 12 years old with ALL receiving HD-MTX. Children with preexisting renal disease and exposed to nephrotoxic drugs two weeks preceding HD-MTX infusion were excluded. HD-MTX was administered over 24 hours (BFM-2009 protocol) with 12 hours of prehydration. Solitary MTX levels at 36 hours (MTX36) were outsourced, and 6-8 doses of leucovorin were given six-hourly. Hydration was continued till last dose of leucovorin. Various factors affecting HMN (rise in creatinine to 1.5 times baseline) were recorded: age, sex, type of ALL, risk group of ALL, first dose of MTX, dose of MTX, undernourishment, serum protein, and albumin along with C-reactive protein and MTX36 levels. RESULTS: Forty-four children who received 150 HD-MTX cycles were analyzed. HMN was seen in 14% of cycles. On univariate analysis, undernourishment, MTX36 levels, hypoproteinemia, and hypoalbuminemia were significantly associated with HMN. On multivariate analysis, hypoalbuminemia and MTX36 levels significantly predicted the development of HMN with odds ratios of 4.71 and 1.45. CONCLUSION: Hypoalbuminemia and solitary serum MTX levels predict HMN in centers where serial MTX level monitoring is not feasible.

[Effect of omega-3 fatty acids on hypoalbuminemia in acute heart failure patients with increased inflammatory activity]. / Efecto de los ácidos grasos omega-3 sobre la hipoalbuminemia en pacientes con insuficiencia cardiaca aguda y actividad inflamatoria elevada.

INTRODUCTION: Introduction: inflammatory activity (IA) is a cause of hypoalbuminemia in patients with acute heart failure (AHF). Objectives: the main objective of this study was to evaluate whether an AI modulator treatment contributes to correcting albuminemia in this context. Methods: in this clinical trial 43 patients with AHF, hypoalbuminemia (serum albumin  3.4 g/dl), and elevated IA [C-reactive protein (CRP)  25 mg/l] were randomly assigned to receive omega-3 fatty acids (4 g daily) or placebo for 4 weeks. Albuminemia and CRP were reassessed at weeks 1 and 4. An analysis of variance for repeated measures was performed. Results: mean age was 75.6 ± 8.8 years, 72.1 % were male, and the most frequent etiology was ischemic (46.5 %). The two groups were homogeneous in their baseline characteristics. A significant increase in albumin concentration was found at week 4 from baseline (p for the effect of time < 0.001), with no differences between groups at week 1 or week 4. CRP decreased significantly in week 1 (p for the effect of time < 0.001), with no differences between groups in either week 1 or week 4. Conclusion: in patients with AHF, hypoalbuminemia, and elevated AI albuminemia normalizes in week 4, while CRP already drops significantly during the first week. In this context both effects are independent of the addition of high doses of omega-3 fatty acids.

INTRODUCCIÓN: Introducción: la actividad inflamatoria (AI) es causa de hipoalbuminemia en los pacientes con insuficiencia cardiaca aguda (ICA). Objetivos: el objetivo principal de este estudio fue evaluar si un tratamiento modulador de la AI contribuye a corregir la albuminemia en este contexto. Métodos: en este ensayo clínico, 43 pacientes con ICA, hipoalbuminemia (albúmina sérica ≤ 3,4 g/dl) y AI elevada [proteína C-reactiva (PCR)  25 mg/l] fueron asignados aleatoriamente a recibir ácidos grasos omega-3 (4 g diarios) o placebo durante 4 semanas. La albuminemia y la PCR se reevaluaron en las semanas 1 y 4. Se realizó un análisis de la varianza para medidas repetidas. Resultados: la edad media era de 75,6 ± 8,8 años, el 72,1 % eran varones y la etiología más frecuente era la isquémica (46,5 %). Los dos grupos fueron homogéneos en sus características basales. Se encontró un incremento significativo de la concentración de albúmina en la semana 4 con respecto a la basal (p del efecto tiempo < 0,001), sin que se hallaran diferencias entre los grupos ni en la semana 1 ni en la 4. La PCR descendió significativamente ya en la semana 1 (p del efecto tiempo < 0,001), sin que se encontraran diferencias entre los grupos ni en la semana 1 ni en la 4. Conclusión: en los pacientes con ICA, hipoalbuminemia y AI elevada, la albuminemia se normaliza en la semana 4 mientras que la PCR desciende significativamente en la primera semana. En este contexto, ambos efectos son independientes de la adición de altas dosis de ácidos grasos omega-3.

Lymphedema complicated by protein-losing enteropathy with a 22q13.3 deletion and the potential role of CELSR1: A case report.

INTRODUCTION: 22q13.3 deletion syndrome is a well-known syndrome characterized by typical clinical findings including neonatal hypotonia, absent or severely delayed speech, intellectual disability, and other various features, and detection of a heterozygous deletion of chromosome 22q13.3 with the involvement of at least part of SHANK3. It is reported that 10% to 29% of patients with 22q13.3 deletion syndrome present lymphedema. Protein-losing enteropathy (PLE) has never been reported in 22q13.3 deletion syndrome. PATIENT CONCERNS: The patient presented to our institution for refractory hypoalbuminemia and chronic lymphedema in both legs. DIAGNOSIS: The patient manifested intellectual disability, absent speech, tooth grinding, dysmorphic face, and abnormal hands and toenails. Copy-number variation sequencing confirmed the maternal deletion in 22q13.31-q13.33 (chr22:46285592-51244566, hg19). The patient was genetically diagnosed with 22q13.3 deletion syndrome. INTERVENTIONS: Low-fat diets and medium-chain triglycerides supplements were prescribed. The patient was recommended to wear compression garments and elevate legs. OUTCOMES: The symptom of diarrhea was resolved, but hypoalbuminemia persisted. Lower extremities lymphedema was gradually becoming severe. CONCLUSIONS: Primary lymphedema and PLE can occur simultaneously in a patient with 22q13.3 deletion syndrome. The 2 phenotypes could share the same genetic etiology of congenital lymphatic abnormalities. CELSR1 deletion may play a role in lymphatic dysplasia. The case also provides additional proof of the pathogenic effect of CELSR1 on hereditary lymphedema.

Frailty predicts outcome of partial nephrectomy and guides treatment decision towards active surveillance and tumor ablation.

PURPOSE: To examine frailty and comorbidity as predictors of outcome of nephron sparing surgery (NSS) and as decision tools for identifying candidates for active surveillance (AS) or tumor ablation (TA). METHODS: Frailty and comorbidity were assessed using the modified frailty index of the Canadian Study of Health and Aging (11-CSHA) and the age-adjusted Charlson-Comorbidity Index (aaCCI) as well as albumin and the radiological skeletal-muscle-index (SMI) in a cohort of n = 447 patients with localized renal masses. Renal tumor anatomy was classified according to the RENAL nephrometry system. Regression analyses were performed to assess predictors of surgical outcome of patients undergoing NSS as well as to identify possible influencing factors of patients undergoing alternative therapies (AS/TA). RESULTS: Overall 409 patient underwent NSS while 38 received AS or TA. Patients undergoing TA/AS were more likely to be frail or comorbid compared to patients undergoing NSS (aaCCI: p < 0.001, 11-CSHA: p < 0.001). Gender and tumor complexity did not vary between patients of different treatment approach. 11-CSHA and aaCCI were identified as independent predictors of major postoperative complications (11-CSHA ≥ 0.27: OR = 3.6, p = 0.001) and hospital re-admission (aaCCI ≥ 6: OR = 4.93, p = 0.003) in the NSS cohort. No impact was found for albumin levels and SMI. An aaCCI > 6 and/or 11-CSHA ≥ 0.27 (OR = 9.19, p < 0.001), a solitary kidney (OR = 5.43, p = 0.005) and hypoalbuminemia (OR = 4.6, p = 0.009), but not tumor complexity, were decisive factors to undergo AS or TA rather than NSS. CONCLUSION: In patients with localized renal masses, frailty and comorbidity indices can be useful to predict surgical outcome and support decision-making towards AS or TA.

Kidney dysfunction and oxidative stress in doxorubicin-induced nephrotic rat: Protective role of sesame oil.

Doxorubicin (DOX) is an antineoplastic agent which it's clinical use has been limited due to its major side effects including cardiotoxicity and nephrotic syndrome. Sesame oil (SO) is an important edible oil with many pharmacologic effects. The aim of the present study was to investigate the effect of SO against DOX-induced nephropathy in the rat. In this study, two doses of SO (3 and 6 mL/kg) were administrated orally for six consecutive weeks and DOX (mg/kg) was intravenously injected on the 4th day of the experiment. Blood and urine samples were collected on days 1, 14, 30, and 42 for subsequent measurement of biochemical parameters. The left kidneys were removed for subsequent assessment of total thiol content, malondialdehyde (MDA) concentration, and renal activities of catalase and superoxide dismutase enzymes. DOX caused significant proteinuria, hypoalbuminemia, and hyperlipidemia compared to control group. Significant decrease in antioxidant enzyme activities and total thiol contents and significant increase in MDA levels were also observed following DOX injection when compared to control group. Oral administration of SO significantly reversed DOX-induced proteinuria, hypoalbuminemia, and hyperlipidemia compared to DOX group. Furthermore, compared to DOX group, SO significantly increased total thiols content. MDA concentration significantly decreased following SO administration when compared to DOX group. The current study suggests that SO is able to improve kidney function as well as kidney tissue oxidative damage in DOX-induced nephrotic the rat.

Serum Albumin Levels: Who Needs Them?

OBJECTIVES: The purpose of this critical narrative review is to discuss common indications for ordering serum albumin levels in adult critically ill patients, evaluate the literature supporting these indications, and provide recommendations for the appropriate ordering of serum albumin levels. DATA SOURCES: PubMed (1966 to August 2020), Cochrane Library, and current clinical practice guidelines were used, and bibliographies of retrieved articles were searched for additional articles. STUDY SELECTION AND DATA EXTRACTION: Current clinical practice guidelines were the preferred source of recommendations regarding serum albumin levels for guiding albumin administration and for nutritional monitoring. When current comprehensive reviews were available, they served as a baseline information with supplementation by subsequent studies. DATA SYNTHESIS: Serum albumin is a general marker of severity of illness, and hypoalbuminemia is associated with poor patient outcome, but albumin is an acute phase protein, so levels vacillate in critically ill patients in conjunction with illness fluctuations. The most common reasons for ordering serum albumin levels in intensive care unit (ICU) settings are to guide albumin administration, to estimate free phenytoin or calcium levels, for nutritional monitoring, and for severity-of-illness assessment. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Because hypoalbuminemia is common in the ICU setting, inappropriate ordering of serum albumin levels may lead to unnecessary albumin administration or excessive macronutrient administration in nutritional regimens, leading to possible adverse effects and added costs. CONCLUSIONS: With the exception of the need to order serum albumin levels as a component of selected severity-of-illness scoring systems, there is little evidence or justification for routinely ordering levels in critically ill patients.

Successful management of portal vein thrombosis in a Yorkshire Terrier with protein-losing enteropathy.

BACKGROUND: Portal vein thrombosis (PVT) is a rare presentation in dogs with protein-losing enteropathy (PLE). Rivaroxaban, an oral, selective, direct factor Xa inhibitor, has not been reported to be administrated for canine PVT and the effect is unclear in dogs with PLE. CASE PRESENTATION: An 11-year-old Yorkshire Terrier presented with moderate ascites. The dog had severe hypoalbuminemia (1.2 g/dL), and a portal vein thrombus was confirmed on computed tomographic angiography (CTA). On endoscopic examination, it became apparent that the hypoalbuminemia was caused by PLE, which was consequent of lymphatic dilation and lymphoplasmacytic enteritis. Therefore, the dog was initially treated with oral administrations of spironolactone and clopidogrel, with dietary fat restriction. However, a follow-up CTA showed no changes in the ascites, thrombus, and portal vein to aorta (PV/Ao) ratio. Therefore, the dog was additionally prescribed rivaroxaban and low-dose prednisolone for the portal vein thrombus and hypoalbuminemia due to lymphoplasmacytic enteritis, respectively. Following the treatment, the PV/Ao ratio decreased because of a decrease in the thrombus and the ascites disappeared completely with an elevation of albumin concentration (1.9 g/dL). CONCLUSIONS: This case report demonstrated that oral administration of rivaroxaban combined with low-dose glucocorticoid was effective management for PVT in a dog with PLE.

The necessity of routine postoperative laboratory tests after total hip arthroplasty for hip fracture in a semi-urgent clinical setting.

BACKGROUND: Recent studies suggest that routine postoperative laboratory tests are not necessary after primary elective total hip arthroplasty (THA). This study aims to evaluate the utility of routine postoperative laboratory tests in patients undergoing THA for hip fracture in a semi-urgent clinical setting. MATERIALS AND METHODS: This retrospective study included 213 consecutive patients who underwent primary unilateral THA for hip fractures. Patient demographics, clinical information, and laboratory tests were obtained from the electronic medical record system. Multivariate logistic regression analysis was performed to identify risk factors associated with abnormal laboratory test-related interventions. RESULTS: A total of 207 patients (97.18%) had abnormal postoperative laboratory results, which were mainly due to anemia (190/213, 89.20%) and hypoalbuminemia (154/213, 72.30%). Overall, 54 patients (25.35%) underwent a clinical intervention, 18 patients received blood transfusion, and 42 patients received albumin supplementation. Factors associated with blood transfusion were long operative time and low preoperative hemoglobin levels. Factors associated with albumin supplementation were long operative time and low preoperative albumin levels. Of the 33 patients with abnormal postoperative creatinine levels, 7 patients underwent a clinical intervention. For electrolyte abnormalities, sodium supplementation was not given for hyponatremia, three patients received potassium supplementation, and one patient received calcium supplementation. CONCLUSIONS: This study demonstrated a high incidence of abnormal postoperative laboratory tests and a significant clinical intervention rate in patients who underwent THA for hip fracture in a semi-urgent clinical setting, which indicates that routine laboratory tests after THA for hip fracture are still necessary for patients with certain risk factors. LEVEL OF EVIDENCE: Level III. Trial registration Clinical trial registry number ChiCTR1900020690.

Perioperative improvement in serum albumin level in patients with left ventricular assist device.

BACKGROUND: The negative impact of baseline hypoalbuminemia on clinical outcome following left ventricular assist device (LVAD) implantation is well known. However, the implications of perioperative change in serum albumin levels on post-LVAD outcomes remain uninvestigated. METHODS: Among consecutive patients with baseline serum albumin <3.5 g/dl who received durable LVAD implantation between April 2014 and August 2017 and were followed for 1 year, the impact of perioperative change in serum albumin level from baseline to 3 months post-LVAD on the incidence of adverse events was investigated. RESULTS: Sixty-eight patients (median 60 years and 69% male) were included. Serum albumin change was an independent predictor of the occurrence of adverse events with an adjusted hazard ratio of 0.32 (95% confidence interval, 0.13-0.78) and a cutoff change of 0.7 g/dl. Those with albumin increase >0.7 g/dl had higher 1-year freedom from adverse events (45% vs. 14%, p = .008), dominantly due to lower incidence of death or sepsis compared with those without (p < .05 for both). CONCLUSION: Among those with baseline hypoalbuminemia, a considerable perioperative increase in serum albumin levels following LVAD implantation was associated with lower mortality and morbidity. The implication of aggressive nutrition intervention on LVAD patients is the next concern.

[Effect of postoperative hypoalbuminemia and supplement of human serum albumin on the development of poor wound healing following lumbar internal fixation surgery].

Objective: To analyze the association between postoperative hypoalbuminemia and poor wound healing, and to evaluate whether postoperative supplementation of human serum albumin can improve postoperative wound healing after lumbar internal fixation surgery. Methods: From January 2014 to December 2018, 602 patients who underwent lumbar internal fixation surgery in the Department of Orthopedics, Zhujiang Hostiptal of Southern Medical University were identified. There were 250 males (41.5%) and 352 females (58.5%), with an average age of (60±12) years. All patients' clinical records were reviewed, including demographics data, comorbidity data, preoperative serum laboratory values, intraoperative factor, postoperative serum laboratory values and wound healing, and the incidence rate of poor wound healing was calculated. The statistical analyses were performed with R software and Empower(R) to analyze the factors related to poor wound healing. Multiple logistic regression models were performed with adjustment for the potential confounders to evaluate the effect of postoperative hypoalbuminemia and supplementation of human serum albumin on the development of poor wound healing. Results: Poor wound healing occurred in 51(8.47%) patients. After adjusting for the confounding factors, multiple regression analysis showed that there was no correlation between postoperative albumin levels and poor wound healing(OR=1.00, 95%CI: 0.91-1.10, P=1.000). Compared with patients with postoperative normal albumin level, postoperative hypoalbuminemia would increase the risk of poor wound healing by 13% (OR=1.13, 95%CI: 0.47-2.70, P=0.787). There was no correlation between supplementation of human serum albumin and poor wound healing in patients with normal albumin levels or postoperative hypoalbuminemia (P>0.05). Conclusions: There is no correlation between postoperative hypoalbuminemia and poor wound healing after lumbar internal fixation surgery. Postoperative supplementation of human serum albumin can't improve wound healing.

Effects of Nutritional Treatment on the Frequency of Pneumonia in Bedridden Patients Receiving Oral Care.

Objective Pneumonia develops in bedridden patients, even in those receiving oral care, and malnutrition is associated with the development of pneumonia. We examined the effects of nutritional treatment on the prevention of pneumonia. Patients and Methods We retrospectively examined the effects of nutritional treatment on the prevention of pneumonia by analyzing the records of bedridden patients (n=68; mean age: 68.0 years) who stayed in a hospital for 2 years or longer. Results Among the analyzed patients, pneumonia developed in 52 (76%) patients, and the mean frequency of pneumonia was 1.6 times per year during the first year of stay. In a multivariate analysis, the serum albumin level at admission in the pneumonia group was lower than that in the non-pneumonia group. The frequency of pneumonia during the second year of stay was lower than that during the first year of stay. Serum levels of albumin and total protein (TP) at one year after admission were higher than those at admission in all analyzed patients, and in all patients (n=52) and elderly (≥65 years) patients (n=31) in the pneumonia group. The proportions of patients with hypoalbuminemia (<3.5 g/dL) and hypoproteinemia (<6.5 g/dL) at one year after admission were lower than those at admission. The increases in the proportions of patients presenting a reduced frequency of pneumonia were correlated with increases in the proportions of patients presenting increased levels of albumin and/or TP. Conclusion Nutritional treatment may reduce the frequency of pneumonia by improving malnutrition in bedridden patients receiving oral care.

Zinc and protein metabolism in chronic liver diseases.

The capacity to metabolize proteins is closely related to the hepatic functional reserve in patients with chronic liver disease, and hypoalbuminemia and hyperammonemia develop along with hepatic disease progression. Zinc deficiency, which is frequently observed in patients with chronic liver disease, significantly affects protein metabolism. Ornithine transcarbamylase is a zinc enzyme involved in the urea cycle. Its activity decreases because of zinc deficiency, thereby reducing hepatic capacity to metabolize ammonia. Because the glutamine-synthesizing system in skeletal muscles compensates for the decrease in ammonia metabolism, hyperammonemia does not develop in the early stages of chronic liver disease. However, branched-chain amino acids (BCAAs) are consumed with the increase in glutamine-synthesizing system reactions, leading to a decreased capacity to synthesize proteins, including albumin, due to amino acid imbalance. Upon further disease progression, skeletal muscle mass decreases because of nutritional deficiency, as well as the further decreased capacity to metabolize ammonia in the liver, whereby the capacity to detoxify ammonia reduces as a whole, resulting in hyperammonemia. BCAA supplementation therapy for nutritional deficiency in liver cirrhosis improves survival by correcting amino acid imbalance via recovery of the capacity to synthesize albumin, while zinc supplementation therapy improves the capacity to metabolize ammonia in the liver. Here, the efficacy of a combination of BCAA and zinc preparation for nutritional deficiency in liver cirrhosis, as well as its theoretical background, was reviewed.

Switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrient improves the branched-chain amino acid-to-tyrosine ratio in patients with cirrhosis with hypoalbuminemia: a prospective study.

OBJECTIVE: The present study aimed to elucidate the effect of switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrient in patients with cirrhosis with hypoalbuminemia. METHODS: Twenty-six patients with cirrhosis with hypoalbuminemia despite treatment with branched-chain amino acid granules containing 12 g of branched-chain amino acid were enrolled in the prospective study. The branched-chain amino acid-enriched nutrient and control groups were composed of 16 and 10 patients, respectively. The patients in branched-chain amino acid-enriched nutrient group switched to branched-chain amino acid-enriched nutrient mixture containing 12.2 g of branched-chain amino acid and 410 kcal with a half of it consumed as a late evening snack, and the patients in the control group continued branched-chain amino acid granules. Laboratory data related to nutrition parameter were assessed at baseline, 3 months after baseline, and at 6 months after baseline. RESULTS: Two patients were withdrawn; hence, nine and 15 patients in the branched-chain amino acid granules and branched-chain amino acid-enriched nutrient groups, respectively, were subjected to full analysis. Serum albumin levels and total lymphocyte counts in both groups did not change in the study period. The branched-chain amino acid-to-tyrosine ratio in the branched-chain amino acid-enriched nutrient group significantly increased from baseline to 6 months after baseline (P = 0.030), whereas that in the control group did not increase. CONCLUSION: Switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrients improves branched-chain amino acid-to-tyrosine ratio in patients with cirrhosis with hypoalbuminemia.