An Emulated Clinical Trial of Deprescribing Proton Pump Inhibitors in Patients With Cirrhosis.

INTRODUCTION: Proton pump inhibitors (PPI) are overused and carry harms in cirrhosis. Deprescribing is advocated but has not been trialed. METHODS AND FINDINGS: We emulated a clinical trial using Medicare data. All patients were receiving chronic PPI therapy before a compensated cirrhosis diagnosis. We compared the risk death/decompensation over 3 years between continuous users and deprescribers. We find that PPI deprescription is associated with less ascites and that cumulative PPI use is associated with more ascites and encephalopathy. Ultimately, 71% of deprescribers restart PPIs. DISCUSSION: PPI deprescribing has benefits but requires ongoing support and alternative therapies for gastrointestinal symptoms.

ALBUMIN VERSUS STANDARD MEDICAL TREATMENT IN BRAZILIAN PUBLIC AND PRIVATE HEALTHCARE SYSTEMS.

•To assess the economic impact of implementing long-term albumin infusions in patients with cirrhosis and ascites in Brazil •Incremental cost per cirrhotic patient treated with long-term albumin was estimated based on the rates of complications and healthcare resource utilization from the ANSWER trial and local costs from the public and private healthcare system perspective in Brazil. •Implementation of long-term albumin could save up to 118,759 BRL and 189,675 BRL per patient treated in the public and private healthcare system setting, respectively. •Should results from the ANSWER trial translate into real-world effectiveness, addition of albumin to standard medical treatment could lead to improved clinical outcomes and reduced costs. Background - Cirrhosis is one of the final stages of chronic liver disease. Common causes of cirrhosis include alcoholism and viral hepatitis infections. Cirrhosis can progress from an asymptomatic, compensated phase to decompensation and the appearance of overt symptoms. There is no specific treatment for decompensated cirrhosis. The ANSWER trial positioned long-term albumin infusions as a potential treatment for patients with cirrhosis and uncomplicated ascites. Objective - This study assesses the economic impact of albumin infusions following the ANSWER trial regimen in Brazilian patients with decompensated cirrhosis from the public and private healthcare systems perspectives. Methods - The incremental cost per patient per year was calculated for standard medical treatment (SMT) plus long-term albumin infusions versus SMT alone. Costs of diuretics and albumin were obtained from Banco de Preços em Saúde and the Drug Market Regulation Chamber. Costs for complication and procedures were gathered from the published literature. Costs were transformed to 2021 Brazilian reals (BRL). Incidences of clinical complications and treatments were gathered from the ANSWER trial. Univariate sensitivity analysis was performed by increasing and decreasing all inputs by 20%. Results - The cost per patient per year was 118,759 BRL and 189,675 BRL lower for patients treated with SMT and albumin (compared to SMT only) for the public and private healthcare systems, respectively. The additional cost of albumin was offset by reduced complications and treatments (149,526 BRL and 249,572 BRL, respectively). The univariate sensitivity analysis showed cost savings for both healthcare systems in all the scenarios assessed. Conclusion - This economic analysis suggests that, if the ANSWER trial clinical outcomes translate into real-world effectiveness, addition of albumin infusions to SMT in patients with decompensated cirrhosis may lead to cost savings for the public and private healthcare systems in Brazil.

Cirrhosis and hernia repair in a cohort of 6352 patients in a tertiary hospital: Risk assessment and survival analysis.

The prevalence of hernias in patient with cirrhosis can reach up to 40%. The pathophysiology of cirrhosis is closely linked to that of the umbilical hernia, but other types are also common in this population. The aim of this study is to evaluate factors that influence in the prognosis after hernia repair in patients with cirrhosis. A historical cohort of 6419 patients submitted to hernia repair was gathered. Clinical, epidemiological data and hernia characteristics were obtained. For patient with cirrhosis, data from exams, surgery and follow-up outcomes were also analyzed. Survival curves were constructed to assess the impact of clinical and surgical variables on survival. 342 of the 6352 herniated patients were cirrhotic. Patient with cirrhosis had a higher prevalence of umbilical hernia (67.5% × 24.2%, P < .001) and a lower prevalence of epigastric (1.8% × 9.0%, P < .001) and lumbar (0% × 0.18%, P = .022). There were no significant differences in relation to inguinal hernia (P = .609). Ascites was present in 70.1% of patient with cirrhosis and its prevalence was different in relation to the type of hernia (P < .001). The survival curve showed higher mortality for emergency surgery, MELD > 14 and ascites (HR 12.6 [3.79-41.65], 4.5 [2.00-10.34], and 6.1 [1.15-20.70], respectively, P < .05). Hernia correction surgery in patient with cirrhosis has a high mortality, especially when performed under urgent conditions associated with more severe clinical conditions of patients, such as the presence of ascites and elevated MELD.

Tunneled Peritoneal Catheter vs Repeated Paracenteses for Recurrent Ascites: A Cost-Effectiveness Analysis.

PURPOSE: To compare the cost-effectiveness of tunneled peritoneal catheter (TPC) versus serial large-volume paracenteses (LVP) for patients with recurrent ascites. MATERIALS AND METHODS: Retrospective, single-institution analysis of 100 consecutive patients undergoing LVP and eventual TPC placement (2015-2018) was performed with extraction of procedural complications and hospital admissions. LVPs were associated with 17 adverse events (AEs) while only 9 AEs occurred after TPC placement. While undergoing routine LVP, the patients had 30 hospitalizations monthly (177 days in total) and 10 hospitalizations monthly (51 days) after TPC placement. A cost-effectiveness analysis with Markov modeling was performed comparing TPC and LVP. Costs were based on Medicare reimbursement rates. Statistical analyses include base case calculation, Monte Carlo simulations, and deterministic sensitivity analyses. RESULTS: TPC placement was the dominant strategy with a comparable health benefit of 0.08060 quality-adjusted life-years (QALY) (LVP: 0.08057 QALY) at a lower cost of $4151 (LVP: $8401). Probabilistic sensitivity analysis showed TPC was superior in 97.49% of simulations. Deterministic sensitivity analysis demonstrated the superiority of TPC compared to LVP if the TPC complication rate was < 9.47% per week and the complication rate for LVP was > 1.32% per procedure. TPC was more cost-effective when its procedural cost was < $5427 (base case: 1174.5), and remained as such when the cost of LVP was varied as much as $10,000 (base case: $316.48). CONCLUSION: In this study, TPC was more cost-effective than LVP in patients with recurrent ascites due to the reduced risk of infection, emergency department visits, and length of hospitalization stays.

Assessment of adrenal response in patients with stable cirrhosis and ascites using different short Synacthen tests and definitions.

BACKGROUND AND AIMS: The definition of relative adrenal insufficiency (RAI) in patients with cirrhosis remains controversial. We investigated the serum and salivary cortisol (SalC) response after low-dose and standard-dose Synacthen test in patients with stable cirrhosis and ascites. METHODS: Ninety-five cirrhotic patients with ascites were prospectively evaluated from January 2014 to January 2018. Low-dose [adrenocorticotrophic hormone (ACTH): 1 µg] and standard-dose (ACTH: 250 µg) Synacthen test were successively performed. Paired serum total and saliva cortisol were taken at baseline, 30 min (low-dose test) and 60 min (standard-dose test). Salivary and Δserum total cortisol criteria included post-ACTH SalC < 12.7 ng/ml and/or SalC increase <3 ng/ml and serum total cortisol increase <9 µg/dl, respectively. RESULTS: The prevalence of RAI varied according to the definition used. SalC-defined RAI was significantly more common after low-dose than standard-dose test (54.7% vs. 20%; P < 0.001). Δserum total cortisol-defined RAI was also significantly more frequent after low-dose than standard-dose test (66.3% vs. 24.2%; P < 0.001). Considering low-dose test/SalC criteria as reference diagnostic criteria, standard-dose/salivary and Δserum total cortisol criteria showed low specificity for RAI diagnosis (43.9% and 52.7%, respectively). Survival probability was significantly lower in patients with low-dose test/SalC-defined RAI compared to those without (53.8% vs. 79.1%; P = 0.01). SalC-defined RAI after low-dose test was significantly more common than that defined after standard-dose test (72.7% vs. 30.3%; P < 0.001) among patients who died. CONCLUSION: Low-dose test/SalC definition can identify RAI in about half of patients with stable cirrhosis and ascites and is associated with increased mortality.

PleurX peritoneal catheter drainage system for vacuum-assisted drainage of treatment-resistant, recurrent malignant ascites: a NICE Medical Technology Guidance.

The PleurX peritoneal drainage catheter for drainage of malignant ascites in a community setting has been evaluated by the NICE Medical Technologies Evaluation Programme. This article outlines the evidence included in the Sponsor's submission, the independent critique by the External Assessment Centre (EAC) and the recommendations made by the Medical Technologies Advisory Committee (MTAC). In accordance with the scope issued by NICE, the intervention technology was the indwelling PleurX peritoneal catheter drainage system, the comparator was large-volume paracentesis (LVP; inpatient or outpatient) and the population was patients with treatment-resistant, recurrent malignant ascites. Nine studies (ten papers) were identified with a total of 180 PleurX-treated patients; six were case series with more than four patients that, despite being low in the hierarchy of evidence, provided useful safety information. Technical success of the initial PleurX placement procedure was 100% across five studies which reported this outcome. One study reported equal complication rates between patients treated with indwelling PleurX catheters (40 patients and 40 catheters) and those receiving repeated LVPs (67 patients and 392 procedures), 7.5% (3/40; 95% CI 1.6, 20) and 7.5% (5/67; 95% CI 2.2, 15), respectively. All remaining studies were single-arm and reported complication rates of between 0% and 59%; this wide range was largely due to variation in the definition of complications and adverse events. Using validated tools, one case series reported improvements in several ascites-related symptoms after placement of the PleurX catheter; however, an overall quality-of-life improvement at 12 weeks was not demonstrated. Positive patient opinions relating to improved symptom control and convenience were reported in a qualitative study. Cost analysis demonstrated that PleurX offered savings to the NHS when compared with repeated LVPs performed in an inpatient setting. This saving of £679 per patient was driven primarily by reducing hospital bed days (year 2009-2010 values), but would require 23.5 additional community nurse visits. Advice from clinical experts was that additional home visits were overestimated as many patients would receive such visits regardless of whether a PleurX drain had been fitted. The model demonstrated that PleurX would be more expensive than LVP procedures performed in a setting where one or less hospital bed days were used (e.g. day case or outpatient). There was uncertainty surrounding the number of patients for whom insertion of a PleurX drain would be appropriate as well as the point in the care pathway at which such treatment should be administered. MTAC supported the case for adoption and considered that the available evidence showed PleurX was clinically effective, has low complication rates, can improve quality of life and is less costly than inpatient LVP. In Medical Technology Guidance 9 (MTG9), NICE recommended that PleurX peritoneal catheter drainage system be considered for use in patients with treatment-resistant, recurrent malignant ascites.

Prognostic assessment in patients with hepatic encephalopathy.

Hepatic encephalopathy (HE) is a common complication of liver failure that is associated with poor prognosis. However, the prognosis is not uniform and depends on the underlying liver disease. Acute liver failure is an uncommon cause of HE that carries bad prognosis but is potentially reversible. There are several prognostic systems that have been specifically developed for selecting patients for liver transplantation. In patients with cirrhosis the prognosis of the episode of HE is usually dictated by the underlying precipitating factor. Acute-on-chronic liver failure is the most severe form of decompensation of cirrhosis, the prognosis depends on the number of associated organ failures. Patients with cirrhosis that have experienced an episode of HE should be considered candidates for liver transplant. The selection depends on the underlying liver function assessed by the Model for End-stage Liver Disease (MELD) index. There is a subgroup that exhibits low MELD and recurrent HE, usually due to the coexistence of large portosystemic shunts. The recurrence of HE is more common in patients that develop progressive deterioration of liver function and hyponatremia. The bouts of HE may cause sequels that have been shown to persist after liver transplant.

Percutaneous radiofrequency ablation of hepatocellular carcinoma: assessment of safety in patients with ascites.

OBJECTIVE: The objective of our study was to assess whether percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is a safe procedure in patients with ascites. MATERIALS AND METHODS: From October 2005 to January 2008, 35 patients with one or more HCCs and ascites were referred to our department for planning sonography of RFA. In 15 patients, RFA was determined to be unfeasible. One patient was excluded from the study because of the absence of ascites at the time of RFA. Percutaneous ultrasound-guided RFA was performed in the remaining 19 patients with 24 HCCs. The electrode tract was cauterized at the time of electrode removal. Retrospective assessments of the preprocedural platelet counts and prothrombin times were performed, and patients were evaluated for bleeding complication by checking vital signs, checking serum hemoglobin level, and using CT to determine whether the attenuation value of ascites had increased > 30 HU. RESULTS: There were no cases of mortality or major complications that developed after RFA. No significant difference in the maximum thickness of the perihepatic ascites and in the hemoglobin level between the pre- and postprocedural measurements was detected. Hemoperitoneum as a minor complication was noted in two (10.5%) of 19 patients. However, in those two patients, vital signs were stable, follow-up laboratory data were normal, and hemoperitoneum had been completely absorbed on CT images obtained 1 month after RFA. CONCLUSION: Percutaneous RFA for HCC can be performed safely in patients with ascites.

Comparison between handgrip strength, subjective global assessment, and prognostic nutritional index in assessing malnutrition and predicting clinical outcome in cirrhotic outpatients.

OBJECTIVE: This study compared three methods of assessing malnutrition in cirrhotics and correlated nutritional status with clinical outcome. METHODS: This cross-sectional study evaluated nutritional status by subjective global assessment (SGA), prognostic nutritional index (PNI), and handgrip strength (HG) in outpatients with cirrhosis (n = 50) and two control groups with hypertension (n = 46) and functional gastrointestinal disorders (n = 49). Patients with cirrhosis were followed for 1 y to verify the incidence of major complications, the need for transplantation, and death. RESULTS: Among patients with cirrhosis, 88% were Child-Pugh A and only 12% were Child-Pugh B. Among these, prevalences of malnutrition were 28% by SGA, 18.7% by PNI, and 63% by HG (P < 0.05). HG, but not SGA or PNI, predicted a poorer clinical outcome in patients with cirrhosis because major complications such as uncontrolled ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and hepatorenal syndrome developed in 65.5% of malnourished patients versus 11.8% of well-nourished ones (P < 0.05). No significant differences by any method were seen between the two groups regarding liver transplantation or death. CONCLUSIONS: There was a high prevalence of malnutrition in cirrhotic outpatients, especially when assessed by HG, which was superior to SGA and PNI in this study. HG was the only technique that predicted a significant incidence of major complications in 1 y in undernourished cirrhotic patients.

Assessment of intestinal permeability and absorption in cirrhotic patients with ascites using combined sugar probes.

Gastrointestinal dysfunction in patients with cirrhosis may contribute to complications such as malnutrition and spontaneous bacterial peritonitis. To determine whether cirrhotic patients with ascites have altered intestinal function, we compared intestinal permeability and absorption in patients with liver disease and normal subjects. Intestinal permeability and absorption were investigated in 66 cirrhotic patients (48 with ascites, 18 without ascites) and 74 healthy control subjects. Timed recovery of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in urine following oral administration was measured in order to assess active and passive carrier-mediated, and nonmediated, absorptive capacity, as well as intestinal large-pore/small-pore (lactulose/rhamnose) permeability. Test sugars were measured by quantitative thin-layer chromatography and results are expressed as a percentage of test dose recovered in a 5-h urine collection. Sugar excretion ratios relating to small intestinal permeability (lactulose/rhamnose) and absorption (rhamnose/3-O-methyl-D-glucose) were calculated to avoid the effects of nonmucosal factors such as renal clearance, portal hypertension, and ascites on the recovery of sugar probes in urine. Compared with normal subjects, the mean lactulose/rhamnose permeability ratio in cirrhotic patients with ascites was significantly higher (0.058 vs. 0.037, P < 0.001) but not in cirrhotic patients without ascites (0.041 vs. 0.037). Cirrhotic patients with ascites had significantly lower mean recoveries of 3-O-methyl-D-glucose (23.0 vs. 49.1%; P < 0.001), D-xylose (18.8 vs. 34.5%; P < 0.001), L-rhamnose (4.0 vs. 9.1%; P < 0.001), and lactulose (0.202 vs. 0.337%; P < 0.001) than normal subjects. However, the mean rhamnose/3-O-methyl-D-glucose ratio was the same in cirrhotic patients with ascites as normal subjects (0.189 vs. 0.189), indicating that the reduction in probe recovery was due to nonmucosal factors. Compared with normal subjects, cirrhotic patients with ascites have abnormal intestinal permeability, measured by urinary lactulose/rhamnose excretion, and normal small intestinal absorption, assessed by the urinary rhamnose/3-O-methyl-D-glucose ratio. Low urine recovery of sugar probes found in cirrhotic patients appears to be the result of nonintestinal factors affecting clearance rather than reduced intestinal absorption.

Umbilical varix presenting as an incarcerated umbilical hernia--a costly mistake if not recognised.

Incarcerated umbilical hernias commonly present as emergencies. Often they are diagnosed clinically and repaired surgically. In the case reported here, surgery could have been complicated by a major haemorrhage. An accurate history, high index of suspicion and attention to detail are paramount.

Improved assessment of body cell mass by segmental bioimpedance analysis in malnourished subjects and acromegaly.

BACKGROUND: Estimation of body cell mass (BCM) has been regarded valuable for the assessment of malnutrition. AIM: To investigate the value of segmental bioelectrical impedance analysis (BIA) for BCM estimation in malnourished subjects and acromegaly. METHODS: Nineteen controls and 63 patients with either reduced (liver cirrhosis without and with ascites, Cushing's disease) or increased BCM (acromegaly) were included. Whole-body and segmental BIA (separately measuring arm, trunk, leg) at 50 kHz was compared with BCM measured by total-body potassium. Multiple regression analysis was used to develop specific equations for BCM in each subgroup. RESULTS: Compared to whole-body BIA equations, the inclusion of arm resistance improved the specific equation in cirrhotic patients without ascites and in Cushing's disease resulting in excellent prediction of BCM (R(2) = 0.93 and 0.92, respectively; both P<0.001). In acromegaly, inclusion of resistance and reactance of the trunk best described BCM (R(2) = 0.94, P<0.001). In controls and in cirrhotic patients with ascites, segmental impedance parameters did not improve BCM prediction (best values obtained by whole-body measurements: R(2)=0.88 and 0.60; P<0.001 and <0.003, respectively). CONCLUSION: Segmental BIA improves the assessment of BCM in malnourished patients and acromegaly, but not in patients with severe fluid overload.

Cost-analysis of prophylactic antibiotics in spontaneous bacterial peritonitis.

BACKGROUND & AIMS: Antibiotic prophylaxis has been shown to decrease the incidence of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and ascites. The aim of this study was to test whether antibiotic prophylaxis for SBP is cost-effective and to compare the costs associated with different patient groups and treatment strategies. METHODS: A cost-effectiveness analysis was performed using a Markov chain model. The costs incurred during 1-year treatment with prophylactic antibiotics vs. no prophylaxis in patients with cirrhosis and ascites were calculated. The incidence rates of primary and recurrent SBP and the mortality rate of SBP were obtained from the literature. Total direct costs of SBP treatment were determined from the wholesale price of drugs and from disbursements by the Health Care Financing Administration. RESULTS: Norfloxacin prophylaxis resulted in savings between $2216 and $8545 per patient per year, depending on the patient group studied. Trimethoprim-sulfamethoxazole prophylaxis resulted in savings between $2934 and $9251 per patient per year. The groups that benefited most from prophylaxis were patients with an ascitic fluid total protein concentration of < or = 1 g/dL and those with a previous history of SBP. CONCLUSIONS: The use of prophylactic antibiotics to decrease the incidence of SBP is a cost-saving strategy in patients with cirrhosis and ascites.

Influence of liver failure, ascites, and energy expenditure on the response to oral nutrition in alcoholic liver cirrhosis.

The influence of liver failure, ascites, and energy expenditure on the response to oral nutrition was assessed in a group of 55 alcoholic cirrhotic patients. Caloric intake, nutritional status, resting energy expenditure (REE), and Child-Pugh score were evaluated before and after 1 mo of oral nutrition. Patients were severely malnourished, 73% had muscular midarm circumference (MMAC) below the 5th percentile of a reference population, 51% had triceps skinfold thickness below the 25th percentile. Eleven patients were in class A of Child, 19 in class B, and 25 in class C. Twenty-six patients were nonascitic, whereas ascites was resolved in 10 ascitic patients by the end of the study and 19 patients had refractory ascites. Liver damage was more pronounced and did not improve during the study in patients with refractory ascites. Caloric intake was approximately 40 kcal/kg of body weight and was in the same range in the three groups according to Child classification. Fat mass (FM) increased, respectively, from 17.4% +/- 1.7% to 19.5% +/- 1.4%, P < 0.01, in Child A patients; from 17.1% +/- 1.4% to 19.3% +/- 1.4%, P < 0.001, in Child B patients; and from 17.6% +/- 1.5% to 18.8% +/- 1.5%, P < 0.05, in Child C patients. The increase in FM was comparable in the three groups, whereas MMAC and the creatinine/height ratio did not change significantly. FM was lower and did not increase in patients with refractory ascites. Child C patients were characterized by an increase in the rate of glucose oxidation (P < 0.02) and a decrease in the rate of lipid oxidation (P < 0.05). High-density lipoprotein cholesterol and apolipoprotein (Apo) A1 were reliable indices of improvement of liver function in patients with severe liver failure, ApoA1 was also a marker of improvement of metabolic impairment. With respect to the measured REE/predicted REE ratio calculated according to Harris-Benedict equation (r), 19 patients were considered hypermetabolic (r < 1.1), 30 normometabolic (0.9 < r < 1.1), and 6 hypometabolic (r < 0.9). An increase in FM correlated with r (P < 0.01) and was more marked in hypermetabolic patients. In contrast to the other two groups, Child-Pugh score and nutritional status remained unchanged in the hypometabolic patients. These results show that severe liver failure did not preclude improvement of nutritional status provided caloric intake was high. In Child C patients, improvement of nutritional status paralleled improvement of liver function and normalization of oxidative metabolism. Refractory ascites had negative effects on changes in nutritional status and liver function. Despite adequate caloric intake to energy requirements, hypometabolism has a poor prognosis regarding both nutritional status and liver function.

Trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in cirrhosis: a randomized trial.

OBJECTIVE: To assess the efficacy and safety of trimethoprim-sulfamethoxazole for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis and ascites. DESIGN: A randomized controlled trial. SETTING: University-affiliated Veterans Affairs medical center. PATIENTS: 60 consecutive patients with cirrhosis and ascites. INTERVENTIONS: Consecutive patients were randomly assigned to receive either no prophylaxis or trimethoprim-sulfamethoxazole, one double-strength tablet daily, five times a week (Monday through Friday). Patient entry was stratified by serum bilirubin (> 51 mumol/L [> 3 mg/dL]), ascitic fluid protein (< 1 g/dL), and serum creatinine (> 177 mumol/L [> 2 mg/dL]) levels to ensure that high-risk patients would be similarly distributed in the two groups. The median duration of follow-up for the study patients was 90 days. MAIN OUTCOME MEASURES: Spontaneous bacterial peritonitis or spontaneous bacteremia as defined by objective criteria. RESULTS: Spontaneous bacterial peritonitis or spontaneous bacteremia developed in 27% (8 of 30) of patients who did not receive prophylaxis compared with 3% (1 of 30) of patients receiving trimethoprim-sulfamethoxazole (P = 0.025). Overall, infections developed in 9 of 30 patients (30%) not receiving prophylaxis and in 1 of 30 patients (3%) receiving trimethoprim-sulfamethoxazole (P = 0.012). Death occurred in 6 of 30 patients (20%) who did not receive prophylaxis and in 2 of 30 patients (7%) who received trimethoprim-sulfamethoxazole (P = 0.15). Side effects--particularly, hematologic toxicity--could not be attributed to trimethoprim-sulfamethoxazole in any patient. CONCLUSIONS: Trimethoprim-sulfamethoxazole was efficacious, safe, and cost-effective for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis.

Energy expenditure in patients with hepatocellular carcinoma.

BACKGROUND: An increase in resting energy expenditure (REE) is considered to contribute to the weight loss experienced by patients with cancer. However, alternations in basal metabolism vary among patients with different neoplasms. REE in patients with hepatocellular carcinoma (HCC), a common malignant tumor in Taiwan, was evaluated. METHODS: Fifty-seven male patients with HCC and 60 male control subjects without known cancer were entered in the study. The groups did not differ significantly in age, body weight, and height. Indirect calorimetry was used to measure REE. Oxidative rates of endogenous substrates also were calculated. RESULTS: REE was significantly higher in the HCC group than the control group (22.12 +/- 0.36 kcal/kg/day versus 20.99 +/- 0.27 kcal/kg/day, P < 0.05; and 115.3 +/- 4.3 kcal/100 mg creatinine versus 102.2 +/- 3.8 kcal/100 mg creatinine, P < 0.05). A higher measured-to-predicted-REE ratio also was observed in the HCC group (101.5% +/- 1.4% versus 93.6% +/- 1.0%; P < 0.005). REE in patients with HCC did not differ according to whether patients had liver cirrhosis or ascites. In addition, REE of patients with large and medium tumors were higher than were those of patients with small tumors, but no difference was found between the REE of patients with small tumors and the control subjects. Also observed were an increase in oxidation of fat with a decrease in oxidation of protein in patients with HCC and a relative decrease in the contribution of fat with an increase in the contribution of carbohydrates to REE after the increase of tumor size. CONCLUSIONS: The results suggest that patients with HCC are hypermetabolic and the elevation in REE is related to tumor size, not to the presence of liver cirrhosis or ascites.