Aldo J. Montano-Loza

Severe muscle depletion in patients on the liver transplant wait list: Its prevalence and independent prognostic value

As detected by cross‐sectional imaging, severe muscle depletion, which is termed sarcopenia, holds promise for prognostication in patients with cirrhosis. Our aims were to describe the prevalence and predictors of sarcopenia in patients with cirrhosis listed for liver transplantation (LT) and to determine its independent prognostic significance for the prediction of waiting‐list mortality. Adults listed for LT who underwent abdominal computed tomography/magnetic resonance imaging within 6 weeks of activation were retrospectively identified. The exclusions were hepatocellular carcinoma, acute liver failure, prior LT, and listing for multivisceral transplantation or living related LT. Sixty percent of the 142 eligible patients were male, the median age was 53 years, and the median Model for End‐Stage Liver Disease (MELD) score at listing was 15. Forty‐one percent were sarcopenic; sarcopenia was more prevalent in males versus females (54% versus 21%, P < 0.001) and increased with the Child‐Pugh class (10% for class A, 34% for class B, and 54% for class C, P = 0.007). Male sex, the dry‐weight body mass index (BMI), and Child‐Pugh class C cirrhosis (but not the MELD score) were independent predictors of sarcopenia. Sarcopenia was an independent predictor of mortality (hazard ratio = 2.36, 95% confidence interval = 1.23‐4.53) after adjustments for age and MELD scores. In conclusion, sarcopenia is associated with increased waiting‐list mortality and is poorly predicted by subjective nutritional assessment tools such as BMI and subjective global assessment. If this is validated in larger studies, the objective assessment of sarcopenia holds promise for prognostication in this patient population. Liver Transpl 18:1209–1216, 2012.

Sarcopenia as a prognostic index of nutritional status in concurrent cirrhosis and hepatocellular carcinoma.

Background and Aims: Abnormal body composition such as severe skeletal muscle depletion or sarcopenia has emerged as an independent predictor of clinical outcomes in a variety of clinical conditions. This study is the first study to report the frequency and prognostic significance of sarcopenia as a marker of nutritional status in patients with hepatocellular carcinoma (HCC). Methods: We analyzed 116 patients with HCC who were consecutively evaluated for liver transplant. Skeletal muscle cross-sectional area was measured by CT. Sarcopenia was defined using previously established cutpoints. Results: Ninety-eight patients were males (85%), and the mean age was 58±6 years. Sarcopenia was present in 35 patients (30%). By univariate Cox analysis, male sex (HR, 3.84; P=0.02), lumbar skeletal muscle index (HR, 0.97; P=0.04), INR (HR, 8.18; P<0.001), MELD score (HR, 1.19; P<0.001), Child-Pugh (HR, 3.95; P<0.001), serum sodium (HR, 0.84; P<0.001), TNM stage (HR, 2.59; P<0.001), treatment type (HR, 0.53; P<0.001), and sarcopenia (HR, 2.27; P=0.004) were associated with increased risks of mortality. By multivariate Cox regression analysis, only MELD score (HR, 1.08; P=0.04), Child-Pugh (HR, 2.14; P=0.005), sodium (HR, 0.89; P=0.01), TNM stage (HR, 1.92; P<0.001), and sarcopenia (HR, 2.04; P=0.02) were independently associated with mortality. Median survival for sarcopenic patients was 16±6 versus 28±3 months in nonsarcopenic (P=0.003). Conclusions: Sarcopenia is present in almost one third of patients with HCC, and constitutes a strong and independent risk factor for mortality. Our results highlight the importance of body composition assessment in clinical practice.

Severe muscle depletion predicts postoperative length of stay but is not associated with survival after liver transplantation: Sarcopenia After Liver Transplantation

Muscle depletion or sarcopenia is associated with increased mortality in patients with cirrhosis; how it affects mortality after liver transplantation requires further study. In this study, we aimed to establish whether sarcopenia predicts increased morbidity or mortality after liver transplantation. We analyzed 248 patients with cirrhosis who had a computed tomography (CT) scan including the third lumbar vertebra before liver transplantation. Data were recovered from medical charts, the skeletal muscle cross‐sectional area was measured with CT, and sarcopenia was defined with previously published sex‐ and body mass index–specific cutoffs. One hundred sixty‐nine patients (68%) were male, and the mean age at transplantation was 55 ± 1 years. The etiologies of cirrhosis were hepatitis C virus (51%), alcohol (19%), autoimmune liver diseases (15%), hepatitis B virus (8%), and other etiologies (7%). Sarcopenia was present in 112 patients (45%), and it was more frequent in males (P = 0.002), patients with ascites (P = 0.02), and patients with higher bilirubin levels (P = 0.05), creatinine levels (P = 0.02), international normalized ratios (P = 0.04), Child‐Pugh scores (P = 0.002), and Model for End‐Stage Liver Disease scores (P = 0.002). The median survival period after liver transplantation was 117 ± 17 months for sarcopenic patients and 146 ± 20 months for nonsarcopenic patients (P = 0.4). Sarcopenic patients had longer hospital stays (40 ± 4 versus 25 ± 3 days; P = 0.005) and a higher frequency of bacterial infections within the first 90 days after liver transplantation (26% versus 15%, P = 0.04) in comparison with nonsarcopenic patients. In conclusion, sarcopenia is one of the most common complications in patients with cirrhosis and is predictive of longer hospital stays and a higher risk of perioperative bacterial infections after liver transplantation, but it is not associated with increased mortality. Liver Transpl 20:640–648, 2014.

Risk factors for recurrence of autoimmune hepatitis after liver transplantation

Autoimmune hepatitis has been reported to recur after liver transplantation. The aim of our study was to evaluate the risk factors associated with recurrence of autoimmune hepatitis. Forty‐six patients that underwent liver transplantation because of end‐stage liver disease secondary to autoimmune hepatitis were studied. Recurrence of autoimmune hepatitis was diagnosed in 11 of the 46 (24%) patients, and the overall 5‐year probability of recurrence was 18%. By univariate Cox analysis, the features before liver transplantation associated with a higher risk of recurrence were concomitant autoimmune disease [hazard ratio (HR), 3.74; 95% confidence interval (CI), 1.05–13.36; P = 0.04], high aspartate aminotransferase (HR, 1.09; 95% CI, 1.03–1.14; P = 0.002), high alanine aminotransferase (HR, 1.09; 95% CI, 1.03–1.20; P = 0.003), and high immunoglobulin G (IgG; HR, 1.25; 95% CI, 1.11–1.41; P = 0.0003). Moreover, patients with recurrence had a higher frequency of moderate to severe inflammatory activity (HR, 5.3; 95% CI, 1.55–18.79; P = 0.008) and plasma cell infiltration in the liver explant (HR, 5.8; 95% CI, 1.52–22.43; P = 0.01). In the multivariate Cox analysis, only the presence of moderate to severe inflammation (HR, 6.9; 95% CI, 1.76–26.96; P = 0.006) and high IgG levels before liver transplantation (HR, 7.5; 95% CI, 1.45–38.45; P = 0.02) were independently associated with the risk of autoimmune hepatitis recurrence. In conclusion, patients with concomitant autoimmune disease, high aspartate aminotransferase, alanine aminotransferase, and IgG before the transplant, or moderate to severe inflammatory activity or plasma cell infiltration in the liver explant have a higher risk of recurrent disease. These findings suggest that recurrence of autoimmune hepatitis may reflect incomplete suppression of disease activity prior to liver transplantation. Liver Transpl 15:1254–1261, 2009.

Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis

Obesity is frequently associated with cirrhosis, and cirrhotic patients may develop simultaneous loss of skeletal muscle and gain of adipose tissue, culminating in the condition of sarcopenic obesity. Additionally, muscle depletion is characterized by both a reduction in muscle size and increased proportion of muscular fat, termed myosteatosis. In this study, we aimed to establish the frequency and clinical significance of sarcopenia, sarcopenic obesity and myosteatosis in cirrhotic patients.

Inclusion of Sarcopenia Within MELD (MELD-Sarcopenia) and the Prediction of Mortality in Patients With Cirrhosis

OBJECTIVES:Limitations of the Model for End-Stage Liver Disease (MELD) score include its failure to assess the nutritional and functional status of cirrhotic patients. Our objectives were to evaluate the impact of sarcopenia in cirrhosis and whether the inclusion of muscularity assessment within MELD could improve the prediction of mortality in patients with cirrhosis.METHODS:We included 669 cirrhotic patients who were consecutively evaluated for liver transplantation. Skeletal muscle index at the third lumbar vertebra (L3 SMI) was measured by computed tomography, and sarcopenia was defined using previously published gender and body mass index–specific cutoffs. Using Cox proportional hazards regression, a novel MELD-sarcopenia score was derived.RESULTS:Sarcopenia was present in 298 patients (45%); sarcopenic patients had shorter median survival than non-sarcopenic patients (20±3 vs. 95±24 months, P<0.001). By Cox regression analysis adjusted for age, gender, and hepatocellular carcinoma, both MELD (hazard ratio (HR) 1.08, 95% confidence interval (CI) 1.06–1.10, P<0.001), and the L3 SMI (HR 0.97, 95% CI 0.96–0.99, P<0.001) were associated with mortality. Overall, the c-statistics for 3-month mortality were 0.82 (95% CI 0.78–0.87) for MELD and 0.85 (95% CI 0.81–0.88) for MELD-sarcopenia (P=0.1). Corresponding figures for 1-year mortality were 0.73 (95% CI 0.69–0.77) and 0.77 (95% CI 0.73–0.80), respectively (P=0.03). The c-statistics for 3-month mortality in patients with MELD<15 (0.85 vs. 0.69, P=0.02) and refractory ascites (0.74 vs. 0.71, P=0.01) were significantly higher for MELD-sarcopenia compared with MELD.CONCLUSIONS:Modification of MELD to include sarcopenia is associated with improved prediction of mortality in patients with cirrhosis, primarily in patients with low MELD scores. External validation of this prognostic index in larger cohorts of cirrhotic patients is warranted.

The association of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs in peptic ulcer disease

BACKGROUND AND AIM Peptic ulcer disease (PUD) affects 10% of the world population. Helicobacter pylori infection and the use of a nonsteroidal anti-inflammatory drug (NSAID) are the principal factors associated with PUD. The aim of the present study was to evaluate a cohort of patients with PUD and determine the association between H pylori infection and NSAID use. PATIENTS AND METHODS The medical charts of patients with endoscopic diagnosis of PUD were retrospectively reviewed from September 2002 to August 2003. Patients were divided into three groups according to ulcer etiology: H pylori infection (group 1); NSAID use (group 2); and combined H pylori infection and NSAID use (group 3). RESULTS One hundred two patients were evaluated: 36 men (35.3%) and 66 women (64.7%). Forty patients had H pylori infection, 43 had used NSAIDs and 15 had combined H pylori infection and NSAID use; four patients with ulcers secondary to malignancy were excluded. The frequency of women was significantly higher in group 2 (P=0.01). The mean age of patients in group 1 was significantly lower than in the other two groups (P=0.003). PUD developed earlier in group 3 than in group 2 (5.0+/-4.7 months versus 1.4+/-2.1 months, respectively, P=0.018). Thirty-two patients (32.7%) had bleeding peptic ulcer. Group 2 had a higher risk of bleeding peptic ulcer than the other two groups (P=0.001). CONCLUSIONS The development of PUD was observed earlier in the combined H pylori and NSAID group than in patients with only NSAID use. This suggests a synergic effect between the two risks factors in the development of PUD.

Locoregional radiological treatment for hepatocellular carcinoma; Which, when and how?

Hepatocellular carcinoma (HCC) is one of the most frequent and deadliest cancers worldwide. Liver transplantation, surgical resection or local ablation offer the best survival advantages but most patients either present when the tumor is in an advanced stage or the degree of underlying liver disease precludes these options. Several therapies have been proposed for these patients with proven survival benefits. These therapies comprise the locoregional treatment for HCC, and include percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and drug-eluting bead (DEB). PEI and RFA are considered curative treatments for early stage HCC; whereas TACE is a standard of care for intermediate stages. Additionally, evaluation of response to locoregional treatment in HCC is important, as objective response may become a surrogate marker for improved survival. Currently, there are several criteria for response assessment, including the World Health Organization (WHO), the Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver Criteria (EASL), and the modified RECIST (mRECIST); however, there has been poor correlation between the clinical benefit provided by locoregional interventional therapies and conventional methods of response assessment. The aim of our study was to review and analyze the current evidence for radiological interventions in HCC, and to propose evidence based recommendations to improve the management of these patients.

Frequency, Behavior, and Prognostic Implications of Antimitochondrial Antibodies in Type 1 Autoimmune Hepatitis

Background Antimitochondrial antibodies (AMA) can occur in autoimmune hepatitis, but their durability and prognostic significance are uncertain. Objectives Determine the frequency, behavior, and prognostic implications of AMA in type 1 autoimmune hepatitis. Methods One hundred thirty patients were tested for AMA by the same enzyme-linked immunosorbent assay at accession and during 123±9 months of observation (mean, 6±0.2 determinations/patient). Findings were correlated with clinical and histologic features and treatment outcomes. Results Twenty-four patients (18%) had AMA, including 17 who had the antibodies at accession (71%) and 7 who developed them during follow-up (29%). AMA persisted in 13 patients (54%) who were tested on 5±1 occasions during 141±33 months. Cholestatic histologic features occurred as commonly in patients with and without AMA at presentation (18% vs. 10%, P=0.4). AMA disappeared in 4 patients, and they developed in 7 patients after 34±7 months. Late expression of antibodies was not associated with a higher frequency of cholestatic histologic changes than continued seronegativity (14% vs. 9%, P=0.5). Remission (83% vs. 76%, P=0.4) and treatment failure (8% vs. 11%, P>0.9) occurred as commonly in both groups. Conclusions AMA can appear and disappear. They do not identify a subgroup that requires different treatment or that evolves quickly into a cholestatic syndrome.

Cyclosporine A protects against primary biliary cirrhosis recurrence after liver transplantation.

Primary biliary cirrhosis (PBC) reoccurs in a proportion of patients following liver transplantation (LT). The aims of our study were to evaluate the risk factors associated with PBC recurrence and determine whether recurrent disease constitutes a negative predictor for survival. One hundred and eight patients receiving LT for end‐stage PBC were studied. Recurrent disease was diagnosed in 28 patients (26%). Probability of recurrent PBC at 5 years was 13% and 29% at 10 years with an overall incidence of 3.97 cases per 100 patient years. By univariate Cox analysis use of tacrolimus (HR 6.28, 95% CI, 2.44–16.11, p < 0.001) and mycophenolate mofetil (HR 5.21, 95% CI, 1.89–14.33, p = 0.001) were associated with higher risk of recurrence; whereas use of cyclosporine A (CsA) and azathioprine were associated with reduced risk of recurrence (HR 0.13, 95% CI 0.05–0.35, p < 0.001 and HR 0.27, 95% CI 0.11–0.64, p = 0.003, respectively). In the multivariate Cox analysis, only CsA was independently associated with protection against recurrence (HR 0.17, 95% CI 0.06–0.71, p = 0.02). Five‐year probability of survival was 83% and 96%, in patients without and with recurrence (log‐rank test, p = 0.3). Although PBC transplant recipients receiving CsA have a lower risk of disease recurrence, the development of recurrent PBC did not impact on long‐term patient survival.