Barbara Lattanzi

Sarcopenia in liver cirrhosis: the role of computed tomography scan for the assessment of muscle mass compared with dual-energy X-ray absorptiometry and anthropometry.

Background Sarcopenia evaluated by computed tomography (CT) scan at the lumbar site has been identified as a risk factor for morbidity and mortality in cirrhosis. Aim The aim of this study was to compare the measurement of muscle mass through CT scan, considered the gold standard, with other reliable techniques to evaluate the rate of agreement between different available methods for the assessment of muscle mass in cirrhosis. The correlation between measurements of muscle mass and of muscle strength was also investigated. Patients and methods Adult patients eligible for liver transplantation were studied. Lumbar skeletal muscle cross-sectional area was measured by CT and muscle depletion was defined using previously published cut-offs. Mid-arm muscle circumference was calculated following anthropometric measures. The Fat-Free Mass Index and the Appendicular Skeletal Muscle Index were calculated using dual-energy X-ray absorptiometry. Muscle strength was evaluated using the Hand Grip test. Results Fifty-nine patients with cirrhosis were included. Sarcopenia was diagnosed in 76% of the patients according to CT evaluation. A significant reduction in Fat-Free Mass Index and Appendicular Skeletal Muscle Index was observed in 42–52% of the patients, whereas 52% showed a mid-arm muscle circumference less than 10th percentile. Skeletal muscle mass evaluation through CT was only weakly correlated with dual-energy X-ray absorptiometry and anthropometry evaluation. No correlation was observed between CT measurement of muscle mass and Hand Grip test. Conclusion CT scan can identify the highest percentage of sarcopenia in cirrhosis and no other techniques are actually available as a replacement. Future efforts should focus on approaches for assessing both skeletal muscle mass and function to provide a better evaluation of sarcopenia in cirrhotic patients.

Increased risk of cognitive impairment in cirrhotic patients with bacterial infections.

BACKGROUND & AIMS A causal relationship between infection, systemic inflammation, and hepatic encephalopathy (HE) has been suggested in cirrhosis. No study, however, has specifically examined, in cirrhotic patients with infection, the complete pattern of clinical and subclinical cognitive alterations and its reversibility after resolution. Our investigation was aimed at describing the characteristics of cognitive impairment in hospitalized cirrhotic patients, in comparison with patients without liver disease, with and without infection. METHODS One hundred and fifty cirrhotic patients were prospectively enrolled. Eighty-one patients without liver disease constituted the control group. Bacterial infections and sepsis were actively searched in all patients independently of their clinical evidence at entry. Neurological and psychometric assessment was performed at admission and in case of nosocomial infection. The patients were re-evaluated after the resolution of the infection and 3months later. RESULTS Cognitive impairment (overt or subclinical) was recorded in 42% of cirrhotics without infection, in 79% with infection without SIRS and in 90% with sepsis. The impairment was only subclinical in controls and occurred only in patients with sepsis (42%). Multivariate analysis selected infection as the only independent predictor of cognitive impairment (OR 9.5; 95% CI 3.5-26.2; p=0.00001) in cirrhosis. The subclinical alterations detected by psychometric tests were also strongly related to the infectious episode and reversible after its resolution. CONCLUSIONS Infections are associated with a worse cognitive impairment in cirrhotics compared to patients without liver disease. The search and treatment of infections are crucial to ameliorate both clinical and subclinical cognitive impairment of cirrhotic patients.

The spread of multi drug resistant infections is leading to an increase in the empirical antibiotic treatment failure in cirrhosis: a prospective survey.

Background The spread of multi-resistant infections represents a continuously growing problem in cirrhosis, particularly in patients in contact with the healthcare environment. Aim Our prospective study aimed to analyze epidemiology, prevalence and risk factors of multi-resistant infections, as well as the rate of failure of empirical antibiotic therapy in cirrhotic patients. Methods All consecutive cirrhotic patients hospitalized between 2008 and 2013 with a microbiologically-documented infection (MDI) were enrolled. Infections were classified as Community-Acquired (CA), Hospital-Acquired (HA) and Healthcare-Associated (HCA). Bacteria were classified as Multidrug-Resistant (MDR) if resistant to at least three antimicrobial classes, Extensively-Drug-Resistant (XDR) if only sensitive to one/two classes and Pandrug-Resistant (PDR) if resistant to all classes. Results One-hundred-twenty-four infections (15% CA, 52% HA, 33% HCA) were observed in 111 patients. Urinary tract infections, pneumonia and spontaneous bacterial peritonitis were the more frequent. Forty-seven percent of infections were caused by Gram-negative bacteria. Fifty-one percent of the isolates were multi-resistant to antibiotic therapy (76% MDR, 21% XDR, 3% PDR): the use of antibiotic prophylaxis (OR = 8.4; 95%CI = 1.03-76; P = 0,05) and current/recent contact with the healthcare-system (OR = 3.7; 95%CI = 1.05-13; P = 0.04) were selected as independent predictors. The failure of the empirical antibiotic therapy was progressively more frequent according to the degree of resistance. The therapy was inappropriate in the majority of HA and HCA infections. Conclusions Multi-resistant infections are increasing in hospitalized cirrhotic patients. A better knowledge of the epidemiological characteristics is important to improve the efficacy of empirical antibiotic therapy. The use of preventive measures aimed at reducing the spread of multi-resistant bacteria is also essential.

Sarcopenia Is Risk Factor for Development of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt Placement

Background & Aims Hepatic encephalopathy (HE) is an important complication in patients with cirrhosis who received transjugular intrahepatic portosystemic shunts (TIPS). We investigated whether a decrease in muscle mass was associated independently with the occurrence of HE after TIPS. Methods We performed a prospective study of 46 consecutive patients with cirrhosis (mean age, 58.6 ± 9.1 y; mean model for end‐stage liver disease score, 11.3 ± 3.3; mean Child–Pugh score, 7.6 ± 1.5) who received TIPS from January 2013 through December 2014 at a tertiary center in Rome, Italy. All patients underwent computed tomography analysis at the level of the third lumbar vertebrae to determine the skeletal muscle index; sarcopenia was defined by sex‐specific cut‐off values. We estimated the incidence of the first episode of HE after TIPS, taking into account the competing risk nature of the data (death or liver transplantation). Results Twenty‐six patients (57%) were found to have sarcopenia. Twenty‐one patients (46%) developed overt HE in the 7 ± 9 months after TIPS placement; all of these patients were sarcopenic, according to the skeletal muscle index. Of the 25 patients without HE after TIPS, only 5 had sarcopenia. In multivariate analysis, model for end‐stage liver disease score (subdistribution hazard ratio, 1.16; 95% confidence interval, 1.01–1.34; P = .043) and sarcopenia (subdistribution hazard ratio, 31.3; 95% confidence interval, 4.5–218.07; P < .001) were associated independently with the development of HE after TIPS placement. Conclusions In a prospective study of 46 patients with cirrhosis, we found muscle wasting, probably owing to reduced processing of ammonia, to be associated with the development of HE after TIPS placement. Sarcopenia should be considered in selecting patients for TIPS therapy. Nutritional status should be evaluated in patients with sarcopenia before TIPS placement, which might reduce the incidence of HE.

Changes in nutritional status after liver transplantation

Chronic liver disease has an important effect on nutritional status, and malnourishment is almost universally present in patients with end-stage liver disease who undergo liver transplantation. During recent decades, a trend has been reported that shows an increase in number of patients with end-stage liver disease and obesity in developed countries. The importance of carefully assessing the nutritional status during the work-up of patients who are candidates for liver replacement is widely recognised. Cirrhotic patients with depleted lean body mass (sarcopenia) and fat deposits have an increased surgical risk; malnutrition may further impact morbidity, mortality and costs in the post-transplantation setting. After transplantation and liver function is restored, many metabolic alterations are corrected, dietary intake is progressively normalised, and lifestyle changes may improve physical activity. Few studies have examined the modifications in body composition that occur in liver recipients. During the first 12 mo, the fat mass progressively increases in those patients who had previously depleted body mass, and the muscle mass recovery is subtle and non-significant by the end of the first year. In some patients, unregulated weight gain may lead to obesity and may promote metabolic disorders in the long term. Careful monitoring of nutritional changes will help identify the patients who are at risk for malnutrition or over-weight after liver transplantation. Physical and nutritional interventions must be investigated to evaluate their potential beneficial effect on body composition and muscle function after liver transplantation.

An empirical broad spectrum antibiotic therapy in health-care-associated infections improves survival in patients with cirrhosis: A randomized trial

Early diagnosis and appropriate treatment of infections in cirrhosis are crucial because of their high morbidity and mortality. Multidrug‐resistant (MDR) infections are on the increase in health care settings. Health‐care–associated (HCA) infections are still frequently treated as community‐acquired with a detrimental effect on survival. We aimed to prospectively evaluate in a randomized trial the effectiveness of a broad spectrum antibiotic treatment in patients with cirrhosis with HCA infections. Consecutive patients with cirrhosis hospitalized with HCA infections were enrolled. After culture sampling, patients were promptly randomized to receive a standard or a broad spectrum antibiotic treatment (NCT01820026). The primary endpoint was in‐hospital mortality. Efficacy, side effects, and the length of hospitalization were considered. Treatment failure was followed by a change in antibiotic therapy. Ninety‐six patients were randomized and 94 were included. The two groups were similar for demographic, clinical, and microbiological characteristics. The prevalence of MDR pathogens was 40% in the standard versus 46% in the broad spectrum group. In‐hospital mortality showed a substantial reduction in the broad spectrum versus standard group (6% vs. 25%; P = 0.01). In a post‐hoc analysis, reduction of mortality was more evident in patients with sepsis. The broad spectrum showed a lower rate of treatment failure than the standard therapy (18% vs. 51%; P = 0.001). Length of hospitalization was shorter in the broad spectrum (12.3 ± 7 days) versus standard group (18 ± 15 days; P = 0.03). Five patients in each group developed a second infection during hospitalization with a similar prevalence of MDR (50% broad spectrum vs. 60% standard). Conclusions: A broad spectrum antibiotic therapy as empirical treatment in HCA infections improves survival in cirrhosis. This treatment was significantly effective, safe, and cost saving. (Hepatology 2016;63:1632‐1639)

An empirical broad spectrum antibiotic therapy in Healthcare‐Associated infections improves survival in cirrhotics: A randomized trial

Early diagnosis and appropriate treatment of infections in cirrhosis are crucial because of their high morbidity and mortality. Multidrug‐resistant (MDR) infections are on the increase in health care settings. Health‐care–associated (HCA) infections are still frequently treated as community‐acquired with a detrimental effect on survival. We aimed to prospectively evaluate in a randomized trial the effectiveness of a broad spectrum antibiotic treatment in patients with cirrhosis with HCA infections. Consecutive patients with cirrhosis hospitalized with HCA infections were enrolled. After culture sampling, patients were promptly randomized to receive a standard or a broad spectrum antibiotic treatment (NCT01820026). The primary endpoint was in‐hospital mortality. Efficacy, side effects, and the length of hospitalization were considered. Treatment failure was followed by a change in antibiotic therapy. Ninety‐six patients were randomized and 94 were included. The two groups were similar for demographic, clinical, and microbiological characteristics. The prevalence of MDR pathogens was 40% in the standard versus 46% in the broad spectrum group. In‐hospital mortality showed a substantial reduction in the broad spectrum versus standard group (6% vs. 25%; P = 0.01). In a post‐hoc analysis, reduction of mortality was more evident in patients with sepsis. The broad spectrum showed a lower rate of treatment failure than the standard therapy (18% vs. 51%; P = 0.001). Length of hospitalization was shorter in the broad spectrum (12.3 ± 7 days) versus standard group (18 ± 15 days; P = 0.03). Five patients in each group developed a second infection during hospitalization with a similar prevalence of MDR (50% broad spectrum vs. 60% standard). Conclusions: A broad spectrum antibiotic therapy as empirical treatment in HCA infections improves survival in cirrhosis. This treatment was significantly effective, safe, and cost saving. (Hepatology 2016;63:1632‐1639)

Hepatic encephalopathy expands the predictivity of model for end‐stage liver disease in liver transplant setting: Evidence by means of 2 independent cohorts

Despite its documented prognostic relevance, hepatic encephalopathy (HE) is not considered in liver transplantation (LT) due to its possible poor objectivity. To override this problem, we aimed to analyze if an objective diagnosis of HE may confer additional mortality risk beyond MELD. Study and validation cohorts of patients with cirrhosis were considered in Italy and Canada, respectively. Patients were considered to be HE+ if an episode of overt HE was documented in a hospitalization. Of the 486 patients enrolled in Italy, 184 (38%) were HE+. During the 6‐month follow‐up, 77 patients died and 50 underwent transplantation. The 6‐month mortality of HE+ versus HE– patients was significantly higher (P < 0.001). Model for End‐Stage Liver Disease (MELD; subdistribution hazard ratio [sHR], 1.2; 95% confidence interval [CI], 1.1‐1.2; P < 0.001), HE+ (sHR, 3.6; 95% CI, 1.8‐7.1; P < 0.001), and sodium (sHR, 0.9; 95% CI, 0.8‐0.9; P < 0.001) were independent predictors of 6‐month mortality. In HE+ patients, short‐term mortality increased across the entire MELD spectrum (range, 6‐40). The results were unchanged by including or excluding patients with hepatocellular carcinoma or stratifying patients according to HE characteristics. The higher 6‐month mortality of HE+ versus HE– patients was confirmed also in the Canadian cohort (P < 0.001; n = 300, 33% HE+; 33 died, 104 transplanted). A similar and statistically significant C‐index increase derived by the incorporation of HE in MELD was observed both in the Italian (from 0.67 to 0.75) and Canadian (from 0.69 to 0.74) cohorts. A score based on MELD plus 7 points (95% CI, 4‐10) for HE+ patients optimally predicted 6‐month mortality in the 2 cohorts. According to the net reclassification index, by not considering HE, 29% of overall patients were misclassified by MELD score. In conclusion, the incorporation of HE in MELD score might improve the listing and allocation policy in LT. Liver Transplantation 22 1333–1342 2016 AASLD.

Graft macrosteatosis and time of T-tube removal as risk factors for biliary strictures after liver transplantation.

Biliary strictures (BS) remain a significant problem following liver transplantation (LT), representing an important cause of morbidity. The purpose of this follow‐up study was to evaluate the incidence and risk factors associated with BS after LT. From 2001 to 2009, 244 consecutive patients underwent LT at our center. Multiple donor and recipient variables were collected for each patient. Exclusion criteria were hepaticojejunostomy, living‐donor LT, and follow‐up less than three months. We reviewed 177 patients, all of whom underwent an end‐to‐end choledochocholedochostomy and T‐tube placement. BS occurred in 23% of patients. Multivariate analysis revealed that graft macrovesicular steatosis >25% (p = 0.05, OR 3.38) and time of T‐tube removal less than six months (p = 0.02, OR 2.53) were independent risk factors for BS. Biliary strictures did not affect patient and graft survival. Donor macrovesicular steatosis represents a risk factor for BS, contributing to liver damage through a reduction in hepatic blood flow. Time of T‐tube removal seems to play a role in the development of BS, although it is unclear whether it represents the cause or the consequence of the development of BS.

A low muscle mass increases mortality in compensated cirrhotic patients with sepsis

Severe infections and muscle wasting are both associated to poor outcome in cirrhosis. A possible synergic effect of these two entities in cirrhotic patients has not been previously investigated. We aimed at analysing if a low muscle mass may deteriorate the outcome of cirrhotic patients with sepsis.