M. Giusto

Cirrhotic Patients Are at Risk for Health Care–Associated Bacterial Infections

BACKGROUND & AIMS Bacterial infections are a frequent and serious burden among patients with cirrhosis because they can further deteriorate liver function. We assessed the epidemiology, risk factors, and clinical consequences of bacterial infections in hospitalized cirrhotic patients. METHODS In a cohort of hospitalized cirrhotic patients (n = 150) referred to a tertiary care setting, all episodes of bacterial infections were recorded prospectively. Infections were classified as community-acquired (CA), health care-associated (HCA), or hospital-acquired (HA). Site of infection, characteristics of bacteria, and prevalence of antibiotic resistance were reported; consequences for liver function and patient survival were evaluated. RESULTS Fifty-four infections were observed among 50 patients (12 CA, 22 HCA, and 20 HA). Bacterial resistance was more frequent among patients with HCA or HA infections (64% of isolates). Mortality was 37% from HA, 36% from HCA, and 0% from CA infections. Independent predictors of infection included a previous infection within the past 12 months (P = .0001; 95% confidence interval [CI], 2.2-10.6), model of end-stage liver disease score ≥ 5 (P = .01; 95% CI, 1.3-6.1), and protein malnutrition (P = .04; 95% CI, 1.5-10). Infectious episodes worsened liver function in 62% of patients. Patients with infection more frequently developed ascites, hepatic encephalopathy, hyponatremia, hepatorenal syndrome, or septic shock. Child class C (P = .006; 95% CI, 1.67-23.7), sepsis (P = .005; 95% CI, 1.7-21.4), and protein malnutrition (P = .001; 95% CI, 2.8-38.5) increased mortality among patients in the hospital. CONCLUSIONS In hospitalized cirrhotic patients, the most frequent infections are HCA and HA; these infections are frequently resistant to antibiotics. As infections worsen, liver function deteriorates and mortality increases. Cirrhotic patients should be monitored closely for infections.

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.

The chronic use of beta-blockers and proton pump inhibitors may affect the rate of bacterial infections in cirrhosis

Bacterial infections are among the most common and life‐threatening complications in cirrhosis. Qualitative and quantitative modifications of the gut microbiota, dysfunction of the intestinal barrier and multiple immune defects are factors that contribute to a pathological ‘bacterial translocation’ (BT), leading to a higher susceptibility to infections in cirrhotic patients. Long‐term therapies, commonly adopted in cirrhotic patients, may influence BT and modify the risk of infection in these patients. To investigate the influence of chronic therapies on the prevalence and microbiological characteristics of infections in cirrhosis.

Cardiac dysfunction in cirrhosis is not associated with the severity of liver disease

BACKGROUND Cirrhotic cardiomiopathy is described as the presence of cardiac dysfunction in cirrhotic patients. The aim of the study was to investigate factors associated with cardiac dysfunction in cirrhotic patients. PATIENTS AND METHODS Seventy-four cirrhotic patients and twenty-six controls performed a conventional echocardiography and Tissue Doppler Imaging (TDI) for systolic and diastolic function. Results were analyzed by using the Guidelines of American Society of Echocardiography. RESULTS In patients with cirrhosis, left ventricular end-diastolic diameter was increased (p<0.001) , peak systolic velocities were decreased (11.3±2.7 vs 13.9±1.4cm/s; p<0.001) and left atrial volumes were increased (32.7±8.3 vs 24±8.5ml, p<0.001) as well as cardiac mass (90.6±23 vs 70.5±22g/m(2), p<0.001). Forty-seven cirrhotic patients (64%) showed diastolic dysfunction at rest: grade I in 37 and grade II in 10 patients. Systolic and/or diastolic dysfunction were not influenced by a more severe liver impairment. Diastolic dysfunction was more prevalent in patients with ascites vs those without (77% vs 56%; p=0.04). CONCLUSION A mild diastolic dysfunction at rest is frequent in cirrhotic patients but cardiac load conditions are confounding factors in this diagnosis. We did not identify an association between severity of liver disease and cardiac dysfunction.

Bone Disorders in Patients With Chronic Liver Disease Awaiting Liver Transplantation

BACKGROUND An important complication of chronic liver disease is osteodystrophy, which includes osteoporosis and the much rarer osteomalacia. Both conditions are associated with significant morbidity through fractures resulting in pain, deformity, and immobility. Liver transplantation may further deteriorate bone metabolism. The aim of the present study was to investigate the frequency and severity of hepatic osteodystrophy among patients with liver cirrhosis who were referred for liver transplantation. We also evaluated modifications in bone metabolism after liver transplantation. MATERIALS AND METHODS We recruited 35 consecutive patients with chronic liver disease who were undergoing assessment for transplantation over a 1-year period. Bone mass in the total skeleton and proximal hip was evaluated using a dual-energy X-ray absorptiometry device (Lunar Prodigy Advance, GE Healthcare, USA). According to World Health Organization recommendations, osteoporosis was defined as a T score < -2.5 and osteopenia as T score between -1 and -2.5. RESULTS We enrolled in the study 35 patients, including 8 females and 27 males of overall mean age of 57 +/- 7, who showed a viral etiology (57%) or alcohol etiology (28%), Child-Pugh 8.7 +/- 2.3. The overall prevalence of osteodystrophy was 40% (26% osteopenia and 14% osteoporosis). No difference was evident according to gender, severity of liver disease (Child-Pugh, Model for End-stage Liver Disease), or origin of liver disease. A subgroup of 10 transplanted patients reached 3-month follow-up, showing total body T score with a significant decrease after 3 months while femoral T scores tended to decrease insignificantly. CONCLUSIONS This study revealed a high prevalence of low bone mineral density among cirrhotic patients before liver transplantation. We suggest that both bone mineral density and biochemical examinations should be considered to be routine tests to identify the status of bone mass and bone metabolism among recipients prior to liver transplantation.

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.

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)