Background and aimsObesity 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.MethodsWe analysed 678 patients with cirrhosis. Sarcopenia, sarcopenic obesity and myosteatosis were analysed by CT scan using the third lumbar vertebrae skeletal muscle and attenuation indexes, using previously validated gender‐and body mass index‐specific cutoffs.ResultsPatients were predominately men (n = 457, 67%), and cirrhosis aetiology was hepatitis C virus in 269 patients (40%), alcohol in 153 (23%), non‐alcoholic steatohepatitis/cryptogenic in 96 (14%), autoimmune liver disease in 55 (8%), hepatitis B virus in 43 (6%), and others in 5 patients (1%). Sarcopenia was present in 292 (43%), 135 had sarcopenic obesity (20%) and 353 had myosteatosis (52%). Patients with sarcopenia (22 ± 3 vs. 95 ± 22 months, P < 0.001), sarcopenic obesity (22 ± 3 vs. 95 ± 22 months, P < 0.001), and myosteatosis (28 ± 5 vs. 95 ± 22 months, P < 0.001) had worse median survival than patients without muscular abnormalities. By multivariate Cox regression analysis, both sarcopenia [hazard ratio (HR) 2.00, 95% confidence interval (CI) 1.44–2.77, P < 0.001], and myosteatosis (HR 1.42, 95% CI 1.02–1.07, P = 0.04) were associated with mortality.ConclusionsSarcopenia, sarcopenic obesity and myosteatosis are often present in patients with cirrhosis, and sarcopenia and myosteatosis are independently associated with a higher long‐term mortality in cirrhosis.

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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 6 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 5 0.002), patients with ascites (P 5 0.02), and patients with higher bilirubin levels (P 5 0.05), creatinine levels (P 5 0.02), international normalized ratios (P 5 0.04), Child-Pugh scores (P 5 0.002), and Model for End-Stage Liver Disease scores (P 5 0.002). The median survival period after liver transplantation was 117 6 17 months for sarcopenic patients and 146 6 20 months for nonsarcopenic patients (P 5 0.4). Sarcopenic patients had longer hospital stays (40 6 4 versus 25 6 3 days; P 5 0.005) and a higher frequency of bacterial infections within the first 90 days after liver transplantation (26% versus 15%, P 5 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. V C 2014 AASLD.

Wait-listed (n ϭ 226) or post-liver transplantation (n ϭ 241) chronic hepatitis B (CHB) patients with lamivudine-resistant hepatitis B virus (HBV) were treated with adefovir dipivoxil for a median of 39 and 99 weeks, respectively. Among wait-listed patients, serum HBV DNA levels became undetectable (Ͻ1,000 copies/mL) in 59% and 65% at weeks 48 and 96, respectively. After 48 weeks, alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 77%, 76%, 60%, and 84% of wait-listed patients, respectively. Among posttransplantation patients, serum HBV DNA levels became undetectable in 40% and 65% at weeks 48 and 96, respectively. After 48 weeks, ALT, albumin, bilirubin, and prothrombin time normalized in 51%, 81%, 76%, and 56% of posttransplantation patients, respectively. Among wait-listed patients who underwent on-study liver transplantation, protection from graft reinfection over a median of 35 weeks was similar among patients who did (n ϭ 34) or did not (n ϭ 23) receive hepatitis B immunoglobulin (HBIg). Hepatitis B surface antigen was detected on the first measurement only in 6% and 9% of patients who did or did not receive HBIg, respectively. Serum HBV DNA was detected on consecutive visits in 6% and 0% of patients who did or did not receive HBIg, respectively. Treatment-related adverse events led to discontinuation of adefovir dipivoxil in 4% of patients. Cumulative probabilities of resistance were 0%, 2%, and 2% at weeks 48, 96, and 144, respectively. In conclusion, adefovir dipivoxil is effective and safe in wait-listed or posttransplantation CHB patients with lamivudine-resistant HBV and prevents graft reinfection with or without HBIg. Liver Transpl 13:349-360, 2007.

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Frailty is strongly and independently associated with an increased risk of unplanned hospitalization or death in outpatients with cirrhosis. The CFS is a rapid screen that could be easily adopted in liver clinics to identify those at highest risk of adverse events.

A breakdown in intestinal barrier function and increased bacterial translocation are key events in the pathogenesis of sepsis and liver disease. Altering gut microflora with noninvasive and immunomodulatory probiotic organisms has been proposed as an adjunctive therapy to reduce the level of bacterial translocation and prevent the onset of sepsis. The purpose of this study was to determine the efficacy of a probiotic compound in attenuating hepatic and intestinal injury in a mouse model of sepsis. Wild-type and interleukin-10 (IL-10) gene-deficient 129 Sv/Ev mice were fed the probiotic compound VSL#3 for 7 days. To induce sepsis, the mice were injected with lipopolysaccharide (LPS) and D-galactosamine (GalN) in the presence and absence of the peroxisome proliferator-activated receptor gamma (PPAR␥) inhibitor GW9662. The mice were killed after 6 hours, and their colons were removed for the measurement of the cytokine production and epithelial function. The functional permeability was assessed by the mannitol movement and cyclic adenosine monophosphate-dependent chloride secretion in tissue mounted in Ussing chambers. The livers were analyzed for bacterial translocation, cytokine production, histological injury, and PPAR␥ levels. The tissue levels of tumor necrosis factor alpha, interferon gamma, IL-6, and IL-12p35 ribonucleic acid were measured by semiquantitative reverse transcription polymerase chain reaction. L iver dysfunction and failure contribute to the high mortality rates seen in patients with Gram-negative sepsis. The presence of lipopolysaccharide (LPS) from Gram-negative bacteria in the systemic circulation results in the activation of the innate immune system and the secretion of high levels of proinflammatory cytokines. In animal models, LPS challenge can induce a systemic reaction resulting in a sepsis-like condition characterized by fever, hypotension, and widespread tissue damage. D-Galactosamine (GalN) increases the susceptibility of mice to LPS-induced shock by impairing liver metabolism. 1 Challenging mice with low doses of LPS in conjunction with GalN results in massive liver apoptosis and increased mortality.Tumor necrosis factor alpha (TNF-␣) plays a central role in the overwhelming systemic inflammatory response to LPS. 2 However, the complete blockade of TNF-␣ production does not improve survival in animals or humans 3 The activation of nuclear factor kappa B (NF-B) has been shown to play a key role in the pathogenesis of sepsis and is a pivotal step in the regulation of several immune and proinflammatory genes, including TNF-␣. 4 The modulation of NF-B activity has been proposed as a strategy for reducing the mortality associated with sepsis. Peroxisome proliferator-activated receptor gamma (PPAR␥) is a nuclear hormone receptor and transcription