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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 55u2009±u20091 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 (Pu2009=u20090.002), patients with ascites (Pu2009=u20090.02), and patients with higher bilirubin levels (Pu2009=u20090.05), creatinine levels (Pu2009=u20090.02), international normalized ratios (Pu2009=u20090.04), Child‐Pugh scores (Pu2009=u20090.002), and Model for End‐Stage Liver Disease scores (Pu2009=u20090.002). The median survival period after liver transplantation was 117u2009±u200917 months for sarcopenic patients and 146u2009±u200920 months for nonsarcopenic patients (Pu2009=u20090.4). Sarcopenic patients had longer hospital stays (40u2009±u20094 versus 25u2009±u20093 days; Pu2009=u20090.005) and a higher frequency of bacterial infections within the first 90 days after liver transplantation (26% versus 15%, Pu2009=u20090.04) 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.

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.

Cholangiocarcinoma: Has There been Any Progress?

Cholangiocarcinoma is the second most common primary hepatic tumour after hepatocellular carcinoma. Primary sclerosing cholangitis is one of the most commonly recognized risk factors for cholangiocarcinoma; however, approximately 90% of patients have no identifiable risk factors. Extrahepatic type is its most common presentation. Cholangiocarcinoma is considered to be a devastating disease, with a poor survival rate and few therapeutic options. Although surgical resection has been considered the best treatment option for localized cholangiocarcinoma, local recurrences of this cancer are very common, and imply persistent micro-metastatic disease in lymph nodes or at surgical margins, even after extended surgical resection. Consequently, the five year survival rate after attempted curative resection is only 20% to 40%. Early studies of liver transplantation for cholangiocarcinoma did not show a survival benefit and, currently, this tumour is considered to be an absolute contraindication for liver transplantation in most transplant centres worldwide. Recently, neoadjuvant chemoradiation in combination with liver transplantation for highly selected patients with cholangiocarcinoma has shown impressive results, with five-year survival rates at approximately 76% to 82%--similar to other standard indications for liver transplantation, such as hepatocellular carcinoma or hepatitis C-induced cirrhosis. However, this success of liver transplantation applies to only a subset of patients and most of the data originated from a single centre. Wider application of this strategy, especially for patients with potentially resectable disease, will require validation by other centres.

The 22/11 risk prediction model: a validated model for predicting 30-day mortality in patients with cirrhosis and spontaneous bacterial peritonitis.

OBJECTIVES:Clinicians do not have a validated tool for estimating the short-term mortality associated with spontaneous bacterial peritonitis (SBP). Accurate prognosis assessment is important for risk stratification and for individualizing therapy. We aimed therefore to develop and validate a model for the prediction of 30-day mortality in SBP patients receiving standard medical treatment (antibiotics and if indicated by guidelines, intravenous albumin therapy).METHODS:We retrospectively identified SBP patients treated at a tertiary care center between 2003 and 2011 (training set). Multivariate regression modeling and receiver operating characteristic (ROC) curves were utilized for statistical analysis. An external data set of 109 SBP patients was utilized for validation.RESULTS:Of the 184 patients in the training set, 66% were men with a median age of 55 years, a median MELD (Model for End-Stage Liver Disease) score of 20, and a 30-day mortality of 27%. Peripheral blood leukocyte count ≥11×109 cells/l (odds ratio (OR) 2.5; 95% confidence interval CI: 1.2–5.2) and MELD score ≥22 (OR 4.6; 95% CI: 2.3–9.6) were independent predictors of 30-day mortality. Patients with neither, one, or both variables had 30-day mortality rates of 8%, 32%, and 52%, respectively. The findings in the validation set mirrored the training set.CONCLUSIONS:In cirrhotic patients with SBP receiving standard therapy, MELD score ≥22 and peripheral blood leukocyte count ≥11×109 cells/l are validated independent predictors of mortality. The mortality in a patient without either poor prognostic variable is ≤10% and with both variables is ≥50%. Trials aiming to reduce mortality should target patients in the moderate-risk to high-risk groups.

Third-Generation Cephalosporin-Resistant Spontaneous Bacterial Peritonitis: A single-Centre Experience and Summary of Existing Studies

BACKGROUNDnSpontaneous bacterial peritonitis (SBP) is the most prevalent bacterial infection in patients with cirrhosis. Although studies from Europe have reported significant rates of resistance to third-generation cephalosporins, there are limited SBP-specific data from centres in North America.nnnOBJECTIVEnTo evaluate the prevalence of, predictors for and clinical impact of third-generation cephalosporin-resistant SBP at a Canadian tertiary care centre, and to summarize the data in the context of the existing literature.nnnMETHODSnSBP patients treated with both antibiotics and albumin therapy at a Canadian tertiary care hospital between 2003 and 2011 were retrospectively identified. Multivariate logistic regression was used to determine independent predictors of third-generation cephalosporin resistance and mortality.nnnRESULTSnIn 192 patients, 25% of infections were nosocomial. Forty per cent (77 of 192) of infections were culture positive; of these, 19% (15 of 77) were resistant to third-generation cephalosporins. The prevalence of cephalosporin resistance was 8% with community-acquired infections, 17% with health care-associated infections and 41% with nosocomial acquisition. Nosocomial acquisition of infection was the only predictor of resistance to third-generation cephalosporins (OR 4.0 [95% CI 1.04 to 15.2]). Thirty-day mortality censored for liver transplantation was 27% (50 of 184). In the 77 culture-positive patients, resistance to third-generation cephalosporins (OR 5.3 [1.3 to 22]) and the Model for End-stage Live Disease score (OR 1.14 [1.04 to 1.24]) were independent predictors of 30-day mortality.nnnCONCLUSIONSnThird-generation cephalosporin-resistant SBP is a common diagnosis and has an effect on clinical outcomes. In an attempt to reduce the mortality associated with resistance to empirical therapy, high-risk subgroups should receive broader empirical antibiotic coverage.

Hyperhomocysteinemia is associated with severity of cirrhosis and negative impact after liver transplantation.

Hyperhomocysteinemia constitutes an independent risk factor for thrombosis and cellular injury promoted by oxidative stress. The clinical significance of hyperhomocysteinemia in cirrhosis and outcomes post‐liver transplantation is poorly documented. In this study, we aimed to determine the prevalence of hyperhomocysteinemia in cirrhosis, evaluate its association with thrombosis and severity of liver disease, and its impact on survival after liver transplantation.

Association between Low Testosterone Levels and Sarcopenia in Cirrhosis: A Cross-sectional Study

INTRODUCTION AND AIMnSarcopenia is an independent predictor of mortality in cirrhosis. Hypogonadism is common in cirrhosis and has been associated with sarcopenia in non-cirrhotic chronic liver disease populations. The aim of this study is to investigate if sarcopenia is associated with low testosterone levels in patients with cirrhosis.nnnMATERIAL AND METHODSnThis is a retrospective analysis of prospectively collected data of 211 cirrhotic patients undergoing evaluation for liver transplantation. Sarcopenia was defined by computed tomography (CT) scan using specific cutoffs of the 3rd lumbar vertebra skeletal muscle index (L3 SMI). Morning testosterone levels were obtained in all patients.nnnRESULTSnOf the 211 patients, sarcopenia was noted in 94 (45%). Testosterone levels were lower in sarcopenic patients (10.7 ± 1.1 vs. 13.7 ± 1.4 nmol/L, p = 0.03) and hypotestosteronemia was more frequent in them too (34 vs. 16%, p = 0.004). In males, those with sarcopenia had lower testosterone levels (14.6 ± 1.4 vs. 21.9 ± 1.8, p = 0.002), and the corresponding frequency of hypotestosteronemia (42 vs. 19%, p = 0.006) was also higher. There were no significant differences in female patients. There was a weak correlation between L3 SMI and testosterone levels (r 0.37, p < 0.001). On multivariable regression analysis including sex, body mass index (BMI), hypotestosteronemia, MELD and etiology of cirrhosis, only hypotestosteronemia (RR 2.76, p = 0.005) and BMI (RR 0.88, p < 0.001) were independently associated with sarcopenia.nnnCONCLUSIONnLow testosterone levels are associated with sarcopenia in male cirrhotic patients. The potential therapeutic effect of testosterone to reverse sarcopenia in these patients warrants evaluation in future trials.INTRODUCTION AND AIMnSarcopenia is an independent predictor of mortality in cirrhosis. Hypogonadism is common in cirrhosis and has been associated with sarcopenia in non-cirrhotic chronic liver disease populations. The aim of this study is to investigate if sarcopenia is associated with low testosterone levels in patients with cirrhosis.nnnMATERIAL AND METHODSnThis is a retrospective analysis of prospectively collected data of 211 cirrhotic patients undergoing evaluation for liver transplantation. Sarcopenia was defined by computed tomography (CT) scan using specific cutoffs of the 3rd lumbar vertebra skeletal muscle index (L3 SMI). Morning testosterone levels were obtained in all patients.nnnRESULTSnOf the 211 patients, sarcopenia was noted in 94 (45%). Testosterone levels were lower in sarcopenic patients (10.7 ± 1.1 vs. 13.7 ± 1.4 nmol/L, p = 0.03) and hypotestosteronemia was more frequent in them too (34 vs. 16%, p = 0.004). In males, those with sarcopenia had lower testosterone levels (14.6 ± 1.4 vs. 21.9 ± 1.8, p = 0.002), and the corresponding frequency of hypotestosteronemia (42 vs. 19%, p = 0.006) was also higher. There were no significant differences in female patients. There was a weak correlation between L3 SMI and testosterone levels (r 0.37, p < 0.001). On multivariable regression analysis including sex, body mass index (BMI), hypotestosteronemia, MELD and etiology of cirrhosis, only hypotestosteronemia (RR 2.76, p = 0.005) and BMI (RR 0.88, p < 0.001) were independently associated with sarcopenia.nnnCONCLUSIONnLow testosterone levels are associated with sarcopenia in male cirrhotic patients. The potential therapeutic effect of testosterone to reverse sarcopenia in these patients warrants evaluation in future trials.

The Development of Hemochromatosis after Treatment for Celiac Sprue

Celiac sprue is a chronic disease characterized by maldigestion and malabsorption. Whereas many diseases have been reported in association with celiac sprue, hemochromatosis has not. A 62-year-old man with celiac sprue and a history of iron deficiency and osteopenic bone disease who developed hemochromatosis is reported. Liver biopsy showed portal tract fibrosis, early nodule formation and increased hepatic iron storage. The patient developed hemochromatosis with hepatic injury two years after his transferrin saturation became elevated and 10 years after he had been placed on gluten-free diet. Lifelong iron accumulation was prevented by chronic malabsorption of iron but hemochromatosis became manifest when his celiac sprue was treated.