Maria Kalafateli

Malnutrition and sarcopenia predict post-liver transplantation outcomes independently of the Model for End-stage Liver Disease score

Although malnutrition and sarcopenia are prevalent in cirrhosis, their impact on outcomes following liver transplantation is not well documented.

Non-variceal Gastrointestinal Bleeding in Patients with Liver Cirrhosis: A Review

BackgroundNon-variceal gastrointestinal (NVGI) bleeding in cirrhosis may be associated with life-threatening complications similar to variceal bleeding.AimTo review NVGI bleeding in cirrhosis.MethodsMEDLINE, Scopus, and ISI Web of Knowledge were searched, using the textwords “portal hypertensive gastropathy,” “gastric vascular ectasia,” “peptic ulcer,” “Dieulafoy’s,” “Mallory–Weiss syndrome,” “portal hypertensive enteropathy,” “portal hypertensive colopathy,” “hemorrhoids,” and “cirrhosis.”ResultsPortal hypertensive gastropathy (PHG) and gastric vascular ectasia (GVE) are gastric lesions that most commonly present as chronic anemia; acute upper GI (UGI) bleeding is a rare manifestation. Management of PHG-related bleeding is mainly pharmacological, whereas endoscopic intervention is favored in GVE-related bleeding. Shunt therapies or more invasive techniques are restricted in refractory cases. Despite its high incidence in cirrhotic patients, peptic ulcer accounts for a relatively small proportion of UGI bleeding in this patient population. However, in contrary to general population, the pathogenetic role of Helicobacter pylori infection remains questionable. Finally, other causes of UGI bleeding include Dieulafoy’s lesion, Mallory–Weiss syndrome, and portal hypertensive enteropathy. The most common non-variceal endoscopic findings reported in patients with lower gastrointestinal bleeding are portal hypertensive colopathy and hemorrhoids. However, the vast majority of studies are case reports and, therefore, the incidence, diagnosis, and risk of bleeding remain undefined. Endoscopic interventions, shunting procedures, and surgical techniques have been described in this setting.ConclusionsThe data on NVGI bleeding in liver cirrhosis are surprisingly scanty. Large, multicenter epidemiological studies are needed to better assess prevalence and incidence and, most importantly, randomized studies should be performed to evaluate the success rates of therapeutic algorithms.

Critical Illness-Related Corticosteroid Insufficiency in Patients With Cirrhosis and Variceal Bleeding

BACKGROUND & AIMS Relative adrenal insufficiency (AI) occurs in patients with cirrhosis with sepsis, but not with variceal bleeding. We evaluated adrenal function in cirrhotic patients with and without bleeding. METHODS Twenty cirrhotic patients with variceal bleeding were evaluated using the short synacthen test (SST) and 10 using the low-dose synacthen test (LDSST) followed by SST. The control group included 60 stable cirrhotic patients, assessed by LDSST (n = 50) or SST (n = 10), and 14 healthy volunteers. AI was diagnosed using SST, based on peak cortisol levels ≤ 18 μg/dL in nonstressed patients or Δmax <9 μg/dL or a total cortisol level <10 μg/dL in stressed patients with variceal bleeding-the current criteria for critical illness-related corticosteroid insufficiency. Using LDSST, diagnosis was based on peak concentrations of cortisol ≤ 18 μg/dL in nonstressed patients and <25 μg/dL (or Δmax <9 μg/dL) in patients with variceal bleeding. We evaluated patients with levels of serum albumin >2.5 g/dL, to indirectly assess cortisol binding. RESULTS All healthy volunteers had normal results from LDSSTs and SSTs. Patients with variceal bleeding had higher median baseline concentrations of cortisol (15.4 μg/dL) than stable cirrhotic patients (8.7 μg/dL, P = .001) or healthy volunteers (10.1 μg/dL, P = .01). Patients with variceal bleeding had higher median peak concentrations of cortisol than stable cirrhotic patients (SST results of 32.7 vs 21 μg/dL, P = .001; LDSST results of 9.3 vs 8.1 μg/dL; nonsignificant), with no differences in Δmax in either test. These differences were greater with variceal bleeding than in stable cirrhotic patients with AI. Subanalysis of patients with albumin levels >2.5 g/dL did not change these differences. CONCLUSIONS Cirrhotic patients with variceal bleeding have AI. Despite higher baseline concentrations of serum cortisol and subnormal Δmax values, they did not have adequate responses to stress, and therefore had critical illness-related corticosteroid insufficiency.

Vitamin D deficiency in patients with liver cirrhosis

There is ongoing evidence that vitamin D is related to the pathophysiology of cirrhosis. Although the incidence of vitamin D deficiency in chronic liver diseases and cirrhosis is strongly documented, its pathogenic association with advanced liver fibrosis remains controversial. There is evidence of a significant relation of 25(OH)D levels with the degree of liver dysfunction, considering that an inverse correlation of 25(OH)D levels with both Child-Pugh score and Model for End-Stage Liver Disease has been reported. In addition, vitamin D deficiency has been shown to increase the risk for overall mortality and infections in patients with cirrhosis. Vitamin D deficiency has been also associated with advanced stages of hepatocellular carcinoma and poor prognosis. Finally, there are studies suggesting that patients with chronic hepatitis C and normal vitamin D levels have higher virological response to treatment. However, there are not enough studies conducted in cirrhotic-only populations. The association between vitamin D and cirrhosis demonstrates a great potential for clinical application. The relation between vitamin D deficiency and the degree of liver function, degree of fibrosis and infectious complications could support its use as a prognostic index and a diagnostic tool.

Impact of muscle wasting on survival in patients with liver cirrhosis.

Muscle wasting is defined as the progressive and generalized loss of muscle mass. Muscle depletion is a common feature of chronic liver disease found in approximately 40% of patients with cirrhosis. Its etiology is multifactorial subsequent to liver failure and its prevalence increases along with disease severity. Cross-sectional analytic morphometry using computed tomography (CT) scan or magnetic resonance imaging are considered by consensus the gold standards to assess muscle size in cirrhosis for research purposes because they are not biased by fluid accumulation. Several studies have assessed the impact of muscle wasting on overall survival of patients in the waiting list for liver transplantation and there is a general agreement that decreased muscle size assessed by CT scan is an independent predictor for mortality in cirrhosis. It has been proposed that the addition of cross-sectional muscle area into the Model for End-stage Liver Disease can increase its prognostic performance. Nevertheless, the use of CT scan in assessing muscle size is inappropriate for routine clinical practice and an alternative cost-effective, easy to use and accurate tool should be developed. In conclusion, muscle wasting has a detrimental impact on survival of patients with cirrhosis and, thus, it remains to be elucidated if nutritional interventions and exercise could improve muscle wasting and, subsequently, survival in this setting.

Adipokines levels are associated with the severity of liver disease in patients with alcoholic cirrhosis

AIM To investigate the adipokine levels of leptin, adiponectin, resistin, visfatin, retinol-binding protein 4 (RBP4), apelin in alcoholic liver cirrhosis (ALC). METHODS Forty non-diabetic ALC patients [median age: 59 years, males: 35 (87.5%), Child-Pugh (CP) score: median 7 (5-12), CP A/B/C: 18/10/12, Model for End-stage Liver Disease (MELD): median 10 (6-25), follow-up: median 32.5 mo (10-43)] were prospectively included. The serum adipokine levels were estimated in duplicate by ELISA. Somatometric characteristics were assessed with tetrapolar bioelectrical impedance analysis. Pearsons rank correlation coefficient was used to assess possible associations with adipokine levels. Univariate and multivariate Cox regression analysis was used to determine independent predictors for overall survival. RESULTS Body mass index: median 25.9 (range: 20.1-39.3), fat: 23.4% (7.6-42.1), fat mass: 17.8 (5.49-45.4), free fat mass: 56.1 (39.6-74.4), total body water (TBW): 40.6 (29.8-58.8). Leptin and visfatin levels were positively associated with fat mass (P < 0.001/P = 0.027, respectively) and RBP4 with TBW (P = 0.025). Median adiponectin levels were significantly higher in CPC compared to CPA (CPA: 7.99 ± 14.07, CPB: 7.66 ± 3.48, CPC: 25.73 ± 26.8, P = 0.04), whereas median RBP4 and apelin levels decreased across the spectrum of disease severity (P = 0.006/P = 0.034, respectively). Following adjustment for fat mass, visfatin and adiponectin levels were significantly increased from CPA to CPC (both P < 0.001), whereas an inverse correlation was observed for both RBP4 and apelin (both P < 0.001). In the multivariate Cox regression analysis, only MELD had an independent association with overall survival (HR = 1.53, 95%CI: 1.05-2.32; P = 0.029). CONCLUSION Adipokines are associated with deteriorating liver function in a complex manner in patients with alcoholic liver cirrhosis.

Development and validation of a mathematical equation to estimate glomerular filtration rate in cirrhosis: The royal free hospital cirrhosis glomerular filtration rate.

Current expressions based on serum creatinine concentration overestimate kidney function in cirrhosis, leading to significant differences between “true” and calculated glomerular filtration rate (GFR). We compared the performance of the four‐variable and six‐variable Modification of Diet in Renal Disease and chronic kidney disease epidemiology with “true,” or measured, GFR (mGFR) and the impact of this difference on Model for End‐Stage Liver Disease (MELD) calculation. We subsequently developed and validated a GFR equation specifically for cirrhosis and compared the performance of the new derived formula with existing GFR formulae. We included 469 consecutive patients who had a transplant assessment between 2011 and 2014. mGFR was measured using plasma isotope clearance according to a technique validated in patients with ascites. A corrected creatinine was derived from the mGFR after application of the Modification of Diet in Renal Disease formula. Subsequently, a corrected MELD was calculated and compared with the conventionally calculated MELD. Stepwise multiple linear regression was used to derive a GFR equation. This was compared with the mGFR in independent external and internal validation sets of 82 and 174 patients with cirrhosis, respectively. A difference >20 mL/minute/1.73 m2 between existing formulae and mGFR was observed in 226 (48.2%) patients. The corrected MELD score was ≥3 points higher in 177 (37.7%) patients. The predicted equation (r2 = 74.6%) was GFR = 45.9 × (creatinine–0·836) × (urea–0·229) × (international normalized ratio–0·113) × (age−0.129 [Corrected November 29, 2016: originally written as “age‐129.”]) × (sodium0·972) × 0.809 (if female) × 0.92 (if moderate/severe ascites). An online calculator is available at http://rfh-cirrhosis-gfr.ucl.ac.uk. The model was a good fit and showed the greatest accuracy compared to that of existing formulae. Conclusion: We developed and validated a new accurate model for GFR assessment in cirrhosis, the Royal Free Hospital cirrhosis GFR, using readily available variables; this remains to be tested and incorporated in prognostic scores in patients with cirrhosis. (Hepatology 2017;65:582‐591).

Endoscopic treatment of esophageal varices in patients with liver cirrhosis.

Variceal bleeding is a life-threatening complication of portal hypertension with a six-week mortality rate of approximately 20%. Patients with medium- or large-sized varices can be treated for primary prophylaxis of variceal bleeding using two strategies: non-selective beta-blockers (NSBBs) or endoscopic variceal ligation (EVL). Both treatments are equally effective. Patients with acute variceal bleeding are critically ill patients. The available data suggest that vasoactive drugs, combined with endoscopic therapy and antibiotics, are the best treatment strategy with EVL being the endoscopic procedure of choice. In cases of uncontrolled bleeding, transjugular intrahepatic portosystemic shunt (TIPS) with polytetrafluoroethylene (PTFE)-covered stents are recommended. Approximately 60% of the patients experience rebleeding, with a mortality rate of 30%. Secondary prophylaxis should start on day six following the initial bleeding episode. The combination of NSBBs and EVL is the recommended management, whereas TIPS with PTFE-covered stents are the preferred option in patients who fail endoscopic and pharmacologic treatment. Apart from injection sclerotherapy and EVL, other endoscopic procedures, including tissue adhesives, endoloops, endoscopic clipping and argon plasma coagulation, have been used in the management of esophageal varices. However, their efficacy and safety, compared to standard endoscopic treatment, remain to be further elucidated. There are safety issues accompanying endoscopic techniques with aspiration pneumonia occurring at a rate of approximately 2.5%. In conclusion, future research is needed to improve treatment strategies, including novel endoscopic techniques with better efficacy, lower cost, and fewer adverse events.

Acceptance of Hepatitis B Vaccination Among Health Care Workers in Western Greece

ABSTRACT Health care personnel are at high risk for hepatitis B virus (HBV) transmission. The aim of the present study was to investigate hepatitis B (HB) knowledge and vaccination acceptance among health care personnel in southwestern Greece, using the Hepatitis B Vaccine Knowledge and Acceptance Questionnaire. One hundred eighty-three employees participated (71 males). Occupation (p < .001), higher education (p < .001), and vaccination (p = .007) were significantly related to HB knowledge. The rate of HBV vaccination coverage was 70.9%. Participants considering themselves at high risk for HBV infection did not report significantly increased vaccination rates. In the multivariate analysis, university personnel (p = .002), occupational category (p < .001), and HB knowledge (p = .049) were significantly associated with vaccination. In conclusion, 29% of hospital personnel were not vaccinated mainly due to negligence. Occupation, education, and knowledge about HB seem to be associated with HBV vaccination.

Non-selective beta-blockers are not associated with increased mortality in cirrhotic patients with ascites

Controversy exists on the impact of non‐selective beta‐blockers (NSBBs) on survival in patients with ascites. We assessed whether NSBB treatment affects survival in a cohort of 316 consecutive patients with ascites undergoing evaluation for liver transplantation.