Hepatitis B Immunoglobulin and/or Nucleos(t)ide Analogues for Prophylaxis Against Hepatitis B Virus Recurrence After Liver Transplantation: A Systematic Review

A combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NUCs) is currently recommended as prophylaxis against the recurrence of hepatitis B virus (HBV) after liver transplantation (LT), but the optimal protocol is a matter of controversy. The aim of this study was the identification of factors associated with post-LT HBV recurrence in patients receiving HBIG and NUCs. We searched MEDLINE and PubMed for studies in English about the effectiveness of HBIG and NUCs [lamivudine (LAM) and/or adefovir dipivoxil (ADV)] against post-LT HBV recurrence (January 1998 to June 2010). Forty-six studies, which included 2162 HBV LT recipients, met the selection criteria. Patients receiving HBIG and LAM experienced HBV recurrence more frequently than patients receiving HBIG and ADV with or without LAM [6.1% (115/1889) versus 2.0% (3/152), P = 0.024], although they also were more frequently treated with indefinite HBIG prophylaxis (90% versus 57%, P < 0.001). For patients receiving HBIG and LAM, a lower frequency of HBV recurrence was associated with a high HBIG dosage (>= 10,000 IU/day) versus a low HBIG dosage (< 10,000 IU/day) during the first week after LT [3.2% (14/440) versus 6.5% (80/1233), P = 0.016], but the HBIG protocol had no impact on HBV recurrence in patients receiving HBIG and ADV. In conclusion, in comparison with the combination of HBIG and LAM, the combination of HBIG and ADV is associated with a lower rate of HBV recurrence after LT. Patients receiving HBIG and LAM should be given a high dosage of HBIG during the first week after LT, but a lower dosage can be used safely in patients receiving HBIG and ADV. Further studies with newer and more potent anti-HBV agents are definitely required. Liver Transpl 17: 1176-1190, 2011. (C) 2011 AASLD

ALBI and PALBI Grades Are Associated with the Outcome of Patients with Stable Decompensated Cirrhosis

Introduction and aim. Studies carried out mainly in patients with hepatocellular carcinoma (HCC), have shown the prognostic significance of albumin-bilirubin (ALBI) grade. Recently, another predictive score incorporating platelet count into ALBI, PALBI grade, was introduced in patients with HCC.Aim. We evaluated the ability of ALBI and PALBI grades in predicting the outcome (mortality / liver transplantation) of patients with stable decompensated cirrhosis with various etiology of liver diseases.Material and methods. We prospectively studied 325 patients with stable decompensated cirrhosis awaiting liver transplantation. Their clinical and laboratory characteristics were recorded including albumin, bilirubin levels, platelets. We estimated ALBI and PALBI grades for every patient. Conventional prognostic scores were also evaluated; Child-Pugh (CTP), Model for End stage Liver Disease (MELD). We followed them up and recorded their outcome.Results. Beyond MELD and CTP, ALBI and PALBI grades proved significant factors associated with the outcome (HR: 2.13, 95%CI [1.59, 2.85], p < 0.001 and HR: 2.06, 95%CI [1.47, 2.9], p < 0.001, respectively), and their predictive capability was established (ROC analysis; AUC: 0.695, 95% CI [0.634, 0.755] and AUC: 0.683, 95% CI [0.621,0.744], respectively). ALBI and PALBI performed better than CTP score (p = 0.0044 and p = 0.014, respectively). Categorization of our patients into three ALBI groups detected statistically different survival times. Accordingly, PALBI grade 3 compared to those with PALBI grade 1 and 2 patients, had worse outcome and significantly higher frequency of cirrhosis-related complicationsConclusions. ALBI and PALBI grades were validated and can be used to predict the outcome in patients with stable decompensated cirrhosi

Chronic kidney disease in patients with non-alcoholic fatty liver disease: What the Hepatologist should know?

The association of non-alcoholic fatty liver disease (NAFLD) with several other diseases has gained increased interest during the recent years. Among them, the association with chronic kidney disease (CKD) has emerged as an important one regarding both its prevalence and significance. The early recognition of this association is important for the prognosis of patients with NAFLD and CKD. Apart from early diagnosis, the accurate assessment of renal function is also crucial in the clinical practice of hepatologists. Several methods have been used in the literature for the evaluation of kidney function in patients with NAFLD up to now. In this respect, calculators (or formulas) for the estimation of Glomerular Filtration Rate (eGFR) and Albumin to Creatinine Ratio (ACR) are simple, practical and easily available methods for this purpose. The aim of this review is to report on the epidemiology and pathophysiology of the relationship between NAFLD and CKD and to describe the different methods of kidney function assessment in patients with NAFLD. The collection of all relevant data regarding this association will provide hepatologists with pertinent knowledge on this topic and allow them to use the most accurate methods for the assessment of kidney function in these patients in their clinical practice

The role of sorafenib in downsizing hepatocellular carcinoma prior to liver transplantation and in treating tumor recurrence

Sorafenib is shown to improve survival in patients with advanced hepatocellular carcinoma (HCC). However, it has as yet not been tested in the liver transplantation (LT) setting. We report a 55-year-old man with multifocal HCC (stage B) related to hepatitis B virus cirrhosis (Child-Pugh B), initially treated with transarterial chemoembolization. After five months, sorafenib was added due to lack of response. This enhanced the downsizing of the tumor and eventually led to a surgically successful LT after 4 months of combined treatment. Sorafenib was re-initiated 15 months post-transplant due to skeletal tumor recurrence and led to patient’s clinical improvement. The patient remains in good clinical condition 3 years after LT. Sorafenib was well tolerated throughout the entire period of administration with no serious or unexpected adverse events. We conclude that sorafenib can be safely used as a bridge to LT and in transplanted patients in case of HCC recurrence

The significance of C-reactive protein to albumin ratio in patients with decompensated cirrhosis

Background Prognostic indicators in patients with decompensated cirrhosis are vital for the estimation of death risk. The ratio of C-reactive protein to albumin (CAR) has been verified as a prognostic marker in patients with hepatocellular carcinoma and decompensated cirrhosis related to hepatitis B virus. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and gamma globulins have been separately studied in cirrhosis. We evaluated the predictive role of CAR and other inflammatory markers in decompensated patients. Methods We prospectively studied 159 patients with stable decompensated cirrhosis, calculating the following indexes: CAR, NLR, LMR, Child-Turcotte-Pugh (CTP), and model for end-stage liver disease (MELD). Results MELD (area under the curve [AUC] 0.814) and CTP score (AUC 0.752) were superior to the other markers above in predicting patients’ mortality (P&lt;0.05). Patients with CAR&lt;2.17 (median value) presented better times of survival: 20 months (12-27) vs. 14 months (10-17) (log rank P=0.015). NLR and LMR barely discriminated patients’ prognosis. In multivariate analysis, only MELD and CTP scores were significant risk factors, whether using the proposed cutoff of 1.3 (hazard ratio [HR] 1.17 [1.106-2.44], P&lt;0.001) or the median 2.17 CAR categorical variable (HR 1.17 [1.104-1.243], P&lt;0.001). When patients who underwent liver transplantation were excluded, apart from the MELD and CTP scores CAR 2.17 was the only significant factor associated with the outcome (HR 3.61 [0.96-13.6], P=0.05) and detected different survival times: 10 (1-48) vs. 11 (2-38) months, log rank P=0.003. Patients with LMR=1.9 presented significantly better renal function, in terms of true glomerular filtration rate (80 +/- 34 vs. 64 +/- 33 mL/min, P=0.004) and creatinine levels: 0.84 (0.1-1.8) vs. 0.98 (0.59-3.3) mg/dL (P=0.001). Conclusion Our findings demonstrate the significance of CAR and LMR in the outcome and renal function of decompensated patients

Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebocontrolled trial. Gastroenterology

unit suggested benefit from treatment with pentoxifylline (PTX), an inhibitor of tumor necrosis factor (TNF), in severe acute alcoholic hepatitis. The aim of the present study was to evaluate this treatment in a larger cohort of patients. Methods: One hundred one patients with severe alcoholic hepatitis (Maddrey discriminant factor &gt; 32) entered a 4-week double-blind randomized trial of PTX (400 mg orally 3 times daily) vs. placebo. Primary endpoints of the study were the effect of PTX on (1) short-term survival and (2) progression to hepatorenal syndrome. On randomization, there were no differences in demographic and clinical characteristics or laboratory values (including TNF) between the 2 groups. Results: Twelve (24.5%) of the 49 patients who received PTX and 24 (46.1%) of the 52 patients who received placebo died during the index hospitalization (P ‫؍‬ 0.037; relative risk, 0.59; 95% confidence interval, 0.35-0.97). Hepatorenal syndrome was the cause of death in 6 (50%) and 22 (91.7%) patients (P ‫؍‬ 0.009; relative risk, 0.29; 95% confidence interval, 0.13-0.65). Three variables (age, creatinine level on randomization, and treatment with PTX) were independently associated with survival. TNF values on randomization were not predictive of survival; however, during the study period they increased markedly in nonsurvivors compared with survivors in both groups. Conclusions: Treatment with PTX improves short-term survival in patients with severe alcoholic hepatitis. The benefit appears to be related to a significant decrease in the risk of developing hepatorenal syndrome. Increasing TNF levels during the hospital course are associated with an increase in mortality rate