Serum Fibrosis Tests Guide Prognosis in Metabolic Dysfunction-Associated Fatty Liver Disease Patients Referred From Primary Care.

BACKGROUND & AIMS: Metabolic dysfunction-associated fatty liver disease (MAFLD) is managed predominately in primary care, however, there is uncertainty regarding how to best identify patients for specialist referral. We examined the accuracy of noninvasive tests as screening tools for the prediction of outcomes in MAFLD patients referred from primary care. METHODS: Patients with MAFLD referred by primary care for specialist review to Sir Charles Gairdner Hospital (cohort 1, n = 626) or tertiary centers within Western Australia (cohort 2, n = 246) were examined. Hepascore, aspartate aminotransferase to platelet ratio, Fibrosis-4 (FIB-4), and nonalcoholic fatty liver disease fibrosis score performed at baseline were examined for their accuracy in predicting liver-related death (LRD), decompensation, and hepatocellular carcinoma. Outcomes were collected from hospital records and data linkage. RESULTS: The median follow-up period was 5.0 years (range, 0.1-13.0 y) and 3.8 years (range, 0.1-10.0 y) in cohorts 1 and 2, respectively. In both cohorts, Hepascore and FIB-4 had the highest area under the curve for the prediction of LRD (0.90-0.95 and 0.83-0.94, respectively), decompensation (0.86-0.91 and 0.86-0.87, respectively), and hepatocellular carcinoma (0.75-0.90 and 0.67-0.85, respectively). The sensitivity and negative predictive values were high (>90%) for Hepascore (cut-off value, 0.60), FIB-4 (cut-off value, 1.30), and nonalcoholic fatty liver disease fibrosis score (cut-off value, -1.455) for all outcomes in cohort 1, and for predicting LRD in cohort 2. Hepascore had the highest specificity, classified the greatest proportion of patients as low risk, and was favored by decision curve analysis as providing the greatest net benefit. CONCLUSIONS: Serum noninvasive tests accurately stratify risk of liver-related outcomes in MAFLD patients and can be used as a screening tool for patients referred for specialist review by primary care.

The natural history of compensated HCV-related cirrhosis: a prospective long-term study.

BACKGROUND & AIMS: The natural history of HCV-related compensated cirrhosis has been poorly investigated in Latin-American countries. Our study evaluated mortality and clinical outcomes in compensated cirrhotic patients followed for 6 years. METHODS: Four hundred and two patients with compensated HCV-related cirrhosis were prospectively recruited in a tertiary care academic center. At the time of admission, patients were stratified as compensated (absence [stage 1] or presence [stage 2] of esophageal varices) as defined by D'Amico et al. Subjects were followed to identify overall mortality or liver transplantation and clinical complication rates. RESULTS: Among 402 subjects, 294 were categorized as stage 1 and 108 as stage 2. Over a median of 176 weeks, 42 deaths occurred (10%), of which 30 were considered liver-related (7%) and 12 non-liver-related (3%); eight individuals (2%) underwent liver transplantation; 30 patients (7%) developed HCC, 67 individuals in stage 1 (22%) developed varices and any event of clinical decompensation occurred in 80 patients (20%). The 6-year cumulative overall mortality or liver transplantation was 15% and 45%, for stages 1 and 2, respectively (p<0.001). The cumulative 6-year HCC incidence was significantly higher among patients with varices (29%) than those without varices (9%), p<0.001. Similarly, the cumulative 6-year incidence of any clinical liver-related complication was higher in patients with stage 2 (66%) as compared to 26% in those with stage 1, respectively (p<0.001). CONCLUSIONS: Our results indicate significant morbidity and mortality and clinical outcome rates in compensated cirrhotic patients with varices (stage 2).

Mortality and complication rates of percutaneous ablative techniques for the treatment of liver tumors: a systematic review.

OBJECTIVES: Reported rates of major complications and mortality of radiofrequency ablation (RFA), microwave ablation (MWA) and percutaneous ethanol injection (PEI) for the treatment of liver tumours were substantially heterogeneous among studies. The aim was to analyse the mortality and major complication rates of percutaneous RFA, PEI and MWA. METHODS: MEDLINE and EMBASE search from January 1982 to August 2010. Randomised clinical trials and observational studies, age >18, more than 50 patients for each technique analysed, studies reporting mortality and major complications were included. Random effects model was performed, with assessment for heterogeneity and publication bias. RESULTS: Thirty-four studies including 9531, 1185, and 1442 patients for RFA, MWA, and PEI, respectively were included. For all ablative techniques pooled proportion mortality rate was 0.16% (95% confidence interval [CI], 0.10-0.24). Pooled mortality rate associated with RFA, PEI and MWA was 0.15% (0.08-0.23), 0.59% (0.14-1.3) and 0.23% (0.0-0.58) respectively. Pooled proportion of major complications was 3.29% (2.43-4.28). Major complication rates associated with RFA, MWA, and PEI was 4.1% (3.3-5.1), 4.6% (0.7-11.8) and 2.7% (0.28-7.4) respectively. CONCLUSIONS: Percutaneous RFA, PEI and MWA can be considered safe techniques for the treatment of liver tumours.

Trends in hepatocellular carcinoma due to non-alcoholic fatty liver disease.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and is associated with hepatocellular carcinoma (HCC), the most frequent malignant liver tumor. The increasing prevalence of obesity and diabetes is influencing the epidemiology of HCC with the most dramatic increases in NAFLD-related HCC seen in Western countries. Although cirrhosis is the major risk factor for HCC in NAFLD, there is increasing recognition that NAFLD-HCC occurs in the absence of cirrhosis. Areas covered: The epidemiology of NAFLD related HCC and its impact on changing the incidence of HCC globally. We overview risk factors for NAFLD-HCC in the presence and absence of cirrhosis and examine trends in liver transplantation (LT) related to NAFLD-HCC. Expert commentary: The incidence of NAFLD-related cirrhosis will continue to rise globally in parallel with risk factors of obesity and diabetes. Consequently, NAFLD-related HCC will become an increasingly important cause of liver-related morbidity and mortality and a common indication for LT worldwide. Further identification of risk factors for NAFLD-HCC and effective treatments for NAFLD are required to reduce this future burden of disease.

The natural history of HCV-related cirrhosis and its temporal progression across the different clinical stages.

PURPOSE: The clinical course of hepatitis C virus-related cirrhosis and its temporal progression across the different clinical stages has not been completely investigated. Our study evaluated the cumulative incidences (CIs) of clinical outcomes marking disease progression across the different clinical stages. METHODS: At baseline, 660 patients were classified as compensated [absence (294), or presence (108) of gastroesophageal varices] or decompensated [ascites (144), variceal bleeding alone (45) or in combination with ascites (17) and encephalopathy alone or together with bleeding and/or ascites (52)]. Subjects were followed for 312 weeks to identify time to a first event marking disease progression. RESULTS: Among compensated patients without varices, the 312-week CIs for developing varices, ascites, and encephalopathy were 37.4, 13.6 and 3.5 %, respectively. The 312-week CIs of development of ascites, bleeding and encephalopathy were 24, 12.5 and 9.9 % for compensated subjects with varices, respectively. Among patients with ascites, the 312-week CIs of bleeding, liver-related deaths/transplant and encephalopathy were 23.5, 27.8, and 47.3 %, respectively. The 312-week CIs of ascites, liver-related deaths/transplant and encephalopathy were 22.5, 14.7 and 5.7 % among patients with bleeding; however, CIs of liver-related deaths were significantly higher in those with ascites plus bleeding (77.6 %). Patients with encephalopathy alone or in combination with ascites and/or bleeding displayed the highest rates of deaths (312 weeks, 90 %). CONCLUSIONS: Among compensated patients, the presence of varices suggests a more accelerated course of the disease. Decompensated patients show the most severe clinical course, particularly in those with a combination of two or more clinical events.

Arterial blood pressure is closely related to ascites development in compensated HCV-related cirrhosis.

BACKGROUND: Arterial blood pressure (BP) is a reliable marker of circulatory dysfunction in cirrhotic patients. There are no prospective studies evaluating the association between different levels of arterial BP and ascites development in compensated cirrhotic patients. Therefore, we evaluated the relationship between arterial BP and ascites development in compensated cirrhotic patients. MATERIALS AND METHODS: A total of 402 patients with compensated HCV-related cirrhosis were prospectively followed during 6 years to identify ascites development. At baseline, patients underwent systolic, diastolic and mean arterial pressure (MAP) measurements. Any history of arterial hypertension was also recorded. The occurrence of events such as bleeding, hepatocellular carcinoma, death and liver transplantation prior to ascites development were considered as competing risk events. RESULTS: Over a median of 156 weeks, ascites occurred in 54 patients (13%). At baseline, MAP was significantly lower in patients with ascites development (75.9 mm/Hg [95%CI, 70.3-84.3]) than those without ascites (93.6 mm/Hg [95% CI: 86.6-102.3]). After adjusting for covariates, the 6-year cumulative incidence of ascites was 40% (95%CI, 34%-48%) for patients with MAP<83.32 mm/Hg. In contrast, cumulative incidences of ascites were almost similar among patients with MAP values between 83.32 mm/Hg and 93.32 mm/Hg (7% [95% CI: 4%-12%]), between 93.32 mm/Hg and 100.31 mm/Hg (5% [95% CI: 4%-11%]) or higher than 100.31 mm/Hg (3% [95% CI: 1%-6%]). The MAP was an independent predictor of ascites development. CONCLUSIONS: The MAP is closely related to the development of ascites in compensated HCV-related cirrhosis. The risk of ascites development increases in 4.4 fold for subjects with MAP values <83.32 mm/Hg.

Model for End-Stage Liver Disease and liver cirrhosis-related complications.

The Model for End-Stage Liver Disease (MELD) score has gained wide acceptance for predicting survival in patients undergoing liver transplantation. The strength of this score remains in the mathematical formula derived from a multivariate Cox regression analysis; it is a continuous scale and lacks a ceiling or a floor effect with a wide range of discrimination. It is based on objective, reproducible, and readily available laboratory data and the wide range of samples which have been validated. Liver cirrhosis complications such as ascites, encephalopathy, spontaneous bacterial peritonitis and variceal bleeding were not considered in the MELD score underestimating their direct association with the severity of liver disease. In this regard, several recent studies have shown that clinical manifestations secondary to portal hypertension are good prognostic markers in cirrhotic patients and may add additional useful prognostic information to the current MELD. We review the feasibility of MELD score as a prognostic predictor in patients with liver cirrhosis-related complications.

Antioxidant and immunomodulatory effects of Viusid in patients with chronic hepatitis C.

AIM: To investigate the efficacy of Viusid, a nutritional supplement, as an antioxidant and an immunomodulator in patients with chronic hepatitis C. METHODS: Sixty patients with chronic hepatitis C who were non-responders to standard antiviral treatment were randomly assigned to receive Viusid (3 sachets daily, n = 30) or placebo (n = 30) for 24 wk. The primary outcome was the change in serum malondialdehyde and 4-hydroxyalkenals (lipid peroxidation products). Secondary outcomes were changes in serum tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin-10 (IL-10). RESULTS: Statistically significant reductions in serum 4-hydroxyalkenals and malondialdehyde levels were observed in both groups in comparison with pretreatment values, but the patients who received Viusid showed a more marked reduction as compared with the control group (P = 0.001). TNF-alpha levels significantly increased from 6.9 to 16.2 pg/mL (P < 0.01) in the patients who received placebo in comparison with almost unchanged levels, from 6.6 to 7.1 pg/mL (P = 0.26), in the patients treated with Viusid (P = 0.001). In addition, IL-10 levels were markedly increased in the patients treated with Viusid (from 2.6 to 8.3 pg/mL, P = 0.04) in contrast to the patients assigned to placebo (from 2.8 to 4.1 pg/mL, P = 0.09) (P = 0.01). Likewise, the administration of Viusid markedly increased mean IFN-gamma levels from 1.92 to 2.89 pg/mL (P < 0.001) in comparison with a reduction in mean levels from 1.80 to 1.68 pg/mL (P = 0.70) in the placebo group (P < 0.0001). Viusid administration was well tolerated. CONCLUSION: Our results indicate that treatment with Viusid leads to a notable improvement of oxidative stress and immunological parameters in patients with chronic hepatitis C.

Application of a biochemical and clinical model to predict individual survival in patients with end-stage liver disease.

AIM: To investigate the capability of a biochemical and clinical model, BioCliM, in predicting the survival of cirrhotic patients. METHODS: We prospectively evaluated the survival of 172 cirrhotic patients. The model was constructed using clinical (ascites, encephalopathy and variceal bleeding) and biochemical (serum creatinine and serum total bilirubin) variables that were selected from a Cox proportional hazards model. It was applied to estimate 12-, 52- and 104-wk survival. The model's calibration using the Hosmer-Lemeshow statistic was computed at 104 wk in a validation dataset. Finally, the model's validity was tested among an independent set of 85 patients who were stratified into 2 risk groups (low risk 8). RESULTS: In the validation cohort, all measures of fit, discrimination and calibration were improved when the biochemical and clinical model was used. The proposed model had better predictive values (c-statistic: 0.90, 0.91, 0.91) than the Model for End-stage Liver Disease (MELD) and Child-Pugh (CP) scores for 12-, 52- and 104-wk mortality, respectively. In addition, the Hosmer-Lemeshow (H-L) statistic revealed that the biochemical and clinical model (H-L, 4.69) is better calibrated than MELD (H-L, 17.06) and CP (H-L, 14.23). There were no significant differences between the observed and expected survival curves in the stratified risk groups (low risk, P = 0.61; high risk, P = 0.77). CONCLUSION: Our data suggest that the proposed model is able to accurately predict survival in cirrhotic patients.