Predicting liver-related events in NAFLD: A predictive model.

BACKGROUND AND AIMS: Management of NAFLD involves noninvasive prediction of fibrosis, which is a surrogate for patient outcomes. We aimed to develop and validate a model predictive of liver-related events (LREs) of decompensation and/or HCC and compare its accuracy with fibrosis models. APPROACH AND RESULTS: Patients with NAFLD from Australia and Spain who were followed for up to 28 years formed derivation (n = 584) and validation (n = 477) cohorts. Competing risk regression and information criteria were used for model development. Accuracy was compared with fibrosis models using time-dependent AUC analysis. During follow-up, LREs occurred in 52 (9%) and 11 (2.3%) patients in derivation and validation cohorts, respectively. Age, type 2 diabetes, albumin, bilirubin, platelet count, and international normalized ratio were independent predictors of LRE and were combined into a model [NAFLD outcomes score (NOS)]. The NOS model calibrated well [calibration slope, 0.99 (derivation), 0.98 (validation)] with excellent overall performance [integrated Brier score, 0.07 (derivation) and 0.01 (validation)]. A cutoff ≥1.3 identified subjects at a higher risk of LRE, (sub-HR 24.6, p < 0.001, 5-year cumulative incidence 38% vs 1.0%, respectively). The predictive accuracy at 5 and 10 years was excellent in both derivation (time-dependent AUC,0.92 and 0.90, respectively) and validation cohorts (time-dependent AUC,0.80 and 0.82, respectively). The NOS was more accurate than the fibrosis-4 or NAFLD fibrosis score for predicting LREs at 5 and 10 years ( p < 0.001). CONCLUSIONS: The NOS model consists of readily available measures and has greater accuracy in predicting outcomes in patients with NAFLD than existing fibrosis models.

Comparative Accuracy of Clinical Fibrosis Markers, Hepascore and Fibroscan® to Detect Advanced Fibrosis in Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Non-invasive tests are widely used to diagnose fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), however, the optimal method remains unclear. We compared the accuracy of simple serum models, a serum model incorporating direct measures of fibrogenesis (Hepascore), and Fibroscan®, for detecting fibrosis in NAFLD. METHODS: NAFLD patients undergoing liver biopsy were evaluated with Hepascore, NAFLD Fibrosis Score (NFS), FIB-4 and AST-platelet ratio index (APRI), with a subset (n = 131) undergoing Fibroscan®. Fibrosis on liver biopsy was categorized as advanced (F3-4) or cirrhosis (F4). Accuracy was determined by area under receiving operating characteristic curves (AUC). Indeterminate ranges were calculated using published cut-offs. RESULTS: In 271 NAFLD patients, 83 (31%) had F3-4 and 47 (17%) cirrhosis. 6/131 (4%) had an unreliable Fibroscan®. For the detection of advanced fibrosis, the accuracy of Hepascore (AUC 0.88) was higher than FIB-4 (0.73), NFS (0.72) and APRI (0.69) (p < 0.001 for all). Hepascore had similar accuracy to Fibroscan® (0.80) overall, but higher accuracy in obese individuals (0.91 vs 0.80, p = 0.001). Hepascore more accurately identified patients with cirrhosis than APRI (AUC 0.85 vs 0.71, p = 0.01) and NFS (AUC 0.73, p = 0.01) but performed similar to FIB-4 and Fibroscan®. For the determination of F3-4, the proportion of patients in indeterminate area was lower for Hepascore (4.8%), compared to FIB-4 (42%), NFS (36%) and APRI (44%) (p < 0.001 for all). CONCLUSIONS: Hepascore has greater accuracy and a lower indeterminate range than simple serum fibrosis tests for advanced fibrosis in NAFLD, and greater accuracy than Fibroscan® in obese individuals.

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.

ABIDE: An Accurate Predictive Model of Liver Decompensation in Patients With Nonalcoholic Fatty Liver-Related Cirrhosis.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is an increasingly important cause of liver cirrhosis and subsequent complications. We retrospectively developed and validated a model to predict hepatic decompensation in patients with NAFLD and cirrhosis and compared this with currently available models. APPROACH AND RESULTS: Baseline variables from an international cohort of 299 patients with biopsy-proven NAFLD with compensated cirrhosis were examined to construct a model using competing risk multivariate regression and Akaike/Bayesian information criteria. Validation was performed in 244 patients with biopsy-proven NAFLD cirrhosis from the United States. Prognostic accuracy was compared with the NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4), Model for End-Stage Liver Disease (MELD), Child-Turcotte-Pugh (CTP), and albumin-bilirubin (ALBI)-FIB-4 score using time-dependent area under the curve (tAUC) analysis. During a median follow-up of 5.6 years (range 2.4-14.1) and 5.4 years (range 1.5-13.8), hepatic decompensation occurred in 81 and 132 patients in the derivation and validation cohorts, respectively. In the derivation cohort, independent predictors of hepatic decompensation (Aspartate aminotransferase/alanine aminotransferase ratio, Bilirubin, International normalized ratio, type 2 Diabetes, and Esophageal varices) were combined into the ABIDE model. Patients with a score ≥4.1 compared with those with a score <4.1 had a higher risk of decompensation (subhazard ratio, 6.7; 95% confidence interval [CI], 4.0-11.2; P < 0.001), a greater 5-year cumulative incidence (37% vs. 6%, P < 0.001), and shorter mean duration to decompensation (3.8 vs 6.7 years, P < 0.001). The accuracy of the ABIDE model at 5 years was good in the derivation (tAUC, 0.80; 95% CI, 0.73-0.84) and validation cohorts (0.78; 95% CI, 0.74-0.81) and was significantly more accurate than the NFS (0.72), FIB-4 (0.74), MELD (0.69), CTP (0.72), and ALBI-FIB-4 (0.73) (all P < 0.001). CONCLUSIONS: In patients with NAFLD and compensated cirrhosis, ABIDE, a predictive model of routine clinical measures, predicts future hepatic decompensation.

Type 2 Diabetes and Metformin Use Associate With Outcomes of Patients With Nonalcoholic Steatohepatitis-Related, Child-Pugh A Cirrhosis.

BACKGROUND & AIMS: Factors that affect outcomes of patients with nonalcoholic steatohepatitis (NASH)-related cirrhosis are unclear. We studied associations of type 2 diabetes, levels of hemoglobin A1c (HbA1c), and use of antidiabetic medications with survival and liver-related events in patients with NASH and compensated cirrhosis. METHODS: We collected data from 299 patients with biopsy-proven NASH with Child-Pugh A cirrhosis from tertiary hospitals in Spain, Australia, Hong Kong, and Cuba, from April 1995 through December 2016. We obtained information on the presence of type 2 diabetes, level of HbA1c, and use of antidiabetic medications. Cox proportional and competing risk models were used to estimate and compare rates of transplant-free survival, hepatic decompensation, and hepatocellular carcinoma (HCC). RESULTS: A total of 212 patients had type 2 diabetes at baseline and 8 of 87 patients developed diabetes during a median follow-up time of 5.1 years (range, 0.5-10.0 y). A lower proportion of patients with diabetes survived the entire follow-up period (38%) than of patients with no diabetes (81%) (adjusted hazard ratio [aHR], 4.23; 95% CI, 1.93-9.29). Higher proportions of patients with diabetes also had hepatic decompensation (51% vs 26% of patients with no diabetes; aHR, 2.03; 95% CI, 1.005-4.11) and HCC (25% vs 7% of patients with no diabetes; aHR, 5.42; 95% CI, 1.74-16.80). Averaged annual HbA1c levels over time were not associated with outcomes. Metformin use over time was associated with a significant reduction in risk of death or liver transplantation (aHR, 0.41; 95% CI, 0.26-0.45), hepatic decompensation (aHR, 0.80; 95% CI, 0.74-0.97), and HCC (aHR, 0.78; 95% CI, 0.69-0.96). Metformin significantly reduced the risk of hepatic decompensation and HCC only in subjects with HbA1c levels greater than 7.0% (aHR, 0.97; 95% CI, 0.95-0.99 and aHR, 0.67; 95% CI, 0.43-0.94, respectively). CONCLUSIONS: In an international cohort of patients with biopsy-proven NASH and Child-Pugh A cirrhosis, type 2 diabetes increased the risk of death and liver-related outcomes, including HCC. Patients who took metformin had higher rates of survival and lower rates of decompensation and HCC.

Fibrosis Severity as a Determinant of Cause-Specific Mortality in Patients With Advanced Nonalcoholic Fatty Liver Disease: A Multi-National Cohort Study.

BACKGROUND & AIMS: Little is known about the natural course of nonalcoholic fatty liver disease (NAFLD) with advanced fibrosis. We describe long-term outcomes and evaluate the effects of clinical and histologic parameters on disease progression in patients with advanced NAFLD. METHODS: We conducted a multi-national study of 458 patients with biopsy-confirmed NAFLD with bridging fibrosis (F3, n = 159) or compensated cirrhosis (222 patients with Child-Turcotte-Pugh scores of A5 and 77 patients with scores of A6), evaluated from April 1995 through November 2013 and followed until December 2016, death, or liver transplantation at hepatology centers in Spain, Australia, Hong Kong, and Cuba. Biopsies were re-evaluated and scored; demographic, clinical, laboratory, and pathology data for each patient were collected from the time of liver biopsy collection. Cox proportional and competing risk models were used to estimate rates of transplantation-free survival and major clinical events and to identify factors associated with outcomes. RESULTS: During a mean follow-up time of 5.5 years (range, 2.7-8.2 years), 37 patients died, 37 received liver transplants, 88 had initial hepatic decompensation events, 41 developed hepatocellular carcinoma, 14 had vascular events, and 30 developed nonhepatic cancers. A higher proportion of patients with F3 fibrosis survived transplantation-free for 10 years (94%; 95% confidence interval [CI], 86%-99%) than of patients with cirrhosis and Child-Turcotte-Pugh A5 (74%; 95% CI, 61%-89%) or Child-Turcotte-Pugh A6 (17%; 95% CI, 6%-29%). Patients with cirrhosis were more likely than patients with F3 fibrosis to have hepatic decompensation (44%; 95% CI, 32%-60% vs 6%, 95% CI, 2%-13%) or hepatocellular carcinoma (17%; 95% CI, 8%-31% vs 2.3%, 95% CI, 1%-12%). The cumulative incidence of vascular events was higher in patients with F3 fibrosis (7%; 95% CI, 3%-18%) than cirrhosis (2%; 95% CI, 0%-6%). The cumulative incidence of nonhepatic malignancies was higher in patients with F3 fibrosis (14%; 95% CI, 7%-23%) than cirrhosis (6%; 95% CI, 2%-15%). Death or transplantation, decompensation, and hepatocellular carcinoma were independently associated with baseline cirrhosis and mild (<33%) steatosis, whereas moderate alcohol consumption was associated with these outcomes only in patients with cirrhosis. CONCLUSIONS: Patients with NAFLD cirrhosis have predominantly liver-related events, whereas those with bridging fibrosis have predominantly nonhepatic cancers and vascular events.

Increasing Incidence of Nonalcoholic Steatohepatitis as an Indication for Liver Transplantation in Australia and New Zealand.

The worldwide increase in obesity and diabetes has led to predictions that nonalcoholic steatohepatitis (NASH) will become the leading indication for orthotopic liver transplantation (OLT). Data supporting this prediction from outside the United States are limited. Thus, we aimed to determine trends in the frequency of NASH among adults listed and undergoing OLT in Australia and New Zealand (ANZ) from 1994 to 2017. Data from the ANZ Liver Transplant Registry were analyzed with patients listed for fulminant liver failure, retransplantation, or multivisceral transplants excluded. Nonparametric trend, Spearman rank correlation, and regression analysis were used to assess trends in etiologies of liver disease over time. Of 5016 patient wait-list registrants, a total of 3470 received an OLT. The percentage of patients with NASH activated for OLT increased significantly from 2.0% in 2003 to 10.9% in 2017 (trend analyses; P < 0.001). In 2017, NASH was the third leading cause of chronic liver disease (CLD) among wait-list registrants behind chronic hepatitis C virus (HCV; 29.5%) and alcohol (16.1%). Similarly, significant increases over time in the percentage of patients undergoing OLT were observed for HCV and NASH (all trend analyses; P < 0.001) but with significant reductions in primary sclerosing cholangitis and cryptogenic cirrhosis (both P < 0.05). By 2017, NASH was the third leading cause of liver disease among patients undergoing OLT (12.4%) and behind chronic HCV (30.2%) and alcohol (18.2%). NASH also became the third most frequent etiology of CLD in patients transplanted (13.8%) with concomitant hepatocellular carcinoma by 2017. In conclusion, NASH is increasing as a primary etiology of liver disease requiring listing and liver transplantation in ANZ.

Diabetes impacts prediction of cirrhosis and prognosis by non-invasive fibrosis models in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) patients with diabetes are at increased risk of cirrhosis and liver-related death, and thus accurate fibrosis assessment in these patients is important. We examined the ability of non-invasive fibrosis models to determine cirrhosis and outcomes in NAFLD patients with and without diabetes. METHODS: Non-alcoholic fatty liver disease patients diagnosed between 2006 and 2015 had Hepascore, NAFLD fibrosis score (NFS), APRI and FIB-4 scores calculated at baseline and were followed up for outcomes of overall and liver-related mortality/liver transplantation, hepatic decompensation and hepatocellular carcinoma (HCC). Model accuracy was determined by Harrell's C-index and by Kaplan-Meier analysis. RESULTS: A total of 284 patients (53% diabetic, 15% cirrhotic) were followed up for a median of 51.4 months, (range 6.1-146). During follow-up, diabetic patients had a greater risk of liver-related death/transplantation, HR 3.4 (95% CI 1.2-9.1) decompensation, HR 4.7 (95% CI 2.0-11.3) and HCC, HR 2.9 (95% CI 1.2-7.3). Among 241 subjects with a baseline liver biopsy, the accuracy of Hepascore, APRI and FIB-4 for predicting cirrhosis was lower amongst diabetics compared to non-diabetics (P < .005 for all). Model accuracy apart from Hepascore, was also significantly lower for predicting liver death/transplantation in patients with diabetes. No patient with a low fibrosis score and without diabetes developed liver decompensation or HCC, whereas up to 21% of diabetic patients with a low fibrosis score developed liver decompensation and up to 27% developed HCC at 5 years. CONCLUSIONS: Non-invasive scoring systems are less accurate at predicting cirrhosis and liver-related outcomes in patients with NAFLD and diabetes.

Development and validation of a noninvasive prediction model for nonalcoholic steatohepatitis resolution after lifestyle intervention.

UNLABELLED: Liver biopsy is the gold standard method to assess nonalcoholic steatohepatitis (NASH) resolution after therapeutic interventions. We developed and validated a simple and noninvasive scoring system to predict NASH resolution without fibrosis worsening after 1 year of lifestyle intervention. This was a prospective cohort study conducted in 261 patients with histologically proven NASH who were treated with lifestyle changes for 52 weeks and underwent a second liver biopsy to confirm NASH resolution. We divided the data into development (140 subjects) and validation (121 individuals) sets. NASH resolution occurred in 28% (derivation group) and 27% (validation group). At the multivariable analysis, weight loss (odds ratio [OR] = 2.75, 95% confidence interval [CI] 1.65-4.58; P < 0.01), type 2 diabetes (OR = 0.04, 95% CI 0.005-0.49; P = 0.01), normal levels of alanine aminotransferase at the end of intervention (OR = 9.84, 95% CI 2.21-44.1; P < 0.01), age (OR = 0.89, 95% CI 0.83-0.97; P = 0.01), and a nonalcoholic fatty liver activity score ≥5 (OR = 0.08, 95% CI 0.01-0.43; P < 0.01) were independent predictors of NASH resolution. The area under the receiver operating characteristic curve of the selected model was 0.956 and 0.945 in the derivation and validation cohorts, respectively. Using a score threshold of ≤46.15, negative predictive values were 92% in the derivation and validation groups, respectively. By applying a cutoff ≥69.72, positive predictive values were 92% and 89% in the derivation and validation groups, respectively. Using both cutoffs, a liver biopsy would have been avoided in 229 (88%) of 261 patients, with a correct prediction in 209 (91%) CONCLUSIONS: A noninvasive prediction model including weight loss, type 2 diabetes, alanine aminotransferase normalization, age, and a nonalcoholic fatty liver activity score ≥5 may be useful to identify NASH resolution in patients under lifestyle intervention. (Hepatology 2016;63:1875-1887).

Serum biomarkers can predict a change in liver fibrosis 1 year after lifestyle intervention for biopsy-proven NASH.

BACKGROUND & AIMS: The dynamic response of serum fibrosis biomarkers to histological changes within the liver following lifestyle intervention (LI) is unknown. We explored relationships between changes in serum biomarkers and liver fibrosis in NASH patients undergoing LI. METHODS: Paired liver biopsies were performed in 261 NASH patients to assess fibrosis change after 1 year of LI. We explored the utility of serum fibrosis markers to predict changes in hepatic fibrosis and developed and internally validated a model for predicting fibrosis improvement in patients with baseline fibrosis. RESULTS: Regression, stabilization and worsening of fibrosis occurred in 51 (20%), 165 (63%) and 45 (17%) patients respectively. By multivariable analysis, change in HbA1c (OR, 0.39, P<.01), platelets (OR, 1.22, P<.01) and NFS (OR, 0.27, P<.01), as well as ALT normalization (OR, 9.7, P<.01) were independently associated with fibrosis improvement, whereas change in platelets (OR, 0.96, P<.01), and NFS (OR, 1.8, P<.01) as well as ALT normalization (OR, 0.21, P<.01) were linked to fibrosis progression. A model, including change in HbA1c, platelet and ALT normalization, was significantly more accurate (AUC of 0.96, 95% CI, l0.94-0.99) than NFS, FIB-4 and APRI for predicting fibrosis improvement. Using a threshold of ≥0.497, positive and negative predictive values were 94% (95% CI, 84-98) and 91% (95% CI, 81-96) respectively. CONCLUSIONS: Change in NFS, platelets and ALT normalization are associated with change in liver fibrosis after 1 year of LI. A model including change in HbA1c, platelet and ALT normalization discriminated patients with fibrosis improvement significantly better than other biomarkers.

Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: It is not clear how weight loss affects histologic features of liver in patients with nonalcoholic steatohepatitis (NASH). We examined the association between the magnitude of weight loss through lifestyle modifications and changes in histologic features of NASH. METHODS: We conducted a prospective study of 293 patients with histologically proven NASH who were encouraged to adopt recommended lifestyle changes to reduce their weight over 52 weeks, from June 2009 through May 2013, at a tertiary medical center in Havana, Cuba. Liver biopsies were collected when the study began and at week 52 of the diet and were analyzed histologically. RESULTS: Paired liver biopsies were available from 261 patients. Among 293 patients who underwent lifestyle changes for 52 weeks, 72 (25%) achieved resolution of steatohepatitis, 138 (47%) had reductions in nonalcoholic fatty liver disease activity score (NAS), and 56 (19%) had regression of fibrosis. At week fifty-two, 88 subjects (30%) had lost ≥5% of their weight. Degree of weight loss was independently associated with improvements in all NASH-related histologic parameters (odds ratios = 1.1-2.0; P < .01). A higher proportion of subjects with ≥5% weight loss had NASH resolution (51 of 88 [58%]) and a 2-point reduction in NAS (72 of 88 [82%]) than subjects who lost <5% of their weight (P < .001). All patients who lost ≥10% of their weight had reductions NAS, 90% had resolution of NASH, and 45% had regression of fibrosis. All patients who lost 7%-10% of their weight and had few risk factors also had reduced NAS. In patients with baseline characteristics that included female sex, body mass index ≥35, fasting glucose >5.5 mmol/L, and many ballooned cells, NAS scores decreased significantly with weight reductions ≥10%. CONCLUSIONS: A greater extent of weight loss, induced by lifestyle changes, is associated with the level of improvement in histologic features of NASH. The highest rates of NAS reduction, NASH resolution, and fibrosis regression occurred in patients with weight losses ≥10%.

The Natural Course of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from "bland steatosis" to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death.

Risk factors associated with the development of hyperamylasemia and post-ERCP pancreatitis in the Cuban National Institute.

CONTEXT: Acute pancreatitis is the most common complication in ERCP, and some risk factors were associated with the development of hyperamylasemia and post-ERCP pancreatitis. OBJECTIVES: identifying new factors associated with the development of hyperamylasemia or post-ERCP pancreatitis in patients attended at our center. MATERIAL AND METHODS: A (retrospective) cohort study was carried out in 170 patients on which a diagnostic-therapeutic ERCP was done due to biliopancreatic disease. 67 patients developed hyperamylasemia (39.4%) and 6 post-ERCP pancreatitis (3.5%). The following diagnostic criteria were applied: Hyperamylasemia: increase in the serum amylase level above the normal value (90 I/U). Acute post-ERCP pancreatitis: clinical: continuous abdominal pain for over 24 hours and biochemical: elevation of amylase3 times above normal value (90 U/I). RESULTS: The number of cannulations more than 4 (19 patients), (p=0.006; RR= 3.00) was associated significantly with the development of hyperamylasemia and the placing of biliary stent (14 patients), (p=0.00; RR= 0.39) was a protective factor. The factors associated with the development of post-ERCP pancreatitis were related with the patient (peridiverticular location of the papilla (p=0.00; RR= 2.00) and the sphincter of Oddi dysfunction (p=0.000; RR=1.20). CONCLUSION: Technical factors were associated with the development of hyperamylasemia, however, the factors associated with the development of post-ERCP pancreatitis in our universe of study were related mainly with the patient.

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).

[Nonalcoholic fatty liver disease. A current perspective]. / Enfermedad hepática por depósitos grasos. Una perspectiva actual.

A review about nonalcoholic fatty liver disease is presented, considering the updated aspects related to pathophysiology, diagnosis and management of this medical condition.

Liver fibrosis quantified by image morphometry predicts clinical outcomes in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Liver fibrosis predicts adverse clinical outcomes, such as liver-related death (LRD) and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the accuracy of semi-automated quantification of collagen proportionate area (CPA) as an objective new method for predicting clinical outcomes. METHOD: Liver biopsies from patients with NAFLD underwent computerized image morphometry of Sirius Red staining with CPA quantification performed by ImageScope. Clinical outcomes, including total mortality, LRD, and combined liver outcomes (liver decompensation, HCC, or LRD), were determined by medical records and population-based data-linkage. The accuracy of CPA for predicting outcomes was compared with non-invasive fibrosis tests (Hepascore, FIB-4, APRI). RESULTS: A total of 295 patients (mean age 50 years) were followed for a median (range) of 9 (0.2-25) years totalling 3253 person-years. Patients with CPA ≥ 10% had significantly higher risks for total death [hazard ratio (HR): 5.0 (1.9-13.2)], LRD [19.0 (2.0-182.0)], and combined liver outcomes [15.6 (3.1-78.6)]. CPA and pathologist fibrosis staging (FS) showed similar accuracy (AUROC) for the prediction of total death (0.68 vs. 0.70), LRD (0.72 vs. 0.77) and combined liver outcomes (0.75 vs. 0.78). Non-invasive serum markers Hepascore, APRI, and FIB-4 reached higher AUROC; however, they were not statistically significant compared to that of CPA except for Hepascore in predicting total mortality (0.86 vs. 0.68, p = 0.009). CONCLUSION: Liver fibrosis quantified by CPA analysis was significantly associated with clinical outcomes including total mortality, LRD, and HCC. CPA achieved similar accuracy in predicting outcomes compared to pathologist fibrosis staging and non-invasive serum markers.

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.