Hepatic steatosis in diabetic patients does not predict adverse liver-related or cardiovascular outcomes.

BACKGROUND & AIMS: Steatosis is a defining feature of nonalcoholic fatty liver disease (NAFLD). However, evidence that severity of steatosis can predict adverse outcomes in NAFLD or nonalcoholic steatohepatitis (NASH) is lacking. The aim of this study was to determine whether steatosis assessed by computed tomography (CT) imaging predicts adverse outcomes in diabetic patients at risk for NAFLD/NASH. METHODS: We studied deaths, liver-related and cardiovascular adverse outcomes in a 5-year retrospective observational cohort of 2343 type 2 diabetic patients in a large care network who had noncontrast CT imaging for clinical indications. We measured steatosis by subtraction of spleen from liver attenuation, a method that showed low sensitivity (0.417) and high specificity (0.882) compared with histopathological scoring. We evaluated outcomes prediction using multivariate Cox proportional hazards modelling of steatosis both as a categorical (≥ 30%) and continuous variable. RESULTS: Steatosis ≥ 30% was present in 233 (9.9%) of the cohort at baseline. Over 5 years, there were 372 total deaths, 18 liver-related and 99 cardiovascular deaths, 48 liver transplants, 51 occurrences of hepatic encephalopathy, 41 hepatocellular carcinomas, 653 myocardial infarctions, 66 strokes, 180 occurrences of angina, 735 occurrences of arrhythmia and 772 occurrences of congestive heart failure. Steatosis had no predictive value for any adverse outcome. Patients with steatosis averaged 8 years younger than those without it. Age had a strong covariate influence on occurrence of total deaths, cardiovascular deaths, myocardial infarctions, arrhythmias and congestive heart failure. CONCLUSION: Although steatosis on imaging is often the abnormality that triggers diagnosis and assessment of NAFLD/NASH, it lacks predictive value for adverse clinical outcomes.

Variation in the γ-glutamyltransferase 1 gene and risk of chronic pancreatitis.

OBJECTIVE: Individuals with chronic pancreatitis are at increased risk for pancreatic cancer. We hypothesized that genetic variation in the γ-glutamyltransferase 1 (GGT1) gene, which was recently reported associated with pancreatic cancer risk in a genome-wide association study, is also associated with risk of chronic pancreatitis. METHODS: Associations between common polymorphisms in GGT1 and chronic pancreatitis were evaluated using data and samples from the North American Pancreatitis Study 2. Patients (n = 496) and control subjects (n = 465) were genotyped for 4 single-nucleotide polymorphisms: rs4820599, rs2017869, rs8135987, and rs5751901. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CI) for chronic pancreatitis risk were calculated using multiple logistic regression models. Interactions with cigarette smoking and alcohol use were explored. RESULTS: Single-nucleotide polymorphisms rs8135987 and rs4820599 were both statistically significantly associated with risk of chronic pancreatitis; compared with common allele homozygotes, individuals with at least 1 minor allele were at increased risk (rs8135987: OR, 1.36; 95% CI, 1.03-1.80 [P(trend) = 0.01]; rs4820599: OR, 1.39; 95% CI, 1.04-1.84 [P(trend) = 0.0]; adjusted for age, sex, race, smoking status, and alcohol use). No significant interactions with cigarette smoking and alcohol use were observed. CONCLUSION: Our results suggest that common variation in the GGT1 gene may also affect risk of chronic pancreatitis.

ABO blood group and chronic pancreatitis risk in the NAPS2 cohort.

OBJECTIVES: A risk association has been observed between non-O blood groups and pancreatic adenocarcinoma. Chronic pancreatitis also increases risk for pancreatic cancer, raising questions as to whether non-O blood groups are a risk for chronic pancreatitis and whether the pathophysiologic pathways are linked. Our goal was to determine whether ABO blood group may affect the risk of chronic pancreatitis. METHODS: The study cohort included chronic pancreatitis patients (n = 499) and healthy controls (n = 631) from the North American Pancreatitis Study 2 study. Genotyping was performed using Sequenom assay of rs8176746 A/C and rs505922 C/T to classify participants into ABO blood groups. RESULTS: O blood group was nonsignificantly more common among cases (44.7% vs 42.0%; P = 0.36), particularly among cases with alcohol-related chronic pancreatitis (49.3% vs 42%; P = 0.060). Alcoholic patients without coexisting high-risk PRSS1, CFTR, or SPINK1 variants had a significant overrepresentation of O blood type when compared with controls (odds ratio, 1.54; 95% confidence interval, 1.09-2.17; P = 0.01). CONCLUSIONS: A, B, and AB blood groups were not associated with a greater likelihood of having chronic pancreatitis and may decrease the risk of chronic pancreatitis in individuals who are very heavy drinkers. These results suggest that the mechanism linking non-O blood type with pancreatic pathology is specific to carcinogenesis.

Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study.

OBJECTIVE: To compare patients with chronic pancreatitis (CP) with constant pain patterns to patients with CP with intermittent pain patterns. METHODS: This was a prospective cohort study conducted at 20 tertiary medical centers in the USA comprising 540 subjects with CP. Patients with CP were asked to identify their pain from five pain patterns (A-E) defined by the temporal nature (intermittent or constant) and the severity of the pain (mild, moderate or severe). Pain pattern types were compared with respect to a variety of demographic, quality of life (QOL) and clinical parameters. Rates of disability were the primary outcome. Secondary outcomes included: use of pain medications, days lost from school or work, hospitalisations (preceding year and lifetime) and QOL as measured using the Short Form-12 (SF-12) questionnaire. RESULTS: Of the 540 CP patients, 414 patients (77%) self-identified with a particular pain pattern and were analysed. Patients with constant pain, regardless of severity, had higher rates of disability, hospitalisation and pain medication use than patients with intermittent pain. Patients with constant pain had lower QOL (by SF-12) compared with patients who had intermittent pain. Additionally, patients with constant pain were more likely to have alcohol as the aetiology for their pancreatitis. There was no association between the duration of the disease and the quality or severity of the pain. CONCLUSIONS: This is the largest study ever conducted of pain in CP. These findings suggest that the temporal nature of pain is a more important determinant of health-related QOL and healthcare utilisation than pain severity. In contrast to previous studies, the pain associated with CP was not found to change in quality over time. These results have important implications for improving our understanding of the mechanisms underlying pain in CP and for the goals of future treatments and interventions.