Pathophysiology and Biomarker Potential of Fatty Acid Ethyl Ester Elevation During Alcoholic Pancreatitis.

BACKGROUND & AIMS: The role of fatty acid ethyl esters (FAEEs) during human alcoholic pancreatitis is unknown. We compared FAEEs levels with their nonesterified fatty acids (NEFAs) precursors during alcohol intoxication and clinical alcoholic pancreatitis. The pathophysiology underlying FAEEs increase and their role as diagnostic biomarkers for alcoholic pancreatitis was investigated. METHODS: A prospective blinded study compared FAEEs, NEFAs, and ethanol blood levels on hospitalization for alcoholic pancreatitis (n = 31), alcohol intoxication (n = 25), and in normal controls (n = 43). Serum FAEEs were measured at admission for nonalcoholic pancreatitis (n = 75). Mechanistic cell and animal studies were done. RESULTS: Median FAEEs were similarly elevated during alcohol intoxication (205 nmol/L; 95% confidence interval [CI], 71.8-515 nmol/L, P < .001) and alcoholic pancreatitis (103.1 nmol/L; 95% CI, 53-689 nmol/L, P < .001) vs controls (1.7 nmol/L; 95% CI, 0.02-4.3 nmol/L) or nonalcoholic pancreatitis (8 nmol/L; 95% CI, 1.1-11.5 nmol/L). Alcoholic pancreatitis increased serum NEFAs (1024 ± 710 µmol/L vs 307 ± 185 µmol/L in controls, P < .05). FAEEs comprised 0.1% to 2% of the parent NEFA concentrations. FAEES correlated strongly with NEFAs independent of ethanol levels in alcoholic pancreatitis but not during alcohol intoxication. On receiver operating characteristic curve analysis for diagnosing alcoholic pancreatitis, the area under the curve for serum FAEEs was 0.87 (95% CI, 0.78-0.95, P < .001). In mice and cells, alcohol administration transiently increased all FAEEs. Oleic acid ethyl ester was the only FAEE with a sustained increase up to 24 hours after intraperitoneal oleic acid plus ethanol administration. CONCLUSIONS: The sustained, alcohol-independent, large (20- to 50-fold) increase in circulating FAEEs during alcoholic pancreatitis results from their visceral release and mirrors the 2- to 4-fold increase in parent NEFA. The large areas under the curve of FAEEs on receiver operating characteristic curve analysis supports their role as alcoholic pancreatitis biomarkers.

Analysis of the Course of Chronic Pancreatitis: Pancreatic Burnout Rates Are Only Increased in a Subgroup of Patients With Alcoholic Chronic Pancreatitis.

OBJECTIVES: The pancreatic burnout hypothesis postulated an increasing absence of pain with simultaneous functional insufficiency in advanced stages of chronic pancreatitis (CP). However, the underlying data remain scarce and contradictory. We aimed to analyze, first, the frequency of a pancreatic burnout in CP, and, second, its association with etiological risk factors. METHODS: We performed a multicenter, retrospective, cross-sectional study with 741 patients with CP categorized according to the M-ANNHEIM classification. Pancreatic burnout was defined by different combinations of exocrine or endocrine insufficiency with partial or complete absence of abdominal pain. RESULTS: The frequency of a pancreatic burnout increased with prolonged disease duration and was observed in a maximum of 38% of patients after 20 years. Development of a pancreatic burnout was significantly associated with alcohol consumption (P < 0.05, Mann-Whitney U test), but not with other etiological risk factors. After a disease duration of more than 10 years, the likelihood of a burnout was 8 times higher in alcoholic CP than in nonalcoholic CP (95% confidence interval, 1.5-42.0; P = 0.015, logistic regression analysis). CONCLUSIONS: A pancreatic burnout does not regularly occur in CP. Increased burnout rates are only observed in patients with alcoholic CP.

The Long-term Prospective Follow-up of Pancreatic Function After the First Episode of Acute Alcoholic Pancreatitis: Recurrence Predisposes One to Pancreatic Dysfunction and Pancreatogenic Diabetes.

BACKGROUND: Data on the prevalence of pancreatic dysfunction after an episode of acute pancreatitis are conflicting. Our aim was to evaluate the natural course of endocrine and exocrine pancreatic function in the long-term follow-up after the first episode of acute alcoholic pancreatitis (AAP). METHODS: A total of 77 patients who survived their first episode of AAP between January 2001 and February 2005 were prospectively followed up for a maximum of 13 years. During the follow-up, patients were repeatedly interviewed and monitored for recurrences, new diabetes, and chronic pancreatitis. The pancreatic function was evaluated repeatedly during the follow-up. RESULTS: Of the patients, 35% had ≥1 recurrent acute pancreatitis (RAP) episodes during the follow-up. New pancreatogenic diabetes developed in 19% of the previously nondiabetic patients, but only in patients with RAP (13/26 vs. 0/42; OR=39; 95% CI, 4.6-327.1). In addition, 55% of the patients developed new prediabetes or diabetes, and even this was more frequent in patients with RAP (86% vs. 42%; OR=8.2; 95% CI, 1.2-54.3). Exocrine dysfunction developed in 24% of the patients and was associated with abnormal findings in the endocrine function (P=0.003). Patients with RAP had a higher overall mortality compared with patients without RAP episodes during the follow-up (36% vs. 13%; HR=4.0; 95% CI, 1.4-11.0). CONCLUSIONS: The risk for pancreatic endocrine dysfunction, pancreatogenic diabetes and mortality increases significantly if the patient has recurrent episodes of AAP. The risk of developing pancreatic dysfunction after AAP should be recognized and pancreatic function should be screened routinely during the years after the first episode of AAP.

Change of Both Endocrine and Exocrine Insufficiencies After Acute Pancreatitis in Non-Diabetic Patients: A Nationwide Population-Based Study.

Acute pancreatitis (AP) is the most common pancreatic disease and consists of an acute inflammation of the pancreas. AP can contribute to endocrine and exocrine insufficiencies in survivors as a result of the key role of the pancreas in both glucose metabolism and nutritional digestion. The aim of this population-based study was to determine the endocrine or exocrine insufficiencies in patients after initial AP with biliary or alcohol-associated causes.We conducted a nationwide cohort study using data from Taiwan's National Health Insurance Research Database collected between 2001 and 2010. A total of 12,284 patients with AP were identified.Alcohol-associated AP (odds ratio, 1.894; 95% CI, 1.520-2.268; P < 0.001) and ≥2 admissions for AP (odds ratio, 1.937; 95% CI, 1.483-2.391; P < 0.001) were significantly associated with newly diagnosed diabetes mellitus after AP. Further, only alcohol-associated AP (odds ratio, 1.215; 95% CI, 1.133-1.297; P < 0.001) was significantly associated with pancreatic exocrine insufficiency after AP. Additionally, alcohol-associated AP (odds ratio, 1.804; 95% CI, 1.345-2.263; P < 0.001) and ≥2 readmissions for AP (odds ratio, 3.190; 95% CI, 2.317-4.063; P < 0.001) were significantly associated with both exocrine and endocrine insufficiencies after AP.Our data showed that alcohol-associated AP, rather than a biliary cause, contributed to a higher extent to exocrine or endocrine insufficiencies. Furthermore, recurrent AP also led to endocrine insufficiency.

Pharmacological attenuation of chronic alcoholic pancreatitis induced hypersensitivity in rats.

AIM: To characterize an alcohol and high fat diet induced chronic pancreatitis rat model that mimics poor human dietary choices. METHODS: Experimental rats were fed a modified Lieber-DeCarli alcohol (6%) and high-fat (65%) diet (AHF) for 10 wk while control animals received a regular rodent chow diet. Weekly behavioral tests determined mechanical and heat sensitivity. In week 10 a fasting glucose tolerance test was performed, measuring blood glucose levels before and after a 2 g/kg bodyweight intraperitoneal (i.p.) injection of glucose. Post mortem histological analysis was performed by staining pancreas and liver tissue sections with hematoxylin and eosin. Pancreas sections were also stained with Sirius red and fast green to quantify collagen content. Insulin-expressing cells were identified immunohistochemically in separate sections. Tissue staining density was quantified using Image J software. After mechanical and heat sensitivity became stable (weeks 6-10) in the AHF-fed animals, three different drugs were tested for their efficacy in attenuating pancreatitis associated hypersensitivity: a Group II metabotropic glutamate receptor specific agonist (2R,4R)-4-Aminopyrrolidine-2,4-dicarboxylate (APDC, 3 mg/kg, ip; Tocris, Bristol, United Kingdom), nociceptin (20, 60, 200 nmol/kg, ip; Tocris), and morphine sulfate (3 mg/kg, µ-opioid receptor agonist; Baxter Healthcare, Deerfield, IL, United States). RESULTS: Histological analysis of pancreas and liver determined that unlike control rats, AHF fed animals had pancreatic fibrosis, acinar and beta cell atrophy, with steatosis in both organs. Fat vacuolization was significantly increased in AHF fed rats (6.4% ± 1.1% in controls vs 23.8% ± 4.2%, P < 0.05). Rats fed the AHF diet had reduced fasting glucose tolerance in week 10 when peak blood glucose levels reached significantly higher concentrations than controls (127.4 ± 9.2 mg/dL in controls vs 161.0 ± 8.6 mg/dL, P < 0.05). This concurred with a 3.5 fold higher incidence of single and small 2-10 cell insulin-positive cell clusters (P < 0.05). Insulin expressing islet of Langerhans cells appeared hypertrophied while islet number and area measurements were not different from controls. Weekly behavioral tests determined that mechanical and heat sensitivities were significantly increased by 4 wk on AHF diet compared to controls. Hypersensitivity was attenuated with efficacy similar to morphine with single dose treatment of either metabotropic glutamate receptor 2/3 agonist APDC, or nociceptin, the endogenous ligand for opioid-receptor-like 1 receptor. CONCLUSION: The AHF diet induces a chronic alcoholic pancreatitis in rats with measurable features resembling clinical patients with chronic pancreatitis and type 3c diabetes mellitus.

Polymorphisms at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study.

OBJECTIVE: Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 loci (rs7057398 in RIPPLY1 and rs12688220 in MORC4). We aimed to refine these findings in a large European cohort. DESIGN: We studied 3062 patients with alcohol-related CP (ACP) or NACP and 5107 controls. Also, 1559 German patients with alcohol-associated cirrhosis or alcohol dependence were included for comparison. We performed several meta-analyses to examine genotype-phenotype relationships. RESULTS: Association with ACP was found for rs10273639 (OR, 0.63; 95% CI 0.55 to 0.72). ACP was also associated with variants rs7057398 and rs12688220 in men (OR, 2.26; 95% CI 1.94 to 2.63 and OR, 2.66; 95% CI 2.21 to 3.21, respectively) and in women (OR, 1.57; 95% CI 1.14 to 2.18 and OR 1.71; 95% CI 1.41 to 2.07, respectively). Similar results were obtained when German patients with ACP were compared with those with alcohol-associated cirrhosis or alcohol dependence. In the overall population of patients with NACP, association with rs10273639 was absent (OR, 0.93; 95% CI 0.79 to 1.01), whereas rs7057398 of the X chromosomal single nucleotide polymorphisms was associated with NACP in women only (OR, 1.32; 95% CI 1.15 to 1.51). CONCLUSIONS: The single-nucleotide polymorphisms rs10273639 at the PRSS1-PRSS2 locus and rs7057398 and rs12688220 at the CLDN2-MORC4 locus are associated with CP and strongly associate with ACP, but only rs7057398 with NACP in female patients.

Short- and long-term results of modified Frey's procedure in patients with chronic pancreatitis: a retrospective Japanese single-center study.

BACKGROUND: The study aim was to determine the short- and long-term results of surgical drainage procedure for chronic pancreatitis at a single center in Japan. METHODS: The records of 28 consecutive patients were retrospectively reviewed. All patients underwent surgery at Kobe University Hospital between June 1999 and April 2013. Long-term follow-up was performed in all patients for a median period of 77 months. RESULTS: The 26 men (93%) and 2 women (7%) had a mean age of 47 years. The etiology of pancreatitis was chronic alcohol abuse in 24 patients (86%). The major indication for surgery was persistent symptoms (97%). Modified Frey's procedure in 21 patients, lateral pancreaticojejunostomy (LPJ) in 6 patients, LPJ and distal pancreatectomy in one patient, were performed. There was no postoperative mortality. Postoperative morbidity occurred in 6 patients (21%). The percentage of pain-free patients after surgery was 97%, and further acute exacerbation was prevented in 97%. Two patients (6%) required subsequent surgery for infectious pancreatic cyst and intraabdominal abscess. Of the patients that completed follow-up, 13 (46%) had diabetes mellitus, including 5 patients (19%) with new-onset diabetes, and 6 patients (19%) developed pancreatic exocrine insufficiency. CONCLUSIONS: Modified Frey's procedure is safe, feasible, and effective to manage chronic pancreatitis. The technique prevents further exacerbations and maintains appropriate pancreatic endocrine and exocrine function.

An update on pancreatic pathophysiology (do we have to rewrite pancreatic pathophysiology?).

This review focuses on seven aspects of physiology and pathophysiology of the exocrine pancreas that have been intensively discussed and studied within the past few years: (1) the role of neurohormonal mechanisms like melatonin, leptin, or ghrelin in the stimulation of pancreatic enzyme secretion; (2) the initiation processes of acute pancreatitis, like fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen by the lysosomal enzyme cathepsin B, or autoactivation of trypsinogen; (3) the role of genes in the pathogenesis of acute pancreatitis; (4) the role of alcohol and constituents of alcoholic beverages in the pathogenesis of acute pancreatitis; (5) the role of pancreatic hypertension, neuropathy, and central mechanisms for the pathogenesis of pain in chronic pancreatitis; (6) the relation between exocrine pancreatic function and diabetes mellitus; and (7) pathophysiology, diagnosis and treatment of pancreatic steatorrhea.

Models of acute and chronic pancreatitis.

Animal models of acute and chronic pancreatitis have been created to examine mechanisms of pathogenesis, test therapeutic interventions, and study the influence of inflammation on the development of pancreatic cancer. In vitro models can be used to study early stage, short-term processes that involve acinar cell responses. Rodent models reproducibly develop mild or severe disease. One of the most commonly used pancreatitis models is created by administration of supraphysiologic concentrations of caerulein, an ortholog of cholecystokinin. Induction of chronic pancreatitis with factors thought to have a role in human disease, such as combinations of lipopolysaccharide and chronic ethanol feeding, might be relevant to human disease. Models of autoimmune chronic pancreatitis have also been developed. Most models, particularly of chronic pancreatitis, require further characterization to determine which features of human disease they include.

Role of the chemokine fractalkine in a rat model of acute necrotizing pancreatitis and the interventional effect of ulinastatin.

BACKGROUND: Severe acute pancreatitis (SAP) is a serious systemic disease with high mortality. This study aims to investigate the role of the chemokine, fractalkine (FKN), in the pathogenesis of SAP and the effects of intervention by ulinastatin on FKN expression in an SAP rat model. METHODS: We randomly divided 72 Sprague Dawley rats into the following groups: SAP, ulinastatin treatment (UT), and control (C). The SAP model was induced by retrograde infusion of 4% sodium taurocholate into the bili-pancreatic ducts of the rats. Rats in the UT group were injected with ulinastatin immediately after establishment of the SAP model. Serum FKN levels were detected by ELISA at various time points. Histopathological analyses of the pancreas and lung were performed. Expressions of FKN mRNA in the tissues of the pancreas and lung were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) at various time points for each group. RESULTS: Serum levels of FKN at 3 h after surgery in the SAP subgroup were significantly higher than those in the C group (P < 0.05). There were no significant differences between the UT and C groups observed at various time points. Expression levels of FKN mRNA in the pancreatic tissues of the SAP group increased gradually. Although we observed no difference between the SAP and C groups (P > 0.05) at 1 hour h after surgery, mRNA levels of FKN in the lung tissues at 3, 6, and 12 h post-surgery in the SAP subgroups were significantly higher than those in the C group for the same time points (P < 0.05). Pathological injury of the pancreatic tissues was more remarkable in the SAP group compared to the UT group. CONCLUSION: FKN may play an important role in the pathogenesis of SAP and SAP-related acute lung injury (ALI). Ulinastatin efficiently interferes with SAP and SAP-related ALI and may be related to inhibition of FKN expression.

Smoking and the course of recurrent acute and chronic alcoholic pancreatitis: a dose-dependent relationship.

OBJECTIVES: Smoking has been shown to affect the course of alcoholic chronic pancreatitis (ACP). However, a dose-dependent relationship between ACP course and the amount of tobacco consumption has not been studied. METHODS: All consecutive smokers with ACP were included prospectively. Thresholds were defined at 10, 15, 20, and 30 pack-years (p.y.) to assess the relationship between tobacco intake and ACP complications. Statistical adjustment on alcohol intake was performed. RESULTS: One hundred eight patients (male, 86%) were included. The median tobacco intake was 30 p.y. (range, 3-90 p.y.) Pancreatic calcifications and duct abnormalities were observed in 70% and 73%, respectively. Pancreatic exocrine insufficiency and diabetes mellitus were observed in 36% and 30%, respectively. No differences in ACP outcome were seen at 10-p.y. threshold. At a 15-p.y. threshold, ACP diagnosis was made earlier (36 versus 46 years; P = 0.0036). At a 20-p.y. threshold, ACP occurred earlier (P = 0.0002), and the patients had more often calcifications (P = 0.05). Similar results were observed at the 30-p.y. threshold, but additionally pancreatic exocrine insufficiency occurred earlier (P = 0.04). CONCLUSION: Tobacco intake accelerates the course of ACP in a dose-dependent fashion, apart from the amount of alcohol intake. A major threshold effect is seen in 20 p.y.

Ethanol administration impairs pancreatic repair after injury.

OBJECTIVES: Alcohol abuse is one of the most common factors associated with acute and chronic pancreatitis. Although it is evident that alcohol abuse can have an important role in the development of pancreatitis, it does not seem that alcohol abuse alone is responsible for this disease. We investigated the involvement of ethanol in the impairment of pancreatic repair after induction of pancreatitis. METHODS: A biologically relevant mouse model of alcoholic pancreatitis, combining long-term ethanol consumption and coxsackievirus infection, was used to investigate the effects of ethanol on pancreatic regeneration. Tissues were harvested and analyzed by reverse transcription-polymerase chain reaction and immunoblot. RESULTS: These studies demonstrate that long-term ethanol consumption impairs the structural repair of the exocrine pancreas. This is accompanied by a delay in the restitution of lipase expression. In addition, impaired expression of the critical pancreatic transcription factors, PDX1 and PTF1, and the mediator of Notch signaling, HES1, was observed. CONCLUSIONS: Long-term ethanol consumption impairs the structural repair and functional restitution of the pancreas after severe injury. These impairments may, in part, be explained by the impaired expression of factors important in the development and maintenance of the exocrine pancreas. Impaired pancreatic regeneration may have a role in the pathogenesis of alcoholic pancreatitis.

Evaluation of sublingual microcirculatory blood flow in the critically ill.

BACKGROUND: The microcirculation regulates the supply of oxygen and nutrients to tissues. The sublingual region is frequently used as a window to microcirculation in critically ill patients. Numerous studies have reported impaired sublingual microcirculatory flow. We hypothesized that the quality of sidestream dark field imaging (SDF) recordings could be systematically analyzed to justify the monitoring of sublingual microcirculation in interventional studies or in clinical practice. METHODS: The sublingual microcirculation in critically ill patients with septic shock, open heart surgery, or alcoholic pancreatitis, and healthy subjects was recorded with a hand held SDF device by one trained investigator in observational setting. A total of 82 video recording sessions were performed and 240 video clips eligible for quality assessment were identified. Quality assessment was performed offline by two investigators independently and blinded for the origin of the video file. RESULTS: Of the 240 clips, pressure artifact was detected in 86 (36%), major blood in 5 (2.1%), major saliva in 21 (8.8%) and extreme brightness causing loss of visible capillaries in 16 (6.7%) clips. The dominating vessel architecture was multiple size vessels in 228 (95%) and repeating capillary loop motif in 12 (5.0%). The mean (± SD) relative size reduction during stabilization was -6.9% (± 4.7%). Excellent technical quality was detected in 74 of 240 (30.8%) recordings. CONCLUSIONS: Our findings highlight the need of a comprehensive training period and reporting of data quality before findings with SDF imaging can be accepted as surrogate end points in interventional studies or as guidance in clinical practice.

Recent advances in the epidemiology of alcoholic pancreatitis.

Clinical observation has defined the medical profile of alcoholic pancreatitis, but its low incidence and prevalence has limited characterizing the disease at a population level, the contribution of environmental exposures, and a clear picture of its natural history. Recent studies have defined the impact of alcohol use and smoking on disease risk, and a threshold for alcohol consumption has been identified. Recurrent attacks of acute pancreatitis have been linked with continued alcohol consumption, and aggressive alcohol intervention has been shown to decrease recurrence. Progression from alcoholic acute pancreatitis to chronic pancreatitis is now believed to occur infrequently, and factors associated with progression have been identified. Alcoholic pancreatitis reduces lifespan in these patients, and the economic impact of pancreatitis is substantial. Efforts are needed to increase awareness of the impact of alcohol consumption and smoking on risk for pancreatitis and the benefits of cessation for primary and secondary prevention.

Clinical profile of calcific and noncalcific chronic pancreatitis in north India.

GOALS: To compare the clinical profile of calcific and noncalcific chronic pancreatitis (CP) in north India. BACKGROUND: The profile of calcific CP has not been adequately studied. STUDY: Detailed demographic data were recorded; hematologic, biochemical, and radiologic investigations were carried out on 225 patients with CP. The patients were divided into calcific and noncalcific groups based on the presence of pancreatic calcification, which was detected on computed tomography. RESULTS: Calcific CP was reported in 46.7% of the patients and noncalcific CP in 53.3%. The mean age, duration of symptoms before presentation, sex ratio, body mass index, and frequency of various symptoms and complications including abdominal pain, ascites, pleural effusion, and segmental portal hypertension was not statistically different between the 2 groups. However, pseudocysts occurred more frequently in noncalcific CP, whereas jaundice because of bile duct stricture, diabetes mellitus, and steatorrhea occurred more frequently in patients with calcific CP (P<0.05). On comparing calcific and noncalcific alcoholic pancreatitis, only steatorrhea was reported more frequently in patients with calcific alcoholic CP. However, pseudocysts and segmental portal hypertension occurred more frequently in noncalcific idiopathic CP, whereas diabetes mellitus occurred more frequently in patients with calcific idiopathic CP (P<0.05). On comparing calcific alcoholic CP with calcific idiopathic CP, we found significantly lower mean age in patients with idiopathic CP and a higher frequency of male patients and pseudocysts in alcoholic CP (P<0.05). CONCLUSION: Calcific CP has a higher frequency of bile duct stricture, diabetes mellitus, and steatorrhea, whereas noncalcific CP has higher frequency of pseudocysts and segmental portal hypertension.

Beer and its non-alcoholic compounds: role in pancreatic exocrine secretion, alcoholic pancreatitis and pancreatic carcinoma.

In this article we provide an overview of the newest data concerning the effect of non-alcoholic constituents of alcoholic beverages, especially of beer, on pancreatic secretion, and their possible role in alcoholic pancreatitis and pancreatic carcinoma. The data indicate that non-alcoholic constituents of beer stimulate pancreatic enzyme secretion in humans and rats, at least in part, by direct action on pancreatic acinar cells. Some non-alcoholic compounds of beer, such as quercetin, resveratrol, ellagic acid or catechins, have been shown to be protective against experimentally induced pancreatitis by inhibiting pancreatic secretion, stellate cell activation or by reducing oxidative stress. Quercetin, ellagic acid and resveratrol also show anti-carcinogenic potential in vitro and in vivo. However, beer contains many more non-alcoholic ingredients. Their relevance in beer-induced functional alterations of pancreatic cells leading to pancreatitis and pancreatic cancer in humans needs to be further evaluated.

Alcoholic pancreatitis: lessons from the liver.

The association between alcohol consumption and pancreatitis has been recognized for over 100 years. Despite the fact that this association is well recognized, the mechanisms by which alcohol abuse leads to pancreatic tissue damage are not entirely clear. Alcohol abuse is the major factor associated with pancreatitis in the Western world. Interestingly, although most cases of chronic pancreatitis and many cases of acute pancreatitis are associated with alcohol abuse, only a small percentage of individuals who abuse alcohol develop this disease. This situation is reminiscent of the association between alcohol abuse and the incidence of alcoholic liver disease. The liver and the pancreas are developmentally very closely related. Even though these two organs are quite different, they exhibit a number of general structural and functional similarities. Furthermore, the diseases mediated by alcohol abuse in these organs exhibit some striking similarities. The diseases in both organs are characterized by parenchymal cell damage, activation of stellate cells, aberrant wound healing, and fibrosis. Because of the similarities between the liver and the pancreas, and the alcohol-associated diseases of these organs, we may be able to apply much of the knowledge that we have gained regarding the effects of alcohol on the liver to the pancreas.