Does Acute Alcoholic Pancreatitis Exist With Preexisting Chronic Pancreatitis?

Although approximately ten percent of patients with chronic alcoholic pancreatitis develop attacks of clinically acute pancreatitis that are indistinguishable from other forms of acute pancreatitis, the relationship between alcohol-induced acute and chronic pancreatitis is still unresolved. 1,2 The classic teaching has been that alcohol causes chronic pancreatitis, and that alcoholics who present with clinically acute pancreatitis have underlying chronic disease. The focus here is on the question whether alcoholic chronic pancreatitis with chronic fibrotic lesions and pancreaticolithiasis always precedes the clinically acute stages of the disease. There have been few biopsy data or longitudinal prospective studies. Based on the conclusions reached at a 1963 Marseilles meeting, 3 acute and chronic pancreatitis have been defined as two separate entities, with the implication that clinically “acute” alcohol-induced pancreatitis has underlying chronic changes. Clinical experience has shown that continuous alcohol abuse often leads to morphologic and functional impairment, with the first clinical manifestations of chronic pancreatitis or acute attacks showing up only after many years; typically, 15 years in females, and 20 years in males. Ethanol feeding alone, even at high doses, has shown either minimal or inconsistent effects on morphologic findings in the experimental animals. 4 However, ethanol feeding in combination with other precipitating causes have demonstrated several mechanisms that play a role in ethanol-induced pancreatic injury. Among these ethanol-induced alterations and mechanisms are increased CCK effect, reduced pancreatic blood-flow and microcirculation, damaging effects of ethanol metabolites, increased pancreatic acinar cell expression of digestive and lysosomal enzymes, and increased glandular enzyme content. Also, nutritional factors have to be taken into account, ethanol metabolites have damaging effects, and there can be pancreatic obstruction and limitations to pancreatic regeneration. 4,5 Earlier work by Weiner and Tennant, 6 who reviewed 4000 autopsies, demonstrated that, of 51 individuals who died after binge drinking, 25 showed acute lesions while only 2 showed chronic pancreatic lesions. Kloppel et al 7 could not detect any chronic pancreatic lesions in a retrospective study with acute, fatal alcohol-induced pancreatitis. Renner et al 8 in 1985 reported the data for 131 cases of “acute” pancreatitis. A majority of the patients in the study with alcohol acute pancreatitis did not have histologic signs of chronic pancreatitis, which again suggests a few patients with acute alcohol-induced pancreatitis do not necessarily have features of chronic changes. Bank et al 9 found normal pancreatic function on secretin/CCK stimulation one year after an acute attack in 10% of their cases. A similar hypothesis was originally proposed by Comfort and colleagues 10 and is now referred to as the necrosis–fibrosis sequence hypothesis, suggesting that chronic pancreatitis is the result of repeated episodes of acute pancreatitis. The data supporting the hypothesis come primarily from pathologic studies 11,12 and a recent prospective clinical trial investigating the outcome of an “acute” alcohol-induced pancreatitis by Ammann et al 13 In the Ammann study, morphologic changes—including necrosis, pseudocysts, calcification, and fibrosis—were examined in 37 surgical and 46 postmortem pancreas specimens of 73 patients who clinically progressed from acute to chronic pancreatitis over 12-year follow-up periods. Pancreatic function was monitored yearly. Surgical interventions were performed at a mean of 4 years from the onset of clinical symptoms. Amman et al supposed that one-third of patients with alcohol-induced chronic pancreatitis may develop true acute pancreatitis with the lesions resolving in spite of progression toward chronic (progressive) pancreatitis. Fibrosis was shown to correlate with progressive pancreatic dysfunction, particularly in 10 patients with 2 histologic assessments. Studies on hereditary pancreatitis by Whitcomb 14 further support the necrosis–fibrosis hypothesis. However, the presented data do not permit the exclusion of the hypothesis that acute pancreatitis occurs generally on the basis of preexisting clinically latent chronic pancreatitis. In this issue of the Journal of Clinical Gastroenterology, Gullo et al report on a recent study intended to establish whether acute alcoholic pancreatitis occurs in a normal pancreas, or in a pancreas that has already been altered by chronic lesions. Pancreatic tissue was taken from six patients having their first attack of acute alcoholic pancreatitis and who had never had abdominal pain or other relevant complaints. In all six, histologic examination revealed both acute and chronic lesions including calcification and fibrosis. These findings are strongly indicative that acute alcoholic pancreatitis develops in a gland already affected by chronic pancreatitis. The years of controversy on this issue are still not over despite the fact that most (>90%) of alcoholic patients who present with a clinically “acute” pancreatitis indeed have an underlying disease—namely, a chronic alcohol-induced pancreatitis. 15 Why only a small proportion of all alcoholics develop pancreatitis, what genetic and environmental factors influence the development of pancreatitis in alcoholics, and what is the exact mechanism of pancreatic injury by alcohol remain unanswered in spite of extensive and ongoing research. A clear definition as to what may or may not be called either an acute or a chronic state of alcohol-induced chronic pancreatitis has still not been reached. Many pancreatologists still believe that a small cadre of patients with proven alcohol-induced pancreatitis do not have underlying chronic disease. 9