**3. Etiology**

It is believed that alcohol is one of the major etiologic factors of chronic pancreatitis, but it is now recognized that alcohol is responsible for 50% of the cases [3]. Therefore, stigmatization of patients with chronic pancreatitis as having an alcohol use disorder is often inaccurate and unfitting. It has been estimated that patients must consume 4–5 alcoholic drinks per day consistently for over 5 years to be at risk [11]. Alcohol exposure has several unwanted effects to the pancreas tissue. Despite common knowledge, it makes pancreas more susceptible to injury rather than directly causing chronic pancreatitis**.**

Usage of tobacco products is another risk factor for chronic pancreatitis. In the past, it was assumed cigarette smoking caused chronic pancreatitis due to concurrent alcohol consumption, but studies demonstrated a link between an independent and dose-dependent response of tobacco usage and chronic pancreatitis [12]. Also, cigarette smoking is a strong risk factor for recurrent acute pancreatitis which can eventually progress to chronic pancreatitis. Smoking is related to the induction of interleukin-22 secondary to aryl hydrocarbons, which promote pancreatic fibrosis [13].

Recurrent episodes of acute pancreatitis can lead to pancreatic fibrosis, gland atrophy, loss of islet of Langerhans which eventually progress into chronic pancreatitis.

Hereditary pancreatitis is another etiologic factor for developing chronic pancreatitis. It is observed as an autosomal dominant mutation of the cationic trypsinogen gene (PRSS1). Hereditary pancreatitis is an autosomal dominant disease with high penetrance up to 80% but some patients can also develop the PRSS1 gene mutation de novo.

Another mutation can also be the cause of chronic pancreatitis. Including genes that encode serine peptidase inhibitor Kazal type 1 (SPINK1), chymotrypsin C (CTRC), calcium-sensing receptor (CASR), claudin (CLDN2) and cystic fibrosis transmembrane conductance regulator (CFTR). Due to CFTR gene mutation cystic fibrosis is another etiologic risk factor for chronic pancreatitis. Also, Carboxypeptidase A1 (CPA1) and carboxyl ester lipase (CEL) gene mutations are thought to be increasing risk factors for chronic pancreatitis.

### *Current Approaches in Chronic Pancreatitis DOI: http://dx.doi.org/10.5772/intechopen.98214*

There are two unique subtypes of chronic pancreatitis. The first subtype is referred to as tropical pancreatitis (previously fibro calculous pancreatitis) which is mostly seen in Southeast Asia, especially in India. Previously, the cause of tropical pancreatitis was believed to be cassava root ingestion. However, this hypothesis has not been supported. Half of the patients who suffer from tropical pancreatitis show SPINK1 gene mutation, but the pathogenesis of the tropical pancreatitis remains unexplained [14].

The other subtype of chronic pancreatitis is autoimmune pancreatitis (AIP) which is subclassified as type 1 AIP (lymphoplasmacytic sclerosing pancreatitis) and type 2 AIP (idiopathic duct-centric pancreatitis). AIP, especially lymphoplasmacytic sclerosing pancreatitis is associated with IgG4-secreting plasma cells in the pancreas. Type 1 AIP has also extra pancreatic manifestations like sclerosing cholangitis and retroperitoneal fibrosis. Patients eventually develop pancreatic calcifications and pancreatic insufficiencies that are indistinguishable from chronic pancreatitis.

Less commonly, hypercalcemia (generally due to parathyroid adenoma), hypertriglyceridemia, autoimmune disorders (eg, celiac disease, inflammatory bowel diseases) can cause chronic pancreatitis.

Approximately 40% of the chronic pancreatitis patients' etiology is unknown [15].
