Cirrhosis - The Causes

Cirrhosis is defined as a condition of irreversible scarring liver as a result of liver tissue by fibrosis due to final phase of chronic liver diseases of that can lead to poor function of the liver and liver failure. According to the statistics, Number of discharges with chronic liver disease or cirrhosis as the first-listed diagnosis: 101,000 in 2009 and Deaths per 100,000 population: 10.3 in 2010(a). Hepatitis B infection cause of the disease is very prevalent in South-East Asia.

A. Causes
Most cases of Cirrhosis are caused by excessive and chronic alcohol drink and hepatitis.
1. Excessive and chronic alcohol drink
Prolonged period of excessive alcohol drink can lead to onset of the disease. In the study to provide a quantitative assessment of the association between alcohol intake and risk of liver cirrhosis, by the Centre for Addiction and Mental Health, showed that alcohol consumption had a significantly larger impact on mortality of liver cirrhosis compared with morbidity. Also, the same amount of average consumption was related to a higher risk of liver cirrhosis in women than in men.(1).

2. Hepatitis
a. Heptitis C
Hepatitis C virus (HCV) infects more than 170 million people worldwide, and thereby becomes a series global health challenge. Chronic infection with HCV is considered one of the major causes of end-stage liver disease including cirrhosis and hepatocellular carcinoma(2).

b. Hepatitis B
Following development of liver cirrhosis in patients with chronic hepatitis B, liver disease may continue to progress and decompensation or hepatocellular carcinoma (HCC) may occur(3).

3. Biliary cirrhosis
a. Primary Biliary cirrhosis
Primary Biliary cirrhosis is defined as a chronic liver diseases as a result of the slow destruction of the bile duct of the liver. According to the study by, Nagasaki University Graduate School of Biomedical Sciences, patients with primary biliary cirrhosis (PBC) exhibit a variety of clinical manifestations and patterns of disease progression. The genetic variants of CYP7A1 and its transcriptional activators (HNF4A and PPARGC1A) may activate bile acid synthesis, resulting in the accumulation of bile acids in hepatocytes and eventually leading to the predisposition to PBC progression(4). Other study in the examined single nucleotide polymorphisms (SNPs) in cytotoxic T-lymphocyte antigen 4 (CTLA4) and solute carrier family 4 anion exchanger, member 2 (SLC4A2), which have been associated with the pathogenesis of PBC in Caucasian patients, found that CTLA4 and SLC4A2 genetic polymorphisms are differentially associated with PBC development and progression, as well as anti-gp210 or anti-centromere antibody production, in Japanese PBC patients(5).

b. Secondary Biliary cirrhosis
Secondary Biliary cirrhosis is defined as a condition of the blocking of the bile duct of the liver as a result infection or iatrogenic bile duct injury (BDI), bile duct strictures, gallstones, sclerosing, etc. 
Secondary biliary cirrhosis was the indication for liver transplantation (LT) in 5 (1.7%) out of 300 LTs performed in our center between Feb 2002 and April 2011, according to the Surgery and Liver Transplantation, M. Curie Hospital, Szczecin(6).

4. Other causes (non-B, non-C liver cirrhosis (NBNC LC))
In a nationwide survey of NBNC LC in Japan at the 15th General Meeting of the Japan Society of Hepatology, 6999 NBNC LC with patients were registered at 48 medical institutions. Epidemiological and clinical factors, indicated that The percentage of NBNC LC among LC patients was 26%. NBNC LC patients were categorized into 11 types according to etiological agents: non-alcoholic steatohepatitis (NASH), 14.5%; alcoholic liver disease (ALD), 55.1%; fatty liver disease (FLD), except NASH, ALD, and other known etiology, 2.5%; primary biliary cirrhosis, 8.0%; other biliary cirrhosis, 0.8%; autoimmune hepatitis, 6.8%; metabolic disease, 0.6%; congestive disease, 0.8%; parasitic disease, 0.2%; other known etiology, 0.2%; and unknown etiology, 10.5%(7).

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Sources
Sources
(a) http://www.cdc.gov/nchs/fastats/liverdis.htm
(1) http://www.ncbi.nlm.nih.gov/pubmed/20636661
(2) http://www.ncbi.nlm.nih.gov/pubmed/23355912
(3) http://www.ncbi.nlm.nih.gov/pubmed/22504333
(4) http://www.ncbi.nlm.nih.gov/pubmed/23354620
(5) http://www.ncbi.nlm.nih.gov/pubmed/21594562
(6) http://www.ncbi.nlm.nih.gov/pubmed/22743721
(7) http://www.ncbi.nlm.nih.gov/pubmed/23347437