Cirrhosis genetic factors

At present, there are only hypothetical explanations for the cause of the contracture and its correlation with liver cirrhosis. A genetic factor probably plays a part, possibly also in combination with genuine epilepsy. Its more frequent incidence in alcoholic cirrhosis points to a disorder in collagen metabolism as a pathogenic factor. 

Alcohol abuse Alcohol abuse is the most common cause of cirrhosis. Nevertheless, no more than 40-60% of alcoholics contract the disease. Thus genetic factors must also be involved in the development of alcoholic cirrhosis. Alcohol itself can be a facilitative factor or cofactor. Moreover, so-called additives contained in various alcoholic beverages in widely different quantities may also be of greater importance than has hitherto been assmned. (100, 171, 186) (s. pp 528, 532) (s. fig. 28.13, 28.14)... 

Cell death occurs by necrosis or apoptosis or both. The target cell determines the pattern of injury, with hepatocyte injury leading to hepatocellular disease and bihary cell injury leading to cholestasis. AH cellular injury induces fibrosis as an adaptive or healing response, with the duration of injury and genetic factors determining whether cirrhosis and ultimately carcinoma occur (Figure 47-13). 

The factors leading to the development of pulmonary hypertension are unclear, although associations with portal hypertension and pregnancy have been detected. Obesity by itself may double the risk of pulmonary hypertension. Additionally, the use of cocaine or oral contraceptives, infection with the human immunodeficiency virus (HIV), the use of anorexic agents, hepatic cirrhosis, genetic susceptibility, and female sex in the third to fourth decades of life also have been implicated as predisposing factors. Exposure of patients to fenfluramine or dexfenfluramine has been associated with 20% of all diagnosed cases of pulmonary hypertension. ... 

Genetics and metabolic risk factors mediate other less common causes of cirrhosis. These diseases vary widely in prevalence, disease progression, and treatment options. 

Non-alcoholic fatty liver disease begins with asymptomatic fatty liver but may progress to cirrhosis. This is a disease of exclusion elimination of any possible viral, genetic, or environmental causes must be made prior to making this diagnosis. Non-alcoholic fatty liver disease is related to numerous metabolic abnormalities. Risk factors include diabetes mellitus, dyslipidemia, obesity, and other conditions associated with increased hepatic fat.26... 

This is a very rare form of chronic hepatic porphyria. As with PCT, the enzymatic defect is a deficiency of uroporphyrinogen decarboxylase. However, the genetic defect is homozygous. It may also be caused by exogenous factors. HEP manifests in early childhood with high photosensitivity, sclerodermia, hypertrichosis and anaemia. The liver shows red fluorescence. Histologically, siderosis and non-specific hepatitis are found. Development of cirrhosis is possible. No effective therapy is known. (314, 316)... 

Genetic hemochromatosis constitutes a high risk factor for the development of hepatocellular carcinoma. It is widely accepted that venesection prevents the evolution of cirrhosis in hemochromatosis and indirectly protects against the development of hepatocellular carcinoma. However, three cases did not conform to the siderosis-cirrhosis-carcinoma sequence, and prompt and adequate iron depletion did not protect against the development of cancer (44). 

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