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Causes and Risk Factors

Almost any chronic liver disease can develop into cirrhosis. One of the most common causes of cirrhosis globally is chronic viral hepatitis, with 30% attributed to chronic hepatitis B virus (HBV) infection and 27% to chronic hepatitis C virus (HCV) infection (Nishioka 2002; Dwyre 2011). Risk factors for infection include intravenous drug use, unprotected intercourse, blood transfusions, and tattoos (Perz 2006). Alcoholic liver disease is the second major worldwide contributor to cirrhosis incidence, accounting for almost one-third of cases (NIDDK 2014a). Non-alcoholic fatty liver disease (NAFLD) and its more severe form, nonalcoholic steatohepatitis (NASH), are common causes of cirrhosis in the United States and are highly associated with obesity and metabolic syndrome (Armstrong 2014). NASH currently affects 2-5% of Americans; NAFLD is present in an additional 10-20% in the United States (NIDDK 2014c; Ferri 2014). NASH is now the third most common cause of cirrhosis after viral hepatitis and alcoholic liver disease (NIDDK 2014a).

Of these, hepatitis C deserves special attention because it is often asymptomatic and may not be detected until cirrhosis is already present, which can be many years after the virus is contracted (NIDDK 2012b). It is a common infection in the United States, affecting over 3 million people. The most common cause of transmission today is the use of shared drug injection needles or equipment. Before 1992, when the blood supply was not tested for it, hepatitis C was transmitted through blood transfusions and organ transplants. Maternal-fetal transmission is also possible (CDC 2014). Hepatitis C viral infection is detectable with blood tests (NIDDK 2012b), and hepatitis C can be treated before it progresses to cirrhosis (Keating 2014; FDA 2013).

Aside from these top causes, there are several other less common chronic liver diseases that can lead to cirrhosis (Baertling 2013; Welty 2014; Haafiz 2010; Liou 2014; Moyer 2009; NIDDK 2012a; Fairbanks 2008):

Autoimmune hepatitis: an autoimmune disease in which the immune system attacks the body’s own hepatocytes

Cholestatic liver diseases (diseases that interfere with the production or flow of bile), such as:

  • Primary biliary cirrhosis: a chronic and slowly progressive inflammatory liver disease that is thought to be autoimmune in origin and results from damage to the small bile ducts
  • Primary sclerosing cholangitis: a condition often associated with inflammatory bowel disease that results in inflammation and fibrosis, which causes narrowing and dilation of the intrahepatic and extrahepatic bile ducts
  • Cystic fibrosis: an inherited condition characterized by thick secretions that mainly affect the lungs, pancreas, intestines, and liver
  • Biliary atresia: congenital malformation of bile ducts

Inherited metabolic disorders, such as:

  • Alpha-1 antitrypsin deficiency: a genetic disease that can cause chronic liver disease, cirrhosis, and hepatocellular carcinoma
  • Wilson’s disease: an inherited copper storage disease
  • Hereditary hemochromatosis: iron storage disease
  • Glycogen storage diseases: excessive liver storage of glycogen
  • Abetalipoproteinemia: inability to synthesize certain lipoproteins and to absorb fats and fat-soluble vitamins

Budd-Chiari syndrome: thrombosis (clotting) of liver blood vessels

Decrease the Risk of Cirrhosis by Treating Chronic Liver Disease

Proper management and treatment of existing liver disease and compensated cirrhosis improves outcomes and may lead to regression of fibrosis in some cases. Salient examples include hepatitis C, in which early diagnosis and innovative treatment may result in a cure, thus preventing cirrhosis entirely (Keating 2014); immunosuppressive treatment of autoimmune hepatitis (Shah 2011; Valera 2011); and cessation of alcohol consumption in alcoholic liver disease (Nusrat 2014).

Alcoholic liver disease. Abstain from alcohol and reduce other risk factors (obesity, smoking) (European Association for the Study of Liver 2012). Psychotherapies promoting abstinence can be beneficial, as can pharmacotherapies that treat alcohol dependence (disulfiram [Antabuse], naltrexone [Revia], acamprosate [Campral], and baclofen [Kemstro] (Jaurigue 2014).

Hepatitis B. Vaccination of high-risk individuals against HBV is a standard public health measure (WHO 2009). Hepatitis B is treated with interferon drugs and nucleoside analogs. Interferon treatments have a relatively high rate of side effects (Papatheodoridis 2002; Scaglione 2012).

Hepatitis C. Pegylated interferon combined with ribavirin has been the standard treatment for hepatitis C for many years, and it results in complete virus clearance in some cases. The exact treatment regimen varies depending on the HCV genotype, whether there has been previous unsuccessful treatment, and whether the patient is eligible for interferon. As is the case with hepatitis B, interferon treatment is often accompanied by severe side effects (Craxi 2003; Pawlotsky 2004; Hofmann 2008; Scaglione 2012). In 2013, two new drug treatments were approved for hepatitis C: sofosbuvir (Sovaldi) and simeprevir (Olysio). Both have been greeted as important advances in the treatment of hepatitis C (Keating 2014; FDA 2013). The cost and pricing of the new drugs have been subject to some controversy (Degasperi 2014; Senior 2014).

Hemochromatosis. Phlebotomy (blood removal), iron chelators (deferoxamine mesylate, deferiprone [Ferriprox], deferasirox [Exjade]) (Heli 2011; Crownover 2013; Fabio 2007; Gattermann 2009)

Primary biliary cirrhosis. Ursodeoxycholic acid, a prescription form of isolated and concentrated bile acid, is the only approved treatment at the time of this writing. However, obeticholic acid, a semi-synthetic bile acid analogue, has been granted the FDA’s fast-track designation, which helps expedite development of new drugs (Lindor 2009; Intercept Pharmaceuticals 2014).

Wilson’s disease. Copper chelators (D-penicillamine [D-Penamine], triethylenetetramine, zinc salts) (Delangle 2012)

Budd-Chiari syndrome. Anticoagulants (low molecular weight heparin, vitamin K antagonists), beta-blockers, balloon angioplasty/stents (Plessier 2012)

Autoimmune hepatitis. Immunosuppressants or immune modulators: prednisone, azathioprine (Imuran), budesonide (Enweluzo 2013; Delgado 2013; Czaja 2012; Wolf 2013)