What is liver cirrhosis
- 1. Group IIIMonday, 13.11.17 Diploma Seminar group work. What is liver cirrhosis?
- 2. Introduction Histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury, that leads to portal hypertension and end stage liver disease. Liver transplantation remains the only curative option for a selected group of patients, but pharmacological therapies that can halt progression to decompensated cirrhosis or even reverse cirrhosis are currently being developed.
- 3. Fibrosis describes encapsulation or replacement of injured tissue by a collagenous scar. Fibrosis progresses at variable rates depending on the cause of liver disease, environmental and host factors Cirrhosis leads to shunting of the portal and arterial blood supply directly into the hepatic outflow (central veins), compromising exchange between hepatic sinusoids and the adjacent liver parenchyma. i) Hepatic sinusoids are lined by fenestrated endothelia which rest on a sheet of permeable connective tissue (the space of Disse) Pathogenesis and pathophysiology of cirrhosis
- 4. ii) The other side of the space of Disse is lined by hepatocytes. iii) In cirrhosis the space of Disse is filled with scar tissue and endothelial fenestrations are lost, a process termed sinusoidal capillarization. The major clinical consequences of cirrhosis are impaired hepatocyte (liver) function, an increased intrahepatic resistance (portal hypertension) and the development of hepatocellular carcinoma (HCC). Pathogenesis and pathophysiology of cirrhosis
- 5. The exact prevalence of cirrhosis worldwide is unknown. Cirrhosis prevalence was estimated at 0.15% or 400,000 in the USA, where it accounted for more than 25,000 deaths and 373,000 hospital discharges in 1998. This may be an underestimation as we recognize the high prevalence of undiagnosed cirrhosis in both NASH and hepatitis C. Similar numbers have been reported from Europe, and numbers are even higher in most Asian and African countries where chronic viral hepatitis B or C are frequent. Epidemiology
- 6. The etiology of cirrhosis is usually identified by the patient’s history combined with serologic and histologic evaluation. Alcoholic liver disease and hepatitis C are the most common causes in the Western world, while hepatitis B prevails in most parts of Asia and sub-Saharan Africa. It is important to know the etiology of cirrhosis, since it can predict complications and direct treatment decisions. Frequently multiple etiological factors contribute to the development of cirrhosis, such as regular (moderate) alcohol consumption, age above 50 years, and male gender as risk factors in chronic hepatitis C, or older age obesity, insulin resistance/type 2 diabetes, hypertension and hyperlipidemia (all features of the metabolic syndrome) in NASH Etiology of cirrhosis
- 7. Frequently indolent, asymptomatic and unsuspected until complications of liver disease present. The diagnosis of asymptomatic cirrhosis is usually made when incidental screening tests such as liver transaminases or radiologic findings suggest liver disease and patients undergo further evaluation and liver biopsy. Initial clinical presentation of patients with decompensated cirrhosis is still common and is characterized by the presence of dramatic and life-threatening complications, such as variceal hemorrhage, ascites, spontaneous bacterial peritonitis, or hepatic encephalopathy Clinical presentation
- 8. Ultrasonography, computerized tomography (CT) and magnetic resonance imaging (MRI) are not sensitive to detect cirrhosis, and final diagnosis still relies on histology The major role of radiography is for the detection and quantitation of complications of cirrhosis, eg; ascites, HCC, and portal vein thrombosis. Ultrasonography and Doppler ultrasonography of portal and central vein diameters and velocities are useful screening tests for portal hypertension and vessel patency Conventional CT and MRI are not useful to define the severity of cirrhosis, while helical CT and MRI with contrast are the modalities of choice when HCC or vascular lesions are suspected Imaging of cirrhosis
- 9. Biopsy is considered the gold standard for diagnosis of cirrhosis, and sequential histological grading of inflammation and staging of fibrosis can assess risk of progression. Biopsy confirmation of cirrhosis is not necessary when clear signs of cirrhosis, such as ascites, coagulopathy, and a shrunken nodular appearing liver are present. The biopsy is obtained by either a (radiographically-guided) percutaneous, transjugular or laparoscopical route. Liver biopsy
- 10. Elimination of the trigger(s) that lead to cirrhosis is likely to retard progression to a higher CPT class and to reduce the incidence of HCC. Patients with alcoholic cirrhosis must abstain, since continued alcohol consumption drives hepatitis which favours hepatic fibrogenesis and decompensation Patients with compensated replicating HCV-cirrhosis benefit from interferon- based antiviral treatment. Long term treatment with oral nucleoside and nucleotide inhibitors of HBV polymerase may not only retard or reverse cirrhosis but were also shown to prevent complications of end stage liver disease. Treatment and Reversibility of cirrhosis
- 11. Genetic predisposition The variable rates of development of cirrhosis amongst individuals with similar risk factors such had long been unexplained. . In a recent gene association study 1,609 out of 24,882 single nucleotide polymorphisms (SNPs) were found to be associated with fibrosis progression in chronic hepatitis C, with the DDX5 gene having a high positive predictive value. Together with established extrinsic risk factors like excess alcohol consumption, obesity or advanced age, these SNPs will allow the establishment of risk profiles for the individual patient RECENT ADVANCES AND FUTURE DIRECTIONS