History

Fact Explanation
Asymptomatic Symptoms occur only when disease progresses into cirrhosis. [1]
Abdominal enlargement Ascites is a major complication of cirrhosis. Portal hypertension which increases in cirrhosis, this increases the hydrostatic pressure within the hepatic sinusoids and favours transudation of fluid into the peritoneal cavity. [2]
Upper gastrointestinal bleeding This also occurs due to cirrhosis. Due to the fibrosis there is decreased hepatic production of coagulation factors. Micelle entry into the small intestine is decreased and it leads to decreased vitamin K absorption,If cholestasis is present it results in reduction of hepatic production of factors II, VII, IX, and X. [3]
History of alcohol intake Hepatic fibrosis occur as a result of the wound-healing response of the liver to repeated injury. Alcohol is primarily metabolized in hepatocytes to acetaldehyde, a step that can be catalyzed by alcohol dehyderogenase (ADH), or cytochrome P450 2E1 (CYP2E1). This metabolism, especially through CYP2E1, leads to the release of reactive oxygen species (ROS) and generation of lipid peroxidation products. Reactive oxygen species are also generated from mitochondria during alcohol metabolism. Therefore, alcohol metabolism leads to the generation of acetaldehyde and ROS in hepatocytes, both of which can activate Activation of hepatic stellate cells (HSCs) through paracrine mechanism. HSCs is the primary event that triggers the process of fibrogenesis. [4],[5]
History of hepatitis infection Hepatic fibrosis is the result of the wound-healing response of the liver to repeated injury. parenchymal cells regeneration and replacement with the necrotic or apoptotic cells occur after an acute viral hepatitis . This process is associated with an inflammatory response and a limited deposition of extra cellular matrix. [5][7]
Drowsiness This occurs due to hepatic encephalopathy following cirrosis. They may have increased permeability of the blood-brain barrier and altered brain energy metabolism. Increased permeability of the blood-brain barrier cause the passage of neurotoxins as short-chain fatty acids,false neurotransmitters (eg, tyramine, octopamine, beta phenylethanolamines), mercaptans, ammonia, and gamma-aminobutyric acid (GABA) into the brain and cause altered metabolism. The symptoms of hepatic encephalopathy can range from mild to severe, therefore it is graded from grade 0 to grade 4. [6]
References
  1. BATALLER R, BRENNER DA. Liver fibrosis J Clin Invest [online] 2005 Feb 1, 115(2):209-218 [viewed 09 August 2014] Available from: doi:10.1172/JCI24282
  2. LINDSAY KL, REYNOLDS TB, HOEFS JC, SANMARCO ME. Ascites. West J Med [online] 1981 May, 134(5):414-423 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1272767
  3. THALHEIMER U. Infection, coagulation, and variceal bleeding in cirrhosis. Gut [online] 2005 April, 54(4):556-563 [viewed 13 August 2014] Available from: doi:10.1136/gut.2004.048181
  4. PUROHIT VISHNUDUTT, BRENNER DAVID A.. Mechanisms of alcohol-induced hepatic fibrosis: A summary of the Ron Thurman Symposium. Hepatology [online] December, 43(4):872-878 [viewed 13 August 2014] Available from: doi:10.1002/hep.21107
  5. BATALLER RAMóN, BRENNER DAVID A.. Liver fibrosis. J. Clin. Invest. [online] 2005 February, 115(2):209-218 [viewed 13 August 2014] Available from: doi:10.1172/JCI24282
  6. YIN M, TALWALKAR JA, GLASER KJ, MANDUCA A, GRIMM RC, ROSSMAN PJ, FIDLER JL, EHMAN RL. A Preliminary Assessment of Hepatic Fibrosis with Magnetic Resonance Elastography Clin Gastroenterol Hepatol [online] 2007 Oct, 5(10):1207-1213.e2 [viewed 13 August 2014] Available from: doi:10.1016/j.cgh.2007.06.012
  7. FRIEDMAN SCOTT L. Liver fibrosis – from bench to bedside. Journal of Hepatology [online] 2003 January, 38:38-53 [viewed 13 August 2014] Available from: doi:10.1016/S0168-8278(02)00429-4

Examination

Fact Explanation
Ascites Ascites is a major complication of cirrhosis. Portal hypertension which increase in cirrhosis increases the hydrostatic pressure within the hepatic sinusoids and favours transudation of fluid into the peritoneal cavity. This can be graded. Grade 1 (mild) - only detectable by ultrasound examination. Grade 2 (moderate) - cause moderate symmetrical distension of the abdomen. Grade 3 (large) - cause marked abdominal distension. [1]
Clubbing The exact etiology of clubbing is still unknown. Vasculitis of digital vasculature by impairing endothelial functions promoting platelet aggregation and causing clubbing is a one hypotheses which explain clubbing in liver cirrhosis. [2]
Pallor Anaemia occur due to the bleeding, undernutrition with deficiency of folate (or iron or vitamin B12), chronic disease, or effects of alcohol (eg, bone marrow suppression).[3]
Jaundice In hepatic fibrosis conjugated hyperbilirubinemia occurs due to Hepatocellular dysfunction and intrahepatic cholestasis[5]
Petechiae, purpura This also occurs due to cirrhosis. Due to the fibrosis there is decreased hepatic production of coagulation factors. Micelle entry into the small intestine is decreased and it leads to decreased vitamin K absorption,If cholestasis is present, it results in reduction of hepatic production of factors II, VII, IX, and X. [4]
References
  1. LINDSAY KL, REYNOLDS TB, HOEFS JC, SANMARCO ME. Ascites. West J Med [online] 1981 May, 134(5):414-423 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1272767
  2. SARKAR M, MAHESH DM, MADABHAVI I. Digital clubbing Lung India [online] 2012, 29(4):354-362 [viewed 13 August 2014] Available from: doi:10.4103/0970-2113.102824
  3. FRIEDMAN SCOTT L. Liver fibrosis – from bench to bedside. Journal of Hepatology [online] 2003 January, 38:38-53 [viewed 13 August 2014] Available from: doi:10.1016/S0168-8278(02)00429-4
  4. THALHEIMER U. Infection, coagulation, and variceal bleeding in cirrhosis. Gut [online] 2005 April, 54(4):556-563 [viewed 13 August 2014] Available from: doi:10.1136/gut.2004.048181
  5. SINGH V, BHALLA A, SHARMA N, MAHI SK, LAL A, SINGH P. Pathophysiology of jaundice in amoebic liver abscess. Am J Trop Med Hyg [online] 2008 Apr, 78(4):556-9 [viewed 13 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/18385348

Differential Diagnoses

Fact Explanation
Alcoholic liver disease Can cause liver fibrosis eventually. patient has a history of chronic alcohol intake. Alcohol liver disease can be present as alcoholic fatty liver (steatosis), acute alcoholic hepatitis, and alcoholic cirrhosis. [1]
Hepatitis infection Can cause liver fibrosis eventually. It is caused by hepatitis viruses. Hepatitis may be and acute infection or can cause chronic infection. In some cases, hepatitis may lead to liver failure, or even liver carcinoma.[2]
NASH - Nonalcoholic Steatohepatitis It is a multifaceted metabolic disorder. It consist of a spectrum of liver disease ranging from simple steatosis to full blown steatohepatitis that is characterized by steatosis, lobular inflammation, ballooning and fibrosis. The diagnosis requires that there is no history of previous or ongoing significant alcohol consumption. [3]
Heart failure Heart failure patients may present with symptoms similar to liver fibrosis as ascites, dyspnoea and peripheral odema. [4]
References
  1. WALSH K.. Alcoholic liver disease. [online] 2000 May, 76(895):280-286 [viewed 13 August 2014] Available from: doi:10.1136/pmj.76.895.280
  2. LEE WILLIAM M.. Hepatitis B Virus Infection. N Engl J Med [online] 1997 December, 337(24):1733-1745 [viewed 13 August 2014] Available from: doi:10.1056/NEJM199712113372406
  3. VUPPALANCHI R, CHALASANI N. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: Selected practical issues in their evaluation and management Hepatology [online] 2009 Jan, 49(1):306-317 [viewed 13 August 2014] Available from: doi:10.1002/hep.22603
  4. Ashley EA, Niebauer J. Cardiology Explained. London: Remedica; 2004. Chapter 7, Heart failure. Available from: http://www.ncbi.nlm.nih.gov/books/NBK2218/

Investigations - for Diagnosis

Fact Explanation
Liver biopsy The liver biopsy specimen represents valuable material for the assessment of fibrosis and cirrhosis. Even with the limitations related to sampling and interpretation this remains the gold standard for staging chronic liver diseases. Fibrosis due to chronic viral hepatitis and fibrosis due to fatty liver disease evolve two different patterns. In viral hepatitis, fibrosis begins in the portal triads and initially manifests histologically as fibrous expansion of the portal triads. Whereas fibrosis in alcoholic hepatitis and in the adult form of nonalcoholic fatty liver disease begins adjacent to the central veins.[1], [3]
Ultra sound scan of abdomen Ultrasound scanning is used as the first line imaging investigation in patients with suspected liver disorders. There are two major patterns are seen: focal and diffuse disease. Although both hepatic steatosis and fibrosis are diffuse processes, their distribution may vary, resulting in sampling error of up to 10%. ultrasound scanning has the advantage over liver biopsy in providing a rapid overall assessment of liver morphology in addition to being routinely available and completely safe. [2]
CT - computed tomography Provides information similar to that of ultrasonography, can identify complications of cirrhosis as portal hypertension and ascites. But it costs more and it exposes the patient to radiation and contrast media. [1]
MRI Various MR imaging–based techniques have been used in assessment of liver fibrosis as conventional contrast material–enhanced MR imaging, double contrast-enhanced MR imaging, MR elastography, diffusion-weighted imaging, MR perfusion imaging, and MR spectroscopy. The cirrhotic liver develops characteristic morphologic alterations (surface nodularity, widening of fissures, expansion of the gallbladder fossa, notching of the right lobe, atrophy of the right lobe, and relative enlargement of the lateral segments of the left lobe and caudate lobe). These can be visualized with conventional MR imaging. Fibrosis itself is not well visualized with US, CT, or conventional MR imaging, but it may be visible with advanced MR imaging techniques. In patients with precirrhotic stages of liver fibrosis as well as patients with early cirrhosis liver parenchyma usually has a normal MR imaging. In patients with advanced cirrhosis unenhanced MR imaging may depict fibrotic septa and bridges as low-signal-intensity reticulations on T1-weighted images and high-signal-intensity reticulations on T2-weighted images. [3]
References
  1. CAREY E., CAREY W. D.. Noninvasive tests for liver disease, fibrosis, and cirrhosis: Is liver biopsy obsolete?. Cleveland Clinic Journal of Medicine [online] December, 77(8):519-527 [viewed 14 August 2014] Available from: doi:10.3949/ccjm.77a.09138
  2. SAVERYMUTTU SH, JOSEPH AE, MAXWELL JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed) [online] 1986 Jan 4, 292(6512):13-15 [viewed 14 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1338970
  3. FARIA SILVANA C., GANESAN KARTHIK, MWANGI IRENE, SHIEHMORTEZA MASOUD, VIAMONTE BARBARA, MAZHAR SAMEER, PETERSON MICHAEL, KONO YUKO, SANTILLAN CYNTHIA, CASOLA GIOVANNA, SIRLIN CLAUDE B.. MR Imaging of Liver Fibrosis: Current State of the Art1. RadioGraphics [online] 2009 October, 29(6):1615-1635 [viewed 14 August 2014] Available from: doi:10.1148/rg.296095512

Investigations - Fitness for Management

Fact Explanation
Upper gastro intestinal endoscopy It is used in patients with cirrhosis to identify medium or large varices in those areas so that prophylactic treatment may be initiated to reduce the risk of bleeding. [1]
Full blood count Done to evaluate the blood loss and anemia. [2]
References
  1. MILLER V, DOIG CM. Upper gastrointestinal tract endoscopy. Arch Dis Child [online] 1984 Nov, 59(11):1100-1102 [viewed 18 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1628814
  2. CAREY E., CAREY W. D.. Noninvasive tests for liver disease, fibrosis, and cirrhosis: Is liver biopsy obsolete?. Cleveland Clinic Journal of Medicine [online] December, 77(8):519-527 [viewed 16 August 2014] Available from: doi:10.3949/ccjm.77a.09138

Investigations - Followup

Fact Explanation
Liver function test The normal ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is approximately 0.8. A ratio greater than 1.0 provides evidence of cirrhosis. [1]
References
  1. CAREY E., CAREY W. D.. Noninvasive tests for liver disease, fibrosis, and cirrhosis: Is liver biopsy obsolete?. Cleveland Clinic Journal of Medicine [online] December, 77(8):519-527 [viewed 16 August 2014] Available from: doi:10.3949/ccjm.77a.09138

Investigations - Screening/Staging

Fact Explanation
Ultrasound scan Ultrasound scanning has the advantage over liver biopsy in providing a rapid overall assessment of liver morphology in addition to being routinely available and completely safe. Therefore scanning fulfills two important criteria for a good screening procedure to detect liver disease. The major requirement for a screening procedure, however, is a high degree of sensitivity and specificity for detecting major liver diseases. [1]
References
  1. SAVERYMUTTU SH, JOSEPH AE, MAXWELL JD. Ultrasound scanning in the detection of hepatic fibrosis and steatosis. Br Med J (Clin Res Ed) [online] 1986 Jan 4, 292(6512):13-15 [viewed 14 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1338970

Management - General Measures

Fact Explanation
Long-term abstinence from alcohol As alcohol can cause damage to hepatocytes abstinence from alcohol is important. [1]
Management of obesity Obesity reduction can be achieved by controlling the diet and doing exercise. [1]
References
  1. BATALLER R, BRENNER DA. Liver fibrosis J Clin Invest [online] 2005 Feb 1, 115(2):209-218 [viewed 16 August 2014] Available from: doi:10.1172/JCI24282

Management - Specific Treatments

Fact Explanation
Anti inflammatory drugs As inflammation precedes and promotes the progression of liver fibrosis, the use of anti - inflammatory drugs has been proposed. Corticosteroids are only indicated for the treatment of hepatic fibrosis in patients with autoimmune hepatitis and acute alcoholic hepatitis [1]
Liver Transplantation Liver transplantation has a place in the management of patients with decompensated alcohol-related cirrhosis who have failed to improve despite well-documented abstinence from alcohol and expert medical treatment for a period of approximately 6 months. Liver transplantation is indicated when there is end-stage disease with objective evidence of advanced physical incapacitation causing deterioration of health or the quality of life to an unacceptable level due to documented, isolated liver disease; when life expectancy is limited due to liver dysfunction; when previous medical therapy has been optimized and no other therapy other than transplantation offers realistic expectation of hepatic functional improvement and extension of life and when adequate psychosocial support system to aid the patient prior to and during the surgery and to promoted adherence to required post-transplant treatment regimes are available [1]
References
  1. BATALLER R, BRENNER DA. Liver fibrosis J Clin Invest [online] 2005 Feb 1, 115(2):209-218 [viewed 16 August 2014] Available from: doi:10.1172/JCI24282