History

Fact Explanation
Asymptomatic Some patients are asymptomatic until the hepatic function is significantly impaired. [2]
Yellowish discoloration of skin and sclera. Accumulation of bilirubin in the subcutaneous fat and in sclera. [10]
Hematemesis and or malena [2] Esophageal varices develop secondary to portal hypertension. Often bleeding is massive because of defective coagulation secondary to reduced coagulation factor synthesis by the liver.
Reversed sleep wake cycle This is one of the earliest symptoms of hepatic encephalopathy (HE) and it is due to altered melatonin secretion. [6]
Impaired memory [9] An early symptom of HE.
Personality changes Begins to appear from grade 2 HE. [6]
Inappropriate behavior This occurs in grade 3 HE. [6]
Coma [6] Patients with severe hepatic encephalopathy may present with coma.
Abdominal pain Budd Chiary syndrome causes acute onset abdominal pain and symptoms of hepatic failure. [7]
Constitutional symptoms Some patients present with non-specific symptoms like fatigue, malaise, anorexia, muscle wasting and loss of weight. Patients may gain weight due to ascites and generalized edema. [4]
Presence of risk factors Harmful alcohol use is one of the leading causes of cirrhosis. [1] Hepatitis B, C and nonalcoholic fatty liver disease (NAFLD) are all risk factors for cirrhosis. Presence of autoimmune hepatitis, primary and secondary biliary cirrhosis, alpha-1 antitrypsin deficiency, hemochromatosis, Wilson’s disease, chronic right heart failure (cardiac cirrhosis), tricuspid regurgitation, Budd Chiari syndrome and veno-occlusive diseases are other risk factors. [2,3,8]
References
  1. REHM J, TAYLOR B, MOHAPATRA S, IRVING H, BALIUNAS D, PATRA J, ROERECKE M. Alcohol as a risk factor for liver cirrhosis: a systematic review and meta-analysis. Drug Alcohol Rev [online] 2010 Jul, 29(4):437-45 [viewed 24 May 2014] Available from: doi:10.1111/j.1465-3362.2009.00153.x
  2. SCHUPPAN D, AFDHAL NH. Liver Cirrhosis Lancet [online] 2008 Mar 8, 371(9615):838-851 [viewed 24 May 2014] Available from: doi:10.1016/S0140-6736(08)60383-9
  3. CURA MARCO, HASKAL ZIV, LOPERA JORGE. Diagnostic and Interventional Radiology for Budd-Chiari Syndrome1. RadioGraphics [online] 2009 May, 29(3):669-681 [viewed 24 May 2014] Available from: doi:10.1148/rg.293085056
  4. KALAITZAKIS E, SIMRéN M, OLSSON R, HENFRIDSSON P, HUGOSSON I, BENGTSSON M, BJöRNSSON E. Gastrointestinal symptoms in patients with liver cirrhosis: associations with nutritional status and health-related quality of life. Scand J Gastroenterol [online] 2006 Dec, 41(12):1464-72 [viewed 25 May 2014] Available from: doi:10.1080/00365520600825117
  5. CAVANAUGH J, NIEWOEHNER CB, NUTTALL FQ. Gynecomastia and cirrhosis of the liver. Arch Intern Med [online] 1990 Mar, 150(3):563-5 [viewed 25 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/2310274
  6. BLEIBEL W, AL-OSAIMI AM. Hepatic Encephalopathy Saudi J Gastroenterol [online] 2012, 18(5):301-309 [viewed 25 May 2014] Available from: doi:10.4103/1319-3767.101123
  7. MENON K.V. NARAYANAN, SHAH VIJAY, KAMATH PATRICK S.. The Budd–Chiari Syndrome. N Engl J Med [online] 2004 February, 350(6):578-585 [viewed 25 May 2014] Available from: doi:10.1056/NEJMra020282
  8. BLUMGART HL, KATZIN H. "Cardiac Cirrhosis" of the Liver: A Clinical and Pathological Study Trans Am Clin Climatol Assoc [online] 1938:82-86 [viewed 25 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2242083
  9. BASS NM, MULLEN KD, SANYAL A, POORDAD F, NEFF G, LEEVY CB, SIGAL S, SHEIKH MY, BEAVERS K, FREDERICK T, TEPERMAN L, HILLEBRAND D, HUANG S, MERCHANT K, SHAW A, BORTEY E, FORBES WP. Rifaximin treatment in hepatic encephalopathy. N Engl J Med [online] 2010 Mar 25, 362(12):1071-81 [viewed 30 May 2014] Available from: doi:10.1056/NEJMoa0907893
  10. PUNNOOSE ANN R., LYNM CASSIO, GOLUB ROBERT M.. Cirrhosis. JAMA [online] 2012 February [viewed 30 May 2014] Available from: doi:10.1001/jama.2012.82

Examination

Fact Explanation
Abdominal examination The liver is usually not palpated because it is small and shrunken. Splenomegaly occurs due to portal hypertension. Portosystemic collaterals around the umbilicus dilates giving rise to caput medusa appearance. [7] Ascites occurs due to cirrhosis and portal hypertension. [1,3] Abdomen is distended and abdominal dullness is present. Depending on the amount of ascetic fluid, flank dullness, shifting dullness, horse shoe dullness and fluid thrill can be detected. Puddle sign is present in small fluid collections.
Pallor Secondary to recurrent bleeding episodes and nutritional deficiencies. [12]
Jaundice [3] Due to excessive accumulation of bilirubin. [12]
Muscle wasting [3] Protein calorie malnutrition and recurrent infections play a role in the etiology of muscle wasting. [13]
Scratch marks Patients develop pruritus due to retention of bile salts. Repetitive scratching causes scratch marks and polished nails. [17]
Peripheral edema [3] Due to hypoalbuminemia. [12]
Spider telangiectasias [3,12] Excess of estrogen in men is believed to be the reason for the development of spider telangiectasias, but the exact reason is not known. [14]
Palmar erythema [3,12] Due to vasodilators which are not deactivated by the liver. Commonly seen in alcoholic cirrhosis.
Fetor hepaticus [3] Hyperammonemia causes fetor hepaticus. It is present in HE. [15]
Impaired attention and concentration [1,3] According to the West Haven classification minimal impairment is graded as grade 0. Mild lack of awareness and shortened attention span is grade 1. Disorientation belongs to grade 2 and somnolence, disorientation in time and place and marked confusion belongs to grade 3. Coma despite the responsiveness to painful stimuli is grade 4.
Impaired consciousness [1,3] HE results due to reduced detoxification of ammonia and other neuro-toxic metabolites because of the liver failure. [11]
Hyperreflexia [1,3] Pyramidal tract dysfunction in HE results in hyperreflexia which later becomes hypotonia with the development of coma. [16]
Hepatic flaps (asterixis) [1,3] This sign is elicited by asking the patient to keep the hands outstretched and dorsiflexed. Presence of flaps favors the diagnosis of HE, but it can occur in various other metabolic abnormalities as well. Asterixis is absent in grade 0 HE and in grade 4. It is marked in grade 2 and 3 HE.
Transient focal neurologic deficits [3] This is a rare finding of severe HE. Patients may manifest signs suggestive of focal neurological deficits. Transient hemiplegia is common.
Cutaneous manifestations Jaundice, spider angiomata, skin telangiectasias, palmar erythema, leukonychia, and finger clubbing are present. [2,7]
Pleural effusions In the presence of massive ascites pleural effusions can occur due to the direct flow of ascetic fluid in to the pleural cavity. [8]
Signs suggestive of the etiology of cirrhosis Abdominal tenderness, hepatomegaly and ascites can be elicited in Budd Chiari syndrome. [4] Neurological manifestations (chorea, Parkinsonism, dysarthria) and Kayser-Fleischer rings suggest Wilson’s disease. [5] Acanthosis nigricans, obesity, high blood pressure and pheripheral stigmata of hyperlipidemia (xantholesma, xanthomata) all are suggestive of the possibility of metabolic syndrome and non-alcoholic fatty liver disease as the possible etiology. [6] Tricuspid regurgitation and signs of right heart failure is found in cardiac cirrhosis. [9]
References
  1. SCHUPPAN D, AFDHAL NH. Liver Cirrhosis Lancet [online] 2008 Mar 8, 371(9615):838-851 [viewed 24 May 2014] Available from: doi:10.1016/S0140-6736(08)60383-9
  2. HAZIN R., ABU-RAJAB TAMIMI T. I., ABUZETUN J. Y., ZEIN N. N.. Recognizing and treating cutaneous signs of liver disease. Cleveland Clinic Journal of Medicine [online] December, 76(10):599-606 [viewed 25 May 2014] Available from: doi:10.3949/ccjm.76A.08113
  3. BLEIBEL W, AL-OSAIMI AM. Hepatic Encephalopathy Saudi J Gastroenterol [online] 2012, 18(5):301-309 [viewed 25 May 2014] Available from: doi:10.4103/1319-3767.101123
  4. MENON K.V. NARAYANAN, SHAH VIJAY, KAMATH PATRICK S.. The Budd–Chiari Syndrome. N Engl J Med [online] 2004 February, 350(6):578-585 [viewed 25 May 2014] Available from: doi:10.1056/NEJMra020282
  5. ALA AFTAB, WALKER ANN P, ASHKAN KEYOUMARS, DOOLEY JAMES S, SCHILSKY MICHAEL L. Wilson's disease. The Lancet [online] 2007 February, 369(9559):397-408 [viewed 25 May 2014] Available from: doi:10.1016/S0140-6736(07)60196-2
  6. GRUNDY S. M.. Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation [online] 2005 October, 112(17):2735-2752 [viewed 18 May 2014] Available from: doi:10.1161/CIRCULATIONAHA.105.169404
  7. HARI KUMAR KV, RASTOGI SK. Caput medusae in alcoholic liver disease. Niger J Clin Pract [online] 2011 Oct-Dec, 14(4):508-9 [viewed 25 May 2014] Available from: doi:10.4103/1119-3077.91769
  8. MOUROUX J, PERRIN C, VENISSAC N, BLAIVE B, RICHELME H. Management of pleural effusion of cirrhotic origin. Chest [online] 1996 Apr, 109(4):1093-6 [viewed 25 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/8635335
  9. BLUMGART HL, KATZIN H. "Cardiac Cirrhosis" of the Liver: A Clinical and Pathological Study Trans Am Clin Climatol Assoc [online] 1938:82-86 [viewed 25 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2242083
  10. BASS NM, MULLEN KD, SANYAL A, POORDAD F, NEFF G, LEEVY CB, SIGAL S, SHEIKH MY, BEAVERS K, FREDERICK T, TEPERMAN L, HILLEBRAND D, HUANG S, MERCHANT K, SHAW A, BORTEY E, FORBES WP. Rifaximin treatment in hepatic encephalopathy. N Engl J Med [online] 2010 Mar 25, 362(12):1071-81 [viewed 30 May 2014] Available from: doi:10.1056/NEJMoa0907893
  11. SANTIAGO J. MUNOZ. Hepatic Encephalopathy. Med Clin N Am [online] 2008 92:795–812 [viewed 30 May 2014] Available from: http://faculty.vet.upenn.edu/gastro/documents/MedClinNAencephalopathy2008.pdf
  12. PUNNOOSE ANN R., LYNM CASSIO, GOLUB ROBERT M.. Cirrhosis. JAMA [online] 2012 February [viewed 30 May 2014] Available from: doi:10.1001/jama.2012.82
  13. MONTANO–LOZA ALDO J., MEZA–JUNCO JUDITH, PRADO CARLA M.M., LIEFFERS JESSICA R., BARACOS VICKIE E., BAIN VINCENT G., SAWYER MICHAEL B.. Muscle Wasting Is Associated With Mortality in Patients With Cirrhosis. Clinical Gastroenterology and Hepatology [online] 2012 February, 10(2):166-173.e1 [viewed 30 May 2014] Available from: doi:10.1016/j.cgh.2011.08.028
  14. HEIDELBAUGH JJ, BRUDERLY M. Cirrhosis and chronic liver failure: part I. Diagnosis and evaluation. Am Fam Physician [online] 2006 Sep 1, 74(5):756-62 [viewed 30 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16970019
  15. HOFMANN WW. HEPATOCEREBRAL DYSFUNCTION Calif Med [online] 1958 Jul, 89(1):16-21 [viewed 30 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1512934
  16. LEWIS M., HOWDLE P.D.. The neurology of liver failure. QJM [online] December, 96(9):623-633 [viewed 30 May 2014] Available from: doi:10.1093/qjmed/hcg110
  17. KECZKES K, LYELL A. Intractable Pruritus Due to Hepatic Cirrhosis Relieved by Cholestyramine Postgrad Med J [online] 1965 Mar, 41(473):155-157 [viewed 30 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2482948

Differential Diagnoses

Fact Explanation
Congenital hepatic fibrosis This is a relatively rare cause of portal hypertension. Hepatic function is usually spared. [2]
Non-cirrhotic intrahepatic portal hypertension (NCIPH) Schistosomiasis is the commonest cause for NCIPH. Nodular regenerative hyperplasia also belongs to this category. Patients usually present with clinical symptoms of portal hypertension (splenomegaly, hemoptysis, ascites) but without symptoms or signs of cirrhosis (gynecomastia, palmar erythema, spider nevi). Hepatic transaminases are only mildly elevated. [1]
Seizure disorder Hepatic encephalopathy can also present as seizures. Electro-encephalogram helps in differentiating seizure disorders and hepatic encephalopathy. [3]
Congestive cardiac failure Can cause ascites, which is a transudate. Chronic right heart failure is also a causative factor of cirrhosis. [4]
Hypoalbuminemia Causes generalized edema and ascites. Nephrotic syndrome and protein loosing enteropathy are common causes. Cirrhosis can also cause hypoalbuminemia. [5]
Pancreatic ascites Pancreatic ascites can present with progressive abdominal distension, weakness, and varying degree of abdominal pain. Alcoholism is one of the common causative factors which is common to both pancreatic ascites and cirrhosis. [6]
Ovarian malignancy Spreads to the omentum and causes an exudative type of ascites. Lymphocytes are predominant in malignant ascites. About one third of ovarian carcinomas present with ascites. [7,8]
Peritoneal malignancy Either primary or secondary malignancies can cause ascites. [9]
Tuberculosis Cause loss of weight, anorexia and fever. Peritoneal tuberculosis can cause an exudative ascites with numerous lymphocytes. [10]
Granulomatous peritonitis This can cause exudative ascites and can be due to sarcoidosis, foreign bodies, fungal and parasitic infections. Peritoneal tuberculosis is also another cause. [11]
Systemic vasculitis Henoch-Schönlein purpura and systemic lupus erythematosus can cause an exudative type of ascites. [12]
References
  1. HARTLEB M, GUTKOWSKI K, MILKIEWICZ P. Nodular regenerative hyperplasia: Evolving concepts on underdiagnosed cause of portal hypertension World J Gastroenterol [online] 2011 Mar 21, 17(11):1400-1409 [viewed 25 May 2014] Available from: doi:10.3748/wjg.v17.i11.1400
  2. GHADIR MR, BAGHERI M, GHANOONI AH. Congenital hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma: a case report J Med Case Reports [online] :160 [viewed 25 May 2014] Available from: doi:10.1186/1752-1947-5-160
  3. ELEFTHERIADIS N, FOURLA E, ELEFTHERIADIS D, KARLOVASITOU A. Status epilepticus as a manifestation of hepatic encephalopathy. Acta Neurol Scand [online] 2003 Feb, 107(2):142-4 [viewed 25 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12580865
  4. SAKASHITA N, ANDO Y, HARAOKA K, TERAZAKI H, YAMASHITA T, NAKAMURA M, TAKEYA M. Severe congestive heart failure with cardiac liver cirrhosis 10 years after orthotopic liver transplantation for familial amyloidotic polyneuropathy. Pathol Int [online] 2006 Jul, 56(7):408-12 [viewed 25 May 2014] Available from: doi:10.1111/j.1440-1827.2006.01978.x
  5. FADELL EDWARD J.. Chronic Hypoalbuminemia and Edema Associated With Intestinal Lymphangiectasia. JAMA [online] 1965 November [viewed 25 May 2014] Available from: doi:10.1001/jama.1965.03090210081030
  6. KOHATSU S. Pancreatic Ascites West J Med [online] 1976 Mar, 124(3):230-231 [viewed 28 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1130014
  7. CVETKOVIC D. Early events in ovarian oncogenesis. Reprod Biol Endocrinol [online] 2003 Oct 7:68 [viewed 28 May 2014] Available from: doi:10.1186/1477-7827-1-68
  8. PUIFFE ML, LE PAGE C, FILALI-MOUHIM A, ZIETARSKA M, OUELLET V, et al. Characterization of Ovarian Cancer Ascites on Cell Invasion, Proliferation, Spheroid Formation, and Gene Expression in an In Vitro Model of Epithelial Ovarian Cancer Neoplasia [online] 2007 Oct, 9(10):820-829 [viewed 28 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040209
  9. TEO M. Peritoneal-based malignancies and their treatment. Ann Acad Med Singapore [online] 2010 Jan, 39(1):54-7 [viewed 28 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/20126816
  10. LAL N, SOTO-WRIGHT V. Peritoneal tuberculosis: diagnostic options. Infect Dis Obstet Gynecol [online] 1999, 7(5):244-247 [viewed 28 May 2014] Available from: doi:10.1002/(SICI)1098-0997(1999)7:5<244::AID-IDOG7>3.0.CO;2-1
  11. TINKER MA, BURDMAN D, DEYSINE M, TEICHER I, PLATT N, AUFSES AH JR. Granulomatous Peritonitis Due to Cellulose Fibers From Disposable Surgical Fabrics: Laboratory Investigation and Clinical Implications Ann Surg [online] 1974 Dec, 180(6):831-835 [viewed 28 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1343805
  12. KAGEYAMA Y, YAGI T, MIYAIRI M. Systemic lupus erythematosus associated with massive ascites and pleural effusion in a patient who presented with disseminated intravascular coagulation. Intern Med [online] 2002 Feb, 41(2):161-6 [viewed 28 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11868607

Investigations - for Diagnosis

Fact Explanation
Full blood count Thrombocytopenia is seen with portal hypertension. Platelet counts less than 160,000 × 10(9)/L should raise the suspicion of cirrhosis in any patient. [5]
Hepatic transaminases Both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are elevated. [5]
Prothrombin time [4] Prolonged.
Serum bilirubin [4] Often elevated. Higher the bilirubin levels in blood, higher the risk of spontaneous bacterial peritonitis. [8]
Serum albumin Reduced due to diminished hepatic synthesis. [6]
Liver biopsy Cirrhosis is a pathological diagnosis. Although imaging studies can suggest cirrhosis biopsy is necessary for confirmative diagnosis. [1,3]
Ascetic fluid full report Differentiates ascites due to portal hypertension from other causes. In portal hypertension ascetic fluid is a transudate and protein content is less than 2.5g/dL and serum-ascites albumin gradient (SAAG) is greater than 1.1g/dL. [7]
Abdominal imaging Ultrasound scan, CT and MRI can be used in assessing the hepatic architecture. Ultrasound scan has low sensitivity in detecting early cirrhosis. [1] Ultrasound scan combined with Doppler can diagnose Budd Chiari syndrome. [2]
References
  1. SCHUPPAN D, AFDHAL NH. Liver Cirrhosis Lancet [online] 2008 Mar 8, 371(9615):838-851 [viewed 24 May 2014] Available from: doi:10.1016/S0140-6736(08)60383-9
  2. CURA MARCO, HASKAL ZIV, LOPERA JORGE. Diagnostic and Interventional Radiology for Budd-Chiari Syndrome1. RadioGraphics [online] 2009 May, 29(3):669-681 [viewed 24 May 2014] Available from: doi:10.1148/rg.293085056
  3. STARR SP, RAINES D. Cirrhosis: diagnosis, management, and prevention. Am Fam Physician [online] 2011 Dec 15, 84(12):1353-9 [viewed 29 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22230269
  4. BLAKE JC, SPRENGERS D, GRECH P, MCCORMICK PA, MCINTYRE N, BURROUGHS AK. Bleeding time in patients with hepatic cirrhosis. BMJ [online] 1990 Jul 7, 301(6742):12-15 [viewed 29 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1663385
  5. RUNYON BRUCE ALLEN. A Primer on Detecting Cirrhosis and Caring for These Patients without Causing Harm. International Journal of Hepatology [online] 2011 December, 2011:1-8 [viewed 29 May 2014] Available from: doi:10.4061/2011/801983
  6. LEE JS. Albumin for End-Stage Liver Disease Korean J Intern Med [online] 2012 Mar, 27(1):13-19 [viewed 29 May 2014] Available from: doi:10.3904/kjim.2012.27.1.13
  7. RUNYON BA, MONTANO AA, AKRIVIADIS EA, ANTILLON MR, IRVING MA, MCHUTCHISON JG. The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. Ann Intern Med [online] 1992 Aug 1, 117(3):215-20 [viewed 29 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/1616215
  8. ALANIZ C, REGAL RE. Spontaneous Bacterial Peritonitis: A Review of Treatment Options P T [online] 2009 Apr, 34(4):204-210 [viewed 30 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2697093

Investigations - Fitness for Management

Fact Explanation
Full blood count Anemia is a common finding due to chronic gastrointestinal bleeding, folate deficiency, B12 deficiency, hemolysis, and hypersplenism. [1] Thrombocytopenia occurs secondary to hypersplenism and reduced synthesis of thrombopoietin. [2]
Coagulation profile Synthesis of clotting factors is impaired resulting coagulopathy. [3]
Serum electrolytes Done as an assessment of fitness for surgery. [5]
Pulmonary capillary wedge pressure Measured to assess the pre-operative fitness before liver transplant. [4]
References
  1. GONZALEZ-CASAS ROSARIO. Spectrum of anemia associated with chronic liver disease. WJG [online] 2009 December [viewed 24 May 2014] Available from: doi:10.3748/wjg.15.4653
  2. RUNYON BRUCE ALLEN. A Primer on Detecting Cirrhosis and Caring for These Patients without Causing Harm. International Journal of Hepatology [online] 2011 December, 2011:1-8 [viewed 29 May 2014] Available from: doi:10.4061/2011/801983
  3. BOSCH JAIME, REVERTER JUAN CARLOS. The coagulopathy of cirrhosis: Myth or reality?. Hepatology [online] December, 41(3):434-435 [viewed 29 May 2014] Available from: doi:10.1002/hep.20639
  4. SAWANT PRABHA, VASHISHTHA C., NASA M.. Management of Cardiopulmonary Complications of Cirrhosis. International Journal of Hepatology [online] 2011 December, 2011:1-11 [viewed 29 May 2014] Available from: doi:10.4061/2011/280569
  5. Practice advisory for preanesthesia evaluation. An updated report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation. [viewed 29 May 2014] Available from: http://www.guideline.gov/content.aspx?id=36197

Investigations - Followup

Fact Explanation
Serum ammonia Increased in hepatic encephalopathy, but normal amounts do not exclude the possibility of hepatic encephalopathy. [5,6]
Full blood count Leukocytosis suggests the possibility of spontaneous bacterial peritonitis. [7]
Ascetic fluid full report In spontaneous bacterial peritonitis (SBP), polymorphonuclear cells increases (more than 250/mm3). [8]
Ascetic fluid culture Aids in isolating the organism causing SBP. Escherichia coli, Klebsiella species, Streptococcus pneumoniae, and other gram-negative enteric organisms are the common causes. [8]
Serum electrolytes and serum creatinine Detects hepato-renal syndrome. [3]
Measurement of portal venous pressure Elevated in portal hypertension. This is an independent predictor of patients’ survival. [9]
Pulse oxymetry Patients with hepato-pulmonary syndrome (HPS) have low oxygen saturation (less than 70mm Hg). This is due to excess nitric oxide production and pulmonary artery vasodilatation. [4]
Pulmonary capillary wedge pressure Increased in portopulmonary hypertension. [10]
Screening for hepatocellular carcinoma (HCC) Elevated alpha-feto protein and ultrasound scan, CT or MRI evidence of hepatic focal lesions should be looked for in screening of HCC. [1,2]
Upper gastrointestinal endoscopy Regular variceal surveillance is indicated in all patients with cirrhosis. [11,12]
References
  1. JELIC S., SOTIROPOULOS G. C.. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology [online] December, 21(Supplement 5):v59-v64 [viewed 16 May 2014] Available from: doi:10.1093/annonc/mdq166
  2. EL-SERAG HASHEM B.. Hepatocellular Carcinoma. N Engl J Med [online] 2011 September, 365(12):1118-1127 [viewed 24 May 2014] Available from: doi:10.1056/NEJMra1001683
  3. GINèS P, GUEVARA M, ARROYO V, RODéS J. Hepatorenal syndrome. Lancet [online] 2003 Nov 29, 362(9398):1819-27 [viewed 24 May 2014] Available from: doi:10.1016/S0140-6736(03)14903-3
  4. SCHUPPAN D, AFDHAL NH. Liver Cirrhosis Lancet [online] 2008 Mar 8, 371(9615):838-851 [viewed 24 May 2014] Available from: doi:10.1016/S0140-6736(08)60383-9
  5. ELGOUHARI H. M., O'SHEA R.. Q: What is the utility of measuring the serum ammonia level in patients with altered mental status?. Cleveland Clinic Journal of Medicine [online] 2009 April, 76(4):252-254 [viewed 30 May 2014] Available from: doi:10.3949/ccjm.76a.08072
  6. Do Ammonia Levels Correlate with Hepatic Encephalopathy? Am Fam Physician. [online] 2003 Oct 1;68(7):1408-1410. [viewed 30 May 2014] Available from: http://www.aafp.org/afp/2003/1001/p1408.html
  7. KAMAL AMANY TALAAT, OSMAN EMAN NAGIB, SHAHIN RASHA YOUSSEF. Role of ascitic fluid C3 in spontaneous bacterial peritonitis. Egyptian Journal of Medical Human Genetics [online] 2012 February, 13(1):81-85 [viewed 30 May 2014] Available from: doi:10.1016/j.ejmhg.2011.10.005
  8. KOULAOUZIDIS A, BHAT S, KARAGIANNIDIS A, TAN W C, LINAKER B D. Spontaneous bacterial peritonitis. Postgraduate Medical Journal [online] 2007 June, 83(980):379-383 [viewed 30 May 2014] Available from: doi:10.1136/pgmj.2006.056168
  9. PATCH D, ARMONIS A, SABIN C, CHRISTOPOULOU K, GREENSLADE L, MCCORMICK A, DICK R, BURROUGHS A K. Single portal pressure measurement predicts survival in cirrhotic patients with recent bleeding. Gut [online] 1999 February, 44(2):264-269 [viewed 30 May 2014] Available from: doi:10.1136/gut.44.2.264
  10. TROY PJ, WAXMAN AB. Portopulmonary Hypertension: Challenges in Diagnosis and Management Therap Adv Gastroenterol [online] 2009 Sep, 2(5):281-286 [viewed 30 May 2014] Available from: doi:10.1177/1756283X09338431
  11. ARGUEDAS MR, HEUDEBERT GR, ELOUBEIDI MA, ABRAMS GA, FALLON MB. Cost-effectiveness of screening, surveillance, and primary prophylaxis strategies for esophageal varices. Am J Gastroenterol [online] 2002 Sep, 97(9):2441-52 [viewed 30 May 2014] Available from: doi:10.1111/j.1572-0241.2002.06000.x
  12. STARR SP, RAINES D. Cirrhosis: diagnosis, management, and prevention. Am Fam Physician [online] 2011 Dec 15, 84(12):1353-9 [viewed 29 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22230269

Investigations - Screening/Staging

Fact Explanation
PT/INR Used in calculation of MELD (Model for End Stage Liver Disease) score and Child-Pugh score. The MELD score predicts the short term (3 months) survival. [1,2,3]
Serum albumin Used in calculation of Child-Pugh score. [2,3]
Serum bilirubin Used in calculation of Child-Pugh score and MELD score. [1,2,3]
Serum bilirubin Used in calculation of MELD score. [1,2,3]
References
  1. KREMERS WK, VAN IJPEREN M, KIM WR, FREEMAN RB, HARPER AM, KAMATH PS, WIESNER RH. MELD score as a predictor of pretransplant and posttransplant survival in OPTN/UNOS status 1 patients. Hepatology [online] 2004 Mar, 39(3):764-9 [viewed 30 May 2014] Available from: doi:10.1002/hep.20083
  2. STARR SP, RAINES D. Cirrhosis: diagnosis, management, and prevention. Am Fam Physician [online] 2011 Dec 15, 84(12):1353-9 [viewed 29 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/22230269
  3. TSOCHATZIS EMMANUEL A, BOSCH JAIME, BURROUGHS ANDREW K. Liver cirrhosis. The Lancet [online] 2014 May, 383(9930):1749-1761 [viewed 30 May 2014] Available from: doi:10.1016/S0140-6736(14)60121-5

Management - General Measures

Fact Explanation
Health education Public awareness should be raised about the common and preventable causes of cirrhosis, like harmful use of alcohol, hepatitis B and C infection, and non-alcoholic fatty liver disease. [6,10] Patients with cirrhosis should be advised to restrict salt and protein intake. Nutritional supplements or healthy balanced diet with low protein is indicated. Regular physical exercise will help to delay and prevent the muscle wasting.
Treatment of causative factors Auto-immune hepatitis is treated with immunosuppression (prednisone and azathioprine). Interferon and other antiviral agents are used to treat chronic viral hepatitis. [11,12] Phlebotomy is indicated in hemochromatosis. Primary biliary cirrhosis is treated with ursodeoxycholic acid. Trientine, penicillamine and zinc is used in the treatment of Wilson’s disease. Anticoagulation with intravenous heparin followed by oral warfarin or subcutaneous low-molecular-weight heparin is indicated in Budd Chiari syndrome. [8] Angioplasty and or stent placement will re-establish the vessel patency. [9]
Management of hepatorenal syndrome [14,10] Intravenous fluid, albumin or fresh frozen plasma administration are helpful measures. Hemodialysis may be needed in refractory renal failure. Liver transplantation is carried out as the final option of treatment.
Management of hepatic encephalopathy Lactulose (30mL once or twice a day) administration and treatment of any infection or precipitating factor (hypovolemia, metabolic disturbances, gastrointestinal bleeding, infection, constipation) should be done. Lactulose can reduce the intestinal absorption of ammonia and also facilitate the quick passage of intestinal contents reducing the duration of absorption. L-ornithine L-aspartate, sodium benzoate are other available treatment options. [4,10] Nutritional needs should be supplied via a nasogastric tube to prevent the risk of aspiration. Other supportive care include, urinary catheterization, maintaining skin and oral hygiene.
Management of ascites [13] Dietary sodium restriction, diuretics and therapeutic abdominal paracenthesis are treatment options. Peritoneovenous, portosystemic and transjugular intrahepatic portosystemic shunts are also helpful. [3] Spironolactone (50-300mg once daily) is the diuretic of choice in management of ascites. Spironolactone is used either alone or in combination with furosemide in severe ascites. Intravenous albumin and vasopressin (V2 receptor antagonists) are used in the management of ascites. [7,10]
Management of variceal bleeding Nonselective beta blockers (propranolol, nadolol) are indicated to reduce portal hypertension. [5] Endoscopic treatment options like banding, injection of scleroscents are indicated in treatment of esophageal varices. [10]
Antibiotic prophylaxis of spontaneous bacterial peritonitis (SBP) Patients with a history of SBP are given antibiotic prophylaxis with norfloxacin (400mg daily) and trimethoprim-sulfamethoxazole (5 days a week) to prevent the recurrence of SBP. [1,2] Patients with gastrointestinal bleeding are prescribed norfloxacin (400mg orally twice per day) for 7 days to minimize the risk of SBP.
Treatment of SBP Antibiotics should be prescribed for the treatment. [10]
Management of abdominal hernia Massive ascites can cause umbilical and inguinal hernias. Umbilical hernia should not be repaired unless it is irreducible, or strangulated, since the risk of elective risk is significantly higher than the risk of complications of the umbilical hernia. [22]
Treatment of anemia [15] These include hematinic, erythropoietin or blood transfusion.
Zinc sulfate (220mg orally twice daily) Zinc deficiency is seen in many patients with cirrhosis. It is also effective in preventing muscle cramps. Zinc is indicated in patients with Wilson’s disease as well. [16,17]
Treatment of osteoporosis Vitamin D and oral calcium supplements are indicated for patients with increased risk. [18]
Vaccination Patients with cirrhosis should be vaccinated against hepatitis A, influenza and pneumococci. [19,20,21] These infections increase the morbidity and mortality in patients with cirrhosis. [21]
References
  1. GINéS PERE, et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: Results of a double-blind, placebo-controlled trial. Hepatology [online] 1990 October, 12(4):716-724 [viewed 24 May 2014] Available from: doi:10.1002/hep.1840120416
  2. SINGH NINA. Trimethoprim-Sulfamethoxazole for the Prevention of Spontaneous Bacterial Peritonitis in Cirrhosis. Ann Intern Med [online] 1995 April [viewed 24 May 2014] Available from: doi:10.7326/0003-4819-122-8-199504150-00007
  3. OCHS ANDREAS, et al. The Transjugular Intrahepatic Portosystemic Stent–Shunt Procedure for Refractory Ascites. N Engl J Med [online] 1995 May, 332(18):1192-1197 [viewed 24 May 2014] Available from: doi:10.1056/NEJM199505043321803
  4. SUSHMA S., DASARATHY S., TANDON RAKESH K., JAIN SATISH, GUPTA SURYA, BHIST MAHENDER S.. Sodium benzoate in the treatment of acute hepatic encephalopathy: A double-blind randomized trial. Hepatology [online] 1992 July, 16(1):138-144 [viewed 24 May 2014] Available from: doi:10.1002/hep.1840160123
  5. D'AMICO GENNARO, PAGLIARO LUIGI, BOSCH JAIME. The treatment of portal hypertension: A meta-analytic review. Hepatology [online] 1995 July, 22(1):332-354 [viewed 24 May 2014] Available from: doi:10.1002/hep.1840220145
  6. REHM J, TAYLOR B, MOHAPATRA S, IRVING H, BALIUNAS D, PATRA J, ROERECKE M. Alcohol as a risk factor for liver cirrhosis: a systematic review and meta-analysis. Drug Alcohol Rev [online] 2010 Jul, 29(4):437-45 [viewed 24 May 2014] Available from: doi:10.1111/j.1465-3362.2009.00153.x
  7. ARROYO V, GIN S P, GERBES A L, DUDLEY F J, GENTILINI P, LAFFI G, REYNOLDS T B, RING-LARSEN H, SCH LMERICH J. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Hepatology [online] 1996 January, 23(1):164-176 [viewed 24 May 2014] Available from: doi:10.1002/hep.510230122
  8. CURA M, HASKAL Z, LOPERA J. Diagnostic and interventional radiology for Budd-Chiari syndrome. Radiographics [online] 2009 May-Jun, 29(3):669-81 [viewed 24 May 2014] Available from: doi:10.1148/rg.293085056
  9. FISHER N C, MCCAFFERTY I, DOLAPCI M, WALI M, BUCKELS J A C, OLLIFF S P, ELIAS E. Managing Budd-Chiari syndrome: a retrospective review of percutaneous hepatic vein angioplasty and surgical shunting. Gut [online] 1999 April, 44(4):568-574 [viewed 24 May 2014] Available from: doi:10.1136/gut.44.4.568
  10. SCHUPPAN D, AFDHAL NH. Liver Cirrhosis Lancet [online] 2008 Mar 8, 371(9615):838-851 [viewed 24 May 2014] Available from: doi:10.1016/S0140-6736(08)60383-9
  11. SUNG J. J. Y., TSOI K. K. F., WONG V. W. S., LI K. C. T., CHAN H. L. Y.. Meta-analysis: treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. [online] 2008 November, 28(9):1067-1077 [viewed 24 May 2014] Available from: doi:10.1111/j.1365-2036.2008.03816.x
  12. LOK AS, MCMAHON BJ, PRACTICE GUIDELINES COMMITTEE, AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES (AASLD). Chronic hepatitis B: update of recommendations. Hepatology [online] 2004 Mar, 39(3):857-61 [viewed 24 May 2014] Available from: doi:10.1002/hep.20110
  13. GINèS P, CáRDENAS A, ARROYO V, RODéS J. Management of cirrhosis and ascites. N Engl J Med [online] 2004 Apr 15, 350(16):1646-54 [viewed 24 May 2014] Available from: doi:10.1056/NEJMra035021
  14. GINèS P, GUEVARA M, ARROYO V, RODéS J. Hepatorenal syndrome. Lancet [online] 2003 Nov 29, 362(9398):1819-27 [viewed 24 May 2014] Available from: doi:10.1016/S0140-6736(03)14903-3
  15. QAMAR AA, GRACE ND. Abnormal hematological indices in cirrhosis Can J Gastroenterol [online] 2009 Jun, 23(6):441-445 [viewed 16 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721814
  16. TSOCHATZIS EMMANUEL A, BOSCH JAIME, BURROUGHS ANDREW K. Liver cirrhosis. The Lancet [online] 2014 May, 383(9930):1749-1761 [viewed 30 May 2014] Available from: doi:10.1016/S0140-6736(14)60121-5
  17. MATSUOKA S, MATSUMURA H, NAKAMURA H, OSHIRO S, ARAKAWA Y, HAYASHI J, SEKINE N, NIREI K, YAMAGAMI H, OGAWA M, NAKAJIMA N, AMAKI S, TANAKA N, MORIYAMA M. Zinc Supplementation Improves the Outcome of Chronic Hepatitis C and Liver Cirrhosis J Clin Biochem Nutr [online] 2009 Nov, 45(3):292-303 [viewed 30 May 2014] Available from: doi:10.3164/jcbn.08-246
  18. NAIR S. Vitamin D Deficiency and Liver Disease Gastroenterol Hepatol (N Y) [online] 2010 Aug, 6(8):491-493 [viewed 30 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950664
  19. SAYYAD B, et al. Efficacy of influenza vaccination in patients with cirrhosis and inactive carriers of hepatitis B virus infection. Iran Red Crescent Med J [online] 2012 Oct, 14(10):623-30 [viewed 30 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/23285414
  20. MCCASHLAND TM, PREHEIM LC, GENTRY MJ. Pneumococcal vaccine response in cirrhosis and liver transplantation. J Infect Dis [online] 2000 Feb, 181(2):757-60 [viewed 30 May 2014] Available from: doi:10.1086/315245
  21. KEEFFE EB. Hepatitis A and B Superimposed on Chronic Liver Disease: Vaccine-Preventable Diseases Trans Am Clin Climatol Assoc [online] 2006:227-238 [viewed 30 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1500906
  22. SILVA FELIPE DUARTE, et al. Hérnias abdominais e inguinais em pacientes cirróticos: qual é a melhor conduta?. ABCD, arq. bras. cir. dig. [online] 2012 March, 25(1):52-55 [viewed 30 May 2014] Available from: doi:10.1590/S0102-67202012000100012

Management - Specific Treatments

Fact Explanation
Liver transplantation [1] Severe cardiomyopathy, pulmonary disease, active alcohol abuse, malignancy other than HCC and sepsis are contraindications for liver transplantation.
References
  1. SCHUPPAN D, AFDHAL NH. Liver Cirrhosis Lancet [online] 2008 Mar 8, 371(9615):838-851 [viewed 24 May 2014] Available from: doi:10.1016/S0140-6736(08)60383-9