LIVER CIRRHOSIS AND COMPLICATAIONS Definition Cirrhosis represents the final common histologic pathway for a wide variety of chronic liver diseases. Cirrhosis is defined histologically as a diffuse hepatic process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules. The progression of liver injury to cirrhosis may occur over weeks to years. Some patients with cirrhosis are completely asymptomatic and have a reasonably normal life expectancy. Some have most severe symptoms of end-stage liver disease and have a limited chance for survival. Common signs and symptoms may stem from §  Decreased hepatic synthetic function (eg, coagulopathy) §  Decreased detoxification capabilities of the liver (eg, hepatic encephalopathy) §  Portal hypertension (eg, variceal bleeding). Etiology 1. Most common cause is Hepatitis B. Chronic Hepatitis C also causes cirrhosis. 2.Alcoholic liver disease 3.Autoimmune hepatitis 4.Biliary cirrhosis –Primary or secondary Secondary biliary cirrhosis associated with chronic extrahepatic bile duct obstruction 5.Primary sclerosing cholangitis 6.Hemochromatosis 7.Wilson disease 8.Alpha-1 antitrypsin deficiency 9.Granulomatous disease (eg, sarcoidosis) 10.Type IV glycogen storage disease 11.Drug-induced liver disease ü  Methotrexate ü  Alpha methyldopa ü  Amiodarone 12.Venous outflow obstruction (eg, Budd-Chiari syndrome, veno-occlusive disease) 13.Chronic right-sided heart failure –Cardiac cirrhosis Pathophysiology of Hepatic Fibrosis -Alteration in the normally balanced processes of extra cellular matrix production and degradation. -Extra cellular matrix, is composed of collagens (especially types I, III, and V), glycoproteins, and proteoglycans. -Stellate cells(ito cells), located in the perisinusoidal space, are essential for the production of extracellular matrix. They may become activated into collagen-forming cells by a variety of paracrine factors. -Factors released by hepatocytes, Kupffer cells, and sinusoidal endothelium following liver injury. Factors include transforming growth factor beta1 (TGF-beta1 The classic sinusoidal cause of portal hypertension is cirrhosis Schistosomiasis is the most common noncirrhotic cause of variceal bleeding worldwide. The classic postsinusoidal condition is an entity known as veno-occlusive disease. Obliteration of the terminal hepatic venules eg pyrrolizidine alkaloids and high-dose chemotherapy that precedes bone marrow transplantation. Post hepatic portal HTN ü  Chronic right-sided heart failure ü  Tricuspid regurgitation ü  Obstructing lesions of the hepatic veins and inferior vena cava. The latter and the symptoms they produce are termed Budd-Chiari syndrome. Predisposing conditions include hypercoagulable states, tumor invasion into the hepatic vein or inferior vena cava, and membranous obstruction of the inferior vena cava. Inferior vena cava webs are observed most commonly in South and East Asia and are postulated to be due to nutritional factors. Symptoms of Budd-Chiari syndrome are attributed to decreased outflow of blood from the liver, with resulting hepatic congestion and portal hypertension. These symptoms include hepatomegaly, abdominal pain, and ascites. Cirrhosis only ensues later in the course of disease. Differentiating Budd-Chiari syndrome from cirrhosis by history or physical examination may be difficult. Thus, Budd-Chiari syndrome must be included in the differential diagnosis of conditions that produce ascites and varices. Hepatic vein patency is checked most readily by performing an abdominal ultrasound with Doppler examination of the hepatic vessels. Abdominal CT scan with intravenous contrast, abdominal MRI, and visceral angiography also may provide information regarding the patency of hepatic vessels. Consequences of portal hypertension. Normal as 3-6 mm Hg. Portal hypertension is defined as a sustained elevation of portal pressure above normal. Portal pressure above 8 mm Hg is believed to be the threshold above which ascites potentially can develop. Portal pressure above 12 mm Hg is the threshold for the potential formation of varices. High portal pressures may predispose patients to an increased risk of variceal hemorrhage. ASCITIS Ascites is defined as an accumulation of excessive fluid within the peritoneal cavity and may be a complication of both hepatic and nonhepatic diseases. The 4 most common causes of ascites ü  Cirrhosis ü  Neoplasm ü  congestive heart failure ü  tuberculous peritonitis  -Attributing ascites to diseases of nonperitoneal or peritoneal origin is more useful. -Serum-ascites albumin gradient (SAAG) used for differentiating these conditions. Nonperitoneal diseases produce ascites with a SAAG greater than 1.1 g/dL  -Chylous ascites, caused by obstruction of the thoracic duct or cisterna chyli, most often is due to malignancy (eg, lymphoma) but occasionally is observed postoperatively and following radiation injury. Chylous ascites also may be observed in the setting of cirrhosis. The ascites triglyceride concentration is greater than 110 mg/dL. In addition, ascites triglyceride concentrations are greater than those observed in plasma. Patients should be placed on a low-fat diet, which is supplemented by medium-chain triglycerides. Treatment with diuretics and large-volume paracentesis may be required. Hepatorenal syndrome -Renal dysfunction observed in patients with cirrhosis and is caused by the vasoconstriction of large and small renal arteries and the impaired renal perfusion that results. -The syndrome may represent an imbalance between renal vasoconstrictors and vasodilators. Plasma levels of a number of vasoconstricting substances are elevated in patients with cirrhosis and include angiotensin, antidiuretic hormone, and norepinephrine. Renal perfusion appears to be protected by vasodilators, including prostaglandins E2 and I2 and atrial natriuretic factor. -Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis. They may potentiate renal vasoconstriction, with a resulting drop in glomerular filtration. Thus, the use of NSAIDs is contraindicated in patients with decompensated cirrhosis. -Most patients with hepatorenal syndrome are noted to have minimal histological changes in the kidneys. Kidney function usually recovers when patients with cirrhosis and hepatorenal syndrome undergo liver transplantation. In fact, a kidney donated by a patient dying from hepatorenal syndrome functions normally when transplanted into a renal transplant recipient. -Hepatorenal syndrome progression may be slow (type II) or rapid (type I). Type I disease frequently is accompanied by rapidly progressive liver failure. Hemodialysis offers temporary support for such patients. -In type II hepatorenal syndrome, patients may have stable or slowly progressive renal insufficiency. Many such patients develop ascites that is resistant to management with diuretics. - In hepatorenal syndrome, renal dysfunction cannot be explained by preexisting kidney disease, prerenal azotemia, the use of diuretics, or exposure to nephrotoxins. -Nephrotoxic medications, including aminoglycoside antibiotics, should be avoided in patients with cirrhosis.  -Patients with early hepatorenal syndrome may be salvaged by aggressive expansion of intravascular volume with albumin and fresh frozen plasma and by avoidance of diuretics.. Clinical features of ascites – -abdominal distention - bulging flanks -shifting dullness -Elicitation of a "puddle sign" in patients in the knee-elbow position. -A fluid wave may be elicited in patients with massive tense ascites. Paracentesis in the diagnosis of ascites -Determining whether ascites is exudates or transudate. -Paracentesis also should be performed when SBP is suggested by the presence of abdominal pain, fever, leukocytosis, or worsening hepatic encephalopathy. Table 3. Ascites Tests -Mirocoscopy, culture and Sensitivity §  Cell count and differentials §  Gram stain §  Stain for AFB §  Cultures-special medial for mycobacterium -Biochemistry §  Albumin with simultaneous Serum Albumin for Serum Asitic Albumin Gradient(SAAG) §  LDH §  Bilirubin §  Amylase §  Glucose -Ascitic fluid with more than 250 PMNs/mm3 defines neutrocytic ascites and SBP. -Many cases of ascites fluid with more than 1000 PMNs/mm3 (and certainly >5000 PMNs/mm3) are associated with appendicitis or a perforated viscus with resulting bacterial peritonitis. Appropriate radiologic studies must be performed in such patients to rule out surgical causes of peritonitis. -Lymphocyte-predominant ascites possibility of underlying malignancy or tuberculosis. -Grossly bloody ascites may be observed in malignancy and tuberculosis. -The yield of ascites culture increased by directly inoculating 10 mL of ascites into aerobic and anaerobic culture bottles at the patient's bedside. Medical treatment of ascites Sodium restriction -Salt restriction is the first line of therapy. Less than 2000 mg sodium per day. Refractory ascites less than 500 mg sodium per day. Diuretics -Considered the second line of therapy. -Spironolactone (Aldactone) blocks the aldosterone receptor at the distal tubule. It is dosed at 50-300 mg once per day. Although the drug has a relatively short half-life, its blockade of the aldosterone receptor lasts for at least 24 hours. Adverse effects ü  Hyperkalemia ü  gynecomastia, and lactation. Other potassium-sparing diuretics, including amiloride and triamterene, may be used as alternative agents, especially in patients complaining of gynecomastia. -Furosemide (Lasix) may be used as a solo agent or in combination with spironolactone. The drug blocks sodium reuptake in the loop of Henle. - It is dosed at 40-240 mg per day in 1-2 divided doses.  -Aggressive diuretic therapy in patients with massive ascites can safely induce a 0.5- to 1-kg weight loss per day -Diuretic therapy should be held in the event of electrolyte disturbances, azotemia, or induction of hepatic encephalopathy. -Albumin infusion may protect against the development of renal insufficiency in patients with SBP. Patients receiving cefotaxime and albumin at 1 g/kg/day experienced a lower risk of renal failure HEPATIC ENCEPAHALOPATHY Definition -Hepatic encephalopathy is a syndrome observed in some patients with decompensated cirrhosis that is marked by §  Personality changes §  Intellectual impairment §  Depressed level of consciousness. -The diversion of portal blood into the systemic circulation appears to be a prerequisite for the syndrome. -Thus may also develop in patients who do not have cirrhosis who undergo portocaval shunt surgery. Pathogenesis The ammonia hypothesis -Ammonia is produced in the GI tract by bacterial degradation of amines, amino acids, purines, and urea. -Normally, ammonia is detoxified in the liver by conversion to urea and glutamine. - In liver disease or portosystemic shunting, portal blood ammonia is not converted efficiently to urea. Increased levels of ammonia may enter the systemic circulation because of portosystemic shunting. -Ammonia has multiple neurotoxic effects, including §  Altering the transit of amino acids, water, and electrolytes across the neuronal membrane. §  Inhibit the generation of both excitatory and inhibitory postsynaptic potentials. -Therapeutic strategies to reduce serum ammonia levels tend to improve hepatic encephalopathy. However, approximately 10% of patients with significant encephalopathy have normal serum ammonia levels. Furthermore, many patients with cirrhosis have elevated ammonia levels without evidence of encephalopathy. The gamma-aminobutyric acid(GABA) hypothesis -GABA is a neuroinhibitory substance produced in the GI tract. -When GABA crosses the extra permeable blood-brain barrier of a patient with cirrhosis, it interacts with supersensitive postsynaptic GABA receptors. -The GABA receptor, in conjunction with receptors for benzodiazepines and barbiturates, regulates a chloride ionophore. Binding of GABA to its receptor permits an influx of chloride ions into the postsynaptic neuron, leading to the generation of an inhibitory postsynaptic potential.  -Administration of benzodiazepines and barbiturates to patients with cirrhosis increases GABA-ergic tone and predisposes patients to depressed consciousness. -The GABA hypothesis is supported by fact that flumazenil (a benzodiazepine antagonist) transiently can reverse hepatic encephalopathy in patients with cirrhosis. Clinical features of hepatic encephalopathy The symptoms of hepatic encephalopathy may range from mild to severe .Symptoms are graded on the following scale: Grade 1 ü  Mild confusion ü  euphoria or depression ü  decreased attention ü  slowing of ability to perform mental tasks ü  irritability ü  disorder of sleep pattern (ie, inverted sleep cycle) 7-Organic brain syndrome 8-Postseizure encephalopathy Management of hepatic encephalopathy NB -Nonhepatic causes of altered mental function must be excluded in patients with cirrhosis who have worsening mental function. -A check of the blood ammonia level may be helpful in such patients. -Medications that depress CNS function, especially benzodiazepines, should be avoided. -Precipitants of hepatic encephalopathy should be corrected (eg, metabolic disturbances, GI bleeding, infection, constipation). Medications 1.Lactulose -In acute onset of severe encephalopathy symptoms and in patients with milder, chronic symptoms. -This nonabsorbable disaccharide stimulates the passage of ammonia from tissues into the gut lumen and inhibits intestinal ammonia production. - Initial lactulose dosing is 30 mL orally once or twice daily. Dosing is increased until the patient has 2-4 loose stools per day. Dosing should be reduced if the patient complains of diarrhea, abdominal cramping, or bloating. Higher doses of lactulose may be administered via either a nasogastric tube or rectal tube to hospitalized patients with severe encephalopathy. Other cathartics, including colonic lavage solutions that contain polyethylene glycol (PEG) (eg, Go-Lytely), also may be effective in patients with severe encephalopathy. 2. Neomycin and other antibiotics (eg, metronidazole, oral vancomycin, paromomycin, oral quinolones) serve as second-line agents. They work by decreasing the colonic concentration of ammoniagenic bacteria. Neomycin dosing is 250-1000 mg orally 2-4 times daily. 3.Low-protein diets- High levels of aromatic amino acids contained in animal proteins lead to increased blood levels of the false neurotransmitters tyramine and octopamine, with resulting worsening of encephalopathy symptoms. OTHER MANIFESTATIONS OF CIRRHOSIS -Many patients with cirrhosis experience fatigue, anorexia, weight loss, and muscle wasting. -Cutaneous manifestations of cirrhosis include jaundice, spider angiomata, skin telangiectasias , palmar erythema, white nails, disappearance of lunulae, and finger clubbing, especially in the setting of hepatopulmonary syndrome. -Patients with cirrhosis may experience increased conversion of androgenic steroids into estrogens in skin, adipose tissue, muscle, and bone. Males may develop gynecomastia and impotence. Loss of axillary and pubic hair is noted in both men and women. Hyperestrogenemia also may explain spider angiomata and palmar erythema. Hematologic manifestations -Anemia may result from folate deficiency, hemolysis, or hypersplenism, varices -Thrombocytopenia usually is secondary to hypersplenism and decreased levels of thrombopoietin. -Coagulopathy results from decreased hepatic production of coagulation factors. If cholestasis is present, decreased micelle entry into the small intestine leads to decreased vitamin K absorption, with reduction in hepatic production of factors II, VII, IX, and X. Patients with cirrhosis also may experience fibrinolysis and disseminated intravascular coagulation. MANAGEMENT OF LIVER CIRRHOSIS -Specific medical therapies may be applied to many liver diseases in an effort to diminish symptoms and prevent or forestall the development of cirrhosis. Examples include §  prednisone and azathioprine for autoimmune hepatitis §  Interferon and other antiviral agents for hepatitis B and C §  phlebotomy for hemochromatosis §  ursodeoxycholic acid for primary biliary cirrhosis §  zinc and penicillamine for Wilson disease. -These therapies become progressively less effective if chronic liver disease evolves into cirrhosis. Once cirrhosis develops, treatment is aimed at the management of complications as they arise. - Certainly variceal bleeding, ascites, and hepatic encephalopathy are among the most serious complications experienced by patients with cirrhosis. However, attention also must be paid to patients' chronic constitutional complaints. Nutrition Many patients complain of anorexia, which may be compounded by the direct compression of ascites on the GI tract. Care should be taken to assure that patients receive adequate calories and protein in their diets. Patients frequently benefit from the addition of commonly available liquid and powdered nutritional supplements to the diet. Only rarely can patients not tolerate proteins in the form of chicken, fish, vegetables, and nutritional supplements. Institution of a low-protein diet in the fear that hepatic encephalopathy might develop places the patient at risk for the development of profound muscle wasting. Adjunctive therapies -Zinc deficiency Commonly is observed in patients with cirrhosis. Treatment with zinc sulfate at 220 mg orally twice daily may improve dysgeusia and can stimulate appetite. Furthermore, zinc is effective in the treatment of muscle cramps and is adjunctive therapy for hepatic encephalopathy. -Pruritus Is a common complaint in both cholestatic liver diseases (eg, primary biliary cirrhosis) and in noncholestatic chronic liver diseases (eg, hepatitis C). Although increased serum bile acid levels once were thought to be the cause of pruritus, endogenous opioids are more likely to be the culprit pruritogens. Mild itching complaints may respond to treatment with antihistamines. Cholestyramine  is the mainstay of therapy for the pruritus of liver disease. Other medications that may provide relief against pruritus include ü  Ursodeoxycholic acid ü  Ammonium lactate 12% skin cream ü  Naltrexone (an opioid antagonist) ü  Rifampin ü  Gabapenin ü  Ondansetron. Monitoring the patient with cirrhosis -Patients with cirrhosis should undergo routine follow-up monitoring of their §  complete blood count §  renal §  liver chemistries §  prothrombin time. -Monitor stable patients 3-4 times per year -Follow-up endoscopy is performed in 2 years if varices are not present. If varices are present, treatment is initiated with a nonselective beta-blocker (eg, propranolol, nadolol), aiming for a 25% reduction in heart rate. Such therapy offers effective primary prophylaxis against the new onset of variceal bleeding. -

) -Increased collagen deposition in the space of Disse (the space between hepatocytes and sinusoids) and the diminution of the size of endothelial fenestrae lead to the capillarization of sinusoids. -Activated stellate cells also have contractile properties.  -Both capillarization and constriction of sinusoids by stellate cells contribute to the development of portal hypertension. Pathophysiology of Portal Hypertension -The normal liver has the ability to accommodate large changes in portal blood flow without appreciable alterations in portal pressure.  -Portal hypertension results from a combination of increased portal venous inflow and increased resistance to portal blood flow. -Intrahepatic vascular resistance is explained by fixed changes in the hepatic architecture. Such changes include the formation of regenerating nodules and the production of collagen by activated stellate cells. Collagen, in turn, is deposited within the space of Disse. -Stellate cells serve as contractile cells for adjacent hepatic endothelial cells. The nitric oxide produced by the endothelial cells, in turn, controls the relative degree of vasodilation or vasoconstriction produced by the stellate cells. In cirrhosis, decreased local production of nitric oxide leads to increased resistance. -The portal hypertension of cirrhosis is caused by the disruption of hepatic sinusoids. However, portal hypertension may be observed in a variety of noncirrhotic conditions classified as Pre hepatic and intra-hepatic causes. Pre hepatic causes ü  Splenic vein thrombosis ü  Portal vein thrombosis. These conditions commonly are associated with hypercoagulable states and with malignancy (eg, pancreatic cancer). Intrahepatic Divided into presinusoidal, sinusoidal, and postsinusoidal conditions. The classic form of presinusoidal disease is caused by the deposition of Schistosoma oocytes in presinusoidal portal venules, with the subsequent development of granulomata and portal fibrosis.. Ascitis can be broadly classified as: a)Non-peritoneal Ascitis b)Peritoneal Ascitis Non Peritoneal Ascitis In transudative ascites, fluid was cross the liver capsule because of an imbalance in Starling forces. ascites protein was less than 2.5 g/dL. Classic causes of transudative ascites are portal hypertension secondary to cirrhosis and congestive heart failure. a)Intrahepatic portal hypertension §  Cirrhosis §  Fulminant hepatic failure §  Veno-occlusive disease b) Extrahepatic portal hypertension §  Hepatic vein obstruction (ie, Budd-Chiari syndrome) §  Congestive heart failure c) Hypoalbuminemia §  Nephrotic syndrome §  Protein-losing enteropathy §  Malnutrition d) Miscellaneous disorders §  Myxedema §  Ovarian tumors §  Pancreatic ascites §  Biliary ascites e) Chylous §  Secondary to malignancy §  Secondary to trauma §  Secondary to portal hypertension In exudative ascites, fluid was said to weep from an inflamed or tumor-laden peritoneum. In general, ascites protein was greater than 2.5 g/dL. Examples included peritoneal carcinomatosis and tuberculous peritonitis Peritoneal Causes of Ascites a)Malignant ascites §  Primary peritoneal mesothelioma §  Secondary peritoneal carcinomatosis b) Granulomatous peritonitis §  Tuberculous peritonitis §  Fungal and parasitic infections (eg, Candida, Histoplasma, Cryptococcus, Schistosoma mansoni, Strongyloides, Entamoeba histolytica) §  Sarcoidosis §  Foreign bodies (ie, talc, cotton and wood fibers, starch, barium) b) Vasculitis §  Systemic lupus erythematosus §  Henoch-Schönlein purpura c) Miscellaneous disorders §  Eosinophilic gastroenteritis §  Whipple disease §  Endometriosis -However, physical examination findings are much less sensitive than performing abdominal ultrasonography, which can detect as little as 30 mL of fluid. Furthermore, ultrasound with Doppler can help assess the patency of hepatic vessels -Factors associated with worsening of ascites include excess fluid or salt intake, malignancy, venous occlusion (eg, Budd-Chiari syndrome), progressive liver disease, and spontaneous bacterial peritonitis (SBP). Spontaneous bacterial peritonitis -SBP is observed in 15-26% of patients hospitalized with ascites. The syndrome arises most commonly in patients whose low-protein ascites (<1 g/dL) contains low levels of complement, resulting in decreased opsonic activity. - SBP appears to be caused by the translocation of GI tract bacteria across the gut wall and also by the hematogenous spread of bacteria. The most common causative organisms are Escherichia coli, Streptococcus pneumoniae, Klebsiella species, and other gram-negative enteric organisms. -Classic SBP is diagnosed by the presence of neutrocytosis, which is defined as greater than 250 polymorphonuclear (PMN) cells per mm3 of ascites, in the setting of a positive ascites culture. Culture-negative neutrocytic ascites is observed more commonly. -Both conditions represent serious infections that carry a 20-30% mortality rate. Treatment 5-day course of cefotaxime at 1-2 g intravenously every 8 hours. Alternatives include oral ofloxacin and other intravenous antibiotics with activity against gram-negative enteric organisms. Many authorities advise repeat paracentesis in 48-72 hours in order to document a decrease in the ascites PMN count to less than 250 cells/mm3 and to assure the efficacy of therapy. Other complications of massive ascites ü  Abdominal discomfort ü  Anorexia ü  Decreased oral intake ü  Diaphragmatic elevation may lead to symptoms of dyspnea. ü  Pleural effusions may result from the passage of ascitic fluid across channels in the diaphragm. ü  Umbilical and inguinal hernias are common in patients with moderate and massive ascites. Timely large-volume paracentesis also may help to prevent this disastrous complication. Large-volume paracentesis -Aggressive diuretic therapy is ineffective in controlling ascites in approximately 5-10% of patients. -Such patients with massive ascites may need to undergo large-volume paracentesis in order to receive relief from symptoms of abdominal discomfort, anorexia, or dyspnea. The procedure also may help reduce the risk of umbilical hernia rupture. -Large-volume paracentesis is thought to be safe in patients with peripheral edema and in patients not currently treated with diuretics. Peritoneovenous shunts -LeVeen shunts and Denver shunts -Plastic tubing inserted subcutaneously under local anesthesia connects the peritoneal cavity to the internal jugular vein or subclavian vein via a pumping chamber. -These devices are successful at relieving ascites and reversing protein loss in some patients. Complications include §  Peritoneal infection, sepsis §  Disseminated intravascular coagulation §  Congestive heart failure §  Shunts may clot and block -a reasonable form of therapy for patients with refractory ascites who are not candidates for TIPS or liver transplantation. Portosystemic shunts and transjugular intrahepatic portosystemic shunts(TIPS) -Main Indication for portocaval shunt surgery is the management of refractory variceal bleeding. - But by decompressing the hepatic sinusoid, may improve ascites. Complications include §  Hepatic encephalopathy §  Stent stenosis requiring revision. §  Mortality from the surgery -TIPS is an effective tool in managing massive ascites in some patients. Ideally, TIPS placement produces a decrease in sinusoidal pressure and a decrease in plasma renin and aldosterone levels, with subsequent improved urinary sodium excretion.  -TIPS use should be reserved for patients with Child class B cirrhosis or patients with Child class C cirrhosis without severe coagulopathy or encephalopathy. Liver transplantation  Liver transplantation should be considered as a potential means of salvaging the patient prior to the onset of intractable liver failure or hepatorenal syndrome.  Grade 1          ü   Alert  Grade 2 ü  Drowsiness ü  Lethargy ü  gross deficits in ability to perform mental tasks ü  obvious personality changes, ü  inappropriate behavior ü   intermittent disorientation (usually for time) Grade 3 ü  Somnolent but arousable. ü  Unable to perform mental tasks ü  Disorientation to time and place ü  Marked confusion, amnesia ü  occasional fits of rage ü  speech is present but incomprehensible Grade 4 ü  Coma, with or without response to painful stimuli -. Findings upon physical examination include asterixis and fetor hepaticus. Investigations Laboratory 1)An elevated arterial or free venous serum ammonia level is the classic abnormality 2) (EEG) changes of high-amplitude low-frequency waves and triphasic waves. In some patients - EEG may be helpful in the initial workup of a patient with cirrhosis and altered mental status when ruling out seizure activity may be necessary. 3)-CT scan and MRI studies of the brain may be important in ruling out intracranial lesions when the diagnosis of hepatic encephalopathy is in question. Common precipitants of hepatic encephalopathy. Common precipitants of hyperammonemia in cirrhotic patients and worsening mental status are ü  Diuretic therapy ü  Renal failure ü  GI bleeding ü  Infection ü  Constipation ü  Dietary protein overload ü  Medications, notably opiates, benzodiazepines, antidepressants, and antipsychotic agents. Differential diagnosis for hepatic encephalopathy 1-Intracranial lesions (eg, subdural hematoma, intracranial bleeding, cerebrovascular accident, tumor, abscess) 2-Infections (eg, meningitis, encephalitis, abscess) 3-Metabolic encephalopathy (eg, hypoglycemia, electrolyte imbalance, anoxia, hypercarbia, uremia) 4-Hyperammonemia from other causes (eg, secondary to ureterosigmoidostomy, inherited urea cycle disorders) 5-Toxic encephalopathy due to alcohol (eg, acute intoxication, alcohol withdrawal, Wernicke encephalopathy) 6-Toxic encephalopathy due to drugs (eg, sedative-hypnotics, antidepressants, antipsychotic agents, salicylates) Pulmonary and cardiac manifestations -Patients with cirrhosis may have impaired pulmonary function. Pleural effusions and the diaphragmatic elevation caused by massive ascites may alter ventilation-perfusion relations. Interstitial edema or dilated precapillary pulmonary vessels may reduce pulmonary diffusing capacity.  -Patients also may have hepatopulmonary syndrome (HPS). In this condition, pulmonary arteriovenous anastomoses result in arteriovenous shunting. -Classic HPS is marked by the symptom of platypnea and the finding of orthodeoxia, but the syndrome must be considered in any patient with cirrhosis who has evidence of oxygen desaturation. HPS most readily is detected by echocardiographic visualization of late-appearing bubbles in the left atrium following the injection of agitated saline. -Some cases of HPS may be corrected by liver transplantation. Pulmonary hypertension is observed in approximately 1% of patients with cirrhosis. Its etiology is unknown. Hepatocellular carcinoma &cholangiocarcinoma -Hepatocellular carcinoma (HCC) occurs in 10-25% of patients with cirrhosis -HCC is observed less commonly in primary biliary cirrhosis and is a rare complication of Wilson disease. -Cholangiocarcinoma occurs in approximately 10% of patients with primary sclerosing cholangitis. Other diseases associated with cirrhosis -Other conditions that appear with increased incidence in patients with cirrhosis include peptic ulcer disease, diabetes, and gallstones. Assessment of the severity of cirrhosis The most common tool for gauging prognosis in cirrhosis is the Child-Turcotte-Pugh (CTP) system. CTP score may predict life expectancy in patients with advanced cirrhosis. A CTP score of 10 or greater is associated with a 50% chance of death within 1 year. Child-Turcotte-Pugh Scoring System for Cirrhosis Child class A=5-6 points Child class B=7-9 points Child class C=10-15 points Class A, have normal bilirubin and albumin values, with no evidence of ascites, encephalopathy, or malnutrition. Class B patients have more severe disease, characterized by mild hyperbilirubinemia and hypoalbuminema, and mild degrees of ascites and encephalopathy with good nutritional status. Patients with the most advanced cirrhosis. Class C have at least moderate elevations of bilirubin and hypoalbuminemia, with marked ascites, severe encephalopathy, and obvious malnutrition. Osteoporosis Supplementation with calcium and vitamin D is important in patients at high risk for osteoporosis, especially patients with chronic cholestasis, patients with primary biliary cirrhosis, and patients receiving corticosteroids for autoimmune hepatitis. Bisphosphonate (eg, alendronate sodium). The discovery of decreased bone mineralization upon bone densitometry studies Muscle wasting -Regular exercise, including walking and even swimming, should be encouraged in patients with cirrhosis, lest the patient slip into a vicious cycle of inactivity and muscle wasting Vaccinations Patients with chronic liver disease should receive vaccination to protect them against hepatitis A. Other protective measures include vaccination against hepatitis B, pneumococci, and influenza. Drug hepatotoxicity in the patient with cirrhosis Medications frequently associated with drug-induced liver disease include NSAIDs, isoniazid, valproic acid, erythromycin, amoxicillin/clavulanate, ketoconazole, and chlorpromazine. -NSAID use may predispose patients with cirrhosis to develop GI bleeding. Patients with decompensated cirrhosis are at risk for NSAID-induced renal insufficiency, presumably because of prostaglandin inhibition and worsening of renal blood flow. Other nephrotoxic agents such as aminoglycoside antibiotics also should be avoided. Surgery in the patient with cirrhosis . A study of nonshunt abdominal surgeries demonstrated a 10% mortality rate for patients with Child class A cirrhosis as opposed to a 30% mortality rate for patients with Child class B cirrhosis and a 75% mortality rate for patients with Child class C cirrhosis. Thus, unless absolutely necessary, surgery should be avoided in the patient with cirrhosis.

	1 points	2 points	3 points
Encephalopathy	None	Stage 1-2	Stage 3-4
Ascites	Absent	Slight	Moderate
Bilirubin (mg/dL)	<2	2-3	>3
Bilirubin in PBC or PSC (mg/dL)	<4	4-10	10
Albumin (g/dL)	>3.5	2.8-3.5	<2.8
Prothrombin time (seconds prolonged or INR)	<4 s or INR <1.7	4-6 s or INR 1.7-2.3	>6 s or INR >2.3