Liver Cirrhosis: Not always due to alcohol abuse.

Cirrhosis represents a late stage of progressive hepatic fibrosis characterized by distortion of the hepatic architecture and the formation of regenerative nodules. It is generally considered to be irreversible in its advanced stages at which point the only option may be liver transplantation. Patients with cirrhosis are susceptible to a variety of complications and their life expectancy is markedly reduced. CLINICAL MANIFESTATIONS Patients with cirrhosis may present in a variety of ways. They may have stigmata of chronic liver disease discovered on routine physical examination. They may have undergone laboratory or radiologic testing or an unrelated surgical procedure that incidentally uncovered the presence of cirrhosis. They may present with decompensated cirrhosis, which is characterized by the presence of dramatic and life-threatening complications, such as variceal hemorrhage, ascites, spontaneous bacterial peritonitis (SBP), or hepatic encephalopathy.Some patients never come to clinical attention. In older reviews, cirrhosis was diagnosed at autopsy in up to 30 to 40 percent of patients. All patients with cirrhosis should undergo diagnostic endoscopy to document the presence of varices and to determine their risk for variceal hemorrhage. Patients at high risk for development of variceal hemorrhage should be considered for primary prophylaxis. I like Variceal Banding. Much to often Liver Cirrhosis is being related to excessive alcohol ingestion. Even though alcoholism is a common cause of this entity, it is by far not the only cause of this often deadly disease. Liver cirrhoses is not curable, but it is definitely preventable in many instances, if one recognizes and minimizes certain risk factors. The liver, the largest of our organs, is a real laboratory. With many many functions, essential for the human body. Within the liver cell carry out, complex enzymatic processes take place and many essential nutrients as well as glycogen, proteins, fat and vitamins are stored. Generally speaking, it is a very resistant organ that rarely ever fails to perform, contrary to the teachings and beliefs of many naturist, quacks and charlatans, who readily blame the liver for many diverse symptoms, without any scientific basis. HOW IS CIRRHOSIS DIAGNOSED? Physical Examination . A physical examination may reveal the following findings in a patient with cirrhosis:

A liver biopsy is the only definite method for diagnosing cirrhosis. It also helps determine its cause, treatment possibilities, the extent of damage, and the long-term outlook. For example, hepatitis C patients who show no significant liver scarring when biopsied appear to have a low risk for cirrhosis. Percutaneous Liver Biopsy. This approach uses a needle inserted through the abdomen to obtain a tissue sample from the liver. Various forms of needles are used, including those that use suction or those that cut out the tissue. If cirrhosis is suspected, a cutting needle is the better tool. This approach should not be used in patients with bleeding problems, and it must be used with caution in patients with ascites or severe obesity. Laparoscopy. This procedure employs small abdominal incision through which the physician inserts a thin tube that contains small surgical instruments and a tiny camera to view the surface of the liver. This is generally reserved for staging cancer or for ascites with unknown causes. Biopsies can be dangerous, so they cannot be performed on patients who have test results that indicate 1

clotting problems, on those who have had previous liver biopsies, or who have ascites . Imaging Tests. Ultrasound examination of the abdomen is useful to confirm hepatosplenomegaly and may also reveal enlargement or venous obstruction of the portal or splenic veins with portal hypertension. Cavernous transformation of the portal vein can also be identified and the presence of esophageal varices is suggested. New ultrasound modalities are beginning to estimate portal vein flow. Blood Tests . Routine tests of liver function may be quite normal in cirrhosis. A decreased serum albumin and a prolonged prothrombin time directly reflect impaired hepatic function in the truest sense. An increased serum gamma globulin accompanies many forms of chronic liver disease. AST and ALT are often moderately elevated, while alkaline phosphatase may be normal or increased, particularly with biliary obstruction. Bilirubin is usually normal. Increased total serum globulin is common. A normochromic normocytic (occasionally macrocytic) anemia, thrombocytopenia, and leukopenia may be present. With alcohol-related liver disease, the anemia is occasionally macrocytic. COMPLICATIONS Ascites is the accumulation of fluid within the peritoneal cavity. It is the most common complication of cirrhosis. Nearly 60 percent of all patients with compensated cirrhosis will develop ascites in 10 years . The two-year survival of patients with ascites is approximately 50 percent . Spontaneous bacterial peritonitis Spontaneous bacterial peritonitis (SBP) is an infection of preexisting ascitic fluid without evidence for an intraabdominal secondary source such as a perforated viscus . SBP is almost always seen in the setting of end-stage liver disease . Manifestations of SBP include fever, abdominal pain, abdominal tenderness, and altered mental status. Some patients are asymptomatic and present with only mild laboratory abnormalities. Hepatorenal Syndrome.The hepatorenal syndrome refers to the development of acute renal failure in a patient who usually has advanced hepatic disease, due to cirrhosis or less often metastatic tumor or severe alcoholic hepatitis. Rather than being a new disease, the hepatorenal syndrome usually represents the end-stage of a sequence of reductions in renal perfusion induced by increasingly severe hepatic injury. The initial reductions in glomerular filtration rate are often masked clinically since associated decreases in muscle mass and hepatic urea production minimize elevations in the plasma creatinine concentration and blood urea nitrogen. Hepatorenal syndrome (HRS) is the development of renal failure in patients with advanced chronic liver disease, occasionally fulminant hepatitis, who have portal hypertension and ascites. Estimates indicate that at least 40% of patients with cirrhosis and ascites will develop HRS during the natural history of their disease. Causes: Risk factors for developing HRS have been reported based on a large series of patients with cirrhosis and ascites. Patients with marked sodium and water retention, characterized by a low urinary sodium excretion (<5 mEq/L) and dilutional hyponatremia, have a higher probability of developing HRS compared to patients with less sodium and water retention. Another important risk factor is the presence of severe disturbances in the systemic circulation (mean arterial pressure <80 mm Hg) associated with marked activation of the RAAS and SRS. Surprisingly, patients with advanced liver disease, defined by a high Child-Pugh score or worsening albumin, bilirubin, and prothrombin levels, are not at higher risk of developing HRS. Mortality/Morbidity: Importantly, be aware that 2 different forms of HRS are described. Although their pathophysiology is similar, their manifestations and outcomes are quite different. Type 1 HRS is characterized by rapid and progressive renal impairment and is precipitated most commonly by SBP. Type 1 HRS occurs in approximately 25% of patients with SBP, despite rapid resolution of the infection with antibiotics. Without treatment, median survival of patients

with type 1 HRS is less than 2 weeks and virtually all patients die within 10 weeks after the onset of renal failure. Type 2 HRS is characterized by a moderate and stable reduction in the GFR and commonly occurs in patients with relatively preserved hepatic function. Median survival is 3-6 months. Although this is markedly longer than type 1 HRS, it is still shorter compared to patients with cirrhosis and ascites who do not have renal failure. The following is a list of risk factors associated with the development of HRS in patients with cirrhosis who are nonazotemic. All measurements were obtained after a minimum of 5 days on a low-salt diet and without diuretics. Low urinary sodium excretion (<5 mEq/L) Low serum sodium (dilutional hyponatremia) Reduced free-water excretion after water load Low mean arterial pressure. High plasma renin activity Increased plasma norepinephrine Low plasma osmolality High urine osmolality High serum potassium Previous episodes of ascites Absence of hepatomegaly Presence of esophageal varices Poor nutritional status Moderately increased serum urea (>30 mg/dL) Moderately increased serum creatinine (>1.5 mg/dL) Moderately reduced GFR (<50 mL/min) Variceal hemorrhage.Variceal hemorrhage is a devastating complication that occurs in 25 to 40 percent of patients with cirrhosis . Prior to the widespread use of current therapies for acute variceal hemorrhage, the mortality rate of a single variceal hemorrhage was 30 percent and only one-third of patients survived for one year . Although survival has improved with modern techniques for controlling variceal hemorrhage, mortality rates remain high. Hepatopulmonary Syndrome The hepatopulmonary syndrome (HPS) is considered to be present in patients with the following triad: 1. Liver disease. 2 .Increased alveolar-arterial gradient while breathing room air 3.Evidence for intrapulmonary vascular abnormalities, referred to as intrapulmonary vascular dilatations (IPVDs). Estimates of the prevalence of HPS among patients with chronic liver disease range from 4 to 47 percent, depending upon the diagnostic criteria and methods used. Even in cirrhotic patients lacking HPS, mild hypoxemia is common and is presumably caused by ascites, with resulting diaphragmatic elevation and ventilation/perfusion mismatch. Hypoxemia is seen in one-third of decompensated cirrhotic patients. Hepatopulmonary syndrome (HPS) is the triad of chronic liver disease, increased alveolar-arterial oxygen gradient on room air, and intrapulmonary arteriovenous shunting (due to subpleural arteriovenous microshunts that resemble spider angiomas . Patients present with the gradual onset of hypoxemia that is commonly more severe in the upright position. Laboratory abnormalities include hypoxemia, and decreased diffusing capacity for CO2. The majority of patients with HPS demonstrate marked improvement in symptoms when given 100% oxygen. HPS is a relative contraindication to liver transplant surgery, however, some patients with HPS may actually improve following transplant. Chest radiograph abnormalities are detected in 46-100% of patients with HPS . Medium sized (1.5 to 3 mm), bilateral, basilar, nodular or reticulonodular opacities, with normal lung volumes, are 3

characteristic of HPS and represent dilated subpleural lung vessels. Hepatic Encephalopathy Hepatic encephalopathy describes the spectrum of potentially reversible neuropsychiatric abnormalities seen in patients with liver dysfunction. Disturbance in the diurnal sleep pattern (insomnia and hypersomnia) is a common early feature that typically precedes overt neurologic signs. More advanced neurologic features include the presence of asterixis, hyperactive deep tendon reflexes, and less commonly, transient decerebrate posturing. Hepatocellular carcinoma Patients with cirrhosis have a markedly increased risk of developing hepatocellular carcinoma (HCC). The incidence in well compensated cirrhosis is approximately 3 percent per year . Patients with most forms of chronic hepatitis are not at an increased risk until cirrhosis develops. Exceptions to this rule are patients with chronic hepatitis B virus infection who can develop HCC in the absence of cirrhosis Certain causes of cirrhosis appear to have a relatively increased risk for HCC. Patients with cirrhosis from hepatitis B, hepatitis C, and hemochromatosis are at the highest risk, while those with cirrhosis from autoimmune hepatitis, nonalcoholic steatohepatitis, and Wilson's disease appear to have a lower risk.

Alcoholic hepatitis regularly causes ascites with or without cirrhosis.

Diuretic-resistant cirrhotic ascites is considered to be present when one or both of the

following two criteria is present in the absence of therapy with a nonsteroidal antiinflammatory drug (NSAID), which can induce renal vasoconstriction and diminish diuretic responsiveness An inability to mobilize ascites despite compliance with dietary sodium restriction (as confirmed by a 24-hour urine collection containing less than 78 meq of sodium) and the administration of maximum tolerable doses of oral diuretics (400 mg/day of spironolactone and 160 mg/day of furosemide). The 78 meq of sodium represents the recommended 88 meq intake minus 10 meq in nonurinary losses. Patients who gain weight despite excreting more than 78 meq of sodium per day are not compliant with the diet. The development of prohibitive diuretic-related complications, such as progressive azotemia, hepatic encephalopathy or progressive electrolyte imbalance. Causes of Cirrhosis Although most often associated with alcohol abuse, cirrhosis of the liver can result from many causes. Almost any chronic liver disease can lead to cirrhosis. This list gives some of the many causes: Alcoholic liver disease most common cause. Chronic viral hepatitis B, C and D Postnecrotic cirrhosis: Hepatitis, a viral infection of the liver, usually causes this disease, although poisonous substances may also cause it. Two types of hepatitis, hepatitis B or hepatitis C, cause 25-75% of these cases. Large areas of scar tissue mix with large areas of healing nodules. Chronic autoimmune hepatitis Non-alcoholic Steatohepatitis, Malnutrition and Diabetes: Steatohepatitis is the medical term for an enlarged, fatty liver. The condition is usually caused by alcoholism, but can also be the result of malnutrition, obesity and diabetes. Nonalcoholic steatohepatitis (liver inflammation that can be caused by fatty liver) Inherited metabolic diseases (e. g. hemochromatosis, Wilson disease, Galactosemia) Chronic bile duct diseases (e. g. primary biliary cirrhosis) When small tubes that help you digest food become blocked, your body mistakenly turns on itself and reacts against these bile

tubes. Gallstones often block tubes and cause this type of cirrhosis. The disease usually affects women aged 35-60 years Chronic congestive heart failure Your heart is a pump that pushes blood throughout your body. When your heart doesn't pump well, blood "backs up" into the liver. This congestion causes damage to your liver. It may become swollen and painful. Later it becomes hard and less painful. The cause of the heart failure may be from heart valve problems, smoking, or infection of the heart muscle or the sac around the heart Parasitic infections (e. g. schistosomiasis) Long term exposure to toxins or drugs. Alpha-1-antitrypsin Deficiency: This is a hereditary disorder that prevents the body from properly utilizing the alpha-1-antitrypsin protein. In some cases, alpha-1-antitrypsin builds up in the liver, where excess amounts can lead to tissue scarring.

Liver Cirrhosis is a disease of this noble organ, which is not easily understood by the lay person. This disease comprises the destruction (necrosis) of the individual liver cells and its substitution for scar tissue, a process which is irreversible. Often this is consequence of chronic alcohol abuse, but may also be the result of previous infection with hepatitis B,C,D . Specially hepatitis C which can develop in chronic viral hepatitis is frequently related to liver cirrhosis. Other causes of liver cirrhosis are diseases of metabolic origin. Metabolic defects may cause the deposition of cirrhosis inducing substances into the liver cells. Wilsons disease as well as Galactosemia are such entities. In Wilsons disease, a specific enzyme deficiency causes the deposition of copper particles in liver tissue. In Galactosemia , the deficiency of the enzyme Galactose 1 Uridiltransferase , necessary for metabolism of galactose, is responsible for the abnormal deposition of galactose in the tissues, leading to mental retardation, cataracts and liver cirrhosis.Liver injury that results in cirrhosis also may be caused by a number of inherited diseases such as cystic fibrosis, alpha-1 antitrypsin deficiency, hemochromatosis and glycogen storage diseases others causes of liver cirrhosis are prolonged exposure to environmental toxins, and repeated bouts of heart failure with liver congestion. Prescription Drug abuse or even the prolonged or simultaneous ingestion of some Over the Counter remedies, may cause liver cirrhosis. Special attention should be given to the abuse of acetaminophen and paracetamol, which is widespread here in El Salvador as well as in many other countries, and is being self-medicated for a diverse variety of symptoms including "hangovers", since liver cirrhosis may be a consequence of this abuse. Specially the ingestion of acetaminophen during "hangovers" should be avoided since the alcohol toxicity and the acetaminophen liver toxicity are a dangerous combination for the liver. In normal persons large doses of acetaminophen are needed to damage liver cells while patients with chronic alcoholism may suffer massive liver damage when exposed to small therapeutic doses of this drug. For this reason acetaminophen should be avoided in chronic alcoholic patients.

What Are the Symptoms of Cirrhosis?

People with cirrhosis often have few symptoms at first. At the beginning 5

The person may experience fatigue, weakness, and exhaustion. Loss of appetite is usual, often with nausea and weight loss. As liver function declines, less protein is made by the organ. For example, less of the protein albumin is made, which results in water accumulating in the legs (edema) or abdomen (ascites). A decrease in proteins needed for blood clotting makes it easy for the person to bruise or to bleed. With respect to the clinical signs and symptoms of liver cirrhosis In the later stages this entity may present with uncharacteristic clinical features over a long period of time and go undiagnosed over many years. Symptoms and observable symptoms may appear late in the disease and may include loss of libido, nausea, anorexia, vomiting, ocular or total body jaundice, itching, reddening (erythema) of the palms, spider naevi on the chest, gynaecomastia, abdominal swelling, hepatomegaly, splenomegaly, pubic and axillary hair loss, swelling of ankles, abdominal pain, or mores severe manifestations such as encephalopathy, upper G.I. Tract bleeding due to esophageal varices or gastric ulcers or patient may even fall into a comatose state. Due to this diversity of manifestations, special classifications exist that classify a patient according to his or hers clinical features, which range from an asymptomatic state to an advanced life threatening condition. The definite diagnosis of liver cirrhosis can only be obtained through liver biopsy. Other diagnostic methods such as ultrasound, CT Scan, MRI can detect certain morphologic abnormalities associated with cirrhosis, although these changes are usually seen in advanced disease only. Liver cirrhosis in its initial stages can most often not be diagnosed by diagnostic imaging methods. Endoscopy is useful to document the presence of esophageal varices, as well as gastric or duodenal ulcers, often associated with cirrhosis.

What Are the Treatments for Cirrhosis?

As Liver cirrhoses is not curable the Treatment of cirrhosis is aimed at stopping or delaying its progress, minimizing the damage to liver cells, and reducing complications. The major goals of treating the cirrhotic patient include: 1. Slowing or reversing the progression of liver disease. 2. Preventing superimposed insults to the liver. 3. Preventing and treating the complications 4. Determining the appropriateness and optimal timing for liver transplantation

Slowing or reversing the progression of liver disease Although cirrhosis is generally considered to be irreversible in its advanced stages, the exact point at which it becomes irreversible is unclear . Some chronic liver diseases respond to treatment even when the liver disease has progressed to cirrhosis. Thus, specific therapies directed against the underlying cause of the cirrhosis should be instituted. As examples: The 10-year survival rate in patients with cirrhosis from autoimmune hepatitis who are treated with steroids or immunosuppressive agents approaches 90 percent. This number is similar to survival rates of treated patients with autoimmune hepatitis who do not have cirrhosis. Abstinence from alcohol improves survival in alcoholic cirrhosis. Interferon therapy slows the progression of cirrhosis in patients with chronic hepatitis C virus infection, and may also decrease fibrosis and the risk of hepatocellular carcinoma Treatment of patients with chronic hepatitis B with lamivudine may result in significant improvement in liver function and histology.

Cirrhosis of the liver is irreversible but treatment of the underlying liver disease may slow or stop the progression. Such treatment depends upon the underlying etiology. Termination of alcohol intake will stop the progression in alcoholic cirrhosis and for this reason, it is important to make the diagnosis early in a chronic alcohol abuser. Risk Factors for Developing Cirrhosis from Hepatitis C. Between 20% and 30% of people with Hepatitis C develop cirrhosis after twenty years. (It should be noted that even in patients with cirrhosis, survival rates in one study were nearly 80% at 10 years in these patients.) The following conditions put people with hepatitis C at higher risk for liver damage: ESOPHAGEAL VARICES The presence of varicose veins in the esophagus constitutes a serious condition which is potentially life-threatening. It is an entity which is readily discovered by Video-endoscopy. Amonst the causes of esophageal varices one must consider liver cirrhosis as the most frequent, but also portal hypertension and thrombosis of the portal or splenic veins can be made responsible in some cases. For this reason a Video-endoscopic procedure should be performed on all patients in which liver cirrhosis is suspected. Although the definite diagnosis of liver cirrhosis can only be made with a liver biopsy, the presence of esophageal varices in itself constitutes an indirect sign of liver cirrhosis with a 95% accuracy. The potentially life-threatening aspect of esophageal varices lies in the danger of their profuse bleeding , considered to be one of the severest hemorrhages of the whole g.i. tract. The ptient presents with bloody vomiting and black stools (melena). If this condition is not treeated promptly hypotension (fall in blood pressure) will set in and patient may succumb. Esophageal varices are dilated blood vessels within the wall of the esophagus. Patients with cirrhosis develop Portal Hypertension. When Portal Hypertension occurs, blood flow through the liver is diminished. Thus, blood flow increases through the microscopic blood vessels within the esophageal wall. As this blood flow increases, the blood vessels begin to dilate. This dilation can be profound. The original diameter of the blood vessels is measured in millimeters while the final, fully established, esophageal varix may be 0.5 to 1.0 cm or larger in diameter. Bleeding varices are a life-threatening complication of portal hypertension (increased blood pressure in the portal vein caused by liver disease). Increased pressure causes the veins to balloon outward. The vessels may rupture, causing vomiting of blood and bloody stools or tarry black stools. If a large volume of blood is lost, signs of shock will develop. Any cause of chronic liver disease can cause bleeding varices Esophageal varices are dilated blood vessels within the wall of the esophagus. Patients with cirrhosis develop Portal Hypertension. When Portal Hypertension occurs, blood flow through the liver is diminished. Thus, blood flow increases through the microscopic blood vessels within the esophageal wall. As this blood flow increases, the blood vessels begin to dilate. This dilation can be profound. The original diameter of the blood vessels is measured in millimeters while the final, fully established, esophageal varix may be 0.5 to 7

1.0 cm or larger in diameter. Bleeding varices are a life-threatening complication of portal hypertension (increased blood pressure in the portal vein caused by liver disease). Increased pressure causes the veins to balloon outward. The vessels may rupture, causing vomiting of blood and bloody stools or tarry black stools. If a large volume of blood is lost, signs of shock will develop. Any cause of chronic liver disease can cause bleeding varices. For more endoscopic details, download the video clip by clicking on the endoscopic image. Wait to be downloaded complete then Press Alt and Enter for full screen.