HEPATIC DISORDERS

  HEPATIC DISORDERS

                   

 LIVER:

Liver is one of the largest organs in the body. The main functions of the liver include protein synthesis ,storage and metabolism of fats and carbohydrates, detoxification of drugs and other toxins, excretion of bilirubin and metabolism of hormones. The liver has considerable reserve capacity reflected in its ability to function normally despite surgical removal of 70-80% of the organ or the presence of significant disease. It is noted for its capacity to regenerate rapidly.

The hepatocyte is the functioning unit of liver. The portal tract is the “service network” of the liver and contains an artery and a portal vein delivering blood to the liver and bile duct which forms part of the biliary drainage system. There are a number of other cell population in the liver, but two of the most important are Kuppfer cells and stellate cells.

ACUTE LIVER DISEASE:

Acute liver disease is a self-limiting episode of hepatocyte damage which in most cases resolves spontaneously without clinical sequel. The history of acute liver disease is less than 6 months.

CHRONIC LIVE DISEASE:

Chronic liver disease occurs when permanent structural changes within in the liver develop secondary to long-standing cell damage, with the consequent loss of normal liver architecture. The history of chronic liver disease is more than 6 months.

EPIDEMIOLOGY OF HEPATIC DISORDER IN PAKISTAN:-

Over 170 million people worldwide are chronically infected with hepatitis c virus.In cases,reported from one of the largest tertiary care hospital of karachi, authors analyzed 5193 cases fulfilling all criteria of viral hepatitis and admitted during 1987-2007.

CAUSES OF LIVER DISEASE:

1-VIRAL INFECTIONS

Viruses commonly affect the liver, resulting in a transient and innocuous hepatitis. Viral hepatitis is a systemic disease with primary inflammation of the liver by any one of a heterogenous group of hepatotropic viruses.

HEPATITIS :

Viral hepatitis is inflammation of the liver caused by a virus. Viral hepatitis is a liver disease that is caused by exposure to one of the five hepatitis viruses. Each virus is named after a letter of the alphabet, hepatitis A through E. Though other viruses can cause hepatitis, only the five are considered hepatitis viruses.

Each of the five hepatotropic viruses is alike in many ways. They all infect the cells of the liver causing inflammation. Depending on which virus is causing trouble, there is often an acute illness that produces similar signs and symptoms.

Causative agent :

Viral hepatitis is a disease of the liver caused by one of several viruses: hepatitis A, B, C, D, E, F and  G.Hepatitis D and E are very rare.

The following seven viruses are known as causative agents of acute hepatitis: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), hepatitis E virus (HEV), hepatitis G virus (HGV) and TT virus (TTV). All these viruses except for HAV and HEV cause chronic hepatitis; HBV and HCV are the major causative viruses of chronic hepatitis, which may progress to liver cirrhosis and eventually to hepatocellular carcinoma (HCC)

Symptoms of viral hepatitis :

• Jaundice, which causes a yellowing of the skin and eyes.
• Fatigue.
• Abdominal pain.
• Loss of appetite.
• Nausea.
• Vomiting.
• Diarrhea.
• Low grade fever.
• Headache.

However, some people do not have symptoms.

How can produce the diseases :

Viral hepatitis is caused by the hepatitis A, B, C D and E viruses. Hepatitis A & E can be transmitted by contaminated food or water. Hepatitis  B and C occur when blood or bodily fluids from an infected person enter the body of an un-infected person. These viruses can be transmitted through various means, such as illicit intravenous drug use, unprotected sex, or from a mother to her newborn during birth. Blood transfusions, especially those received before 1990, used to be a source of hepatitis B and C, but blood used in transfusions is now screened for the hepatitis viruses.

Diagnosis:

Doctors diagnose hepatitis based on a physical examination and the results of blood tests. In addition to specific tests for hepatitis antibodies, doctors will order other types of blood tests to evaluate liver function.

Specific Tests for Hepatitis A:

Blood tests are used to identify IgM anti-HAV antibodies, substances that the body produces to fight hepatitis A infection.

Specific Tests for Hepatitis B:

There are many different blood tests for detecting the hepatitis B virus. Standard tests include:

• Hepatitis B surface antigen (HBsAg). A positive result indicates active infection, either acute or chronic.
• Antibody to hepatitis B core antigen (Anti-HBc). A positive result indicates either recent infection or previous infection.
• Antibody to HBsAg (Anti-HBs). A positive result indicates immunity to hepatitis B either from having been infected with the virus in the past or having had received the vaccine.

Specific Tests for Hepatitis C:

Tests to Identify the Virus . The standard first test for diagnosing hepatitis C is known as enzyme-linked immunosorbent assay (ELISA), which is used to test for hepatitis C antibodies. Antibodies can usually be detected by ELISA 4 - 10 weeks after infection.

Tests to Identify Genetic Types and Viral Load . Additional tests called hepatitis C virus RNA assays may be used to confirm the diagnosis. They use a polymerase chain reaction (PCR) to detect the RNA (the genetic material) of the virus. Such tests should be used if ELISA results show positive HCV antibody and may be performed if there is some doubt about a diagnosis but the doctor still firmly believes the virus is present. HCV RNA can be detected through blood tests as early as 2 - 3 weeks after infection.

Liver Biopsy . Liver biopsy may be helpful both for diagnosis and for determining treatment decisions. Only a biopsy can determine the extent of injury in the liver. Some doctors recommend biopsies only for patients who do not have genotypes 2 or 3 (as these genotypes tend to respond well to treatment). A liver biopsy in patients with other genotypes may help clarify risk for disease progression and allow doctors to reserve treatment for patients with moderate-to-severe liver scarring (fibrosis). Even in patients with normal alanine aminotrasferase (ALT) liver enzyme levels, a liver biopsy can reveal significant damage.

Tests for Liver Function

In people suspected of having or carrying viral hepatitis, doctors will measure certain substances in the blood.

• Bilirubin . Bilirubin is one of the most important factors indicative of hepatitis. It is a red-yellow pigment that is normally metabolized in the liver and then excreted in the urine. In patients with hepatitis, the liver cannot process bilirubin, and blood levels of this substance rise. (High levels of bilirubin cause the yellowish skin tone known as jaundice.)
• Liver Enzymes (Aminotransferases). Enzymes known as aminotransferases, including aspartate (AST) and alanine (ALT), are released when the liver is damaged. Measurements of these enzymes, particularly ALT, are the least expensive and most noninvasive tests for determining severity of the underlying liver disease and monitoring treatment effectiveness. Enzyme levels vary, however, and are not always an accurate indicator of disease activity. (For example, they are not useful in detecting progression to cirrhosis.)
• Alkaline Phosphatase (ALP). High ALP levels can indicate bile duct blockage.
• Serum Albumin Concentration . Serum albumin measures protein in the blood (low levels indicate poor liver function).
• Prothrombin Time (PT). The PT test measures in seconds the time it takes for blood clots to form (the longer it takes the greater the risk for bleeding).

Hepatitis A :

Hepatitis A virus is a picornavirus, a small single strand RNA virus

How is hepatitis A spread :

Hepatitis A is spread primarily through food or water contaminated by feces from an infected person. Rarely, it spreads through contact with infected blood.

Who is at risk for hepatitis A :

People most likely to get hepatitis A are

• international travelers, particularly those traveling to developing countries
• people who live with or have sex with an infected person
• day care children and employees, during outbreaks
• men who have sex with men
• users of illicit drugs

How can hepatitis A be prevented :

The hepatitis A vaccine offers immunity to adults and children older than age 1. The Centers for Disease Control and Prevention recommends routine hepatitis A vaccination for children aged 12 to 23 months and for adults who are at high risk for infection. Treatment with immune globulin can provide short-term immunity to hepatitis A when given before exposure or within 2 weeks of exposure to the virus. Avoiding tap water when traveling internationally and practicing good hygiene and sanitation also help prevent hepatitis A.

 The treatment for hepatitis A :There is no specific treatment for hepatitis A. Rest is recommended when the symptoms are most severe. Hepatitis A usually resolves on its own over several weeks.

Hepatitis B :

Hepatitis B virus belongs to the hepadnavirus family of double stranded DNA viruses

How is hepatitis B spread :

Hepatitis B is spread through contact with infected blood, through sex with an infected person, and from mother to child during childbirth, whether the delivery is vaginal or via cesarean section.

Signs and Symptoms of hepatitis B :

About 30% of people infected with the hepatitis B virus have no signs or symptoms; signs and symptoms are more common in adults than in children. When signs and symptoms appear they include: jaundice (yellowing of the skin and eyes), fatigue, abdominal pain, loss of appetite, nausea, vomiting, and joint pain.

Who is at risk for hepatitis B :

People most likely to get hepatitis B are

• people who live with or have sexual contact with an infected person
• men who have sex with men
• people who have multiple sex partners
• injection drug users
• immigrants and children of immigrants from areas with high rates of hepatitis B
• infants born to infected mothers
• health care workers
• hemodialysis patients
• international travelers

How can hepatitis B be prevented :

The hepatitis B vaccine offers the best protection. All infants and unvaccinated children, adolescents, and at-risk adults should be vaccinated. For people who have not been vaccinated, reducing exposure to the virus can help prevent hepatitis B. Reducing exposure means using latex condoms, which may lower the risk of transmission; not sharing drug needles; and not sharing personal items such as toothbrushes, razors, and nail clippers with an infected person. 

The treatment for hepatitis B: The treatment goal for the hepatitis B virus is to render the infection inactive and help control disease progression.

There are two types of treatments available to help treat the hepatitis B virus (HBV): injectable interferon-alpha and oral direct inhibitors of the virus, like lamivudine, adefovir, entecavir, and telbivudine.

Hepatitis C :

Hepatitis C virus is a flavivirus, a single stand RNA virus;

How is hepatitis C spread :

Hepatitis C virus (HCV) primarily affects injection-drug users who share needles, non-sterile instruments, and other drug equipment. Approximately two-thirds to three-quarters of new HCV infections each year are related to injectable drug use; cleaning the equipment with bleach does not always completely kill the virus.

Another way of getting HCV is through a blood transfusion from an infected donor, especially for people who received a transfusion before 1990. The risk of getting HCV this way is extremely low now because all blood donors go through universal blood testing

There is a 5% risk of a mother passing the hepatitis C virus to her newborn.

Hepatitis C is spread primarily through contact with infected blood. Less commonly, it can spread through sexual contact and childbirth.

Signs and Symptoms of hepatitis C :

About 80% of people infected with the hepatitis C virus have no signs or symptoms. When signs and symptoms appear they include: jaundice (yellowing of the skin and eyes), fatigue, dark-coloured urine, abdominal pain, loss of appetite, and nausea.

Who is at risk for hepatitis C :People most likely to be exposed to the hepatitis C virus are

• injection drug users
• people who have sex with an infected person
• people who have multiple sex partners
• health care workers
• infants born to infected women
• hemodialysis patients

How can hepatitis C be prevented :

There is no vaccine for hepatitis C. The only way to prevent the disease is to reduce the risk of exposure to the virus. Reducing exposure means avoiding behaviors like sharing drug needles or personal items such as toothbrushes, razors, and nail clippers with an infected person.

The treatment for hepatitis C :

The  treatment for people diagnosed with new hepatitis C virus (HCV) infections is to get rid of the virus. Many people with chronic hepatitis C will feel well for years. But in 10%-20% of people, chronic HCV may lead to irreversible and potentially fatal scarring of the liver. This is called cirrhosis. In severe cases HCV may lead to liver cancer or liver failure and a liver transplant may be necessary.

About 15-25% of people infected with the hepatitis C virus (HCV) have a mild case of the disease and get rid of it on their own in a brief amount of time. When this happens, the HCV antibodies remain detectable in the blood but the actual virus does not. Unfortunately, most people who become infected with HCV will have the infection for a long time and possibly for the rest of their lives. If this is the case, your doctor may refer you to a specialist to decide whether or not you need treatment. Drug treatment is usually a combination of two drugs: pegylated interferon and ribavirin. Pegylated interferon (a drug used to help fight infection) is given by injection under the skin once a week. Ribavirin is an antiviral drug and is taken as a pill twice a day. Therapy typically lasts from 12 weeks to one year depending on response and the strain of the HCV virus (viral genotype). This combination can get rid of the virus in about half of treated patients. It is recommended not to drink alcohol, as it can worsen liver disease.

Hepatitis D : Hepatitis D which is also known as Delta agent is a circular RNA that is more similar to a plant a viroid than a complete virus.

How is hepatitis D spread :

Hepatitis D is spread through contact with infected blood. This disease only occurs at the same time as infection with hepatitis B or in people who are already infected with hepatitis B.

Who is at risk for hepatitis D :

Anyone infected with hepatitis B is at risk for hepatitis D. Injection drug users have the highest risk. Others at risk include

• people who live with or have sex with a person infected with hepatitis D
• people who received a transfusion of blood or blood products before 1987

How can hepatitis D be prevented :

People not already infected with hepatitis B should receive the hepatitis B vaccine. Other preventive measures include avoiding exposure to infected blood, contaminated needles, and an infected person’s personal items such as toothbrushes, razors, and nail clippers.

The treatment for hepatitis D :

Chronic hepatitis D is usually treated with pegylated interferon, although other potential treatments are under study..

Hepatitis E :

Hepatitis E, also an RNA virus, is similar to a calicivirus.

EV is a non-enveloped, single stranded virus which has been reported to cause large outbreaks of acute hepatitis in South East and Central Asia, the Middle East, Africa, and Mexico. Commercial enzyme immunoassays are available and detection of specific IgM suggests recent infection, while IgG suggests immunity to previous exposure. As specificity and sensitivity of the assays is not optimal, interpretation of the results should be considered carefully. RT-PCR has been developed but is used mainly for research. The virus spreads by the faecal–oral route, often by contaminated water.

How is hepatitis E spread :

Hepatitis E is spread through food or water contaminated by feces from an infected person. This disease is uncommon in the United States.

Who is at risk for hepatitis E :

People most likely to be exposed to the hepatitis E virus are

• international travelers, particularly those traveling to developing countries
• people living in areas where hepatitis E outbreaks are common
• people who live with or have sex with an infected person

How can hepatitis E be prevented :

There is no U.S. Food and Drug Administration (FDA)-approved vaccine for hepatitis E. The only way to prevent the disease is to reduce the risk of exposure to the virus. Reducing risk of exposure means avoiding tap water when traveling internationally and practicing good hygiene and sanitation.

The treatment for hepatitis E :

Hepatitis E usually resolves on its own over several weeks to months.

Latest Advances:

1 .      Limitation of LFTs: Routinely used CLFTs are not sensitive and specific enough to correctly diagnose liver disease. Some vital parameters of CLFTs might be altered in many non liver diseases and there may be chances of normal CLFTs in many liver diseases also, thus it creates a dilemma in clinicians’ mind to rule out liver disease from non-liver disease. Commonly performed serum liver enzymes are also of limited value in diagnosis and monitoring of liver diseases. Development and application of laboratory tests that can identify liver disease at the earliest have the potential of reducing the healthcare costs and suffering associated with liver diseases.

2 .      Lamivudine Treatment Is Beneficial in Patients With Severely Decompensated Cirrhosis and Actively Replicating Hepatitis B: Lamivudine is beneficial in a selected subgroup of patients with severely decompensated cirrhosis caused by actively replicating HBV infection. The improvement in hepatic function may be of sufficient magnitude to abrogate the urgent need of OLT in some patients and confer a survival advantage. However, there are clearly patients who fail to respond to lamivudine, and urgent OLT remains the only viable treatment option.

3 .      The clinical implications of hepatitis B virus genotype: In the past decade, we have witnessed advances in research regarding the clinical implications of HBV genotype. In brief, compared to genotype A and B patients, genotype C and D patients have later and infrequent HBeAg seroconversion as well as a higher risk of disease progression (including HCC) and therefore, a poorer clinical outcome. Although genotype A and B patients have a better response to IFN-based therapy than genotype C and D patients, no significant association can be found between HBV genotype and therapeutic response to nucleos(t)ide analogues. On the basis of accumulating lines of evidence, it is recommended that HBV carriers should be routinely genotyped to help identify those who are at higher risk of liver disease progression, and who can benefit most from IFN-based therapy. At the start of this new decade, clinical trials stratified by different genotypes and treatment regimens are mandatory to determine the optimal treatment strategy for chronic hepatitis B patients.

4 .      Recent advances in liver stem cell therapy: Although liver transplantation remains the only conventional treatment, liver cell transplantation is an experimental procedure which has been successfully used in clinical trials in patients with acute liver failure, chronic liver disease with end-stage cirrhosis. Extraordinary progress has been made in the field of hepatic progenitors and iPS. Liver precursor cells (oval cells) are recognized as bipotential precursor cells in the damaged liver. They can rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis in animal models of liver injury. Similarly, iPS are somatic cells obtained from patients and differentiated into hepatocytes in vitro. Future studies of iPS are designed to develop of specific conditions to expand and in vitro differentiate somatic cells into functionally mature liver cells.

2-ALCOHOL

Liver diseases related to recent alcohol consumption presents a broad spectrum, ranging from the relatively benign fatty liver disease to the development of alcoholic hepatitis. An estimated 20% of alcohol abusers develop progressive liver fibrosis, which can eventually lead to alcoholic cirrhosis , typically after a period of 10-20 years of heavy indulgence.

The central event in the development of hepatic fibrosis is the transformation of hepatic stellate cells into matrix secreting cells producing pericellular fibrosis. This network of collagen fibers develops around the liver cells and gradually leads to hepatocyte cell death. The extent of fibrosis progresses and micronodular fibrotic bands develop characterizing alcoholic cirrhosis. The anatomical changes within the liver increase resistance to blood flow from the portal system, causing an increase in pressure within the system resulting in portal hypertension. The rate of disease progression is very strongly linked to whether or not patients continue to consume alcohol.

3-NON-ALCOHOL RELATED FATTY LIVER DISEASES

Liver pathology that is very similar to alcohol-induced disease is now well recognized in a number of settings including obesity, diabetes mellitus, and metabolic syndrome. A a result, the entities of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been introduced.

4-IMMUNE DISORDERS

Autoimmune disease can affect the hepatocyte or bile duct and is characterized by the presence of auto-antibodies and raised immunoglobulin levels.

i)Autoimmune hepatitis(AIH)

AIH is an unresolving  inflammation of the liver characterized by the presence of auto-antibodies (anti smooth muscle type 1) or anti kidney, liver microsomal, hypergammaglobulinemia and an interface hepatitis on liver histology. It is usually a chronic, progressive disease which can occasionally present acutely with a severe hepatitis.

Treatment corticosteroid and/or azathioprine are the standard therapy for AIH. Prednisone or prednisolone are administered at doses of 40-60mg/day alone or at lower doses when combined with azathioprine. The steroid dose is reduced over a 6-week to 3-months period to a target maintenance dose of 7.5mg/day or lower. Azathioprine at a dose of 1-1.5mg/kg/day is used as an adjunct to corticosteroid therapy.

Newer corticosteroid such as budesonide, with fewer side effects, have also been used effectively and may have greater role in future treatment of AIH.

ii)Primary biliary cirrhosis (PBC)

PBC is an autoimmune disease of the liver which predominantly affects middle aged women. It is characterized by the presence of antimitochondrial antibodies and a granulomatous destruction of the interlobular bile ducts leading to progressive ductopenia, fibrosis and cirrhosis.

Treatment  UDCA (urso deoxycholic acid) , the only medication widely used to treat PBC , reduces the retention of bile acids and increases their hepatic excretion. Therefore it is effective in protecting against the cytotoxic effects of dihydroxy bile acids which accumulate in PBC. However, UDCA does not appear to prevent ongoing bile duct injury and disease progression. Therefore, liver transplantation remains the only effective option in patients with end-stage disease. Immunosuppressive agents have also been assessed.

iii)Primary sclerosing cholangitis (PSC)

PSC is an idiopathic chronic inflammatory disease resulting in intra and extra hepatic strictures, cholestasis and eventually cirrhosis. There is a strong association with inflammatory bowl disease, particularly ulcerative colitis; 75%of PSC patients have ulcerative colitis and 5-8% of patients with ulcerative colitis develop PSC.

Treatment  there is no effective treatment for this condition, UDCA can be used to manage associated cholestasis, and doses as high as 15mg/kg/day have been advocated despite the limited evidence that it alters the natural history of the disease. Transplantation is the only effective treatment option in patients with advanced disease.

5-VASCULAR ABNORMALITIES

The Budd-Chiari syndrome (BCS) is a rare, hetrogenous and potentially fatal condition related to the obstruction of the hepatic venous flow out tract. The prevalence of underlying thrombophilia  is markedly in patients with BCS.

Treatment   early recognition and immediate use of anti coagulation has vastly improved outcome. More advanced disease can be treated in a number of ways including veno-plasty , transjugular intrahepatic portosystemic shunt, surgical shunts or liver transplantation.

6-METABOLIC AND GENETIC DISORDERS

There are various inherited metabolic disorders that can affect the functioning of liver.

i)Haemochromatosis

 hereditary haemochromatosis is the most commonly identified genetic disorder in the Caucasian population. It is associated with increased absorption of dietary iron resulting in deposition within the liver , heart, pancreas, joints, pituitary gland and other organs. This can lead to cirrhosis and hepatocellular carcinoma.

ii)Wilson’s disease

wilson’s disease is an autosomal recessive disorder of copper metabolism. The disorder leads to excessive absorption and deposition of dietary copper within the liver , brain, kidneys, and other tissue. Presentation can vary widely from chronic hepatitis, asymptomatic cirrhosis.

Treatment    this rare autosomal recessive condition is usually managed with chelation therapy. Penicillamine is the agent of choice in Wilson’s disease as it promotes urinary copper excretion in affected patients and prevents copper accumulation in presymptomatic individuals. Initial treatment of 1.5-2g/day is given in divided doses.

Therapy related adverse effects include renal dysfunction, haematological abnormalities, and disseminated lupus erythematosis. Therefore, regular monitoring of full blood count and electrolytes is required as well as small dose of pyridoxine o counteract the antipyridoxine effects of penicillamine and the associated neurological toxicity.

iii)α_1-Antitrypsin deficiency

this is an autosomal recessively inherited disease and is the most common genetic metabolic liver disease. The disease results in a reduction in α₁-antitrypsin which is protective against a variety of proteases including trypsin, chymotrypsin, elastase and proteases present in neutophils. The homozygous form of the disease is associated with the development of liver disease and cirrhosis.

iv)Glycogen storage disease

it is a rare disease. Enzymatic deficiencies at specific steps in the pathway of glycogen metabolism cause impaired glucose production and accumulation of abnormal glycogen in the liver.

v)Gilbert’s syndrome

it is characterized by persistent mild unconjugated hyperbilirubenaemia. It is an asymptomatic condition requiring no therapy, although patients may inappropriately associate being jaundiced with the symptoms of the condition that triggered the increase in the bilirubin level.

7)DRUGS

Drugs are an important cause of abnormal liver function tests and acute liver injury, including drug induced liver injury. Drugs can also be relevant to a number of chronic liver diseases including steatosis, fibrosis/cirrhosis autoimmune and vascular disease.

CLINICAL MENIFESTATON

SMPTOMS OF LIVER DISEASES

Weakness, increased fatigue and general malaise are common.

Weight loss and anorexia are commonly seen in chronic liver disease and loss of muscle bulk is a characteristic of very advanced disease.

Abdominal discomfort  may be described by the patients with an enlarged liver or spleen.

Jaundice , pruritis, bleeding complications.

SIGNS OF LIVER DISEASE

Cutaneous sign   hyper pigmentation , scratch marks suggest pruritis , palmar erythema, highly polished nails or white nails(leukonychia)

Abdominal distension

Jaundice

Portal hypertension

Ascites

INVESTIGATIONS

Biochemical tests

LFTs , aspartate transaminase and alanine transaminase are two intracellular enzymes present in hepatocytes which are released into the blood of patients as a consequence f hepatocyte  damage.

Laboratory investigation of aetiology

Screening of hepatitis A B and c. autoantibodies and immunoglobulins to screen for autoimmune disease.

Imaging technique

Ultrasound assess the size shape and texture of liver and screens for dilatation of the biliry tract. CT scan and MR scan are also used.

Liver biopsy

It is an invasive procedure .it remains the gold standard in estabilishing a diagnosis and assessing the severity of chronic liver disease.

CIRRHOSIS

When something attacks and damages the liver, liver cells are killed and scar tissue is formed. This scarring process is called fibrosis (pronounced “fi-bro-sis”), and it happens slowly over many years. When the whole liver is scarred, it shrinks and hardens. This is called cirrhosis, and usually this damage cannot be undone.

Causes

·         Any illness that affects the liver over a long period of time.

·         Alcohol

·         Viruses e.g. Hepatitis C and B.

·         Buildup of fat in liver of Obese and Diabetics.

·         Inheritance.

·         Prescribed and over-the-counter medicines.

·         Environmental poisons.

·         Autoimmune hepatitis.

Symptoms

·         Loss of appetite

·         Tiredness

·         Nausea

·         Weight loss

·         Spider-like blood vessels

·         Severe itching

·         Jaundice, a yellow discoloration of the skin and whites of the eye

Complications

·         Fluid buildup and painful swelling of the legs(edema) and abdomen (ascites)

·         Bruising and bleeding easily

·         Enlarged veins in the lower esophagus(esophageal varices) and stomach (gastropathy) and bleeding

·         Enlarged spleen (splenomegaly)

·         Stone-like particles in gallbladder and bile duct (gallstones)

·         Mental confusion (hepatic encephalopathy)

·         Liver cancer (hepatocellular carcinoma)

Treatment  

Currently there is no cure for cirrohsis, however, doctors can delay the progress, minimize cell damage and reduce the complications of the disease .

       1)      Preventing bleeding from Esophageal Varices

Bleeding varices can be very severe, causing death if not treated immediately. Signs of bleeding varices include vomiting of large amounts of fresh blood or clots. Larger varices have a higher risk of breaking and bleeding, and treatment is started with medications called Beta Blockers.

Beta blockers help reduce blood flow and pressure in varices. They include

·         Propranolol (Inderal®), taken twice a day

·         Nadolol (Corgard®), taken once a day

·         Carvedilol (Coreg®), taken twice a day

         2) Managing ascites

·         Avoiding further liver damage Patients who drink alcohol must stop all alcohol consumption.

·         Low salt (sodium) diet; The buildup of ascetic fluid is not the result of too much water intake, but rather the body’s inability to keep in too much sodium (salt). For this reason, it is important to cut down on salt intake, not water intake. Dietary sodium intake is usually restricted to less than 2000 mg per day (about 1 teaspoon). Most salt in a person’s diet comes from processed foods, not from the salt shaker.

·         Diuretic therapy ("Water Pills") These medications help the body get rid of extra sodium and water through the kidneys. Common medications include spironolactone (Aldactone) and furosemide (Lasix). One treatment plan begins with 100 mg of spironolactone and 40 mg of furosemide every AM.

·         Paracentesis (Tap) Paracentesis is the draining of fluid out of the abdomen with a needle. This is done using local anesthetic (lidocaine). Tap provides a very quick relief of ascites symptoms, but it does not correct the underlying cause so the fluid eventually returns.

 Living with Cirrhosis

   1)      Low sodium (salt)

A low salt diet is important for patients with liver disease, particularly those with leg swelling or ascites (fluid in the abdomen ) Try to eat less than 2,000 mg of sodium per day. High salt foods include: all foods in restaurants or fast food places, most canned food, pickles, tomato juice, chips and crackers.

   1)      Fluid intake

Drinking lots of fluid will not make ascites or leg swelling worse; only salt will do that. Most patients with cirrhosis do not need to limit fluid intake, unless sodium level is less than 125 mmol/L.

   2)      Medications

·         Patients with cirrhosis must avoid pain medications called “non-steroidal anti-inflammatory agents (NSAIDS)”. These include over-the-counter medications such as ibuprofen (Motrin®, Advil®), naprosyn (Aleve®), as well as some prescription medications.

·         Most other prescription medications are safe for the liver. In particular, statins such as Lipitor® and Zocor® can be used for treating cholesterol in patients with liver disease.

·         If a person has cirrohsis as a result of hepatitis B or C, the doctor may administer antiviral drugs to reduce cell injury. Currently the only FDA approved drug for hepatitis A and B is an antiviral drug called interferon alfa-2b. 

   3)      Screening for liver cancer

 People with cirrhosis are at increased risk for liver cancer – the risk is about 1 in 100 per year (each year, out of 100 patients with cirrhosis, one will develop liver cancer). All patients with cirrhosis should have an ultrasound and blood test called an alfa-fetoprotein (AFP) every 6 months.  

4)Vaccination

Vaccination against hepatitis A and B is recommended. The schedule is shots at 0, 1, and 6 months. The yearly influenza vaccination (flu shot) is also recommended.