New approach could reverse liver failure

Liver Disease Survivors Guide

Renowned Health Specialist experienced in working with numerous people with liver disorders share with you and: Explains how the liver works and how liver disorders develop in Simple English without Medical Jargon. Shares the facts about cirrhosis of the liver. Explains complications and treatments in simple language. Talks about Nutrition in Liver Disease. Explains Alternative Treatments available. Talks about the latest research developments in liver disease treatment. Shares resources for Liver disease forums and help-lines. Gives you the true in-depth stories from survivors and how they coped with the challenges of liver disorder. Shares touching stories of family members who had to cope with their loved ones suffering from cirrhosis of the liver, and the strategies they used to cope with them. With Liver Disease Survivors Guide, you will discover : Credible information on Liver disease obtained from detailed interviews with specialist doctors, explained in simple language. Healthy steps in dealing with liver disorders. What to do and what not to do while learning to adapt to the liver disorder. Remarkable stories in patients own words. It gives you a real emotional experience of a person with serious liver disorder and how they view the world. Latest research on liver disorders. Best resources and direct links to forums. Direct links to get professional help and identify the best experts in your area. Alternative treatments and therapies available for liver disorders. No medical jargon or difficult language, the book is written in simple and easy to understand language.

Liver Disease Survivors Guide Summary


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Cirrhosis and chronic liver disease

Compensated cirrhosis Decompensated cirrhosis Decompensated cirrhosis Longstanding damage to the liver eventually causes scarring and cirrhosis. Many forms of liver injury produce cirrhosis and the exact cause needs to be determined in each case to guide further treatment.

Diseases and disorders

Liver damage is often caused by infections or drugs and may be acute or chronic. Acute liver disease can rapidly progress to liver failure, or can resolve, either spontaneously or with appropriate treatment. Chronic liver disease may cause cirrhosis, which is characterized by a variety of signs and symptoms and changes throughout the body, including the effects of hepatic portal venous hypertension.

Eliseo J Prez Stable MD Anna M Npoles Springer PhD

THE HEALTH STATUS OF Latinos often has been referred to as an epidemiologic paradox. On the basis of the lower socioeconomic status of Latinos compared with non-Latino whites (henceforth called whites), one would predict higher indicators of morbidity and mortality for most diseases. Despite major barriers to health care, including lack of access to primary care and less preventive care, epidemiologic data indicate that Latinos have a better health profile for the leading causes of death (heart disease, cancer, and cerebrovas-cular diseases) than do whites. National surveys indicate that this finding may be attributable to lifestyle factors, which may be culturally influenced, such as lower smoking rates. Nonetheless, Latinos continue to be disproportionately affected by selected conditions such as human immunodeficiency virus (HIV) infection, diabetes mellitus, cirrhosis of the liver, homicides, and cancers of the cervix, liver, gallbladder, and stomach. Much of this disproportionate...

Sir Harold Gillies i882i960

It is terrifying to think what will happen when the mystery of organ transference has been solved it can be as revolutionary as the cleaving of the atom. Anybody would be able to go into his local organ bank and, for a not insurmountable sum, trade in a weak heart or a feeble brain for a better one, or a cirrhotic liver for a healthier one. In Principles and Art of Plastic Surgery with Ralph Millard

Treatment and Outcome

Most types of drug-induced hepatitis are treated by stopping the offending drug. The outcome depends on how severe the liver injury is. it ranges from rapid reversal of mildly abnormal liver function tests to death from liver failure. hepatitis B A common viral infection transmitted from person to person by blood or body fluids that results in acute and chronic liver inflammation, cirrhosis, and liver cancer. in the united states, approximately 200,000 cases occur annually. The liver complications of hepatitis B infection are the most frequent and serious ones, but musculoskele-tal symptoms can also occur.

Not Just a Picky Eater

An 18-month-old white female was transferred from an outside hospital for further evaluation of possible liver failure. Three weeks earlier, her parents noted repeated episodes of a decreased energy level and lethargy with tremors and shaking when the child was eating. Initial laboratory results ordered by the primary care physician were as follows

Screening for Hereditary Hemochromatosis

A recent study compared proband genetic testing and screening of healthy patients in a primary care setting.3 This study assessed the phenotypic expression of disease through history, examination, serum iron indices, and liver biopsy in 672 asymptomatic C282Y homozygotes identified through either family screening of probands or genetic screening in the family practice setting. There were comparable levels of hepatic iron concentration, hepatic fibrosis, and cirrhosis in subjects from each group. Of the 672 homozygotes detected, 39.1 had significant hepatic iron loading and were therefore at risk for long-term complications. Cirrhosis was found in 5.6 of male and 1.9 of female asymptomatic homozygotes. Twenty-five patients in the study had repeat liver biopsies. In all cases in which cirrhosis was not present, removal of excess iron by treatment of disease resulted in improvement of the liver fibrosis score. This study shows that genetic-based screening is equally beneficial for the...

NAcetyipbenzoquinoneimine NAPQI

The laboratory is valuable in assisting the physician in treating acetaminophen overdose. Most importantly, the serum concentration of acetaminophen can be measured and is related to the patient's risk of liver injury and liver failure. The laboratory also helps to identify persons with drinking histories who are at risk of acetaminophen overdose despite consuming relatively small amounts of acetaminophen. These alcoholic patients have extremely high levels of AST enzyme when they present to the emergency department. In other words, patients with a history of acetaminophen use are at elevated risk if AST is above normal. They are candidates for antidotal therapy even if the serum acetaminophen is normal.

Epidemiology Of Alcoholic Chronic Pancreatitis

Although excessive alcohol consumption is frequently observed in patients with chronic pancreatitis, clinically overt alcoholic pancreatitis is observed in only about 5 of heavy drinkers. A prospective study of patients with alcoholic chronic pancreatitis demonstrated an incidence of 8.2 cases per year per 100,000 individuals and an overall prevalence of 27.4 cases within a population of 100,000 individuals.4 Further information regarding the frequency of subclinical pancreatic damage in patients with excessive alcohol consumption was obtained in autopsy studies. These studies revealed that about 20 of all alcoholics exhibit histological features of chronic pancreatitis without suffering signs of chronic pancreatitis prior to death. In an investigation of 99 alcoholic patients who died from alcohol-related disease, 18 presented with perilobular sclerosis as evidence of alcohol-induced pancreatic damage.9 In another study of 783 patients that had died of alcoholic liver cirrhosis, 20...

Answers and Discussion

Q1. (Answer b) Adriamycin, in common with virtually all chemotherapeutic agents, has high potential toxicity. In the case of this drug, the limiting toxicity is cardiac. More drug might have been beneficial in attacking the tumor but it would likely have been cardiotoxic. There was no mention in his history of chemical abnormalities nor of myocardial infarction during his treatment for the angiosarcoma. Q2. (Answer c) Alcohol is responsible for a range of liver pathology. Heavy drinking causes fatty liver that may progress to hepatitis that may progress to cirrhosis. Some small number of alcoholics develop liver cancer. The specific pathology resulting from alcohol is not predictable but it is certain that alcoholism correlates with risk of hepatic cancer. A history of alcohol abuse puts this patient in a higher risk category. Whether this is merely additive to the risk that arises from vinyl chloride exposure or whether it is greater than the additive risk predicted from each factor...

Paracetamol acetaminophen

Paracetamol is a potent cause of fulminant liver failure when taken in accidental or deliberate overdose. Paracetamol is normally mainly detoxified by conjugation with glucuronide. A small proportion is also oxidized by microsomal oxidases, forming a toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), which is then inactivated by conjugation with sulphate, derived from glutathione. However, in overdose, conjugation is saturated and a large amount of NAPQI is generated, which exhausts the liver's capacity for sulphation. NAPQI damages hepatocytes, further reducing the ability to neutralize the toxin. If administered soon enough, an antidote, -acetylcysteine, which replenishes hepatic glutathione stores by donating sulphate groups, may prevent liver failure.

Hypercoagulable States

Tion from liver failure, sepsis, and or malnutrition and increased protein loss secondary to nephrotic syndrome and inflammatory states.5 In addition, hyperhomocysteinemia may occur because of enzymatic defects or because of deficiencies in Vitamins B6 and B12 and folate. The acquired hypercoagulable disorders are listed in Table 38.2.

Variability in the effects of alcohol sex and race

The principle of Paracelsus is crucial here, and the emphasis must be on the word 'moderate', as there is no doubt that higher levels of drinking lead to liver disease and a variety of other diseases. It is no accident that the level of liver cirrhosis is also relatively high in France.

Attitudes Toward Psychotropic Medications

G related a complex life history that included lifelong physical and sexual abuse that started with her own family, prostitution during her adolescent years, lack of education, polysubstance abuse, marginal work as a barmaid, multiple abusive relationships, recurrent pelvic infections (including treated syphilis), and finally in the last several years a stable relationship with her husband, who was a recovered alcoholic patient with advanced cirrhosis of the liver. The gynecological examinations were being conducted for recurrent pelvic pain and infertility however, the medical record described several interactions in which Ms. G and her husband became angry with the doctor, and she refused further examination. The notes also reflected anger and frustration on the part of the medical residents (non-Spanish-speaking) attempting to examine her.

Liver cancer and masses

Primary liver cancer (hepatoma) is rare, except in chronic liver disease and cirrhosis, particularly when the liver disease is caused by hepatitis B virus infection. People with primary sclerosing cholangitis (PSC) are particularly prone to develop cancer of the biliary epithelium, cholan-giocarcinoma. Non-malignant hepatic adenoma is associated with the use of the oral contraceptive pill. The most commonly occurring cancers in the liver are metastatic deposits from cancer of the stomach, colon, pancreas and breast.

Hereditary Hemochromatosis and its Relationship to Porphyria Cutanea Tarda

Hereditary hemochromatosis (HH) is a common autosomal recessive inherited disorder of iron metabolism in which excess iron absorption leads to deposition of iron in multiple organs, resulting in cirrhosis, diabetes, skin bronzing, cardiomyopathy, and or hypogo-nadism. Genetic studies have linked the disease-causing gene to the HLA locus on chromosome 6, called the HFE gene. HH has a carrier frequency of up to one in eight people of northern European descent, although 10-15 of patients who go on to develop hemochromatosis do not appear to carry a recognized HFE mutation.10 The implicated HH gene was initially called HLA-H because of its location within the major his-tocompatibility locus, but it is not thought to have immunologic function, and it later came to be known as the HFE gene.10 Two of the major HFE mutations are single-nucleotide substitutions, including C282Y (resulting in substitution of tyrosine for cysteine at amino acid 282 in the HFE protein), and H63D (a common...

Clinical features

Patients may develop signs of liver failure, including deep jaundice, hepatic encephalopathy, ascites, bruising due to decreased circulating coagulation factors, and hypoglycaemia due to the reduced hepatic glu-coneogenesis. Liver failure is a medical emergency requiring urgent treatment.

Silybum marianum See silymarin

Silymarin The seeds of milk thistle (Silybum mari-anum) have been cultivated for centuries as a medicinal remedy, and are considered by some to have liver-protecting properties. An extract is available under the name silymarin proponents suggest that it is useful for liver-based problems, including cirrhosis, jaundice, chronic hepatitis, and damage due to drugs, alcohol, and poisoning from chemicals and diarrhea. Some reports have suggested that silymarin may stimulate certain immune functions and may protect the liver during hepatitis. To date, no studies of silymarin in pwas have been conducted. No toxic effects of sily-marin have been reported, although it is possible that because of its purported effect on the liver and kidneys, the compound may effect the absorption of other medications. Silymarin concentrations vary in milk thistle capsules, pills, and teas, and

Splenic fever See anthrax

Splenomegaly Enlargement of the spleen. In HIV this can be caused by the HIV infection itself, idiopathic THROMBOCYTOPENIC PURPURA (ITP), cirrhosis of the liver, or certain chronic infections. The spleen may or may not return to normal size when treatment of HIV is begun.

Man with Fever and Acute Polyarthritis

The patient gave a history of occasional sore throats that were rarely treated with antibiotics and a history of intermittent knee pain for several years. He complained of dysuria of one-week duration. He had no regular sexual partner and reported a new sexual contact one month previously. Social history revealed a seventh-grade education and employment as a parking lot attendant. His father died of cirrhosis and his mother, of suicide. He did not smoke but drank approximately 10 beers per week.

Pathophysiology of Porphyria Cutanea Tarda

Iron stores in the liver in PCT range from normal to the lower end of hemochromatosis range iron.8 At least 80 of PCT patients show hepatic siderosis, and 65 exhibit an increase in total body iron stores. However, fewer than 25 of PCT patients meet the strict definition of hemochromatosis, and cirrhosis of the liver is unusual.6 In terms of clinical disease, remission follows hepatic iron depletion, while iron administration may exacerbate the condition, consistent with the iron-dependent nature of PCT.

Prevention and Health Screening

Lored to meet the specific needs of Latino subgroups and to make full use of the community's resources, including the skills and commitment of its people. Improvement of modifiable risk factors such as nutritional habits, alcohol consumption, cigarette smoking, sedentary lifestyle, obtaining health care screenings, and environmental exposures need to be addressed by linguistically, culturally, and educationally appropriate methods. Largely preventable diseases such as invasive cervical cancer, cirrhosis, and lung cancer can be greatly reduced through reductions in associated risk behaviors. In 1998, 11 of Latinos reported an interval of greater than 3 years since their last health care contact compared with 5.0 of whites (National Center for Health Statistics 2000). Among children younger than 18 years, 19.5 of Latinos reported no health care visits within the past 12 months compared with 10.7 of white children (National Center for Health Statistics 2000). Thus, increased access to...

Liver function tests 287

Liver function The liver has many critical functions, including filtering blood, eliminating toxins, secreting bile (a fluid that helps absorb and digest fat), and making clotting factors. It also converts sugar into triglycerides (lipids) and glycogen (a carbohydrate) to be stored for energy and, between meals, converts triglycerides, glycogen, and amino acids into blood sugar to meet the body's immediate energy needs. The work of the liver is particularly critical to the brain and central nervous system. These tissues receive their energy supply only from sugar, and so are extremely vulnerable to liver failure.

Adolescent Female with Tremor Depression and Hepatitis

Because of the patient's anemia and elevated bilirubin, further studies were ordered to rule out hemolytic disease. The patient's conjugated bilirubin was 4.0 mg dL (68 mmol L), and a corrected reticulocyte count was 4.2 (reference range 0.5 -1.5), confirming the presence of hemolysis. A Coombs test was negative. Despite her glycosuria, a haemoglobin A1c was normal at 5.4 , and 2-hour postprandial serum glucose was only 114 mg dL (6.3 mmol L). Ultrasonographic examination of her abdomen showed a normal gallbladder without stones and no dilated intra- or extrahepatic ducts. Her liver was inhomogeneous and slightly enlarged with a prominent portal vein, suggesting cirrhosis with active inflammation. The spleen was slightly enlarged at 13.5 cm. A small amount of ascitic fluid was noted. Further evaluation of the abnormal liver studies included the following To unequivocally establish the diagnosis, a liver biopsy was performed. Because of the patient's poor coagulation status, this was...

Acute idiopathic polyneuritis The medical name

Alcohol can cause poor coordination, suppressed inhibitions, and slow mental processes. it can produce physical and psychological dependence, the risk of brain, nerve and heart damage, cirrhosis, and certain cancers. Withdrawal can lead to delirium tremens and convulsions.

Differential Diagnosis

Carcinoembryonic antigen (CEA) was one of the first identified tumor markers. It is largely expressed during fetal development however, this protein is also expressed in certain adult tissues. Elevated CEA concentrations may indicate the presence of a tumor. However, blood concentrations of CEA may be increased in conditions other than cancer, including cirrhosis, pancreatitis, renal failure, and even heavy smoking, all of which may result in elevated CEA concentrations.8 Again, ASCO guidelines state CEA is not recommended for screening, diagnosis, staging, or routine surveillance of breast cancer patients after primary therapy and also suggest that Routine use of CEA for monitoring response of metastatic disease to treatment is not recommended. However, in the absence of readily measurable disease, or an elevated MUC-1 marker (CA 15-3 and or CA 27-29), a rising CEA may be used to suggest treatment failure.7

Differential Diagnosis of Hyponatremia

But the central intravascular volume is decreased, as in congestive heart failure, hepatic cirrhosis, or the nephrotic syndrome, and a vicious cycle is established. The decreased blood volume is sensed by peripheral baroreceptors and results in increased aldosterone and antidiarectic hormone (ADH) even though TBW is excessive. The kidneys properly reabsorb Na+ and H2O in response to the increased aldosterone and ADH to restore the blood volume, but this simply results in further increases in TBW and further dilution of Na+. In this setting urine Na+ will be low.

Civil Rights Act of 1991 105

Infection progresses to cirrhosis in 20 percent of patients. In some persons with chronic HCV infection liver cancer develops. The effect of HIV on HCV is a two to three times more rapid progression to cirrhosis than in HIV-negative individuals. More HIV-positive persons also have cirrhosis and higher mortality rates than their HIV-negative counterparts. The ability to lower HIV viral load to undetectable levels has no effect on HCV, and protease inhibitors are not active against HCV. Treatment for HCV may have potential impact on the coinfected state. To date there is no vaccination for HCV. The gold standard treatment at the present time for HCV is combination therapy. See hepatitis.

Isoniazid genetic factors in toxicity

More patients had been treated this was serious toxicity to the liver. It was noticed that a significant number of patients (maybe as many as 20 per cent) showed signs of mild liver dysfunction, which usually subsided without even stopping the drug. In a small number, certainly fewer than i per cent and possibly only 0.1 per cent, the liver dysfunction was progressive and could end in fatal liver failure.

Nonalcoholic Fatty Liver Disease NAFLD

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of histological changes in the liver in patients who drink < 20-30 g of alcohol per day, ranging from simple fatty infiltration (steatosis) to a pattern of injury characterized by inflammation, hepatocyte degeneration, and fibrosis, known as nonalcoholic steatohepatitis (NASH), and to frank cirrhosis. The histological changes in NAFLD are indistinguishable from those observed in alcoholic liver disease. Although the quantity of alcohol considered harmful is > 30 g day in men and > 20 g day in women, there is no consensus on the amount necessary to cause liver damage. Additionally, patients' self-reporting of alcohol consumption is frequently inaccurate. In general, simple steatosis is considered a reversible condition. However, NASH may progress to cirrhosis in up to 10-15 of patients. In fact, NASH is currently considered the major cause of cryptogenic cirrhosis. As NASH progresses to cirrhosis, steatosis and hepatocyte...

Definition of Alcoholic Liver Disease

This case is classic for alcohol-induced cirrhosis with its three major complications ascites, portosystemic encephalopathy, and bleeding from esophageal varices. This patient suffered also from many of the other complications of persistent alcohol abuse acute alcoholic hepatitis, peripheral neuropathy, withdrawal syndrome, and spontaneous bacterial peritonitis. These manifestations in any patient further complicate management of the cirrhosis and darken the prognosis. Alcoholic liver disease (ALD) includes three conditions hepatic steatosis or fatty liver, alcoholic hepatitis, and cirrhosis.1,2 Heavy alcohol abuse, even for as little as few days can lead to hepatic steatosis, the earliest stage of ALD and the most common alcohol induced liver disorder. This condition can be reversed when alcohol consumption stops. Heavy use of alcohol for longer periods of time may lead to the development of the more severe and potentially lethal alcoholic hepatitis.3 Only 10-15 of abusers actually...

How alcohol is broken down and how it affects the liver

In addition to requiring an enzyme, the breakdown of alcohol requires a co-enzyme called NAD, which is converted into NADH when the alcohol is metabolized. The large increase in the level of NADH at the expense of NAD, and the lack of utilization of other sources of energy such as carbohydrate, leads to an increase in the production of fat, some of which accumulates in the liver after a heavy bout of drinking. This 'fatty liver', if maintained by regular and excessive drinking, seems to be a necessary stage in the eventual development of liver disease, like hepatitis and cirrhosis, which occurs in some alcoholics. The presence of the fat impairs the ability of the liver to function. The other effect of the change in the proportions of the coenzymes is that glucose is not produced, and this is made worse if the heavy drinker does not eat a normal diet from which glucose might be obtained. Blood glucose levels can therefore be dangerously low. Alcoholic hepatitis, which occurs in about...

Adult Male with New Onset Ascites

A 56-year-old white male presented with abdominal and ankle swelling of several months' duration. There was no history of chronic medical problems, except for impotence over the past 3-4 years for which he occasionally took sildenafil. The patient was on no other medications. He was a successful accountant, married with three children. He was a -pack day smoker and drank two or three beers each day. His father had been killed during World War II, and he had an uncle who died of liver cirrhosis 10-15 years previously. He had two brothers and two sisters who were all in good health. Because of his abnormal serum iron and transferrin saturation values, a diagnosis of hereditary hemochromatosis (HH) causing cirrhosis and portal hypertension was suspected. Confirmation of HH was made by molecular analysis for the G845A (C282Y) mutation of the HFE gene1 using PCR amplification of peripheral WBC DNA followed by enzymatic digestion with Rsal. The patient was homozygous for this common...

Definition of Disease13

The hepatic involvement of Wilson's disease can take several forms, including the insidious onset of cirrhosis, chronic active hepatitis, or fulminant liver failure. In the first and most common presentation, patients develop complications of cirrhosis such as ascites, bleeding esophageal varices, and liver failure (e.g., coagulopathy, spider angio-mata, hyperbilirubinemia, encephalopathy). The liver is usually small and not palpable often there is little hepatocellular necrosis, and serum aminotransferases may even be normal. When patients present with a chronic active hepatitis like picture, the liver is usually enlarged, and aminotransferase elevations are 2-4X ULN with AST usually > ALT. Histological examination of the liver seldom can distinguish between wilsonian cirrhosis or chronic active hepatitis and other causes (e.g., viral, autoimmune diseases, or drug toxicity). Copper studies are essential for the differential diagnosis of these patients. Fulminant liver failure due...

Pathophysiology Diagnosis and Management of Hereditary Hemochromatosis

Iron loading in HH can affect several organs, with the manifestations of end-organ damage usually appearing in the 40s-60s age range in men and slightly later in women. Women are somewhat protected since they lose iron over many years with menses. In the liver, iron overload can lead first to occult, then clinically evident cirrhosis, and eventually to development of malignant hepatoma. In the pancreas, iron loading of the islets of Langerhans causes glucose intolerance or frank diabetes. Cardiomyopathies and arrhythmias can develop with iron deposition in cardiac myocytes. Testicular atrophy and impotence occur in men as a result of decreased gonadotropin production by the iron-loaded pituitary. Women can develop secondary amenorrhea. Chondrocalcinosis develops in joint synovia and leads to a pseudogout picture. Hyperpigmentation of skin may be observed, but is actually due to increased melanin rather than iron deposition. Because each of these manifestations more often are caused by...

The Extracellular Matrix

Pancreatic stellate cells (Figure 3.7) are identified in the normal organ by their shape (stellate), their content of lipid vesicles rich in retinol and retinyl esters, and the presence in their cytosol of the intermediate filament protein vimentin.38 Like hepatic stellate cells, these cells, which are thought to be a homology of the so-called Ito cells,39,40 are presumed to be activated to produce fibrosis, characteristic of cirrhosis and chronic pancreatitis. Activation of pancreatic stellate cells causes loss of the lipid accumulations and accumulation of smooth muscle alpha actin, producing cells with the features of myofibroblasts.38 Stellate extensions of pancreatic stellate cells and the presence of lipid droplets may be demonstrated by electron microscopy. The actin filaments in activated stellate cells may be similarly demonstrated.

Symptoms of Alcoholic Liver Disease

Ascites from malignant ascites.11'12 In alcoholic cirrhosis, levels of protein and albumin in the fluid are very low. With spontaneous bacterial peritonitis, the absolute PMN count is, > 250 cells mL. Antibiotic treatment of the infection is imperative. In alcoholic hepatitis, AST and ALT are mildly elevated, and AST more so than ALT. Because these enzyme assays evaluate hepatocellular necrosis, levels may actually be normal in quiescent cirrhosis. Alkaline phosphatase (ALP) and g-glutamyltransferase (GGT) are synthesized in excess by biliary ductular cells reacting to irritation or inflammation of the intra- or extrahepatic biliary system levels are commonly increased in many liver and biliary diseases, including ALD, biliary obstruction, and metastatic tumor. GGT is also present in microsomes and thus is especially sensitive to alcohol-induced liver disease and may be increased when ALP is still normal. On the other hand, increased ALP with normal GGT is reason to look for a...


Confirmation of the diagnosis of Wilson's disease usually requires a liver biopsy with quantitation of the liver copper. All patients with Wilson's disease will have a markedly elevated hepatic copper, > 250 mg g dry weight. Values < 40 mg g dry weight are felt to exclude the diagnosis. Cautions include using disposable biopsy needles and placing the sample in copper-free plasticware. Variable copper distribution in patients with cirrhosis can give inaccurate results if too small a biopsy core (< 1 cm) is analyzed. Heterozygotes for the Wilson's disease gene often have low serum ceruloplasmin but usually have intermediate hepatic copper concentration. However, other cholestatic liver disorders such as primary biliary cirrhosis, sclerosing cholangitis, biliary obstruction or atresia, and Indian childhood cirrhosis can also display high liver copper concentrations. These entities are usually associated with normal or high serum ceruloplasmin and have other distinguishing features.


Liver transplantation has been performed in a number of Wilson's disease patients, usually for fulminant liver failure. Transplantation is also indicated in patients who do not respond to chelation therapy or who cannot be managed with oral chelation therapy because of either noncompliance or drug sensitivities. The fact that liver transplantation completely resolves copper accumulation is further evidence that the defect of Wilson's disease is primarily one of hepatic excretion.

Common disorders

Liver disorders can cause many symptoms and signs, ranging from vague malaise to fulminant liver failure, with disordered coagulation and coma. Typical features include jaundice, fatigue, loss of appetite and pain in the right upper quadrant of the abdomen. Because of the great reserve capacity of the liver, extensive damage may remain asymptomatic. Viral hepatitis is common throughout the world. Liver abscesses, caused by amoebae, bacteria and parasites, are common in some parts of the world. Drugs and toxins, including medications, also commonly affect the liver and the most important of these is alcohol. Chronic damage may cause scarring and lead to cirrhosis. Overwhelming liver damage, either acutely or chronically, causes liver failure. Although primary liver cancer is rare, metastatic cancers are common (see Chapters 33, 38, 41 & 42).

Interval SI Units

An abdominal ultrasound revealed increased echogenicity of the liver with somewhat prominent caudate lobe suggestive of cirrhosis but no focal liver lesions. The spleen was slightly enlarged, at 14 cm in size. There was also a small amount of free fluid seen in the perihepatic region. Color flow Doppler ultrasound imaging showed patent hepatic vasculature with normal directional flow. A subsequent upper endoscopy was performed that showed only mild portal hypertensive gastropathy but no esophageal or gastric varices. Because of the presence of several clinical, laboratory, imaging, and endoscopic findings that were suggestive, but not definitive, for cirrhosis, a percutaneous liver biopsy was performed. The biopsy revealed significant fatty change (60 ) within the liver parenchyma. Portal areas showed mild chronic lymphocytic infiltration without interface changes. Hepatic lobules showed significant hepatocyte degeneration (balloon degeneration and Mallory hyaline) and moderate...

Portal hypertension

Liver cirrhosis is the commonest cause of portal hypertension but it may also occur when the liver is congested in chronic heart failure or with portal vein thrombosis, for example following trauma or infection. Portal hypertension causes splenomegaly and ascites. Portosystemic shunting causes varices to form and, particularly if there is severe underlying liver disease, it causes hepatic encephalopathy.


Cylert (pemoline) A stimulant medication sometimes used to treat attention deficit hyperactivity disorder (adhd). Because of its association with life-threatening liver failure, Cylert is not ordinarily considered as first-line drug therapy for ADHD, and it was withdrawn from sale in Canada in September 1999 because of complications. treatment and the occurrence of signs of liver failure. Of the 13 cases, 11 ended in death or liver transplantation, usually within four weeks of the onset of signs and symptoms of liver failure.

Toxic tea

A study in two hospitals in South Africa identified twenty children suffering from this type of liver disease which was thought to be due to the use of traditional remedies. Most of the children had fluid in the abdominal cavity and an enlarged liver, indicating liver damage and dysfunction. There was a high level of illness and mortality, and in those who survived the disease progressed to liver cirrhosis. In four cases pyrrolizidine alkaloids were detected in the urine of the children.2


This is the deposition of fibrous tissue, collagen, usually on a chronic basis, in various parts of the liver. As the normal hepatocytes are replaced by collagen there is a progressive impairment in liver functions such as drug detoxification and other hepatic metabolic processes. Blood and biliary flow also are affected. The best example of a toxicant causing cirrhosis is ethyl alcohol, although other chemicals may also cause this disorder. There is no specific chemical test for cirrhosis. The diagnosis is suspected on the basis of the patient's history and can be confirmed by microscopic evaluation of a needle biopsy.


This term literally means inflammation of the liver. It is caused mainly by viruses and may be diagnosed on the basis of highly specific serological tests that distinguish among hepatitis A, B, C, and D. Hepatitis A is extremely common and has affected more than 50 of the populations of many large urban areas. Inflammation of the liver may also arise from chemicals and, as was true of cirrhosis, alcohol is a common cause of chemically induced hepatitis. Chemical hepatitis is significantly less common than viral hepatitis. Hepatitis is characterized by dramatic elevations of AST and ALT, up to 1000x the upper limit of normal. Interestingly, the disease may be further differentiated on the basis of the ratio of these two enzymes. Viral hepatitis is suggested by greater elevations of ALT, approximately twice the levels of AST. In the case of alcoholic hepatitis the ratio is reversed, i.e., AST is about twice the elevation of ALT. This is consistent with the characteristically more...

New Research

The various hepatitis viruses differ in their likelihood of producing chronic infection. For example, hepatitis A infection is not usually serious, whereas hepatitis B and C can lead to liver failure and death. When the liver is damaged, it cannot excrete the waste substance called bilirubin, which then builds up in the blood. This causes a yellow tinge to skin and eyes, called jaundice.

Hepatitis C

The virus that causes hepatitis C was identified in 1988 and was first known as non-A, non-B hepatitis. in the United States, hepatitis C virus is linked to 20 percent of all clinical hepatitis cases and is the leading cause of chronic hepatitis. it causes liver cancer, kills up to 10,000 Americans a year, and causes almost half of all deaths from liver failure. More than half of all patients exposed to the virus become carriers, and up to 20 percent of these carriers develop cirrhosis, a severe liver disease.

Urea cycle

Rare inherited defects in urea cycle enzymes cause hyperammon-aemia and neurological dysfunction. Urea cycle activity is also reduced in severe liver disease and, when this occurs rapidly, as in fulminant liver failure, hyperammonaemia can cause acute hepatic encephalo-pathy, resulting in severe neurological damage, with incoordination, drowsiness, coma, and death due to cerebral oedema.

Liver fibrosis

Although there is an abundance of data demonstrating that LPS is elevated in patients with cirrhosis 43-45 and a key player in liver injury and inflammation, there are only a few studies addressing the role of LPS signaling in liver fibrosis. Studies from the middle of the last century have suggested a role for bacteria in the development of fibrosis induced by CCl4 or choline-deficient diet 17, 18 . Furthermore, it has been shown that TLR4 is expressed on two key mediators of hepatic fibrogenesis, Kupffer cells and hepatic stellate cells. Kupffer cells initiate fibrogenesis by secreting proinflammatory and profibrogenic cytokines which act on other cells types including the hepatic stellate cell (as outlined in Fig. 3). The role of LPS and TLR4 in the early stage of alcoholic liver disease has been clearly demonstrated in the TLR4-mutated C3H HeJ strain, but fibrogenesis has not yet been studied in this mouse model 41 . Activated hepatic stellate cells are the main source of...

HCV infection

Hepatitis C virus (HCV) is a single-stranded hepatotrophic RNA virus which causes a chronic infection of the liver that may lead to the development of cirrhosis and hepatocellular carcinoma. Hepatitis C virus has developed several strategies to evade the immune system resulting in failure to eradicate the virus in most infected individuals 48 . A recent report provides evidence that HCV may evade the attack from the innate immune system by inducing the degradation of TRIF, one of the TLR adaptor proteins 49 . NS3 impedes both IRF-3 and NF-kB activation by reducing functional TRIF abundance and by generating cleavage products with dominant-negative activity 49 . Thus, HCV has not only developed strategies to avoid attack from the adaptive immune system, but also from the innate immune system. HCV core and NS3 proteins may also activate TLR2 in monocytes and macrophages to induce TNF-a, IL-6 and IL-8 production through NF-kB, JNK p38 AP-1 and ERK pathways 46 . These changes may...

The sick doctor

Contrary to their expectations doctors get sick. We have already seen that they are stressed and as a consequence have a high incidence of psychological illness, drug-related problems, alcohol abuse, and suicide, quite apart from the normal gamut of physical illness. Ramirez and colleagues found a 27 prevalence of psychiatric morbidity in consultants.23 Their higher risk of suicide has been documented at 11 to 5 7 times that of the normal population.24 They have a three times greater incidence of cirrhosis than the general population.25

Tolerance to alcohol

The effects of excess alcohol on the human liver. A liver with alcoholic cirrhosis (bottom), compared to a normal human liver (top). 22. The effects of excess alcohol on the human liver. A liver with alcoholic cirrhosis (bottom), compared to a normal human liver (top).

Chronic Pancreatitis

There are several different causes for chronic pancreatitis, but in developed countries, by far the most common cause is heavy consumption of alcohol, accounting for about two-thirds of all cases of this disease (see Chapter 15). Moderate drinking or even occasional bouts of binge drinking do not seem to cause chronic pancreatitis, but prolonged regular intake in daily amounts of 80 grams of alcohol per day can produce chronic pancreatitis. One study performed in the U.K. revealed a nearly linear consumption between the frequency of chronic pancreatitis and the amount of alcohol consumed.7 Heavy drinking is also the major risk factor for liver cirrhosis, but it is difficult to predict whether a particular alcohol consumer will develop cirrhosis, pancreatitis, or neither disease. It is unusual for a heavy drinker to develop both pancreatitis and alcoholic cirrhosis. Table 19.1, based upon data from a large multicenter study of chronic pancreatitis, lists some of the characteristics of...


Despite the positive effects of optimal levels of copper, deleterious effects may occur if a threshold level is exceeded. Wilson's disease (hepatolenticularic degeneration) is one of the diseases linked to the excess of copper in the body. It results from a dysfunction of the copper transmission process, which occurs due to a lack of suitable enzyme to catalyze the process of copper deletion from detached bonds with albumins and binding to ceruloplasma. The condition leads to neuron degradation, liver cirrhosis, and occurrence of colorful rings on the cornea (DiDonato and Sarkar, 1997).

Orgasm 355

As HAART has proved very successful in keeping people healthy PWAs have begun to die of problems that were not faced in the era of opportunistic infection. For many HIV disease patients that may mean end-stage liver or kidney disease. Then transplantation may be the only option for survival. Liver failure can result from complications of hepatitis B or C and renal problems can result from neuropathy or diabetes related to HAART. HIV-positive individuals who are nevertheless healthy have begun to explore possible transplantation. The united Network for organ sharing (uNos) which maintains all waiting lists for organs around the united states, considers this is a possibility. uNos has never forbidden HIV-positive individuals to add their names to waiting lists. (They still do not allow HIV-positive persons, among other restrictions, to sign up to donate organs.) Early studies of end results of transplants into HIV-positive people have been promising. The problem may be that medical...

Laboratory Data

Patients with AIP usually show increased levels of serum pancreatic enzymes, hypergammaglobulinemia, IgG, IgG4, and presence of several autoantibodies such as antinuclear, antilactoferrin (LF), anticarbonic anhy-drase (CA-II) antibody, and rheumatoid factor.19 However, antimitochondrial (M2) antibody specific for PBS is rarely observed (Figure 23.1). CA-II and LF are distributed in the ductal cells of several exocrine organs, including the pancreas, salivary gland, biliary duct, and distal renal tubules. Serum levels of IgG4 immune complexes and the IgG4 subclass of immune complexes are often increased in AIP.20 Our patients with stenosis of CBD show increased serum IgG4 as well as abnormality of the serum bilirubin and hepato-biliary enzymes. In these cases, other liver diseases such as viral hepatitis, autoimmune hepatitis, or primary biliary cirrhosis (PBC) should be ruled out. The pancreatic exocrine function shows slightly or moderately abnormal. Eight of our 20 patients showed...


Tis are associated with handling or consumption of raw or improperly cooked fish. Contact with unusual or exotic pets, although less common, is also a source of infection. Most pet-related cases of Edwardsiella gastroenteritis involved contact with or handling turtles (Marsh and Gorbach, 1982 Nagel et al., 1982). However, other pets, including reptiles, have been implicated in transmission (Fang et al., 1991). Cases of E. tarda septicemia most often occur in immunocompro-mised persons. The most common underlying risk factor in such individuals is hepatic cirrhosis 50 of persons developing E. tarda bacteremia have liver-related disease such as hepato-splenomegaly, icterus or hepatoma (Janda and Abbott, 1993). Wound infections typically result from penetrating or blunt trauma to mucosal surfaces exposed to either aquatic environments or inhabitants. Table 8 lists the main risk factors associated with E. tarda infections.

Nightmares 367

Tyrosinemia Babies with this disorder have trouble processing the amino acid tyrosine, which builds up in the body, causing mild retardation, language problems, liver problems, and death from liver failure. A special diet, or even a liver transplant, may be needed to treat the condition.

Disorders of Smell

Many diseases, including neurological problems, endocrine diseases, hereditary disease, cirrhosis, or kidney failure, may also interfere with the sense of smell. Damage to brain tissue caused by stroke or toxic chemicals may alter the sense of smell, as can dietary deficiencies (especially in vitamin A, vitamin B12, or zinc).

Viral hepatitis

Hepatitis B and C viruses are transmitted by blood and sexual contact, or from mother to child. They can cause acute hepatitis, as well as chronic hepatitis that may progress to cirrhosis. In the acute phase of hepatitis B infection, patients may develop liver failure. However most develop immunity and recover, with about 10 remaining chronically infected. Acute hepatitis C infection is rarely severe, but results in chronic infection in the majority of infected individuals.

Drugs and toxins

The most common liver-damaging toxin is alcohol, which causes metabolic damage to hepatocytes, partly by interfering with energy metabolism, resulting in fatty liver, and also by inducing inflammation, when it can cause alcoholic hepatitis. Sustained excess drinking can cause cirrhosis.


The most common causes in the Western world are excessive alcohol consumption, chronic viral hepatitis and autoimmune liver disease, particularly primary biliary cirrhosis (PBC), which affects women more frequently than men. There are many other causes, including inherited Multiple causes of cirrhosis can coexist and probably accelerate the rate of liver damage, for example, in people with chronic viral hepatitis or haemochromatosis who also drink alcohol.


Antioxidants applied to fats to protect against rancidity do not cause immediate acute poisonings. However, such substances may accumulate in the human body due to their ability to dissolve in fats. Butylated hydro-xyanisole may undesirably influence their production process and cause cirrhosis of liver in experimental animals. Esters of gallate are known to inhibit enzymes, such as alcaline phosphatase, lipase, tetrapeptidase, cause degenerative changes in testicles, and in animal experiments, inhibit the growth of young animals.

The Liver

Toxic effects to the liver are studied under the topic of hepatotoxicity, and substances that are toxic to the liver are called hepatotoxins. Much is known about hepatotoxicity from the many cases of liver toxicity that are a manifestation of chronic alcoholism.6 Liver injury from excessive alcohol ingestion initially hampers the ability of the organ to remove lipids, resulting in their accumulation in the liver (fatty liver). The liver eventually loses its ability to perform its metabolic functions and accumulates scar tissue, a condition known as cirrhosis. Inability to synthesize clotting factors can cause fatal hemorrhage in the liver.

Karnofsky index

Sold in many health food stores under the name kava. It is used by naturopaths as a treatment for anxiety, nervousness, insomnia, pain, and muscle tension. The U.S. food and drug administration issued a warning in 2002 that the use of this supplement has led to liver failure in people that previously had reported no problems with liver function. Liver abnormalities in patients were also noted in several other countries that issued warnings regarding the herb. It is not known whether excessive amounts of the substance caused the problem, or interactions with other herbs or medications. potential problems overshadow any beneficial usage of this supplement at this time, the warnings indicate.


Edema, the swelling of the feet and ankles, indicates salt and water retention. This situation may occur with heart, renal, or liver failure other causes include severe hypo-albuminemia or secondary hyperaldosteronism or both. In the present case, the elevated jugulovenous pressure indicates right-sided heart failure, and the accentuated pulmonic component of the second heart sound indicates pulmonary hypertension. Since there is no clinical evidence of left-sided heart failure, the right-sided heart failure must be attributed to pulmonary hypertension secondary to lung disease, namely, cor pulmonale. This condition is associated with hypertrophy of the right ventricle. The presence of central cyanosis is suggestive of hypoxemia.

Thyroid Disease

Diabetes), other medical conditions (such as urinary tract infection, enlarged prostate, liver failure, multiple sclerosis, and sleep apnea), and medication (especially diuretics). Some cases are caused or exacerbated by excessive fluid intake after dinner, especially drinks containing alcohol or caffeine.

How Do Statins Work

Up to two of every one hundred people who take a statin have higher-than-normal blood levels of liver proteins called transaminases (pronounced trans-AM-eh-nase). It's not clear if a small increase signals a real problem. An American Heart Association advisory on statin safety calls statin-caused liver failure exceedingly rare. While I think it is prudent to have a liver test done about once a year when taking a statin, that may be more cautious than necessary. Elevated liver transam-inases caused by statins usually revert to normal in days or weeks after stopping the drug, so even an abnormal set of liver tests is no cause for alarm.

Copper toxicity

A number of disorders of copper homeostasis can result in toxicity leading to liver cirrhosis at dietary copper levels which are tolerated by the general population. Copper-induced cirrhosis is mainly restricted to children, possibly because of the lower capacity of their biliary excretory mechanisms.38 Indian Childhood Cirrhosis (ICC) is a fatal condition of copper metabolism which was, at one time, a major cause of infant mortality on the Indian subcontinent. ICC sufferers, usually infants aged between 6 months and 5 years, are often found to have been exposed at an early age to milk contaminated with copper from untinned brass or copper vessels.43 High copper intake, however, is not thought to be the sole cause of the illness both environmental and genetic components are thought to contribute.44 Cases of a similar infantile condition have been reported in Germany and in the Tyrol, Austria.45,46 Incidence of both ICC and Tyrolean Infantile Cirrhosis has dropped in recent years. One...

Angiogenic Disorders

After birth, angiogenesis still contributes to organ growth, but during adulthood most blood vessels remain quiescent angiogenesis only occurs in the cycling ovary and placenta during pregnancy. However, endothelial cells (ECs) retain the remarkable ability of dividing rapidly in response to a physiological stimulus, such as hypoxia and inflammation. Angiogenesis is also reactivated during wound healing and repair. In many disorders, however, this stimulus becomes excessive, and the balance between stimulators and inhibitors is disturbed, resulting in an angiogenic switch. The best-known conditions in which angiogenesis is switched on are malignant, ocular and inflammatory disorders, but many additional processes are affected-such as atherosclerosis, asthma, diabetes, cirrhosis, multiple sclerosis, endometriosis, acquired immunodeficiency syndrome (AIDS), bacterial infections and autoimmune diseases (Table 1). In obesity, adipose tissue may also show excessive growth. A high-fat diet...

The demon drink

It is not immediately obvious why alcohol should have assumed such a high profile in the health promotion campaigns of recent years. Whereas smoking and cholesterol were both linked to diseases which had increased dramatically in prevalance, there was no such rise in conditions associated with alcohol. It has long been recognised, by the public as well as doctors, that acute intoxication sometimes induces violent or self-destructive behaviour and that chronic excess consumption leads to cirrhosis of the liver. In the past, public concerns about the damaging consequences of alcohol excess for the individual and society were expressed in the