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Mild hepatomegaly although in fulmi nant li ve r fai lure the liver will shrink rapidly. Splenomegaly is uncommon, and suggest either underlying pre-existing liver disease, or perhaps infection with a different virus, such as Epst ein B arr, or cytomegalovirus. Persistent nausea and vomiting suggest severe hepat itis, and these increase the risk of hypoglycaemia. Hepatic encephalopathy, although rare, indicat es the severity of the disease basically indicating liver failure.

Inve stiga tions The general pattern of the LFT results will be hepa tic. (see liver tests notes for explanation) Hepatitis

The white cell count is usually normal but will show a degree of lymphocytosis This means that the lymphocytes (which normally make up 20-40% of all circulating WB Cs) will be Hepatitis is liverraised disease erised t normal he presence immune incharact proportion to by t he whiteof cell count.cells wit hin t he liver. You should perform tests for the various indicators of each t ype of virus.

Viral Hepatitis
Differe ntia l diagnosis Many viruses are able to infect the liver, some of these will only affect the liver, whilst others may be syst emic. The symptoms ofA-EDrug i nduce d hepati tis the liver. are the most similar. This is particularly true if the history includes a Hepatitis viruses +G will primarily affect use of NS AIDs or acet aminophen. Mushroom poi soning is also a situation t hat will produce very similar Syst emic viruses t hat will affect the liver include: symptoms. 1/3 of autoimmune hepatitis pat ients will present acut ely in a manner similar to that of viral hepatitis. He rpes viruse s Acute fa tty liver a disease that occurs in pregnancy (and also other sit uations) and can be very serious. It is Epstein is Barr Virus (EBV) infect even less common hepatitis in pregnancy. Cytomegalovi rusthan (CMV) Va rice lla vi rus Viral hepat itis is rus a common cause of jaundice, and should be considered in anyone presenting with high serum Adenovi transaminases. Ye llow fever It is also important remember Ha emorrha to gic viruse s t hat oft en the disease may be anicteric (no jaundice present ). Generally there is no treatment for acute at tacks of hepatitis. Genera l hepatit Chronic effects is after does i nfe require cti on treat wi ment. th a hepa titi s virus The most commonly recognised sign is an acute attack with icteric effects. Most people will make a complete recovery. Symptoms last a few days to a couple of weeks, and include: They are al l RNA vi may ruses, e xcept hep B which is DNA. They all cause cell deat h directly, except hep B where the hepatocytes are killed by your own T- cells. Fever Malaise He patitis A Upper abdominal discomfort Jaundice often lasts a few days to a few and thenin subsides. It isand alsomost one of the last symptoms to autumn. The most common hepatitis virus . Itweeks is oft en seen epidemics, commonly occurs in the develop ion Incubat it2-6 may weeks not develop until 2 weeks after other symptoms, or indeed may not develop at all (ani cte ric he pa titis). Oro-fae ca l tra nsmi ssion. Viral shedding occurs in the faeces at about t he time of t he onset of symptoms. Symptoms usually last 3-6 weeks and then subside. Oft en found in communities wit h overcrowding Development of ascites and oedema is very uncommon, but can still occur in the most serious cases. Oft en found after flooding. The disease may have several waves the patient has several episodes worsening symptoms before Shellfish have also been implicat ed in where transmission possibly due to human of sewage reaching t heir habitat. they make recovery There isnta a full carrier stat e. With some depend Symptoms viruses on (B,age: C &D) there is a chance of developing chronic disease. Very few die from anicteric acute viral hepatitis. < people 4 years - 90% Fulmina l ive r fa ilure can very rarely occur. The term fulminant means the failure occurs very 15 years nt 40 70% ict eric suddenly is severe, but it is reversible. Jaundice, malaise,and abdominal pain, nausea & feverTechnically, 2 weeks fulminant liver disease is where t here is severe encephalopathy that develops within 2 weeks t he onset jaundice. Only one antigen has been found HAV. However, we dontof test for this,of because levels vary a lot during t he course of an infection. Inst ead we test for anit-HAV the levels of which are more predict able. You can see IgM in the blood for the first 6 weeks, t hen IgG after that. Cli nicalDia exa mi nation gnosis abnormal LFTs / +ve IgM anti-HAV Some orAcut all ofethe following features present: liver failure is rare may 0.1 tobe 0.4% Not associa ted with chroni c liver disease Spider naevi (t hese will disappear after recovery). Up to 5 of these are norma l it is only when you have The mortality rate is low around 0.3%, increasing to 2% with age and other co-morbit ies. more t hat they suggest a pat hological cause. Commonly found in water so watch out for salads washed in contaminated water Jaundice Many patients will be asymptomat ic so you may not know that they have had t he disease. URQ tenderness. You get non-specific symptoms including distaste for cigarettes!
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10% of pat ients get a palpable spleen! Extra-hepat ic complicat ions are very rare, but include arthritis, myocardit is and renal failure. It is very common, part icularly in the developing world. In some countries, 100% of the population has been infected by the age of 10 but remember, the disease is often asymptomat ic in children and so often it is not noticed. In western countries, 5-40% of t he populat ion have had t he infection. 10% of pat ients will have a relapse before recovery. Jaundice may occur 1-2 weeks after ot her symptoms. A s t he jaundice worsens, other symptoms may subside, but the urine may become dark and the stools pale, due to int rahepatic cholestasis (i.e. the intrahepat ic bile ducts get blocked). In most people, t he severit y of the virus peaks 4 weeks after infection, and symptoms will be virtually gone 2 weeks later. Admission to hospital is not normally necessary. Rest and diet ary modification seem to have lit tle effect basically, you just have to sit it out! The virus can be killed by boiling water for 10 minutes. Vaccination will provide immunity for 10 years. Some patient s may feel ill for months after t he disease this is known as post hepati tis syndrome is a functional disease t hat is treated by reassurance.

and it

He patitis B Major health problem 300 million carriers. Incubation 1 - 4 mths Parenteral t ransmission sexual, iv, perinat al 70% a nicte ric Jaundice, malaise, abdominal pain, nausea & fever - 1 to 3 mths Diagnosis abnormal LFTs / +ve HBsA g Acut e liver failure rare 0.1 to 0.5% Chronic infection depends on age of infection: 90% of people who get the disease in vertical t ransmission (i. e. from their mum) will develop chronic disease. 5-10% of adults will develop chronic disease. 0.5% of UK populat ion are carriers, but this is as much as 10-15% in some count ries in the developing world. in some far eastern countries, 1/3 of people have hep B! E.g. in Y emen of the population have hep B. Antiviral therapy for chronic infection Prevented by vaccination In chronic HBV 40% men and 15% women die from liver disease In chronic disease, viral DNA may become incorporated int o host DNA. The HbsAg is present on t he surface of infected hepatocytes, and this causes T cells to induce apoptosis in these cells. The pathogenesis is different to that of HA V, where the apoptosis is not induced by the immune syst em, but by t he infected cell it self thus HAV does not have the ability to cause chronic disease. Carrier status is indicated by presence of e antigen. e-antigen positive carrier. If you have anti-Hbs only then you have been immunised If you have anti-Hbs, anti-Hbc(and possibly ant i-Hbe) then you have had previous infection you have now cleared. 30% of people wit h chronic hep B will get cirrhosis. He patitis C This is unusual as hepatitis viruses go, as it very rarely causes acute infection. People will only become aware of infection when t hey develop serious liver disease later in life. 80% of those exposed t o t he virus will develop chronic infection. Spontaneous late clearance of t he disease is very rare. Blood transfusion a nd blood products are a major means of transmission. It is also though that it can be sexually transmitted, but this is not particularly common. Prevalence in the UK is about 0.02%. In A frica it is about 6%, and in Egypt is as high as 19%.
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About 80% of those i n the UK with ha emophili a have hepa titi s C. Major health problem 150 million infect ed. Incubation 6 - 12 wks however this figure is fairly meaningless, due the fact that acute disease is so rare. 85% anicteric. 10-15% of pat ient s will have jaundice and perhaps other general symptoms suggestive of hepat itis. Jaundice, malaise, abdominal pain, nausea & fever - mild Diagnosis abnormal LFTs / +ve anti-HCV Acut e liver failure rare < 0. 1% Chronic infection very common 85% & 1 4 % HCC Antiviral therapy for chronic infection No vaccine available 30% of chronic HCV develop cirrhosis within 20 30 years Worldwide it is the leading cause of liver disease. 95% of new cases in UK are due to IV drug use. Sexual transmission is also possible but less common. Male patients are more likely to develop fibrosis with chronic infection. Interfe ron is the most common t reatment for chronic infect ion. Progression from chronic hepatitis to cirrhosis t akes 20-40 years. This happens more quickly in male patients, immunosupressed patient s, and those who drink a lot of alcohol. About 20% of He p C patients will devel op cirrhosis within 20 yea rs. 5 year survival once cirrhosis has set in is 95%. 10-year is 81% of pat ients will develop complications, such as ascites. Once these have developed, 5-year survival drops to 50% 2-5% of cirrot ic patients will develop hepatocarcinoma.

He patitis D You can only contract this is you are also currently suffering from hepatit is B. You can get two t ypes of infection: Norma l co-e xista nt i nfe ction 90% of cases this actually reduces the severity of t he hep B infection! This is because infection wit h hepatit is D can reduce the replication rate of the hepatit is B virus. These people will usually make a full recovery from an unremarkable acute hepatitis. Superi nfe cti on 10% of cases this greatly worsens prognosis. It is due to chronic infection with both viruses. It is not really known what causes this. It can be detected by very high levels of antiHDV in the blood. With both types of co-infection there is an increased risk of fulminant liver disease. Common mode of transmission is IV drug use (in the UK). In ot her parts of the world it is transmitt ed by close personal contact. It is common in some parts of the Mediterranean, as well as Africa and Sout h A merica. There is only one identified antigen HDV. The test for infection with hep D is a nti -HDV. To prevent hep D, basically, you need to prevent hep B infection! He patitis E Water borne similar to hep A(shell fish and water melons!). 30% of dogs, rodents and pigs carry t he virus. It s presentat ion is very similar to that of hep A. It never goes to chronic. If you get it when pregnant , of mothers will die. Often baby will also die. Thi s doe s not ha ppen wi th hep A. During an acute infection, IgM antibodies (anti-HEV) are present . There is no active or passive immunit y t o hep E .

He patitis G It behaves a bit like hep C. Up to 2% of blood donors in US have this but it is not considered pathogenic.
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Epstein-Ba rr Enlarged liver Enlarged spleen Inflamed lymph nodes

Cytomegalovi rus (CMV)

Autoimmune hepatitis
Autoimmune hepatitis is a cause of chroni c hepatitis. It is also sometimes referred to as hepatitis. Any hepatitis that typically last s >6 months is referred to as chroni c It is characterised by: Increased IgG levels Antib odies against: Li ver speci fic protei ns Non-li ve speci fic proteins Mononuclear infiltrate wit hin t he liver Monocytes, macrophages, lymphocytes, plasma cells, macrophages and mast cells chronic active

There are t hree types of AIH, which can be distinguished histologically: AIH 1 shows the presence of anti-smooth muscle antibodies (A SMAs), andsometimes anti-nucelar antibodies (ANAs) AIH 2 has li ver-ki dney microsomal type 1 antibodies (LKM-1) and sometimes anti-li ver cytosol 1 antibodies (anti-LC1). AIH 3 has ant ibodies to soluble liver protei ns or liver-pancreas anti gen. Actin antibody is related to prognosis. Those with actin antibody presence are more likely to require transplant than those without. HLA-DR3 and HLA-DR4 are associated wit h increased risk for AIH. In HLA-DR3 pati ents the disease tends t o occur earlier, and is more likely to require transplant ation. ANAs antinucl ear anti bodies are present in many autoimmune diseases: Rheumat oid arthritis, SLE, scleroderma, polymyosit is, dermatomyositis, as well as A IH. In many of these diseases the ANA blood test can help diagnosis.

Epide mi ology Auto-immune hepatitis is rare. It W estern Europe and the US there are <1 ca se pe r 100 000 The M:F rat io is 1:3 Pe aks of i ncide nce: A ge 10-20, and 45-70. The lower peak is more common and: Account s for about half of cases Typically premenstrual girls 80% of AI H-2 patients are children Other a utoimmune disea se in the patie nt, or first de gre e re lati ve s: 20% of patients have another autoimmune disease 40% of patients have a first degree relative with an aut oimmune disease Pa thology The disease is t hought to occur in environmental trigger.

geneti cally pre-disposed i ndi viduals

who come into cont act with an

Many patients wit h autoimmune hepatitis have a low CD8 count. They also often have a genet ically determined
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reduced level of CD4 T cells, which are associated with fighting viral infect ion. Thus it may be possible t hat a viral

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reduced level of CD4 T cells, which are associated with fighting viral infect ion. Thus it may be possible t hat a viral infection triggers off the production of autoantibodies in susceptible individuals. For example, t he hepatitis C virus has a close relation to LKM -1 antibody ment ioned above. Drugs and Environmental agents have also been cit ed as possible causes.

Very rarely, AIH may be the result of Hep A, Hep B, EBV M ore commonly AIH is caused by Hep C Pre se nta tion May initially be acute presentation, but will always eventually become chronic. Up to 50% of pat ients present as if an acut e viral hepat itis. In other cases, there is typically an insidious onset Non-specific symptoms: Fatigue Anorexia Weight loss Amenorrhoea Behavioural changes Ab dominal pain Li ver-speci fic problems: Epistaxis nose bleeds Easy b ruising Jaundice Hepatomegaly / splenomegaly (50-60% of cases) Asct ies Signs associated with chronic liver disease: Asterixis, P almar erythema, S pider naevi

Prognosis Many patients will have severe cirrhosis by the time of diagnosis About 25% of patients will have a liver transplant

Metabolic liver diseases

Ha emacromatrosi s problems with iron metabolism and secretion. Skin discolouration Diabet es (pancreatic involvement) Joint involvement (arthiritis) Pituitary sexual dysfunction Heart failure Treat t hem by taking a pint of blood from them every week until ferritin falls below 100. Then aft er that t ake 3-4 pints a year. It is quite common Wi lson s Disea se Cannot excrete copper. Oft en presents to neurologist s with ataxia and cerebellar symptoms. Present in t heir teens with ataxia and nystagmus. Sometimes will also present wit h liver disease. Copper gets deposited around the body. These two metabolic diseases cause irreversible damage, and thus the bet t reatment is to catch it early and
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prevent progression. Other cause s Alpha1 ant i-trypsin without t his your trypsin can go wild and break down elastases. Commonly affects lungs,but can also cause cirrhosis in the liver. You can function wit h only a small proportion of liver

Alcohol and drug-induced Hepatitis Alcohol

This is a very common cause of liver injury. It is caused by excessive alcohol intake. Typically there will be ste atosis of the liver. In this pathological change, fat globules begin to accumulat e in the cytoplasm of liver cells. this can be pretty harmless, and as a result, is not very specific for predict ing if the liver will developed cirrhosis. Mall orys hyali n is an aggregate of filament found in t he hepat ocyt es that, if present , indicate a risk of irreversible changes in hepatocytes, that may ultimately lead t o cirrhosis. Mallorys hyalin is not specific for alcoholic liver disease. When we t alk about alcohol, we are act ually referring t o e tha nol. Ethanol is oxidised to a ce taldehyde. Acetaldehyde is then converted to acetat e by the mitochondria of liver cells. The liver does 90% of this metabolism. Acetate is then released into the bloodstream and taken up by peripheral tissues where it is metabolised to carbon dioxide, fatt y acids and wat er. Alcohol dehydrogena ses are present in many t issues around the body, and some people believe that the gastric mucosa itself is responsible for a lot of alcohol metabolism. Also, alcoholic drinks oft en contain a lot of sugar for example a typical pint of beer contains 250 calories! For t his reason a lot of alcoholics will not lose weight despite severe malnutrition.

Long-term effects of alcohol use are all due to et hanol. The short term effects of alcohol use can often be due to other alcohols present in the drink, such as isoamyl alcohol. These additional alcohols are known as coge ners. Brandy and bourbon contain the highest percentage of cogeners. Epide mi ology 10-30% of heavy drinkers will develop cirrhosis 50% will have fatty liver. Nutritional factors are cont roversial, although it is possible that undernutrit ion and obe4st iy both contribute to liver damage. High alcohol consumpt ion combined with hep C infection also greatly increases the risk of hepat itis. In males with hepat itis, average alcohol consumption was about 16 units/day over a period of 8 years. However, thi s is highly varia bl e. In females, the corresponding figure was 11 unit es/day. Approximately 1/3 of alcoholics have a parent who is an alcoholic.

Pa thology The first sign is fatty liver. This occurs in most heavy drinkers at some time, but it is completely reversible upon cessation of alcohol. The hepat ocyt es have to divert resources away from metabolising fat s t o metabolising alcohol. As a result , fat metabolism is alt ered result ing in fat deposit s inside the cells. There are more fat s released into the blood stream (fat ty acids) and wit hin the hepatocytes, t here is increased synthesis of t riglycerides and fatty acids. Aceta lde hyde is a product of alcohol metabolism. It binds to liver cell proteins, and causes hepatocytes injury, leading to inflammation. This inflammation can be a causat ory factor in cirrhosis. It is likely that this produces Mallorys sign. Alcohol stimulates collagen synt hesis by fibroblast s as well as fibroblast proliferation. Ultimately, the fibrosing process will end up linking hepat ic veins to portal veins, and in these places, cell regeneration occurs, and nodules form this is the st art of the process of cirrhosi s.

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Cli nical si gns Malnutri tion Very thin arms and legs(due to muscle wasting) Swollen abdomen Red tongue (iron-deficiency anaemia) Dry scaly cracked skin (due to zinc / fatty acid deficiency) Endocrine Gynaecomastia Testicular atrophy Loss of body hair Signs of pseudo-Cushings (red face, hump, striae) Fa ce /skin Parotid enlargement Spider naevi Easy bruising Dupuytrens contracture Ne uromuscula r Tremor Memory loss / cognit ive impairment Peripheral myopathy- degradation of muscle Epile psy We rnicke-Korskoff syndrome Ca rdiova scul ar Hypertension Ca rdiomyopathy Hyperdynamic circulation Bone Rib fractures on CXR Spinal osteoporosis (particularly in men)

Generally, patient s with fatty liver have few symptoms, however they may notice nausea and malaise. LFTs may be slightly unusual. Mild alcoholi c hepatitis ma y be indistingui shable from fatty liver disea se - often the t wo co-exist. symptoms of mild alcoholic hepatitis tend t o be more severe: Anorexia Nausea Abdominal pain Weight loss Drugs

The

Ca uses of he pa tomegaly Massive = CRAM Cancer - primary and secondary Right heart failure Alcoholic liver disease with fat ty infiltration Myeloproliferative diseases (ie Chronic myeloid laekaemia, PRubraV era,E ssential Throbocythaemia) Moderate = FAI LL all of the above plus Fatty liver - from DM, obesity Amyloidosis
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Iron - haemochromatosis (excess iron) Lymphoma Laeukaemia - chronic Mild ABI all of the above plus Biliary duct obstruction Infective: Hepatitis HIV EBV CMV Autoimmune Ca uses of Splenomega ly; CHI CAGO

C Cancer H Haematological malignancies anaemia, leukaemia, lymphoma, I Infection (CMV, HEP, HIV, TB, parasitic (malaria)). EBV is the most common community a cquire d Inflammation sarcoid, amyloid C Congest ion; portal hypertension A Autoimmune(RA, SLE ) G Glycogen storage disorders O Other amyloidosis, sarcoidosis Copyright 2010 - Thomas Leach Source URL (re trie ve d on tract/liver/hepatitis 24/ 10/2012 - 10:40 ): http:// almostadoctor.co.uk/content/systems/-gastrointestinal-

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