1. Differential Diagnosis of Hepatomegaly

2. Hepatomegaly is an important physical sign of large number of diseases. Following characteristics of the liver should be noticed on physical examination: 1. Liver size ( Upper and lower borders of the liver, which are determined by percussion by Kurlov’s method. Normal sizes by Kurlov’s are; on mid clavicular line-9-10 cm, on median line-8 cm, and on left costal arch-7 cm). 2. Surface (smooth, nodular). 3. Consistency (dense, soft, firm, hard). 4. Margins (sharp, rounded). 5. Tenderness. 6. Pulsations. 7. Bruit/fraction rub

3. At palpation of liver it is necessary to define properties of margins of liver (soft, dense, sharp, rounded), tenderness, morbidity and surface (smooth, nodular or tubercle). 1. The soft margins of liver with moderately dense consistency, rounded and smooth surface of liver is observed at acute and chronic hepatitis, heart failure, hepatosis, and liver echinococcosis. 2. The sharp margins, dense consistency, rough and microtubercular surface of the liver determines liver cirrhosis, amyloidosis of liver. 3. Very dense consistency (stone like), rough, macrotubercular surface indicates liver cancer.

4. Diagnostic work for finding out the causes of hepatomegaly begins with: - Questioning of the patient, careful collection of anamnesis. - Patient’s contacts with patients of acute viral hepatitis. - Presence of predisposing factors e.g. blood transfusions, operative interventions, injections, alcohol abuse. - Possible communication of hepatomegaly with professional intoxications or with reception of some drugs. - It is necessary to establish illnesses of relatives. - Physical examination of the patient is directed towards the finding of yellowness of sclera, pigmentation of skin and to find extrahepatic signs such as vascular stellas, hepatic palms, gynecomastia, xanthalasm and ascites.

5. The basic biochemical investigations: - Levels of serum bilirubin. - Activity of serum transaminases (ALT, AST) - Alkaline phosphatase. - Common protein and albuminous fraction, albumin sedimentary tests. - Prothrombin index. - Serum cholesterol. - Level of bilirubin and urobilinogen in urine, stercobilin in feces. - Markers of viral hepatitis A,B,C,D,E. - Immunological researches ( defining of immunoglobulins IgM, IgG, IgA, auto antibodies to subcellular structures, antinuclear antibodies, auto antibodies to smooth muscles and mitochondria). - Level of concentration of alpha-fetoprotein.

6. Elementary instrumental methods of investigation: (With their help to successfully confirm lesion of liver and to differentiate focal and diffuse pathology) - Ultrasonography of liver. - Scanning of liver with C189 and Tc199. Research under indications: - Laparoscopy. - Selective angiography. - Puncture biopsy of liver under control of ultrasonography. - CT-scan. - Bromsulphaleony test. - Latex-Agglutination test. - Definition of alpha-fetoprotein by reaction of Abelov-Tataryne.

7. Classification of hepatomegaly The diseases accompanying pre-eminently increase of liver sizes could be divided into 3 major groups. I - st group of liver diseases: 1. Acute liver diseases: - Acute viral hepatitis (A,B,C,D,E). - Acute drug induced hepatitis. - Acute toxic hepatitis. - Acute alcoholic hepatitis. - Acute hepatosis.

8. 2. Chronic liver diseases: - Chronic hepatitis (Viral, autoimmune, drug-induced, cryptogenic) - Liver cirrhosis (viral, druginduced, toxic, alcoholic, autoimmune, billiary, cryptogenic). - Hereditary hepatosis. 3. Focal lesions of liver: - Primary cancer of liver. - Liver echinococcosis. 4. Diseases of vessels of liver: - Budd-Chiari syndrome and disease. - Thrombosis of hepatic veins.

9. 5. Lesions of liver at other diseases (systemic diseases, endocrine disorders, diseases of organs of hematogenesis, parasitic diseases of liver). II - nd group of liver diseases (Diseases Of accumulation): - Fatty hepatosis. - Wilson- Konovalov disease. - Hemochromatosis. - Amyloidosis of liver. - Alpha-antitrypsin insufficiency.

10. IIIrd group of liver diseases (Diseases of cardiovascular system): - Right heart failure. - Constrictive pericarditis. - Congestion of liver. To distinguish the diseases, accompanying pre-eminently increase of liver sizes, it is important to remember their diagnostic criteria:

11. Acute Viral Hepatitis Viral hepatitis A, B, C, D, E. 1. Unfavorable epidemiological anamnesis (Contact with patient of hepatitis A, E) 2. To find out data of blood transfusion and its preparations. 3. Parenteral manipulations, repeated injections (At hepatitis B, C, D.) 4. Period of disease (At hepatitis A, E last from 1.5-3 weeks, at hepatitis B, C, d till 7-8 weeks).

12. 5. The preicteric period: - Fever, subfebril, on later stages temperature is reduced. - Dyspeptic syndrome: decreased appetite, nausea, vomiting, bitterness of mouth, abdominal distension. - Catarrhal syndrome: same as Grippe (Flu). - Intoxication syndrome: weakness, pain in joints and bones. - Astenovegetaitve syndrome: general weakness, muscular weakness, decreased work ability. - Objective examination in preicteric period reveals hepatomegaly and dark urine.

13. 6. Icteric period: - Syndrome of hepatocellular insufficiency - Dark urine. - Acholic stool. - Jaundice of skin. - Itching. - Hepatomegaly. - Hemorrhage. - Nasal bleeding. - Sharply increased activity of transaminases (ALT, AST, LDH3) - Hyperbilirubinemia(increased conjugated and nonconjugated serum bilirubin) - Dysproteinemia (Increased alpha-2 and beta globulins and hypoalbuminemia).

14. 7. Detection of serological markers of viral hepatitis: - Hepatitis A virus- AntiHAVIgM - Hepatitis B virus- HBs Ag, HBeAg, Anti HBc IgM, and DNA-polymerase. - Hepatitis C virus- Anti HCVIgM, HCV- RNA. - Hepatitis D virus- Anti HDVIgM, HDV- RNA + markers of HBV. - Hepatitis E viruse- Anti HEVIgM.

15. Drug induced and Toxic Hepatitis 1. Drugs with hepatotoxic effects are: Tetracyclines, Aminosine, Anti TB drugs, Dopegite, Sulphanilamide, Flothane. 2. Hepatotoxic poisons are chlorinated hydrogen, 4- chloride carbons, salts of heavy metals e.g. Mercury, phosphorus, etc. 3. Drug induced and toxic hepatitis develop rapidly after the period of sensibilization. 4. It has acute onset with expressed signs of intoxication. 5. Usually it is accompanied with expressed allergic manifestations (Urticaria, itching, vasculitis). 6. Expressed cholestatic syndrome is observed with symptoms of jaundice, itching, dark urine, and acholic stool. 7. Hepatomegaly is also seen. 8. CBC reveals eosinophillia. 9. Increased levels of alkaline phophatase, conjugated bilirubin and cholesterol.

16. Acute Hepatosis (Acute toxic dystrophy of liver) It is disease of liver described by dystrophic changes of its parenchyma without expressed mesenchymal- cellular reaction. It is caused by various reasons (Heavy poisoning with phosphorus, Arsenic, Heavy intake of alcohol and/or hepatotoxic medications.

17. Acute Alcoholic Hepatosis 1. In anamnesis heavy alcohol abuse. 2. Dyspeptic syndrome: Nausea, vomiting, diarrhea, anorexia and weight loss. 3. Astenovegetative syndrome. 4. Pain syndrome (Pain in right hypochondrium and epigastric area). 5. Jaundice of hemolytic character. 6. Fever. 7. Blood serum reveals hypercholesterinemia, hypertriglyceridemia, anemia (hemolytic character). 8. Hyperbilirubinemia (Nonconjugated and conjugated). 9. Modorately increased transaminase activity (ALT, AST). 10. Liver biopsy reveals fatty liver (Excessive adipose deposition in hepatocytes).

18. Echinococcosis of Liver 1. Disease is caused by larval stage of Echinococcosus Granulosus. 2. Epidemiological anamnesis reveals contact with dogs, use of water and green vegetables contaminated with dog feces. 3. Disease has slow course. 4. Allergic reactions are seen at early stages (Urticaria, eosinopillia, skin itching). 5. Pain (Feeling of pressure or dull pain) in right hypochondrium or epigastric area. 6. Hepatomegaly (Soft consistency, painless smooth surface). 7. On later stages may appear jaundice and ascites. 8. Positive reaction of Kassoni. 9. Positive reaction of Latex-agglutination with antigens from liquid of echinococcal cyst. 10. Chest X-ray (Upward lifting of right dome of diaphragm) 11. USG and scintigraphy of liver. 12. CT-scan(Focal volumetric formation with regular borders).

19. Budd-Chiari Disease & Syndrome 1. It is obliterating endophlebitis of hepatic vein. If it is primary, it is named as disease but if it occurs secondarily it is termed and syndrome. 2. In either case infringement of outflow of blood from liver promotes development of portal hypertension. 3. Clinically obliteration of hepatic veins leads to development of triad of symptoms. - Hepatomegaly. - Ascites. - Splenomegaly. 4. Hepatomegaly is similar to cirrhosis but there is no cytolytic syndrome or cholestasis. 5. There are no structural infringements of hepatocytes which are characteristic for cirrhosis. 6. Diagnosis is confirmed with help of angiography or spleeno-portography or cavagraphy. 7. Etiology of secondary Budd-Chiari Syndrome are: peritonitis, focal lesions of liver, pericarditis (especially adhesive pericarditis), thrombophlebitis of lower extremities, polycythemia and other conditions.

20. Primary Cancer of Liver Is characterized by: 1. Hepatomegaly (Lower borders of liver reaches below level of umbilicus, consistency is stone like, macro tubercular, liver is deformed due to non-uniform increase in size and palpation is sharply painful) 2. Constant pain syndrome at right hypochondrium, syndrome of minor signs. 3. Intoxication syndrome (Fever, general weakness, loss of appetite and weight). 4. Jaundice and ascites. 5. LFTs are normal. 6. Leukocytosis and considerable elevation of ESR. 7. Positive reaction of Iatrein-Abelov on alpha- fetoprotein. 8. Scientigraphy of liver and CT-scan reveals focal defects.

21. VIRAL CIRRHOSIS OF LIVER (leading syndrome of hepatic insufficiency) -developes after chronic viral hepatitis B, C, D -very early in phase replication appears signs hepatic insufficiency (pain, heaviness in right hypochondria) after error in diet physical exercise, asthenic dyspeptic hemarogic (nasal bloodflow, syndrome of hepatic encephalopathy, jaundice, fever), portal hypertension ascites appears in late stage -Objectively jaundice may be hepatic smell from mouth, signs of hepar encephalopathy and hepar coma, teleangiectasy, hepar is increased in size, densively tuberosity, edge is not right, splenomegaly -palmary erythema, red colored tongue -blood: anemia, thrombocytopenia, signs hypersplenism – dysproteinemia (hypoalbuminemia, hyper alpha-2 and gamma - globulinemia) increased of activity of transaminase ALT, hyperbilirubinemia, conginetive, hypoholesterinemia, hypoprothrombinemia, positive serological markers of viral hepatitis

22. VIRAL CIRRHOSIS OF LIVER (leading syndrome of hepatic insufficiency) - urine: urobilinuria -faeces may be aholic -Ultrasound: structure of liver heterogeneous, increased different echodensity, forms of liver are deformed, increased size of liver and spleen -radioisotope scanning: a big defect of cumullation of drugs -poor cumullations in liver -biopsy of liver – signs macronodular cirrhosis liver

23. ALCOHOLIC CIRRHOSIS OF LIVER (Leading syndrome of portal hypertension) -develops in sequence of linering use of alcohol (daily usage of alcohol in quantity of 60-70 ml within 10-15 years) -early appearance of portal hypertension, late stage – hepatic insufficiency -objective signs: malnutrition, pale skin surface, palmary erythema, vascular stars, ascites, foot edema, strawberry tongue, varicose diletates. Liver of small size, spleen is increased -blood: hupo- and normochrom anemia, signs of hypersplenism, dysproteinemia, hypoalbuminemia, hyper-gamma globulinemia, positive sedimentary tests, hypoprothrombinemia -urine: urobilinuria, many estrogens

24. ALCOHOLIC CIRRHOSIS OF LIVER (Leading syndrome of portal hypertension) -X-ray – varicose veins esophagus, stomach -ultrasound structure of liver is heterogeneous, increased different echodensity, forms of liver are deformed, small size of liver and big size of spleen, extension of portal vein diameter more 1,3sm, spleen vein more 0,8sm -radioisotope scanning, small increase and unequal forms of liver, unequal cumulating of drugs, size of spleen is increased -liver biopsy – signs of micronodular cirrhosis, giallin bodies of Mallori

25. AUTOIMMUNE HEPATITIS – CIRRHOSIS LIVER -female part is more -early signs of inflammation syndrome (or autoimmune or mesenchimal – inflammatory syndrome) systemic and off-liver inflammations (mialgia, artralgia, vasculitis, miocardit, pericardit, glomerulonefrit, lymphoadenopathia), may be other autoimmune distinctions (tireoidit, Shegren syndrome, nonspecific ulcer colitis) -objective signs: jaundice, vasculitis, lymphoadenopathia, allergic skin efflorescence, hepatosplenomegaly -progressive flow -blood – erythrocyte sedimentation rate is increased, hemolytic anemia, distinct hyper-gamma globulinemia, an absence of B, C, D viral hepatitis markers – autoantibodies to different liver elements (antinuclear, smooth-muscle antibodies, antibodies to liver membrane), high rate of Ig A, M, G may be appearance of LE-cells, low rate of T-lymphocytes, harsh increase of aminotransferases more than 10 times, and bilirubine rate conjuncted and non conjuncted

26. BILIARY CIRRHOSIS Biliary cirrhosis results from prolonged biliary obstruction anywhere between the small interlobular bile ducts and papilla of Vater TYPES: - Primary - Primary - Secondary - Secondary

27. PRIMARY BILIARY CIRRHOSIS Primary biliary cirrhosis is a chronic disorder in which small interlobular bile ducts of the liver become progressively damaged and eventually leading to cirrhosis. Women are affected in 90% of cases in the age range 40-50 years. Etiology is unknown, immunological mechanisms may play a part because antimitochondrial antibodies are found in almost all patiens.

28. CLINICAL FEATURES Symptoms: 1. Pruritus (itching): often preceding jaundice a few years (this is the earliest symptom) and is produced by accumulation of bile acids. 2. Jaundice is occasionally present in early stages. 3. Diarrhea – resulting from malabsorbtion of fat sometimes occur (because fat absorbtion requires bile salts which are not available in the gut due to cholestasis) 4. Bone pain or fracture: due to osteomalacia from malabsorbtion of vitamin D which is fat soluble and requires bile salts for absorbtion.

29. CLINICAL FEATURES Signs: 1. Jaundice 2. Zanthelasma – yellowish deposition of cholesterol around the eyes and in xreases of hand (because cholasterol is not excreted in bile due to cholestasis) 3. Hepatomegaly is almost present while the splenomegaly occurs late when portal hypertension develops.

30. PRIMARY BILIARY CIRRHOSIS Investigations 1. LFT: very alkaline phosphatase 2. Antimitochondrial antibodies (AMA) present in >95% of cases 3. Serum cholesterol is high 4. Ultrasound: diffuse alteration in liver architecture 5. Liver biopsy shows: - infiltration of portal tract lymphocytes and plasma cells plasma cells - loss of small bile ducts - portal tract fibrosis - granulomas in about 40% cases

31. PRIMARY BILIARY CIRRHOSIS Diagnosis 1. Pruritus 2. Serum alkaline phosphatase very high 3. Antimitochondrial antibodies present 4. No extrahepatic bile duct obstruction on ultrasound 5. Liver biopsy