Chronic Liver Disease Prensentation Sir, this patient has decompensated chronic liver disease with portal hypertension,

splenomegaly and ascites. My findings include: Presence of an enlarged spleen that is palpable 3cm from the left costal margin. It is non-tender, firm in consistency, smooth surface, regular edge, notch border with no splenic rub. I am unable to get above this mass. The liver is not enlarged with a span of 12 cm in the right mid-clavicular line. The kidneys are not ballotable. There is presence of ascites with shifting dullness and this is not associated with tenderness. He is deeply jaundice and bruising noted on the ULs and LLs with presence of stigmata of CLD including leukonychia, clubbing, palmar erythema, spider naevi and gynaecomastia with loss of axillary hair. There is also presence of bilateral edema. Complications: He is cooperative with the examination with no flapping tremor to suggest hepatic encephalopathy. There are no enlarged Cx LNs and patient is not cachexic looking. There is also no conjunctival pallor noted. Aetiology: I did not find any parotidomegaly, dupytrens contracture, tattoos, surgical scars or thrombosed veins. Treatment: I did not notice any abdominal tap marks but patient has sinus bradycardia, indicating use of beta-blockers. I would like to complete my examination by looking at the patients temperature chart for fever and a rectal examination for hard impacted stools or malena. In summary, this patient has decompensated chronic liver disease with portal hypertension, splenomegaly and ascites. There is presence of bruising, leukonychia, jaundice with no evidence of hepatic encephalopathy. A. The most likely etiology for this gentleman is 1. Chronic ethanol ingestion due to presence of parotidomegaly but no dupytrens contracture; presence of hepatomegaly 2. Chronic hepatitis B infection as patient has tattoos. 3. Chronic hepatitis C infection as I note an abdominal surgical scar with possibility of transfusion in the past B. In the local context, the most likely underlying etiology is chronic ethanol ingestion, chronic hepatitis B and C. C. The most likely aetiology is chronic ethanol ingestion as I notice that this patient has presence of parotidomegaly. In view that there is also a hard irregular liver that is palpable, it raises the possibility of an underlying mitotic lesion of the liver.

D. The most likely aetiology is 1. Primary biliary cirrhosis as she is a middle-aged lady with evidence of CLD with pruritus, xanthelasma and generalised pigmentation. 2. Hemochromatosis as he is a middle-aged gentleman with slate-grey appearance with presence of diabetic dermopathy. I would like to complete the examination by examining the CVS for CMP, urine dipstick for glycosuria and for small testes secondary to pituitary dysfunction. 3. Wilsons disease as the patient has a short stature associated with Kayser Fleisher rings of the eyes and tremor and chorea of the affecting the left upper limb. 4. Haemolytic anaemia (Thalassemia major/intermedius, Hereditary spherocytosis) as the patient has a short stature associated with hyperpigmentation and thalassemic facies with frontal bossing, flat nasal bridge and maxillary hyperplasia. I would like to complete the examination by examining the CVS for CMP, urine dipstick for glycosuria and for small testes secondary to pituitary dysfunction. Questions What is cirrhosis of the liver? Defined pathologically Diffuse liver abnormality Fibrosis and abnormal regenerating nodules What are the causes of liver cirrhosis? Chronic ethanol ingestion Viral hepatitis B and C In UK, the risk for hep C is blood transfusion before Sept 1991 or blood products before 1986 Cardiac failure Others Autoimmune chronic active hepatitis (female) Primary biliary cirrhosis (female) Primary sclerosing cholangitis Haemochromatosis (male) Hemolytic disease Wilsons disease Alpha 1 AT deficiency Galactosemia Type 4 glycogen storage disease Budd-Chiari (in malignancy- PRV or intraabdominal, AI, OCPs, IBD and PNH) Drugs MTX (Look for RA or Psoriasis; Bx before starting MTX and bx every 1.5g accumulated dose), amiodarone, isoniazid, methyldopa (MAMI) Cryptogenic What are the complications of cirrhosis? (5) Portal hypertension

Ascites Tense ascites, SBP Splenomegaly thrombocytopenia Varices Hepatorenal syndrome Dx Cr Clr <40 Absence of other causes for renal impairment Absence of Cr improvement, proteinuria (0.5g/d), hematuria (<50/hpf) and urinary Na <10 Type 1 = rapidly deterioration in renal fn ie doubling of serum Cr in < 2wks to >221 umol/l Type 2 = stable or slowly progressive that does not mean criteria for type 1 Hepatic encephalopathy Stages 1 depression, euphoria, sleep disturbance, slurred speech; may have asterixis, normal EEG 2 lethargy, moderate confusion; asterixis present; abnormal EEG 3 marked confusion, arousable; asterixis present; abnormal EEG 4 coma; abnormal EEG Coagulopathy low platelets and reduced clotting factors HCC

How do you stage cirrhosis of the liver? Child-Pugh staging o Consists of 5 parameters with score ranging from 5 to 15 o Prognosticate o 5 parameters ( 2 clinical and 3 Ix) o Bilirubin (<34, 34-50, >50 umol/l) o INR (<1.7, 1.7-2.3, >2.3) o Albumin (>35, 28-35, <28) o Ascites (mild, moderate, severe) o Encephalopathy (absent, I and II, III and IV) o A 5-6 pts (1 year 100%, 2 year 85%) o B 7-9 (1 year 80%, 2 year 60%) o C 10-15 (1 year 45%, 2 year 35%) How would you investigate? (Note the STEM STATEMENT) (5) Confirming the dx o Abdominal USS or CT Establishing the aetiology o Hep markers, CAGE questionnaire, liver Bx in selected cases Prognosticate o LFT Albumin, bilirubin o INR Complications o Endoscopy of the upper GIT o Mitotic change USS and AFP

o Evaluation of renal function urea, electrolytes and Cr o Evaluation of ascitic fluid Cell count Ascites albumin (SAAG) Gram stain and C/S Others AFB smear and c/s, cytology Evaluation for liver transplant o 5 year survival rate for cirrhosis with ascites is 30-40% vs 70-80% for post liver transplant o MELD score (Model for End Stage liver disease which has bilirubin, creatinine and INR) o Consider for those with refractory ascites, SBP or HRS

When should an abdominal paracentesis be done for a patient with cirrhosis and ascites? Newly diagnosed to r/o SBP Symptomatic fever, abdominal pain, encephalopathy, GI bleed How would you manage? (4) Education and counselling o Stop drinking alcohol, regular follow up Manage the underlying disease o Hepatitis B General measures (stop alcohol, hep A vaccination) Lifelong surveillance for HCC with USS and AFP Antiviral for Immune clearance phase( HBeAg +, ALT raised) Reactivation phase ( HBe Ag -, ALT raised, HBV DNA raised) IFN alpha (SE : influenza-like; neutropenia and thrombocytopenia; neuropsychiatric and unmasking AI disease) Lamivudine (well tolerated but YMDD mutant) o Hepatitis C At risk are IVDAs and transfusion pre 1989 (Singapore) or pretransfusion Sept 1991 or blood pdts before 1986 (UK) General measures Surveillance (HCC and screen for HIV) Indications HCV RNA levels (>50 IU/ml) Raised ALT Bx showing fibrosis and inflammation Treatment Peg interferon Ribavirin o Alcoholic liver disease >21u/wk in males and >14u/wk in females 100% of normal liver develops fatty liver

35% develop alcoholic hepatitis 20% develop cirrhosis 40% of alcoholic hepatitis develop cirrhosis Maddreys discrimination function PT x Bil x 4.6 >32 = severe Treat with corticosteroids or total enteral nutrition (2030 kcal/kg/day) o Others (see notes below) Manage the complications o Hepatic encepholpathy Treat precipitants (see below) Prevent Low protein diet Lactulose o Hepatorenal syndrome Treatment with Noradrenaline infusion, telipressin or midodrine with octreotide plus Albumin infusion (1g/kg on D1 then 20-40g/day) For 5-15 days Prevention (in patient with cirrhosis and ascites) IV albumin NB that hemodialysis does not help in this condition o Ascites (see ascites) o Upper GI bleed Secure VS Urgent endoscopy Operative Prevention Propanolol to reduce HR by 25% or to 55-60 bpm Variceal banding o HCC Definitive treatment o Liver transplant o MARS (Molecular adsorbent Recirculating system)dialysis as an interim measure before liver transplant

What are the factors precipitating decompensation? Infection SBP, pneumonia, UTI GI bleed Constipation Diuretics and electrolyte imbalance Diarrhea and vomiting Sedatives Surgery

What are the nail changes of hypoalbuminaemia? Leukonychia, ie nail bed opacify indicating an albumin level <30g/dL; affecting the thumb and index nails bilaterally initailly Muehrckes lines transverse white lines What are the causes of palmar erythema? CLD RA, thyrotoxicosis and polycythaemia Pregnancy, normal finding What are the causes of anaemia in cirrhotic patients? Anaemia of chronic disease Fe deficiency from GI bleed Hemolysis from hypersplenism Folate and B12 from poor nutrition How many spider naevi should be present to be considered as significant? More than 5 When examining a patient with signs of chronic liver disease, think of: Primary biliary cirrhosis Clinical Female middle age CLD with pruritus, xanthelesma, generalised pigmentation, hepatosplenomegaly Stages Asymmptomtic with normal LFTs (positive Abs) Asymptomatic with abnormal LFTs Symptomatic lethary and pruritus Decompensated Commonly associated with sicca syndrome, arthralgia, Raynauds, Sclerodactyly and Thyroid disease Ix Raised ALP, Anti-Mitochondrial Ab M2 Ab, IgM Lipids Other tests for CLD Histology Granulomatous cholangitis Mx Symptomatic Urosdeoxycholic acid Cholestyramine Fat soluble vitamins Immunosuppression Cyclosporin, steroids, AZA, MTX, tacrolimus, colchicines Liver transplant

Hemochromatosis Clinical Male Slate-grey appearance, hepatomegaly Affects Liver cirrhosis and cancer Pancrease DM Heart failure (CMP) Pituitary dysfunction Pseudogout Therefore requests Urine dipstick, CVS examination and testicular examination Autosomal recessive, HLA-A3, Ch 6 HFE gene, increased Fe absorption with tissue deposition, Ix Raised ferrritin, transferrin saturation and liver Bx Mx Non-pharmological Avoid alcohol Avoid shellfish as they are susceptible to Vibrio vulnificus Venesection Dy/Dx of generalised pigmentation Liver hemochromatosis in males and PBC in females Addisons Uremia Chronic debilitating conditions eg malignancy Chronic haemolytic anaemia Wilsons disease Clinical Short stature Eyes KF rings - greenish yellow to golden brown pigmentation of the limbus of the cornea due to deposition of Cu in Descemets membrane at 12 and 6 oclock position. Also occurs in PBC and cryptogenic cirrhosis Sunflower cataract Extrapyrimidal Tremor and chorea Presents as difficulty writing and speaking in school Pseudogout Penicillamine complications Myasthenic ptosis Lupus malar rash, small hand arthritis Urinalysis for glycosuria from proximal RTA Autosomal recessive, Ch 13, increased Cu absorption and tissue deposition Ix

Low serum ceruloplasmin, increased 24H urinary Cu Liver Bx increased Cu deposition Mx Penicillamine

Ulcerative Colitis Clinical o Skin erythema nodosum, pyoderma gangrenosum o Joint arthropathy LL arthritis, AS, sacroilitis o Aphthous ulcers o Ocular iritis, uveitis and episcleritis o CLD Cirrhosis, chronic active hepatitis, fatty liver PSC, Cholangiocarcinoma, metastatic colorectal cancer, amyloid