Hepatology

Functions of the Liver

Main functions include:

Metabolism of CHO, protein, fat Storage/activation vitamins and minerals Formation/excretion of bile Detoxifier of drugs/alcohol Action as (bacteria) filter and fluid chamber Conversion of ammonia to urea

Generally LFTs reflects 2 patterns of liver disease; 1. Cholestatic Alk P, GGT. 2. Hepatocellular AST, ALT. Factors favouring hepatic origin of Alk P; 1. GGT. 2. 5-nucleotidase.

Type of Hepatitis
A B C D E

Route of transmission

fecal-oral

percutaneous percutaneous percutaneous permucosal permucosal permucosal

fecal-oral

Chronic infection
Prevention

no

yes

yes

yes

no

pre/postexposure immunization

pre/postexposure immunization

blood donor pre/postscreening; exposure risk behavior immunization; modification risk behavior modification

ensure safe drinking water

Hepatitis A - Clinical Features

Is an RNA enterovirus Incubation period: Average 30 days ( 2 - 6 wks ) Complications: Fulminant hepatitis. Cholestatic hepatitis. Relapsing hepatitis Prevention; - Immune Globulin IM, 0.02 mL/kg

- Hepatitis A vaccines .

Pre-exposure (travelers to endemic regions/4-6months) & Post-exposure (within 2-4 wks) for persons > 2 years old . provides long-lasting protection (20 years). (Havrix) use 3 doses at 0, 1, 6 months).

TTT; bed rest, symptomatic ttt e.g. antiemetics, avoid hepatotoxic drugs.

Hepatitis B - Clinical Features

Hepa DNA virus. Mode of transmission; Bl, sexual, perinatal. Incubation period: Average (2 -6 ms). Chronic infection: 30%-90%. Association/ complications of HBV; - Aplastic anemia. - Arthralgia/itis.
- PAN.

- Glomerulonephritis; membranous., MP. - HCC. - urticaria, acrodermatitis.

Acute Hepatitis B Virus Infection with Recovery

Typical Serologic Course

Symptoms HBeAg anti-HBe

Total anti-HBc

Titre
HBsAg IgM anti-HBc anti-HBs

12 16 20 24 28 32 36

52

100

Weeks after Exposure

Progression to Chronic Hepatitis B Virus Infection Typical Serologic Course

Acute (6 months) HBeAg HBsAg Total anti-HBc Chronic (Years) anti-HBe

Titre

IgM anti-HBc

0 4 8 12 16 20 24 28 32 36

52

Years

Weeks after Exposure

Diagnosis
serological tests ; HBsAg - used as a general marker of active infection, persistance > 6 m= chronic infection. HBsAb - used to document recovery and/or immunity to HBV infection. HBc Ag is not detected in the blood. anti-HBc IgM - marker of acute infection, may be the only marker in the window period. anti-HBc IgG - past or chronic infection. It can distinguish past infection from previous vaccine. HBeAg - indicates active replication of virus and therefore infectiveness. Anti-Hbe - virus no longer replicating= no longer infectious . HBV-DNA - indicates active replication of virus, more accurate than HBeAg

HBsAg +ve

Repeat HBs Ag after 6 m to confirm,

if HBs Ag become -ve resolved if HB sAg still +ve

HBe Ag -ve ALT =n =carrier

HBe Ag +ve =chr active

observe

biopsy & TTT

TTT of HBV

HBsAg +ve

+ve HBc Ig M =acute

HBsAg after 6 months

+ve HBc IgG =chronic +ve =chronic

-ve =resolved

1. If acute symptomatic ttt 2. If HBsAg +ve after 6 mths, HBeAg +ve or -ve, HBeAb _ve, PCR>105, enzymes >2folds antiviral ttt. 3. If HBsAg +ve after 6 mths, HBeAg gray zone or normal enzymes biopsy hepatitis activity index > 4 antiviral ttt. 4. If HBeAg-ve, HBeAb +ve, PCR+ve, normal enzymes Carrier (no ttt). 5. Liver cirrhosis nucleozide analogue only.

Treatment
-

Interferon Peg INF 2a (high mw, long life) Mechanism; immune distruction of virally infected cells clear the virus. Dose; 180 Ug/wk Duration; 6 mth for eAg +ve, 12 mths for eAg _ve (mutant form) Indications; chr hepatitis NB; not for normal biopsy or LC (lead to decompensated liver) Response rate is 30 to 40%. Side effects; common; flu like S, N, V, wt loss, loss of hair, depression, mild BM suppression. less common; thyroiditis, BM suppression, seizures, retinopathy, tinitus, teratogenic.

# to IFN therapy; Asolute; Poorly controlled medical condition, DM Anaemia, thrombocytopenia. Poor medication compliance. Alcohol, IV drug abuse, Severe depression. Relative; Autoimmune dis (SLE, Rh, IBD, psoriasis) Neuropathy. Thyroiditis.

Nucleotide analogues;

Lamivudine, Adefovir, entecavir, tenofovir Mechanism; reverse transcriptase inhibitorinhibit viral replication, decrease enzymes but does not clear the virus. Adv; oral, no hep decompensation, delay the progression of LC & HCC. Disadv; relapse , drug resistance mutant strains, no viral clearance. Duration; 1-3 yrs.

NB; there are 8 genotypes for HBV (AH).better response with A &B. HBe Ag-ve mutant forms are more drug resistant but less HCC, common in Egypt.

Response to ttt; 1) virologic; Early response (12 wks) End of ttt response (at 24 or 48 wk) Sustained response (after 6 mths) Non responder (at the end) Breakthrough (reappear while on ttt) Relapse (-ve at the end but +ve during FU). 2) biochemical (normal ALT). 3) Histologic (>2 Hist. A ct. Ind improvement). Predictors of good response; Viral; genotype, titre. Liver; minimal fibrosis, moderate enzymes. Patient; female, Caucasian, lean, compliant, not IC, no alcohol, no other CLD.

Prevention

Vaccination
highly effective recombinant vaccines.

given to those who are at increased risk ; health care workers, neonates.

HBIG post exposure to hepatitis B. It is

particular efficacious within 48 hours, to neonates whose mothers are HBsAg and HBeAg positive. Other measures - screening of blood donors, blood and body fluid precautions, All pregnant women .

Natural History of HCV

Incubation period: Average 6-7 wks (2-6 ms) Chronic HCV----------Cr-------HCC 20-30 y 5-10 y The rule of 20; - 20% of pts with acute infection are symptomatic. - 20% of pts with acute infection clear the virus. - 20-40% with chronic HCV develop C after 20 yrs. - Crr---20%--HCC - 20%-55% of Chronic who receive IFN will obtain a sustained rresponse.

Extrahepatic manifestation of HCV

1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

PCT. Cryo. Leukocytic vasculitis. MPGN. Thyroiditis. Sjogrens. Lichen planus. Vitiligo. IGT (type II DM). B cell lymphoma.

Laboratory Diagnosis

HCV antibody (by EIA or RIBA; more sensitive) appear at least 4 weeks after infection.

HCV-RNA ( in the acute phase), (monitoring the response to antiviral therapy). EIA detect anti-HCV by 4- 10 wks of exposure, while PCR as early as 1-2 wks.

Diagnostic tests for HCV

Category False +ve EIA Resolved infection HCV carrier ALT N N N EIA + + + RIBA _ + + HCV RNA _ _ +

If a low risk patients with normal LFTs has a +ve EIA Only 30-40% will be RIBA +ve. However, in high risk individuals, PPV of ELISA> 95%.

HCV genotypes

6 genotypes. Genotype 1 most common in US, low response rates to TTT, 30% 1 year. Genotype 2,370% response after 6 ms.

TTT guidelines for HCV

Pt ccc PCR +ve, ALT, liver biopsy with inflammation, bridging necrosis Recommendation INF+ ribavirin

PCR +ve, ALT,

Normal ALT Compensated C decompensated C

INF+ ribavirin or do liver biopsy

Observe. Observe, consider TTT Consider transplantation

Treatment

Interferon - may be considered for patients with chronic active hepatitis. The response rate is around 50% but 50% of responders will relapse upon withdrawal of treatment. Ribavirin - combination of interferon and ribavirin is more effective than interferon . progression even in absence of viral response; side effect; teratogenic, hemolysis esp in renal insufficiency..

Hepatitis D - Clinical Features

Coinfection with HBV severe acute disease. low risk of chronic infection. Superinfection usually develop chronic HDV infection. high risk of severe chronic liver disease. may present as an acute hepatitis.

Hepatitis E - Clinical Features

Incubation period: Pregnant women Illness severity:

Chronic sequelae:

As HCV
Increased with age None identified

Alcoholic Liver Disease, Alcoholic hepatitis, and Cirrhosis

Diseases resulting from excessive alcohol ingestion characterized by fatty liver (hepatic steatosis), hepatitis, or cirrhosis . Prognosis depends on degree of abstinence and degree of complications C/P; N/V, anorexia, abd pain, wt. Malnutrition often an issue in these patients TTT; abstinence, good nutrition.

Lab; GGT. MCV (macrocytosis). AST/ALT > 2/1. Ig A. Mallory bodies; dense perinuclear esinophilic fragments in hepatocytes (DD; PBC, wilson). thrombocytopenia. Blood alcohol Bleeding tendency in alcoholic Cirrhosis; 1. synthesis of coagulation factors. 2. Plat. Function defect. 3. Thrombocytopenia ( hyperslenism, BM suppression).

NAFLD
-

Spectrum; steatosis, NASH, cirrhosis. Etiology; 1ry; obese, DM, hyperlipidemia. 2ry; drugs; amiodarone, tamoxifen, steroid, tetracyclin rapid wt loss, malnutrition, jej bypass, TPN. Inv; U/S, MRI, AST/ALT<1, ANA, ASMA +ve in 40%,hyperlipidemia in 20%. TTT; orlistat, wt loss UDCA, antioxidents, Vit E, betaine Statin, gemfibrozil Thiazolidenidione, Metformin.

Autoimmune liver disease

Autoimmune Primary Biliary Cirrhosis (PBC)

Hepatitis(AIH)
Primary Sclerosing Cholangitis (PSC) Autoimmune Cholangitis (AIC)

Overlap Syndromes

The diagnosis requires: exclusion of major causes of liver damage, including alcoholic, viral, drug- and toxin-induced, hereditary metabolic, and NAFLD.

Autoimmune Hepatitis

Young women (10-20 yrs) Typically present with malaise, artharalgia, tender hepatomegaly, 2 ry amenorrhea,. Patients may be asymptomatic AIH may present as acute hepatitis, chronic hepatitis, or well-established cirrhosis ,
Investigation. Type 1, ASMA ,ANA ,Anti-actin, Type 2, Anti-LKMA nti-liver-kid., Type 3, Anti-Soluble liver- antigen , globulins,

Without therapy, most patients die within 10 years of disease onset. With TTT,10 yrs survival = 93%. TTT=steroids + aza for pt with or without Cirrhosis70% remission in 2 yrs. Relapse after remission=50% at 6 ms, 80% at 3 yrs.

Primary Biliary Cirrhosis

Middle aged females C/P; pruritis,Jaundice, steatorrhea( 2ry to cholestasis), hyperpigmentation, xanthelasma. PBC frequently is associated with other autoimmune disorders , such as Sjgren syndrome, Hashimoto thyroiditis, AIHA, arthritis.

Criteria for the diagnosis include:

(1) A cholestatic serum enzyme pattern, Alk. Phosph. (2) Presence of AMAs antimitochondrial. (3) Elevated serum IgM, (4) bile duct lesion of mid-sized IHBD (1),(2) & a compatible histology are regarded as mandatory for the diagnosis of PBC. Liver biopsy lymphocytic portal infiltration. TTT; UDCA, colchicine, transplant.

Primary Sclerosing Cholangitis

Criteria for the diagnosis :

1- RUQ pain , jaundice , pruritis & wt loss A cholestatic enzyme pattern; 2- histologically ., large bile duct (intra & extrahepatic) stenosis & dilatations without prior bile duct surgery or 2ry SC ; mild to moderate portal infiltration.

3- concomitant IBD ( before, during, after UC mainly) in 70 % of the patients, detected by asympt Alk P. but in case of UC, 3% have PSC. 4- presence of pANCAs in > 70% of patients. MRCP, ERCP beading of intra & extrahepatic bile duct. risk of cholangiocarcinoma, retroperitoneal fibrosis. TTT; supportive (UDCA, colchicine), , transplantation.

Autoimmune Cholangitis

AIC (AMA ve PBC) shares many features with PBC including : 1- F>M, 2- fatigue and pruritus, 3- a cholestatic serum enzyme pattern, 4- bile duct lesions (histology), & 5- a slowly progressive course leading to fibrosis and cirrhosis of the liver. Patients with AIC are by definition AMA -ve & often present with serum ANA and/or ASMA.

Criteria
F:M Predominant liver test

AIH
4:1
ALT, AST (7-10 times) ALP (1-3 times)

PBC
9:1
ALT, AST (1-3 times) ALP (6-10 times), -GT

PSC
1:2
ALP, -GT

AIC
9:1
ALP, -GT

Auto antibodies
Histology Diagnosis

ANA, ASMA, LKM, SLA,

interface hepatitis Hepatocellular enzyme pattern,

AMA AMA-M2

p ANCA

ANA, ASMA

Florid bile duct Fibrosing bile lesion duct lesion AMA-M2, cholestatic enzyme pattern, compatible histology BD st./dilat. (choigraphy), cholestatic enzyme pattern, IBD, p ANCA

Florid bile duct lesion Cholestatic AMA-ve, ANA or ASMA +ve, histology compatible with PBC

Overlap Syndromes

Patients with overlap syndromes present with both hepatitic and cholestatic biochemical and histological features of AIH, PBC, and/or PSC, and usually show a progressive course toward liver cirrhosis . AIH-PBC overlap syndromes ...reported in almost 10% of adults with AIH or PBC. AIH-PBC Overlap Syndrome AIH-PSC Overlap Syndrome AIH-AIC Overlap Syndrome Coexistence of PBC and PSC Coexistence of AIH and Chronic HCV

Wilsons Disease

AR. Genetic defect in copper transport ( ATP7B gene on ch 13) hepatic excretion Cu organ deposition. Presentations :

Hepatic, chronic hepatitis, macronodular C, mallory bodies. Neurological;(BG) flapping, chorea, dysarthria, tremors parkinsonism Kayser Fleicher ring Renal; RTA Haematological; coombs ve HA. Endocrinal; hypoparathyroidism pseudogout.

Wilsons Disease

1.
2. 3. -

Inv; Low serum ceruloplasmin High urinary copper. Liver biopsy with orcein stain. TTT; penicillamine for life + pyridoxine, oral Zn Transplantation Family screening with ceruloplasmin.

KF ring

Hemochromatosis

1. 2. 3. 4. 5. 6.

AR, mutation of HFE gene on chr 6. Homozygous C282Y or hetero C282Y/ H63D. Exessive Fe absorption & deposition in various organs; - heart restrictive cardiomyopathy, - pancreas DM, - pituitary hypogonadism, - joints pseudogout, - skin bronzed colour. risk of malignancy HCC. Cause of death; HCC, restrictive cardiomyopathy. Lab; screening by TSAT > 60% in males & 50% in females. Ferritin > 500 Fe, TIBC. Hepatic iron conc (HIC), hepatic iron index (HII), MRI. Liver biopsy staining with prussian blue. Genetic study. TTT; phlebotomy/1-2 wks for 2-3 yrs to Hb<10, ferritin<350,then every 3-4-m for life. Desferroxamine. Irreversible complications are arthropathy, hypogonadism, cirrhosis.

1 antitrypsin

Inhibit neutrophil elastase, its absence emphysema & LC. AR, Pi ZZ phenotype Inv; PAS +ve globules in periportal hepatocytes. Ttt; hepatic transplantation, stop smoking.

Drug induced liver disease

acetaminophen Estrogen Amoxiclave, chlorpromazine, erythro, OCP, Amiodarone,allopurinol OCP, Acute hepatitis. Budd chiari. Cholestasis. Hepatic granuloma. Adenomas +/- intraperitoneal rupture. Cholelithiasis, cholestasis HV thrombosis Peliosis hepatis CAH.

Methyl dopa, INH, nitrofurantoin

MeThotreX, amiodarone, vit A

Cocaine Anabolic steroids , OCP

Cryptogenic C.
Massive ischemic necrosis Peliosis hepatis

Cirrhosis
Etiology Alcoholic C. Diagnosis GGT, MCV, AST/ALT TTT Abstinence

HBV
HCV Hemochromatosis

serology
serology TSAT, Ferritin, hepatic Fe index, HFE gene

INF-2b Lamivudine
INF ribavirin Phlebotomy, desferroxamine

AIH
PBC wilson

ASMA, anti LKM, SLA, ANA

AMA Serum& urine Cu, ceruloplasmin 1 antitrypsin level

Prednisone, azathioprine
ursodiol D-penicillamine, Zn

1 antitrypsin

Enzyme replacement, transplantation

Fulminant Hepatic Failure

- Def; Rapid, severe acute liver injury with

encephalopathy within 8 weeks in someone with a previously normal liver. - pathology; massive necrosis, severe fatty degeneration. - Causes; HEV in pregnancy, Reyes, IV tetracycline, paracetamol toxicity, ecstasy, halogenated anathesia, wilson, viral, Alcohol, mushroom poising, shocked liver. - C/P; enceph, hypoglycemia, Na, bleeding tendency, renal failure. - Ttt; as hep. enceph. - Poor prognostic factors; - Paracetamol; Ph<7.3, s creat>300, PT>100, grade3,4 enceph.

Reyes Syndrome

It is acute encephalopathy + fatty degeneration of the liver Pathogenesis: loss of mitochondrial function . Disturbed FAO + carnitine def Clinical picture: Acute fulminant hepatitis. age 4-12 yrs URTI or chicken pox Mortality 50% Ttt; supportive

The Child-Turcotte-Pugh Classification

1.
2. 3. 4. 5. 6. 7.

8.

Complications of LC; Portal HTN ov, hypersplenism, ascites. Ascites HCC Hep encephlopathy HRS Malnutrition Coagulopathy Endocrinal; amenorrha, testicular atrophy.

Portal hypertension
Def; PV pressure > 12 mmhg. Types According to site of obstruction Prehepatic eg PVT Hepatic: presinusoidal eg CHF sinusoidal eg Cir, postsinusoidal eg VOD Posthepatic eg Budd Chiari synd Clinical Picture

Hematemesis Melena Splenomegaly Hypersplenism Dilated abdominal wall veins Ascites Encephalopathy

upper GIT bleeding;

1.

Ulcers; - high risk ulcers= active bleeding, visible vessel, adherent clot. - Hospitalization for 3 days. - PPI infusion - endoscopy electrocoag, heater probe, injection of absolute alcohol or 1: 10.000 epin. Mallory Weiss; self limiting. Esoph. Varices; - octoreotide -ligation better than injection sclerotherapy - quinolone Ab - chronic non selective BB - decompressive surgery as distal splenorenal shunt in class A & B lower rate of intervension than TIPS. - TIPS; less bleeding, equal mortality but more encephalopathy than endoscopy. Others; gastric or esophageal erosions, malignancy

2.

3.

4.

A) Of an acute attack of hematemesis 1-Resuscitation 2-anti shock measures; IV cannula, line, Ryle, IV crystalloids, colloids, Blood, FFP. 3- hemostatic drugs; Vit K, tranexamic acid, ethamsylate. 4- PPI infusion in PU. 5- Octreotide for esophageal varices. 6- anticoma measures; lactulose, metronidazole, enemas. 7- UGIE for band ligation or injection sclerotherapy + quinolone. 8- sengestaken-blackmore tube for massive uncontrolled bleeding from OV. 9-if still uncontrolled TIPS for high risk,, emergency surgery for low risk. 10- if massive bleeding, source unknown (obscure) enteroscopy or angiography.

Management

B) IN between the attacks; 1- PPI for PU 2- non selective BB; propranolol, quinolone for prophylaxis from SBP, UGI Band ligation or injection sclerotherapy for OV.

Lower GI bleeding
SI bleeding Causes;
1. 2. 3. 4. 5. 6.

Hemorroids Anal fissure Adolescent IBD, jej. Polyp Adult diverticula Elderly vascular ectasia, malignancy Others; dysentry, ischemia, vasculitis, intussuception.

C/P;

If facial, oral telangectasia HHT Acanthosis nigricans Malignancy Perioral pig spots PJS. Investigation; UGIE Colonoscopy Push enteroscopy Videocapsule enteroscopy TC labelled RBC scan (during bleeding) Angiography (tumour, Vs malformation)

Occult bl in stool; - benzidine, guaiac tests False +ve; meat, NSAIDs False ve; vit C, cauliflower (peroxidase containing) Iron darken the test.

PVT

Aetiology: intra abdominal infection umbilical catheterization hypercoagulable state invasion by tumors idiopathic Clinical picture: splenomegaly no hepatomegaly normal LFTs

Veno occlusive disease

Thickening and fibrosis of small hepatic venules and centrilobular veins Aetiology: * Herbs. * toxins (aflatoxin). * drugs . Azathiprine * bone marrow tx

Budd Chiari Syndrome

1.
2. 3.

Obstruction of the main hepatic veins or IVC : Acute onset of abd. Pain& ascites , jaundice with no LL oedema. Risk factors; Chemotherap Irradiation alkaloids

Hepatic Encephalopathy
Def; neuropsychiatric S that may complicate CLD, fulminant LCF & portosystemic shunts. Pathogenesis; protein in the colon bact flora neurotoxins e.g. NH3, mercaptans, false neurotransmitors as octopamine & tyramine dt aromatic & branched chain aa, GABA. Role of ammonia; 1. Bind glutamic acid glutamine - CNS. 2. Bind ketoglutarate CNS energy. Ttt by binding to lactic acid.

Precipitants of Hepatic Encephalopathy

Drugs
Benzodiazepines Narcotics Alcohol

Increased Ammonia Production, Absorption or Entry Into the Brain

Excess Dietary Intake of Protein GI Bleeding Infection Electrolyte Disturbances (ie., hypokalemia) Constipation Metabolic alkalosis

Dehydration
Vomiting Diarrhea Hemorrhage Diuretics Large volume paracentesis

Primary Hepatocellular Carcinoma

 neurologic symptoms Cognitive impairment Inverted sleep rhythm Neuromuscular disturbance Altered consciousness

Stages of Hepatic Encephalopathy

Stage I Apathy II lethargy Symptoms
Slow mentation (Mild Confusion, agitation, irritability, sleep disturbance, decreased attention) Easy arousable, disorientation, inappropriate behavior, drowsiness Somnolent but difficult arousal by vigorous stimuli; pain & voice, slurred speech, confused, aggressive Light Coma; respond to pain only Deep coma; no response

III stupor
IV coma

DD of flapping tremor; 1. Hepatic Encephalopathy. 2. Wilsons dis. 3. Uremia. 4. CO2 narcosis.

DD of irritable coma; 1. Hypoglycemia 2. Subdural hematoma 3. Acute alcohol intoxication 4. Delerium tremens; dt balcohol withdrawal, visual hallucinations, paranoid psychosis, tremors, agitation, pyrexia, tachycardia, sweating, dilated pupil within 3-1 wks, ttt; sedation that GABA as BDZ. 5. Wernickes encephalopathy 6. Drug intoxication 7. Meningitis 8. wilson

Treatment of Hepatic Encephalopathy

1.
2. 3. 4. 5.

6.
7. 8. 9.

10.
11.

Control precipitating factors. Lactulose Antibiotics Enema/4 hr Protein restriction BCAA supplementation Flumazenil (Anexate) BDZ receptor antagonist. Ldopa or bromocriptine ; dopamine agonist; improve NM transmission. Zinc Artificial liver support (hemoperfusion, artificial liver device. Liver transplantation

Definition

Ascites

The presence of free fluid in the peritoneal cavity.

Differential diagnosis F F F. Causes : 1. Portal HTN; SAAG> 1.1g/dl

23-

Prehepatic eg PVT Hepatic: presinusoidal eg CHF, constrictive pericarditis, TI sinusoidal eg Cirrhosis,metastasis, fibrosis, AFL. postsinusoidal eg VOD Posthepatic eg Budd Chiari synd Hypoalbuminemia. SAAG< 1.1g/dl - nephrotic, protein loosing entero, malnutrition. Local causes; SAAG< 1.1g/dl Diseased peritoneum; malignant as P carcinomatosus, mesotholioma, infections as TB, fungal, bact,others; FMF, vasculitis as HSP, granulomatous, esinophilic. Normal peritoneum pancreatic, chylous, myxedema, Meigs S.

Paracentesis
Transudates Ascitic protein Ascitic LDH <3g <200 Exudates >3g > 200

Modified Light criteria

Ascitic/serum LDH
Ascitic/serum protein Examples

<0.6
<0.5 CHF/ cirrhosis/ nephrosis Portal HTN Hypoalb. Meigs S Contrictive pericarditis

> 0.6
> 0.5 TB Fungal SBP Cansers Budd Chiari S

Serum-Ascitic Albumin gradient ( SAAG ratio);

SAAG <1.1 =abn cap. permeability SAAG >1.1 = portal HTN mediated

Nephrotic S
Pancreatitis

CHF/
Budd Chiari

Peritoneal TB
Peritoneal carcinomatosis

cirrhosis

Serositis, CT dis.
Causes of unilateral shifting dullness; 1. TB; lobulated type. 2. Dilated intestinal loop 3. Psoas abcess 4. Subcapsular splenic hematoma

Hepatic ascites
-

Mechanism of hepatic ascites; Hypoalb PHT Renal Na retension Lack of distruction of Est, aldosterone, ADH Complicated; PVT, SBP, HCC, HRS. TTT of ascites Dietary Na restriction; 2 g/d Oral diuretics. Fluid restriction is not necessary unless serum sodium is < 120 mmol/L. A single 4-to-6 L abdominal paracentesis should be performed in patients with tense ascites. Urine sodium excretion can assist in determining patient compliance with diet and diuretic-resistance. Liver transplantation should be considered in eligible patients with cirrhosis and ascites.


1) 2)

Refractory ascites;

Ttt;
1)

Diuretic resistant= can not be mobilized despite Na restriction & max dose of oral diuretics; 400mg spironolactone + 160 mg frusemide. Intractable ascites= can not be mobilized dt diuretic induced complications.

Large volume parasentesis+ an albumin infusion of 8-10 g/ liter of fluid removed 2) TIPS 3) Portosystemic shunt 4) Peritoneovenous shunt 5) Ascites ultrafiltration & reinfusion 6) Liver transplantation 7) Novel ttt; ANP, dopamine, docarbamine, Ve2 receptor antagonists e.g. tolvaptan. Sudden in ascites in previously stable ascites; SBP.,Budd-chuari.,HCC., HRS. Sudden deterioration of liver functions; e.g. sepsis, Hge, alcohol binge. Hepatic hydrothorax; 70% RT dt opening of lymphatic channels through the diaphragm Inv; diagnostic paracentesis must be done to disclose SB empyema (in 10%).

Ascitic fluid clues of specific causes of ascites Causes of ascites Ascitic fluid clues
Peritoneal Carcinomatosis Tuberculous ascites Chylous ascites Cytology malignant cells WBC > 500/mm3 with lymphocyte predominance -TG in ascites > serum (usually > 200mg/dL) - milky, clear by ether - sudan staining - dt intestinal lymph e.g.TB, filaria, nephrotic, ectasia, - dt pseudomyx perit,

Mucinous

Pancreatic ascites

Amylase in ascites > serum (often > 1000 U/L)

TIPS

1.

2. 1. 2. 3.

Indications Resistant, recurrent refractory ascites. Recurrent variceal bleeding. contraindications of TIPS HV thrombosis. SBP Mild to moderate ascites.

SBP
def; An infection of the peritoneal fluid in the absence of a
known or suspected intra-abdominal surgical source of the infection.

Risk factors; GI hemorrhage. previous SBP. ascitic fluid TP < 1gm/dL, S. bilirubin > 3.2 mg/dL low platelet count < 98,000 cells/mm. fulminant hepatic failure.
diagnosis; 1. C/P; fever, abd pain, tenderness, ascites 2. a PNL in ascites 250 cells/mm (or WBCs >500/mm3). 3. a positive ascitic fluid culture (usually of a single organism; enterobacteriaceae 63%, step pneum 15%, enterococci 610%) but often culture ve.

of SBP
Treatment

empiric antibiotic therapy, e.g., 2g of cefotaxime i.v. every 8 hours,or other 3rd G ceph or Amoxacillin-clavulonate or quinolone if not on quinolone prophylaxis for 5 days 1.5g albumin/kg BW within 6 hours of detection and 1g/kg on day 3. Prophylaxis; Oral norfloxacin 400mg 1x2 1ry or 2ry prevention for high risk patients for short term (7d) as 1ry prophylaxis, long term for 2ry prophylaxis

Variants of ascitic fluid infection according to ascitic fluid characteristics

Category Ascitic fluid analysis
Count SBP Culture-negative neutrocytic ascites Secondary bacterial peritonitis PMN 250/mm PMN 250/mm PMN 250/mm Organism(s) Single Negative culture Multiple

Jaundice
Isolated unconjugated hyperbil (direct<15%) Hemolysis Ineffective erythropoiesis Drugs e.g. rifampin, Inherited e.g. gilbert, Cr Najar. Hepatocellular (ALT, AST) - viral, wilson, autoimmune, alcohol, drugs e.g. INH, acetaminophen, toxins as vinyl chloride. Isolated conjugated Rotor, DJ. Cholestatic (ALK P > 4 times) - extrahepatic; U/S dilated bile ducts CT, ERCP. e.g. malignancy, stones, stricture, PSC, parasitic as ascaris, AIDS cholangiopathy. - Intrahepatic serology, biopsy.e.g.viral, alcoholic, PBC, PSC, GVHD, infiltrative dis as TB, lymphoma, sarcoid, amyloid, drugs as OCP, anabolic steroids (pure cholestasis), erythromycin (cholestatic hepatitis).

Gilberts 1 ry cause of isolated indirect bili. Usually caused by fasting states Nicotinic acid test delay & high peak of biliribin ( 3 hrs).

DD

Cholestasis in ICU shock liver, sepsis, TPN. Jaundice after BM transplantation venoocclusive dis, GVHD. AIDS cholangiopathy; Picture of PSc. Cholangitis. Dt infection with CMV or cryptosporidia. ALK =800 but bil often normal. GGT in alcohol, phenytoin,, pancreatitis, cholestasis. Cholestasis; Alk P fractionate, 5nucleotidase, GGT.

DD of jaundice in 3rd trimester of pregnancy

1. 2. 3. 4. 5.

Viral hepatitis (hep E). Herpes hepatis. HELPS. Acute fatty liver of pregnancy Intrahepatic cholestasis.

Pruritis gravidarum; dt intrahepatic cholestasis. Ttt; mild reassurance . Severe cholestyramine, ursodeoxycholic acid.

HCC

Predisposing factors;

1. 2.

3. 4. 5. 6.

LC esp hemochromatosis & alcoholic C. HBV, HCV Aflatoxin (fungal metabolite in food) Androgenic steroids & rarely OCP. Fibrolamellar carcinoma; a microscopic variant consisting of large polyclonal cells arranged in trabiculae separated by parallel bundles of collagen, in young females, of better prognosis. Inv; AFP>400 ng/ml, carboxyprothrombin, spiral CT. TTT; Surgery; resection, transplantation if < 3 cm, good liver function Percutaneous ttt; if < 5cm or 3 <3 cm with no vascular or extrahepatic invasion. e.g. ethanol, acetate injection, cryoprecipitate, hot saline, laser photocoagulaton, radiofrequency ablation, intralesional injection of chemo (cisplatinum). Chemoembolisation; if not fit for surgery or percut but fit liver functions. Systemic; hormonal e.g. Tamoxifen or chemo e.g. capecitabine. Radiotherapy Targeted immunotherapy; anti AFP Ab.

Liver transplantation
Elevated liver enzymes after transplantation; Early few wks to ms 1. Allograft rejection. 2. Drug toxicity. 3. Art. Thrombosis. After 1st yr recurrence of initial dis

HRS

Post-cholecystectomy S;
1. 2.

3.
4. 1. 2. 3. 4. 5. 1. 2.

Causes; Oesophagitis, pancreatitis, radiculopathy Functional BD (hepatic flexure S) Stone in CBD, stricture CBD, FB granuloma Sphincter iof odd dysfunction Management; Liver FTs Abd U/S UGI endoscopy. Biliary manometry Biliary scan TTT; If LFTs , abd U/S normal symptomatic pain releif. If LFTs abnormal, U/SCBD dilatationERCP with manometry or sphincterotomy.

Acute PANCREATITIS
1.

2. 3.

4.
5.

6. 7. 8. 9.

Causes; Gall stones 50%; 75% of pt with unexplained pancreatitis has microlithiasis(microscopic stone dis). Alcoholism Infections; Coxsackie, mumps, ECHO & hep viruses Tumours Drugs; PD FAST VET (pentamidine, didanosine, frusemide, azathioprine, steroids, sulfa, thiazide, valproate, OCP, tetracyclin) Hypertrigyceridemia Hypercalcemia Iatrogenic e.g. ERCP Idiopathic.

C/P; Abd pain, N, V. MOF, shock Cullen's sign (periumbilical discolouration) Grey Turner's sign (flank discoloration) Inv; 1. s. amylase 4 times,levels does not correlate with the severity, macroamylasemia (bound to Ig), urinary amylase/creat. 2. s. lipase; specific, remain high for long time (10d) 3. s trypsin 4. Leuckocytosis, AST, ALP, Ca. 5. Imaging; CT Scan TTT; 1. Bowel rest 2. Analgesic; pethidine 3. Antibiotics; tienem, 3rd G ceph. 4. Correct fluid & electrolytes. 5. Somatostatin IV 6. Plat activating Fact antagonist (lexipafant)

poor prognostic indicators in acute pancreatitis: During 48 hrs Ransons BASline BUNdle Sure Can Help Out Base deficit > 4 meq/l BUN > 5 mmol/l Sequestration of fluid>6L Calcium < 2.0 (<8mg/dl) Hct >10% PaO2 <8 (60 mmHg)

 1. 2. 3. 4. 5. 6. 7. 8.

Complications of acute pancreatitis; Plegmon; a mass of inflamed pancreatic tissue. Pseudocysts. Hypocalcemia Pancreatic abcess; 2-4 wks after ARDS. MOF. Splenic or portal vein thrombosis varices--. Hematemesis. DM, exocrine pancreatic insufficiency.

Pseudocysts; Fluid collections. In 15 % of acute panc. Body & tail Do not have epithelial lining. resolve spontaneously within wks

Causes of a raised amylase are: acute/chronic pancreatitis pancreatic cysts and carcinoma perforated duodenal ulcer ovarian carcinoma . ectopic pregnancy gallstones salivary tumour adenitis ,mumps diabetic ketoacidosis

Chronic Pancreatitis
Causes; 1. Alcohol 2. Cystic fibrosis 3. Hemochromatois 4. Others; traumatic, autoimmune, Hypertrigyceridemia 5. Hypercalcemia

C/P;

Inv;

abd. Pain. Steatorrhoea, B12 deficiency, trypsin is required in the processing of dietary B12 which enables absorption . DM

CT calcifications. ERCP (of choice)..... Chain of lakes Test for exocrine pancreatic functions; - therapeutic test with pancreatic enzymes - secretin test (most sens) - fecal elastase, chemotrypsin - serum trypsinogen. TTT: analgesics, DM, steatorrhea.

 1. 2. 3. 4.

Risk factors; Smoking, advanced age, male gender, black race. Type I DM, chronic pancreatitis. Familial pancreatitis Industrial exposure to petroleum components & leather tanneries. Pathology; adeno, 80& in the head. C/P; cachexia, obst jaundice with palpable GB (courvoisier law), ascites, abd pain, thrombophlebitis ( trousseau sign) Inv; CT, MRI., ERCP. TTT; whipple radical surgery or palliative surgery, chemo, radio.

Pancreatic cancer