CIRRHOSISCIRRHOSIS

ASSIT.PROFASSIT.PROF..

ZAHERZAHER TARIK IBRAHIMTARIK IBRAHIM

AMANY MOHAMAD IBRAHIMAMANY MOHAMAD IBRAHIM

Cirrhosis is a condition in which the liver slowly deteriorates Cirrhosis is a condition in which the liver slowly deteriorates and malfunctions due to chronic injury. Scar tissue replaces and malfunctions due to chronic injury. Scar tissue replaces healthy liver tissue, partially blocking the flow of blood healthy liver tissue, partially blocking the flow of blood through the liver. Scarring also impairs the liverthrough the liver. Scarring also impairs the liver ’’s ability tos ability to::

11--control infectionscontrol infections 22--remove bacteria and toxins from the bloodremove bacteria and toxins from the blood

33--prosecc nutrients, hormones, and drugsprosecc nutrients, hormones, and drugs 44 - -make proteins that regulate blood clottingmake proteins that regulate blood clotting

55--produce bile to help absorb fatsproduce bile to help absorb fats——including cholesterolincluding cholesterol——and fat-soluble vitaminsand fat-soluble vitamins

A healthy liver is able to regenerate most of its own cells A healthy liver is able to regenerate most of its own cells when they become damaged. With end-stage cirrhosis, the when they become damaged. With end-stage cirrhosis, the liver can no longer effectively replace damaged cells. A liver can no longer effectively replace damaged cells. A healthy liver is necessary for survivalhealthy liver is necessary for survival..

DefinitionDefinition::

Cirrhosis results from the necrosisof Cirrhosis results from the necrosisof liver cells followed by fibrosis and liver cells followed by fibrosis and nodule formation the liver nodule formation the liver architecture is diffusely abnormal architecture is diffusely abnormal and this interferes with liver blood and this interferes with liver blood flow and functionflow and function::

11--Portal hypertension Portal hypertension 2 - impaird liver function 2 - impaird liver function

Causes of cirrhosisCauses of cirrhosis 11-- HepatitisB &HepatitisB & Hepatitis CHepatitis C

22-- Cystic fibrosisCystic fibrosis33--Fat that accumulates in the liver Fat that accumulates in the liver

(nonalcoholic fatty liver disease)(nonalcoholic fatty liver disease) 44--Hardening and scarring of the Hardening and scarring of the

bile ducts (primary sclerosing bile ducts (primary sclerosing cholangitis)cholangitis)

55 - -Inability to process sugars in Inability to process sugars in milk (galactosemia)milk (galactosemia)

66--Too much copper accumulated in Too much copper accumulated in the liver (Wilson's disease)the liver (Wilson's disease)

77- - Liver disease caused by your Liver disease caused by your body's immune system body's immune system (autoimmune hepatitis)(autoimmune hepatitis)

88--Poorly formed bile ducts in Poorly formed bile ducts in babies (biliary atresia)babies (biliary atresia)

99-- Iron build up in the body Iron build up in the body (hemochromatosis)(hemochromatosis)

1010--Destruction of the bile ducts Destruction of the bile ducts (primary biliary cirrhosis)(primary biliary cirrhosis).1ohol

1111--Budd-Chiari syndromeBudd-Chiari syndrome1212--Veno-occlusive diseaseVeno-occlusive disease

1313--Drugs (methotrexate)Drugs (methotrexate)1414--α1-Antitrypsin deficiencyα1-Antitrypsin deficiency 1515--Hepatic venous congesionHepatic venous congesion

1616--Idiopathic (cryptogenic)Idiopathic (cryptogenic) 1717--AlcoholAlcohol

1818--Other virusesOther viruses

PathogenesisPathogenesis : Chronic injury to the : Chronic injury to the liver results in inflammation, necrosis and, liver results in inflammation, necrosis and, eventually, fibrosis. Fibrosis is initiated by eventually, fibrosis. Fibrosis is initiated by activation of the stellate cells.Kupffer cells, activation of the stellate cells.Kupffer cells, damaged hepatocytes and activated also damaged hepatocytes and activated also platelets are probably involved. Stellate platelets are probably involved. Stellate cells are activated by many cytokines and cells are activated by many cytokines and their receptors, reactive oxygen signals. In their receptors, reactive oxygen signals. In the early stage of activation the stellate the early stage of activation the stellate cells become swollen and lose retinoids cells become swollen and lose retinoids with upregulation of receptors for with upregulation of receptors for proliferative and fibrogenic cytokines, such proliferative and fibrogenic cytokines, such as platelet-derived growth factor (PDGF), as platelet-derived growth factor (PDGF), and transforming growth factor β1 (TGF-and transforming growth factor β1 (TGF-β1). TGF-β1 is the most potent fibrogenic β1). TGF-β1 is the most potent fibrogenic mediator identifiedmediator identified . .

Inflammatory cells contribute to fibrosis Inflammatory cells contribute to fibrosis via cytokine secretion, in the space of via cytokine secretion, in the space of Disse, the normal matrix is replaced by Disse, the normal matrix is replaced by collagens, predominantly types 1 and 3, collagens, predominantly types 1 and 3, and fibronectin. Subendothelial fibrosis and fibronectin. Subendothelial fibrosis leads to loss of the endothelial leads to loss of the endothelial fenestrations (ports), and this impairs liver fenestrations (ports), and this impairs liver function. Collagenases (matrix function. Collagenases (matrix metalloproteinases, MMPs) are able to metalloproteinases, MMPs) are able to degrade this collagen but are inhibited by degrade this collagen but are inhibited by tissue inhibitors of metalloproteinases tissue inhibitors of metalloproteinases (TIMPs), which are increased in human (TIMPs), which are increased in human liver fibrosis. There is accumulating liver fibrosis. There is accumulating evidence that in the early stages liver evidence that in the early stages liver fibrosis is reversible, particularly when fibrosis is reversible, particularly when inflammation is reduced, e.g. by inflammation is reduced, e.g. by suppressing or eliminating virusessuppressing or eliminating viruses..

PathologyPathology:The characteristic features :The characteristic features of cirrhosis are regenerating nodules of cirrhosis are regenerating nodules separated by fibrous septa and loss of the separated by fibrous septa and loss of the normal lobular architecture within the normal lobular architecture within the nodules nodules two types two types of cirrhosis are of cirrhosis are present: present: MicronodularMicronodular cirrhosiscirrhosis nodules nodules are usually less than 3 mm in size and the are usually less than 3 mm in size and the liver is involved uniformly. This type is liver is involved uniformly. This type is often caused by ongoing alcohol damage often caused by ongoing alcohol damage

or biliary tract diseaseor biliary tract disease

Macronodular cirrhosisMacronodular cirrhosis the the nodules are nodules are of variable size and normal acini may be of variable size and normal acini may be seen within the larger nodules. This type is seen within the larger nodules. This type is often seen following chronic viral hepatitisoften seen following chronic viral hepatitis..

A mixed picture with small and large A mixed picture with small and large nodules is sometimes seennodules is sometimes seen . .

SYMPTOMSSYMPTOMSPatients may be asymptomatic or complain of Patients may be asymptomatic or complain of

non-specific symptoms, particularly fatigue. non-specific symptoms, particularly fatigue. Specific symptoms includeSpecific symptoms include:: : :

Right hypochondrial pain due to liver distensionRight hypochondrial pain due to liver distension-- Abdominal distension due to ascitesAbdominal distension due to ascites-- Ankle swelling due to fluid retentionAnkle swelling due to fluid retention--

--Haematemesis and melaena from Haematemesis and melaena from gastrointestinal haemorrhagegastrointestinal haemorrhage

--Pruritus due to cholestasis - this is often an early Pruritus due to cholestasis - this is often an early symptom of primary biliary cirrhosissymptom of primary biliary cirrhosis

--Breast swelling (gynaecomastia), loss of libido Breast swelling (gynaecomastia), loss of libido and amenorrhoea due to endocrine dysfunctionand amenorrhoea due to endocrine dysfunction

--Confusion and drowsiness due to Confusion and drowsiness due to neuropsychiatric complications (portosystemic neuropsychiatric complications (portosystemic encephalopathyencephalopathy

--fever-loss of body weightfever-loss of body weight--

Signs:1-general signsSigns:1-general signsjaundice-fever-loss of bodyhair-LOSSof body jaundice-fever-loss of bodyhair-LOSSof body

weight-pallor-cacheexiaweight-pallor-cacheexiaSpider naviSpider navi : : Vascular lesions consisting of a Vascular lesions consisting of a

central arteriole surrounded by many smaller vessels central arteriole surrounded by many smaller vessels because of an increase in because of an increase in estradiol. These occur in about . These occur in about 1/3 of cases1/3 of cases

Palmar erythema:ExaggerationsPalmar erythema:Exaggerations of normal speckled of normal speckled mottlingmottling of the palm, because of altered sex of the palm, because of altered sex hormone metabolismhormone metabolism..

Ecchymosis(1to 3cm)-purpura(3m to1cm)Ecchymosis(1to 3cm)-purpura(3m to1cm)or petechia (<3mm)or petechia (<3mm)

Scratch marks (pruritus):due to bile salt deposite Scratch marks (pruritus):due to bile salt deposite in skinin skin

Nail changes : clubbing-terry nail -leuchonychiaNail changes : clubbing-terry nail -leuchonychia

Oedema of the lower limbOedema of the lower limbXanthelasmas-parotid enlargementXanthelasmas-parotid enlargement

22 - -local signslocal signs::Abdominal enlargment Abdominal enlargment ––full flankes-umblical full flankes-umblical

herniaherniaDilated viens-divercation of rectiDilated viens-divercation of recti

Venous humVenous hum:: heard in epigastric region (on heard in epigastric region (on examination by stethoscope) because of collateral examination by stethoscope) because of collateral connections between portal system and the remnant connections between portal system and the remnant of the umbilical vein in portal hypertensionof the umbilical vein in portal hypertension

..Caput medusa:: In portal hypertension, the umbilical In portal hypertension, the umbilical

vein may open. Blood from the portal venous system vein may open. Blood from the portal venous system may be shunted through the periumbilical veins into may be shunted through the periumbilical veins into the umbilical vein and ultimately to the abdominal the umbilical vein and ultimately to the abdominal

wall veins, manifesting as caput medusawall veins, manifesting as caput medusa . . . .

.) .)Liver :Liver :enlarged enlarged ––normal or shrankednormal or shranked

SplenomegalySplenomegaly increase in size of the increase in size of the spleen). Caused by congestion of the red pulp as a spleen). Caused by congestion of the red pulp as a

result of portal hypertensionresult of portal hypertension .) .)Liver size:Liver size:enlarged-normalenlarged-normal or shrankedor shranked

Neurological signs: Neurological signs: (disorientation-(disorientation-

drowsy-hepatic coma)drowsy-hepatic coma): : hepatic encephalopathyhepatic encephalopathy : :

Asterixis Bilateral asynchronous flapping of Bilateral asynchronous flapping of outstretched, dorsiflexed handsoutstretched, dorsiflexed hands

Fetor hepaticus : : Musty odor in breath as a Musty odor in breath as a result of increasedresult of increased dimethyl sulfide dimethyl sulfide

Ascites:Ascites: Accumulation of fluid in the peritoneal cavity giving rise to Accumulation of fluid in the peritoneal cavity giving rise to

flank dullness )needs about 1500 mL to detect flank dullness). flank dullness )needs about 1500 mL to detect flank dullness). causes causes of ascites according to serum-ascites albumin of ascites according to serum-ascites albumin

gradientgradient: :

High: >1.1g/dlHigh: >1.1g/dl

--CirrhosisCirrhosis

--Chronic hepatic Chronic hepatic congestioncongestion

Right sided hart failureRight sided hart failure

Budd Chiari syndromBudd Chiari syndrom

ConstrictiveConstrictive

Low<1.1g/dlLow<1.1g/dl

Peritoneal carcinomatosisPeritoneal carcinomatosis

--PeritonealtuberculosisPeritonealtuberculosis

- -Pancreatic and biliary diseasePancreatic and biliary disease

Nephrotic syndromNephrotic syndrom

Massive liver Massive liver metastases- myxedemametastases- myxedema

Nephrotic syndromeNephrotic syndrome - -

InvestigationsInvestigationsThese are performed to assess the These are performed to assess the

severity and type of cirrhosisseverity and type of cirrhosis . .Liver function :Liver function : Serum albumin Serum albumin

and prothrombin time and prothrombin time are the best are the best indicators of liver function: the outlook is indicators of liver function: the outlook is poor with an albumin level below 28 g/L. poor with an albumin level below 28 g/L. The prothrombin time is prolonged The prothrombin time is prolonged commensurate with the severity of the commensurate with the severity of the liver diseaseliver disease

BilirubinBilirubin

Liver biochemistry :Liver biochemistry : elevation in the elevation in the serum serum Alanine aminotransferase ALP) and serum Alanine aminotransferase ALP) and serum AspartateAspartate aminotransferase (AST)aminotransferase (AST). In . In decompensated cirrhosis all biochemistry is derangeddecompensated cirrhosis all biochemistry is deranged

Total proteinsTotal proteins.. Alkaline phosphataseAlkaline phosphatase . .

Serum electrolytesSerum electrolytes:: A low sodium indicates A low sodium indicates severe liver disease due to a defect in free water clearance severe liver disease due to a defect in free water clearance or to excess diuretic therapyor to excess diuretic therapy

Serum creatinine:Serum creatinine: An elevated concentration An elevated concentration >130 >130 μμmol/L is a marker of worse prognosismol/L is a marker of worse prognosis

In addition, serum In addition, serum α-α-fetoprotein fetoprotein if >200 ng/mL is if >200 ng/mL is strongly suggestive of the presence of a hepatocellular strongly suggestive of the presence of a hepatocellular carcinomacarcinoma. . This can be determinedThis can be determined

. .Lab to detect cause of cirrhosisLab to detect cause of cirrhosis::

11--viral markerviral marker22--serum autoantibodiesserum autoantibodies: :

--Anti-mitochondrial antibody(primary biliary cirrhosis)Anti-mitochondrial antibody(primary biliary cirrhosis)--anti- nuclear,smooth muscle(actin),liver/kidney anti- nuclear,smooth muscle(actin),liver/kidney

microsomal antibody(AUTOIMMUNAmicrosomal antibody(AUTOIMMUNA HEPATITIS)HEPATITIS)

33 - -serum immunoglobulinsserum immunoglobulins::

--IgG (AUTOIMMUNA HEPATITIS )IgG (AUTOIMMUNA HEPATITIS )- - IgM (primary biliary cirrhosisIgM (primary biliary cirrhosis

44--iron indicesiron indices

55 - -copper and caeruloplasmincopper and caeruloplasmin66--alpha 1 antitrypsinalpha 1 antitrypsin

77 - -MARKER OF LIVER CIRRHOSISMARKER OF LIVER CIRRHOSIS88--Anti-nuclear cytoplasmic antibodiesAnti-nuclear cytoplasmic antibodies

99--Genetic analysesGenetic analyses

. .Ultrasound examinationUltrasound examination This can This can demonstrate changes in size and shape of the liver. demonstrate changes in size and shape of the liver. Fatty change and fibrosis produce a diffuse increased Fatty change and fibrosis produce a diffuse increased echogenicity. In established cirrhosis there may be echogenicity. In established cirrhosis there may be marginal nodularity of the liver surface and distortion of marginal nodularity of the liver surface and distortion of the arterial vascular architecture. The patency of the the arterial vascular architecture. The patency of the portal and hepatic veins can be evaluated. It is useful in portal and hepatic veins can be evaluated. It is useful in detecting hepatocellular carcinoma-ascitesdetecting hepatocellular carcinoma-ascites. . ElastographyElastography is being used in diagnosis and follow-up to is being used in diagnosis and follow-up to

avoid liver biopsyavoid liver biopsy..

CT SCANCT SCAN : hepatosplenomegaly, and dilated : hepatosplenomegaly, and dilated collaterals are seen in chronic liver disease. Arterial collaterals are seen in chronic liver disease. Arterial phase-contrast-enhanced scans are useful in the phase-contrast-enhanced scans are useful in the

detection of hepatocellular carcinomadetection of hepatocellular carcinoma . .

EndoscopyEndoscopy is performed for the is performed for the detection and treatment of varices, detection and treatment of varices, and portal hypertensive gastropathy. and portal hypertensive gastropathy. Colonoscopy is occasionally Colonoscopy is occasionally performed for colopathyperformed for colopathy . .

.. MRI scan:MRI scan: This is useful in the This is useful in the diagnosis of benign tumours such as diagnosis of benign tumours such as haemangiomas. MR angiography can haemangiomas. MR angiography can demonstrate the vascular anatomy demonstrate the vascular anatomy and MR cholangiography the biliary and MR cholangiography the biliary treetree..

Liver biopsyLiver biopsy

Scoring system in cirrhosisScoring system in cirrhosis)a)Modified Child – Pugh classification)a)Modified Child – Pugh classification

ScoreScore

11

22 33

AscitesAscites NoneNone MildMild Modrate/severModrate/sever

EncephalopathyEncephalopathyNoneNone MildMild MarkedMarked

BilirubinBilirubin

Umol/lUmol/l ) )))

<<3434 34-5034-50 >>5050

AlbuminAlbumin

g/lg/l ) )))

>.>.3535 28-3528-35 <<2828

Prothrombin Prothrombin time seconds over time seconds over normalnormal

<<44 4-64-6 >>66

Sursurvival % for patient score Sursurvival % for patient score aboveabove

1year1year 5year5year 1010 yearyear

Child AChild A

<<77 ) )))

8282 4545 2525

Child BChild B

))7-97-9 ) )

6262 2020 77

Child CChild C

))1010 )+ )+

4242 2020 00

))bb))Model 0f end stage- liver Model 0f end stage- liver disease )MELD)scoredisease )MELD)score

3.83.8× × LN (bilirubin in mg/dl)+9.6 × LN (bilirubin in mg/dl)+9.6 × LN(creatinine in mg/ dl)+11.2 ×LN (INR)+ 6.4LN(creatinine in mg/ dl)+11.2 ×LN (INR)+ 6.4

To convertTo convertbilirubin from bilirubin from μμmol/L to mg/dL divide by 17mol/L to mg/dL divide by 17

creatinine from creatinine from μμmol/L to mg/dL divide by 88.4mol/L to mg/dL divide by 88.4LN, natural logarithm; INR, international LN, natural logarithm; INR, international

normalized rationormalized ratio..MELD scores (with no complications): 1-year MELD scores (with no complications): 1-year

survival 97% (score <10); 70% (score 30-40)survival 97% (score <10); 70% (score 30-40)

.).)

managementmanagementGenerally, liver damage from cirrhosis Generally, liver damage from cirrhosis

cannot be reversed, but treatment could cannot be reversed, but treatment could stop or delay further progression and stop or delay further progression and reduce complications. A healthy diet is reduce complications. A healthy diet is encouraged, as cirrhosis may be an encouraged, as cirrhosis may be an energy-consuming process. Close follow-energy-consuming process. Close follow-up is often necessary. Antibiotics will be up is often necessary. Antibiotics will be prescribed for infections, and various prescribed for infections, and various medications can help with itchingmedications can help with itching . .

Preventing further liver damagePreventing further liver damage::

Regardless of underlying cause of cirrhosis, there Regardless of underlying cause of cirrhosis, there are drugs known as hepato-toxic effect (high are drugs known as hepato-toxic effect (high dose of paracetamol-alcohol-Halothane-Steroid-dose of paracetamol-alcohol-Halothane-Steroid-contraceptive pills-erythromycin-oral contraceptive pills-erythromycin-oral hypoglycaemics.,etc), avoid this drugs is very hypoglycaemics.,etc), avoid this drugs is very important in hepatic patientsimportant in hepatic patients..

Vaccination of susceptible patients should be Vaccination of susceptible patients should be considered for prevention of chronic liver considered for prevention of chronic liver

diseasesdiseases Hepatitis A andand Hepatitis B..

Treating underlying causesTreating underlying causes:: . .early treatment should be considered for early treatment should be considered for

Hepatitis C,B (interferon-ribavirin-,B (interferon-ribavirin-lamivudine)lamivudine)

interferon for viral hepatitis and interferon for viral hepatitis and corticosteroids for autoimmune hepatitis. corticosteroids for autoimmune hepatitis. Cirrhosis caused byCirrhosis caused by Wilson's disease, , in in which copper builds up in organs, is which copper builds up in organs, is treated withtreated with chelation therapy ( (e.ge.g., ., penicillamine) ) to remove the copperto remove the copper

Stop alcohol intake in alcohilic cirrhosisStop alcohol intake in alcohilic cirrhosis

Tretment of complicationsTretment of complications ascites ascites : Salt restriction-diurietics : Salt restriction-diurietics

Esophageal variceal Esophageal variceal bleedingbleeding::

For portal hypertensionFor portal hypertension propranololpropranolol is is a commonly used agent to lower blood a commonly used agent to lower blood pressure over the portal system. In severe pressure over the portal system. In severe complications from portal complications from portal

transjugular intrahepatic portosystemic shunting

is occasionally indicated to relieve is occasionally indicated to relieve pressure on the portal vein. As this can pressure on the portal vein. As this can worsen encephalopathy, it is reserved for worsen encephalopathy, it is reserved for those at low risk of encephalopathy, and is those at low risk of encephalopathy, and is generally regarded only as a bridge to generally regarded only as a bridge to liver transplantation or as a palliative liver transplantation or as a palliative measuremeasure..

: :Hepatic encephalopathyRestriction protien diet-enema-lactuloseRestriction protien diet-enema-lactulose

:: Hepatorenal syndromeIs defined as urine sodium <10mmol and serum creatinine >1.5 Is defined as urine sodium <10mmol and serum creatinine >1.5

mg/dl after trial of volume expansion without diuretics treatment mg/dl after trial of volume expansion without diuretics treatment by by Terlipressin or noradrenaline with intravenous Terlipressin or noradrenaline with intravenous albuminalbumin improve function in 30% of cases improve function in 30% of cases

Spontaneous bacterial peritonitis(SBP)Spontaneous bacterial peritonitis(SBP): : Symptoms include Symptoms include fevers, , chills, , nausea, , vomiting, , abdominal tenderness and general and general malaisePatients Patients may complain of abdominal pain and worsening may complain of abdominal pain and worsening ascites.Thirteen percent of patients have no signs or ascites.Thirteen percent of patients have no signs or Hepatic encephalopathyHepatic encephalopathy

Diagnosis Diagnosis necessitates paracentesis (needle drainage of the necessitates paracentesis (needle drainage of the ascitic fluid) and laboratory confirmation of ascitic neutrophils > ascitic fluid) and laboratory confirmation of ascitic neutrophils >

250/mm250/mm³³.[1].[1]

Treatment of SBPTreatment of SBP::AntibioticsAntibiotics

After confirmation of SBP, patients need hospital admission for After confirmation of SBP, patients need hospital admission for intravenous antibiotics (most often cefotaxime 2g IV Q8-12H for at intravenous antibiotics (most often cefotaxime 2g IV Q8-12H for at least 5 days or ceftriaxone 2g IV Q24H). They will often also least 5 days or ceftriaxone 2g IV Q24H). They will often also receive intravenous albuminreceive intravenous albumin. A repeat paracentesis. A repeat paracentesis in 48 in 48 hours is sometimes performed to ensure control of infection. Once hours is sometimes performed to ensure control of infection. Once patients have recovered from SBP, they require regular patients have recovered from SBP, they require regular prophylactic antibiotics (e.g. Septra DS 1 tab 5 times/week, prophylactic antibiotics (e.g. Septra DS 1 tab 5 times/week, Ciprofloxacin 750Ciprofloxacin 750  mg PO Q1W, norfloxacin 400mg PO Q1W, norfloxacin 400  mg Q24H) as long mg Q24H) as long as they still have ascitesas they still have ascites..

Intravenous albuminIntravenous albuminA randomized controlled trial found that intravenous albumin on A randomized controlled trial found that intravenous albumin on

the day of admission and on hospital day 3 can reduce renal the day of admission and on hospital day 3 can reduce renal impairmentimpairment

liver transplantationliver transplantation

Poor prognostic indicators inPoor prognostic indicators in cirrhosis cirrhosisBlood testsBlood tests

Low albumin (< 28 g/LLow albumin (< 28 g/L Low serum sodium(<125mmol/L)Low serum sodium(<125mmol/L) : :

Prolonged prothrombin time > 6 secondsProlonged prothrombin time > 6 secondsRaisedcreatinine >130 um/LRaisedcreatinine >130 um/L

ClinicalClinical::Persistent jaundicePersistent jaundice

Persistent hypotensionPersistent hypotension Haemorrhage from varices, particularly with poor liver functionHaemorrhage from varices, particularly with poor liver function _ _

AscitesAscitesNeuropsychiatric complications developing with progressive liverNeuropsychiatric complications developing with progressive liver

Small liverSmall liver Aetiology (e.g. alcoholic cirrhosis,if patient continue drinking)Aetiology (e.g. alcoholic cirrhosis,if patient continue drinking)

Failure of response to treatmentFailure of response to treatment