Cirrhosis of liver(end stage liver disease)

CTGU- Dr. Rkdhaugoda

Cirrhosis of liver• Definition- fibrosis of liver- by any stress factors• Causes- alcohol/ virus/ toxins-drugs/malnutrition/unknown• Pathogenesis-• Complications- portal HTN,ASCITES, HE, BLEEDIND DISODERS, • Clinical features( toxic /effect of causes-lifer failure/coplications)• Investigation- to find out-causes/coplication/ to see organ

dysfunctions• Diagnosis– data collection and analysis• Management- of symptoms/ disease process/ complications/

research management• Management problems –discussion/review- use of stem

knowledge-research-Analysis and applications.

fibrosis

• Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This can be a reactive, benign, or pathological state. In response to injury this is called scarring and if fibrosis arises from a single cell line this is called a fibroma. Physiologically this acts to deposit connective tissue, which can obliterate the architecture and function of the underlying organ or tissue. Fibrosis can be used to describe the pathological state of excess deposition of fibrous tissue, as well as the process of connective tissue deposition in healing.

Mechanism LIVER FIBROSIS?

• Altered ration of hepatocyte- cell damage/cell repair

• Activated- stellate cells - stem-stellate cells• Gap is replaced by another type fibrous –

collagen cells.• Stellate Stem cells more- transforms to-

fibroblasts- which secrets-fibrins/collagens-• Down-regulation of specific- micro-RNA,• INCREASED- tnf-alpha, NFkB-INFLAMMATION

Cirrhosis of liver

End stage of chronic liver diseaseProgressive irreversible liver fibrosis .Caused by various chronic liver diseasesCaused- anatomical and functional changes

resulting in- portal HTN, ASCITES, H/E MALFUNFION OF LIVER, bleeding disorder

pathogenesis

Normal liver CLD- CIRRHOSIS- HEPATOCELLULAR -CA

Cirrhosis of liver

CAUSES of -cirrhosis

• CHRONIC ALCOHOLISM-Fatty liver-chronic alcoholic hepatitis-Cirrhosis• CHRONIC VIRAL HEPATITIS B and C– chronic hepatitis- cirrhosis• HEPATO-TOXIC DRUGS- DRUG INDUCED chronic hepatitis- cirrhosis• Chronic biliary obstruction- chronic hepatitis-cirrhosis• Nonalcoholic steatohepatitis (NASH)-Fatty liver disease- chronic hepatitis-

cirrhosis• Cystic fibrosis• Primary biliary cirrhosis• Cryptogenic( unknown)• Wilson’s disease.

PATHO-PHISIOLOGY

EXPOSURE TO STRESS FACTORS-ALCOHOL/DRUGS/FAT/VIRUSES/OBSTRUCTION/TOXINS

ACUTE INFLAMMATION—ACUTE HEPATITIS IF PERSISTS LONG CHRONIC INFLAMMATION- CHRONIC LIVER DISEASE PRESISTEN SLOW INCREASED LEVEL OF CYTOKINES-TNF-alpha PROGRESSIVE DEPOSITION OF FIBROUS TISSUE REPLACING

NORMAL HEPATOCYTES--- BEYOUND LIMITATION---BECOMES

IRREVERSIBLE---MILD/MODERATE/ SEVERE FORM OF END STAGE OF Chronic liver disease.

APPERANCE OF VARYING DEGREE OF COMPLICATION

COMPLICATIONS OF CIRRHOSIS

• PORTAL HYPERTENSION- esophageal varices• Ascites-• Hepatic encephalopathy- hepatic coma-death• Bleeding disorders-• Cirrhotic patients with ascites are at risk

of spontaneous bacterial peritonitis• Hepato-cellular carcinoma

DRUGS CONTRAINDICATED IN CIRRHOSIS

• NSAIDS- hepato-renal failure/ bleeding disorders• ACE inhibitors- Hepato-renal failure• Codiene- Hepatic encephalopathy• Narcotics-hepatic encephalopathy• Anxiolytics and sedatives- hepatic encephalopathy• Diuretics-HTZ, frusemide- ( hypokalemia)

presentation

• Patient presents –at late stage or with complication- like Ascites, varices, H/E,

• Severe jaundice, fatigue, edema, bleeding disorders• Wt. loss or wt. gained by edema and ascites• Alter sensorium and inverted sleep pattern• Severe anemia due to malnutrition and

bleeding( variceal, GI,epistaxis ,gum bleeding)• With history of chronic alcoholism or HEPATITIS-

B/C

Clinical findings on examination

• Inspection- ecterus, pallor, edema, echymosis, loss of axillary /genital hair, spider nevi ,gynaecomastia,drowzy, distention of abdomen, Palmar erythema,testicular atrophy. Fetor hepaticus is a musty breath odor. Caput medusa are dilated periumbilical collateral vein

• Palpation- liver may be enlarged/ shrinked, acites, splenomegaly, pitting edema,clubbibg

• Percussion- impaired liver dullness.shifting dullness• Ascultation of lung and heart- features of effusion and

severe anemia may be noted

investigation

• LFT(bilirubin, alanine transaminase, alkaline phosphatase, albumin, total protein)

• CBC, platelets• Na+, K ,Urea/creatinine• Coagulation profile-BT,CT PT , • USG/ CT- abdomen• Asctic fluid analysis,• Liver biopsy to confirm –cirrhosis• Endoscopy to see varices

Goal of management

• To prevent further liver damage• To prevent and treat complication

Management of cirrhosis

• Collection of reports and analysis- mark –severity of disease• Counseling – about the disease and treatment plan• Explain- nature of disease and prognosisAdvice for general management. If alcoholic –stop alcohol If drug induced- stop hepatic- toxics drugs High energy and low protein diet Adequate rest vitamin supplement- Decrease constipation- lactulose/ antacids

Management of complications

• Spironolactone – decrease ascites and edema• Peritoneal tapping if huge ascites –embarrassing to respiration• drugs for- portal hypertension- b-blockers-propanolol• To prevent- hepatic encephalopathy- lactulose , potassium

supplement, avoid infection( anti-biotics- metron/cipro) and avoid surgery, avoid hypocalemia.avoid high protien diet.

• Vitamin –k supplement 10 –mg im for 3 days if PT very high• Treatment of severe hypo-protienemia- albumin transfusion

( expensive)• Active esophageal varices- endoscopic banding/sclerotherapy

Management of disease process

• To slow down the fibrosis process-anti-TNF-alpha- pentoxyphyline-

• If cause is viral- anti-viral therapy( lamuvudine , ribavarin )

• Liver transplantation- last resort

prevention

• AVOID ALCOHOL-if taking- screening-if fatty liver, alcoholic hepatitis- treat them.

• Decrease- obesity- regular f/u- fatty liver-• HBV/BCV-screening- regular follow up-appropriate

treatment with antiviral-• LFT/ USG-screening- if find fatty liver-CLD- treat early• Avoid – hepato-toxic drugs.• If found-CLD- treat early with- anti-tnf-alpha and balance

diet-to slow down end stage.• If found late stage-start preventive measure for

complications

Future drugs/ treatment of cirrhosis

• Detection of Sub-clinical –fibrosis of liver-down regulation of spf. microRNA.( BIOMARKER)

• The study showed that serum magnesium levels were decreased in all cases of liver cirrhosis.

• Ref- Serum magnesium level in patients with liver cirrhosis• Authors:Biswajit Das , Prasanna Chandra , K.V. Thimmaraju

Int J Biol Med Res. 2011; 2(3): 709-711

• Magnesium supplementation- to slow down the fibrosis• Logics are- decreased- MAG. In chronic alcohol takings persons.• Viruses uses –intracellular magnesium of host cells- to activate viral enzymes like-RT, POLYMERASE,

PROTEASE, INTEGRASE-they all are magnesium dependent enzymes- net causing intracellular as well as ell extracellular – chronic- hypomagnesaemia- chronic-inflammation-more hepatic -cell- damage –accumulation of fibrous tissue.

• Others – may be- stem cell implantation-to generate new normal hepatocytes. (Recent animal studies suggest that bone marrow stem cell transplantation can lead to regression of liver fibrosis ) .so Stem cell therapy may be a poten tial alternative to liver transplantation.

• Ref- Phase 1 Trial of Autologous Bone Marrow Mesenchymal Stem Cell Transplantation in Patients with Decompensated Liver Cirrhosis.Mehdi Mohamadnejad MD*, Kamran Alimoghaddam MD**, Mandana Mohyeddin-Bonab PhD**, Mohamad Bagheri MD*, Maryam Bashtar BA**,

• MD• Authors’ affiliations: *Digestive Disease Research Center, **Hematology, Oncology, BMT Research Center, Medical Sciences/ Tehran University, †Department of Stem Cells, Royan Institute, Tehran, Iran.

Rx of fibrosis

• antioxidants such as • vitamin E, • silymarin, • phosphatidylcholine, and• S-adenosyl-L-methionine inhibit HSC( hepatic stellate cells) activation, protect

hepatocytes from undergoing apoptosis,-ACE-inhibitors-N-acetyle cystein-magnesium supplement

HEPATIC FAILUREjaundice--encephalopathy

• Acute hepatic failure - hyper acute- occurs-in less than- 7days- virus/paracetamol -acute----8-28 days—cryptogenic/ drugs- sub-acute—29 days-12 weeks----cryptogenic / drugs

-features of hepatic- encephalopathy-lx- LFT/ RFT/ ABG/ VIRAL SEROLOGY/ TOXICOLOGY SCREEN/BT.CT PT

RX- IN-ICU, ACCODING TO UNDERLYING CAUSE.Complications-H/E,RENAL FAILURE,CEREBRAL EDEMA,MOF,

METABOLIC ACIDOSIS• CRHONIC LIVER FAILURE- the most important cause is –

cirrhosis- features of HE and Ascites -seen