NEWER UNDERSTANDING OF FIBROSIS OF LIVER AND MANAGEMENT

1. Cirrhosis of liver
(end stage liver disease)
CTGU- Dr. Rkdhaugoda

2. 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.

3. 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.

4. 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

5. Cirrhosis of liver
End stage of chronic liver disease
Progressive irreversible liver fibrosis .
Caused by various chronic liver diseases
Caused- anatomical and functional changes
resulting in- portal HTN, ASCITES, H/E
MALFUNFION OF LIVER, bleeding disorder

6. pathogenesis
Normal liver CLD- CIRRHOSIS- HEPATOCELLULAR -CA

7. Cirrhosis of liver

8. 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.

9. 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

10. 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

11. 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)

12. 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

13. 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

14. 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

15. Goal of management
• To prevent further liver damage
• To prevent and treat complication

16. Management of cirrhosis
• Collection of reports and analysis- mark –severity of disease
• Counseling – about the disease and treatment plan
• Explain- nature of disease and prognosis
Advice 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

17. 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

18. 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

19. 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

20. 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 potential 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.

21. 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

22. HEPATIC FAILURE
jaundice--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