This document discusses complications of cirrhosis and their management. It covers portal hypertension, ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, and hepatic encephalopathy. Portal hypertension is caused by increased intrahepatic resistance and portal venous flow, and can lead to variceal bleeding and ascites. Ascites is treated initially with diuretics and sodium restriction. Refractory ascites may require repeated large volume paracentesis. Hepatorenal syndrome involves renal dysfunction due to reduced renal perfusion and should be treated aggressively with vasoconstrictors and albumin. Spontaneous bacterial peritonitis involves infection of ascitic fluid and is diagnosed by ascitic fluid analysis.

1. COMPLICATIONS OF
CHIRROSIS AND
MANAGEMENT

2. CONTENT -
1. INTRODUCTION
2. PORTAL HYPERTENSION
3. ASCITIS
4. HEPATORENAL SYNDROME
5. SPONTANEOUS BACTERIAL PERITONITIS
6. HEPATIC ENCHEPHALOPATHY
7. HEPATOPULMONARY SYNDROME

3. INTRODUCTION -
• Cirrhosis is a condition defined histopathologically as development of fibrosis to a
point that there is architectural distortion with formation of regenerative
nodules.
• Natural history of cirrhosis includes a silent asymptomatic phase called as
compensated phase.
• But over time, due to increasing portal pressure and decreasing liver function,
this compensated phase turns into decompensated phase, which is characterised
by development of complications- variceal hemorrhage, Ascites (most common),
encephalopathy, HRS .
• Patients who have developed decompensated cirrhosis should be considered for
liver transplantation.
• This is because in all patients of cirrhosis median survival time is 9years
• But with decompensated cirrhosis it is 1.6 years

4. PORTAL HYPERTENSION :-
• Def- elevation of hepatic venous pressure gradient (HVPG) to >5mm hg.
• Pathogenesis- it is caused by two simultaneously occuring mechanisms
• A) increased intrahepatic resistance –due to regenrative nodules, fibrotic
bands
• B) increased portal venous flow- due to splanchnic vasodilation
• Portal hypertension is directly responsible for 2 major complications of
cirrhosis
• - variceal bleeding
• - ascites

5. Anatomy of portal vein
• Portal vein is a 5.5- 8cm long vein formed by union of superior mesenteric vein
and splenic vein, behind the head of pancreas at about the level of l2 vertebra.
Approximately 2/3rd of hepatic blood flow and ½ of the o2 supply of liver are by
portal vein.
• Normal pressure in the portal vein is 7-10 mmHG or 10-15 mm of normal saline.

6. PATHOPHYSIOLOGY OF PORTAL HYPERTENSION

7. CAUSES

8. Presentation
of Portal
hypertension
• 1) Splenomegaly
• 2) Ascites (in cirrhosis->hypo albuminemic
ascites ;in portal hypertension -> due to
increased hydrostatic pressure)
• 3) portosystemic anastamosis
• i)Varices
• ii)Internal hemorrhoids
• iii) Caput medusae
• iv) Retroperitoneal vein of retzius

9. SITES OF POSTOCAVAL ANASTAMOSIS :-
Site Caval Portal Effect in PHT
Lower end of
esophagus
Esophagal tributries
of hemiazygous vein
Esophagal tributries
of left gastric vein
Esophageal varices
Umbilicus Veins of anterior
abdominal wall
Paraumbilical veins
tributries of left bran
ch of portal vein)
Caput medusa
Lower end of rectum
and anal canal
Middle and inf rectal
veins
Sup rectal veins
Anorectal varices
Internal hemorrhoids

10. VARICEAL
BLEEDING -
• GI bleed in cirrhotics can be due to
1. Esophageal varices
2. Gastric varices
3. Portal hypertensive gastropathy
• Normal portal pressure – 5-10 mmhg
• Portal hypertension >10 mmhg
• Varices form >12mmhg
• Varices rupture and bleed >20 mmhg

11. Esophageal
varices
• Are found in 40% cirrhotics
• Predictors of bleed include-
1. Variceal size>5 mm
2. Hvpg >12mmhg
3. Presence of hepatic cell failure-Child pugh class b
or c
4. Presense of red signs - Red wale sign, hemocystic
spots, diffuse erythema, cherry red spots
3 groups of management
1. Emergency treatment
2. Prophylaxis
3. Defintive

12. Primary
prevention
Pharmacological - Non selective beta
blockers
Isosorbide mono nitrate
Endosopically - Endoscopic variceal ligation
Scleropathy
 NSBB/EVL IS RECOMMENDED FOR
PRIMARY PREVENTION OF MEDIUM OR
LARGE VARICES. COMBINATION IS NOT
RECOMMENDED.
 IF NO VARICES OR SMALL VARICES WITH
NO RED FLAG SIGNS- REPEAT ENDOSCOPY
2ND YEARLY

14. BETA BLOCKER – NSBB / CARVEDILOL
• B1 ANTAGONISM- REDUCES CARDIAC OUTPUT
• B2 ANTAGONISM- SPLANCHNIC VASOCONSTRICTION
• CARVEDILOL BLOCKS B1, B2, A1 TOO. SO IS USEFUL FOR HTN+
VARICES

15. MANAGEMENT OF ACUTE GI BLEED
• RESUSCITATION:
• RESTORE BLOOD VOLUME: CRYSTALLOID INFUSION TO MAINTAIN SBP >90 MMHG.
• PACKED CELL TRANSFUSION TO ACHIEVE HB 8 GM%.
Restrictive strategy(that is <7gm%) .
liberal blood tranfusion strategy(that is <9g%)(because liberal trasnfusion increases
portal pressure and twice as much rebleeding)
• - CORRECT COAGULOPATHY: VITAMIN K, FFP, PLATELET TRANSFUSION
• - ANTIBIOTIC PROPHYLAXIS: 1) INJ CEFTRIAXONE IV 1G /24 HOURS FOR 7 DAY
• 2) TAB NORFLOX BD FOR 7 DAYS
• - PREVENTION OF ENCEPHALOPATHY: LACTULOSE ENEMA

16. CONTROL THE BLEEDING -
COMBINATION OF VASOACTIVE AGENTS AND EVL IS THE GOLD STANDARD FOR CONTROLLING
ACUTE GI BLEED

17. ENDOSCOPIC
VARICEAL
LIGATION
NDOSCOPIC
VARICEAL
LIGATION
• As soon as patient is stabilized, endoscopy to
be performed preferably within 12 hours.
• Once the varices are identified, band ligation
is done
• Bleeding controlled with combo therapy is
90%.
• Rebleeding rate is 30%
• If the first attempt fails, perform 2nd evl
• If it fails- TIPS
• There is risk of post banding ulcer, so PPI till
next session of endoscopy

18. TIPS-TRANSJUGULAR INTRA HEPATIC PORTOSYSTEMIC SHUNT
• It is a shunt within the liver that establishes a communication between
hepatic and portal vein.
• It is a temporary procedure to buy time for further procedures like
transplant.
• Indications-
 intractable bleeding varices
-child class c disease
- refractory ascitis, HRS
• Procedure – access to liver is gained by passing guidewire through IJV-SVC-
IVC- hepatic vein
• Once the catheter is within the hepatic vein, a needle is advanced through
the liver parenchyma into portal vein to create a tract and the tract is
dilated
• A self expanding metal stent, covered by polytetrafluroehtylate is placed
through the tract

20. COMPLICATIONS OF TIPS
TIMING OF COMPLICATION COMPLICATION
• PROCEDURE RELATED(LIFE CAROTID ARTERY PUNCTURE
THREATENING) INTRAPERITONEAL BLEEDING
• EARLY POST PROCEDURE(1-30 DAYS) HEMATOMA AT PUNCTURE SITE
HEPATIC ENCEPHALOPATHY
SHUNT THROMBOSIS(WITHIN 24HOURS)
STENT MIGRATION
• LATE POSTPROCEDURE(>30 DAYS) HEPATIC ENCEPHALOPATHY
SHUNT STENOSIS
PROGRESSIVE LATE HEPATIC FAILURE

22. SECONDARY
PROPHYLAXIS
OF GI BLEED
• Combination of NSBB+EVL is first-line
therapy in the prevention of rebleeding.
• Patients who have a TIPS placed successfully
during the acute episode do not require
NSBBs or EVL.
• TIPS is the recommended rescue therapy in
patients who experience recurrent
haemorrhage despite combination therapy
NSBB+EVL

23. Gastric varices(ectopic varices)
• SARIN CLASSIFICATION-
• 1) Gastroesophageal varices –
A. Type 1: extend 2to 5 cm below GE junction
B. Type 2: in cardia and fundus of stomach
• 2) Isolated gastric varices:
• Type 1- fundus of stomach
• Type 2- body, antrum, pylorus
• Seen in upto a one-third of patients with cirrhosis.
• Risk of bleeding is 25% over 2 years. Highest risk is for fundal varices

24. • Primary prevention- beta blockers
• Secondary prevention- endoscopic
injections of cyanoacrylate in 2 to 3
sessions
• For igv2 type, splenectomy is also
indicated in case of splenic vein
thrombosis which is the most
common cause for it

25. Portal
hypertensive
gastropathy
• Refers to gastric mucosal changes that occur
in patients of portal HTN
• Has characteristic mosaic pattern on
endoscopy
• It has risk of chronic bleeding leading to
anemia.
• It is seen in 80% of cirrhosis patients
• Treatment includes NSBB+iron supplements
• If bleeding persists-
Patient is transfusion dependant- TIPS
Not transfusion dependant- continue with
beta blockers and iron, transfusion sos

26. Siguira/
hassab
surgery
• When all management procedures fail, then
devascularization and transection
• It includes esophageal transaction and
reanastamosis, truncal vagotomy with either
thoracoabdominal or transabominal
portoazygous devasularization of upper half of
stomach and lower 1/3 of esophagus. Highly
effective in controlling active hemorrhage
• If the patient is going for liver transplant
• Within 1 year- TIPS
• >1 year- Siguira

27. Definitve
surgeries:-
Shunt surgeries-
• 1)total shunt- end to side portocaval shunt, side
to side porto caval shunt
• 2) partial shunt – portocaval H graft, mesentrico
caval H graft
Selective shunt – is done nowadays in which varices
are separated from portal system
• Steps-
• 1)ligate and cut splenic vein
• 2) take splenic vein and anastamose to renal vein.
Known as distal spleno renal shunt(DSRS)(Warren
shunt)
• 3) ligate and cut left gastric vein

29. ASCITIS -
• Ascitis is the most common decompensating
event in cirrhosis(58%)
• Ascitis can be of two types – uncomplicated
and refractory ascitis
• Management of uncomplicated ascitis-
• 3 grades-
 grade 1 – minimal ascitis,(signs absent)
detected by USG
 grade 2- moderate ascitis(signs present, no
resp distress)
 grade 3- massive ascitis(respiratory distress
+)

30. Grade 1 and 2
uncomplicated
ascitis
• A)salt restriction- 4.6 grams per day
- VERY low sodium diet leads to diuretic
induced renal failure
• B) diuretics- spironolactone start with
100mg/day
- If no response increase by 100mg/ day
every 3rd day to max of 400mg /day
- If poor response add furosemide 40 mg/
day to max 160mg/day

31. Grade 3
uncomplicated
ascitis
• Treatment of choice-
 large volume paracentesis with albumin infusion.
8 grams of albumin per liter of ascitic fluid
removed
Paracentesis should be followed by diuretics
• Refractory ascitis management-(if no response
even after >7 days of max doses of both diuretics)
• Repeated large volume paracentesis with albumin
infusion every 2 to 4 weeks,followed by salt
restricted diet and diuretics.
• If lvp is more than 2 per month, - TIPS, after which
continue diuretics and salt restricted diet, consider
for liver transplantation

32. HEPATORENAL SYNDROME :-
• HRS has been defined as renal dysfunction that occurs because of
reduced renal perfusion, due to haemodynamic alterations in arterial
circulation, as well as overactivity of the endogenous vasoactive
systems.

34. TREATMENT
• The management of AKI should be started
immediately once a diagnosis has been
made and the cause of AKI identified.
• In patients taking diuretics and/or
b-blockers these should be discontinued.
• In addition, drugs that could be associated
with AKI such as vasodilators, non-steroidal
antiinflammatory drugs and other
nephrotoxic drugs should be immediately
stopped.
• Volume replacement should be used in
accordance with the cause and severity of
fluid losses.

35. • VASOCONSTRICTORS -
Terlipressin , Noradrenaline ,midodrine plus octreitide are used.
• Terlipressin -
- As intravenous boluses - starting from 0.5–1 mg every 4–6 h to
a maximum dose of 2 mg every 4 h.
-As continuous intravenous infusions - starting from 2 mg/day to
maximum dose of 12 mg/day .
• Side effects (mainly by continuous infusion ) which include persistent
diarrhea, abdominal ischemia, peripheral ischemia, angina pectoris,and
circulatory overload .

36. • VOLUME EXPANDERS – ALBUMIN
• Albumin is given 20-40 g per day .
• Monitor for overload .
• Best treatment for HRS - TERLIPRESSIN PLUS ALBUMIN .
• The treatment with vasoconstrictors plus albumin should be
continued until s Cr reaches a final value within 0.3 mg of the
patient’s baseline Creatinine.
• In patients with no response or partial response, the treatment
should be discontinued within 14 days.

37. SPONTANEOUS BACTERIAL PERITONITIS
• Spontaneous bacterial peritonitis (SBP) is the infection of ascitic fluid in the
absence of any intra-abdominal, surgically treatable source of infection .
• Bacterial translocation is the ‘‘passage’’ of bacteria from the lumen to the
mesenteric lymph nodes and thereafter to the blood stream and other extra-
intestinal sites.
• More recently detection of translocation of bacterial products, LPS from Gram-
negative bacteria and peptidoglycans/lipopeptides from Gram-positive bacteria
together with bacterial DNA, through the intestinal wall has been associated with
production of many cytokines.
• High levels of TNFa, IL-6 and IL-1 in patients with cirrhosis cause over-activation
of the sepsis syndrome pathways, leading eventually to renal failure and shock
with reduced chances for survival.

38. • The microorganisms more commonly isolated from cases of SBP are
Escherichia coli -(70%), Klebsiella species (,10%), Proteus species,
Enterococcus faecalis (,4% each), Pseudomonas species (,2%) and
others (,6%).
• Approximately half the episodes of SBP are present at the time of
hospital admission and the remainder are acquired during
hospitalization .
• The most common symptoms and signs in patients with SBP are
pyrexia, increased confusion, diffuse abdominal pain, vomiting and
reduced urine output .

39. Diagnosis of SBP :
• Diagnostic paracentesis in cirrhotics with ascites:
At hospital admission if patients develop any of the following:
1. Local signs of peritonitis -pain, vomiting, diarrhea, ileus) .
2. Systemic signs of infection - fever, leukocytosis, septic shock).
3. Hepatic encephalopathy without any clear precipitating factor
4. Rapid renal function impairment without an apparent cause Prior to antibiotic
prophylaxis, if gastrointestinal bleeding .
• Diagnosis of SBP based on ascitic fluid PMN count >250/mm3; in patients with
bloody ascites: substract 1 PMN per 250 RBC .
• Cultures: Blood cultures and ascitic fluid cultures .

40. SBP Varients -
• Culture negative neutrocytic ascites (CNNA) - The ascitic PMNL count is >250/mm3
but cultures fail to grow any bacteria. It is considered to represent the expected 20%
fail rate of culture to isolate the microorganism and it requires antibiotic treatment as
if it were SBP.
• Bacterascites: positive ascitic fluid culture, ascites PMN <250/mm3, and no evidence
of local or systemic infection.
• Once bacterascites is diagnosed, repeat paracentesis; if:
+ Ascites PMN >250/mm3 - initiate antibiotic treatment
+ Ascites PMN <250/mm3, but culture continues to be positive:
initiate antibiotic treatment .
+ Ascites PMN <250/mm3 and negative culture: bacterascites is resolved,
no more action is required
+ In patients with positive ascitic fluid culture, ascites PMN <250/mm3
and evidence of local or systemic infection: initiate antibiotic treatment

41. • Secondary peritonitis:
Suspected when any of the following:
1. Lack of response to antibiotic treatment.
2. Two or more organisms isolated (particularly anaerobes or fungi) .
3. At least two of the following findings in ascitic fluid: Glucose <50 mg/dl
Protein > 10 g/.
4. Lactic dehydrogenase >normal serum levels
Once secondary peritonitis is suspected: Initiate appropriate radiological
investigation , Add antibiotics against anaerobes and enterococci .

42. TREATMENT -
• Recommendations on treatment of SBP Recommendation
• 1. Antibiotic therapy must be empirically initiated in patients with ascitic fluid
PMN count >250/mm3
• 2. Recommended antibiotics for initial empirical therapy: Cefotaxime; minimum
dose 2 g/12 h, minimum duration 5 days Other: ceftriaxone, ceftazidime,
amoxicillin-clavulanic acid; standard dosage
• In patients with uncomplicated SBP and not under quinolone prophylaxis: oral
ofloxacin is another option
• In patients under quinolone prophylaxis: cefotaxime
• In patients with beta-lactam hypersensitivity: quinolones
• Aminoglycosides should be avoided
• Nasocomical SBP – MEROPENEM

43. Assessment of response to antibiotic therapy:
Periodical clinical evaluation and, at least, one follow-up paracentesis (i.e. after 2
days of antibiotic therapy) to determine ascitic fluid PMN count
Treatment failure when one of the following:
Deterioration of clinical condition within the first hours of antibiotic therapy
Less than 25% decrease in ascitic fluid PMN in follow-up paracentesis as compared
to pre-treatment value.
If treatment failure:
Modify antibiotic therapy according to in vitro susceptibility of isolated organisms
or empirically
Consider the possibility of secondary peritonitis .

45. • Recommendation on prophylaxis of SBP-
• In cirrhotics with upper gastrointestinal hemorrhage:
1. Oral administration of norfloxacin,400 mg/12 h,over a minimum
period of 7 days.
2 .Alternative regimes: combinations of systemic antibiotics
(ciprofloxacin, ofloxacin, amoxicillin-clavulanic acid) .
3. Exclusion of SBP and other infections before starting prophylaxis.
• In non-bleeding cirrhotic patients with ascites:
1. In patients recovering from an SBP episode:
Continuous oral administration of norfloxacin, 400 mg/day.
Consider liver transplantation .
2. In patients without past history of SBP and with:
High ascitic fluid protein (i.e. > 10 g/l): prophylaxis unnecessary
Low ascitic fluid protein (i.e.<10 g/l): no consensus on the necessity
of prophylaxis

47. HEPATIC ENCEPHALOPATHY -
• Hepatic encephalopathy is a brain dysfunction caused by liver insufficiency
and/or PSS, it manifests as a wide spectrum of neurological or psychiatric
abnormalities ranging from subclinical alterations to coma.
• Classification
• Hepatic encephalopathy should be classified
• 1. According to the underlying disease :
Type A resulting from ALF
Type B resulting predominantly from portosystemic bypass or shunting
Type C resulting from cirrhosis

48. 2.According to its time course :
• Episodic HE
• Recurrent HE denotes bouts of HE that occur with a time interval of 6 months or
less.
• Persistent HE denotes a pattern of behavioral alterations that are always present
and interspersed with relapses of overt HE.
3.According to the existence of precipitating factors :
• HE is subdivided into
• Nonprecipitated
• Precipitated

49. GRADING :-

50. TREATMENT :
• Nonabsorbable Disaccharides -
• Lactulose is generally used as initial treatment for HE.
• Prebiotic effect and acidifying nature of lactulose have an additional
benefit beyond the laxative effect.
• DOSE :-25 mL of lactulose syrup every 1- 2 hours until at least two
soft or loose bowel movements per day are produced .
• COMPLICATIONS - aspiration, dehydration, hypernatremia,and severe
perianal skin irritation, and overuse can even precipitate HE.
• RIFAXIMIN- DOSE :- 550MG BD .
• L-ornithine L-aspartate (LOLA).
• Low protein diet.

51. HEPATOPULMONARY SYNDROME -
• Definition
• HPS is a disease process with a triad of:
1. Liver disease / Portal hypertension.
2. Widespread intrapulmonary vasodilatation.
3. Gas exchange abnormality presenting with increased alveolar
arterial oxygen gradient (∆P (A-a)O2) while breathing room air, that
results ultimately in hypoxemia.

52. PATHOPHYSIOLOGY -
• Imbalance of vasodilator and vasoconstrictor agents favoring vasodilators.
• This could be due to
1. Overproduction of the vasodilators from injured hepatobiliary system,
Decrease in their clearance by the liver,
2. Production of a vasoconstrictor inhibitor
3. Normal sensitivity of the pulmonary vessels to vasoconstrictors in response to
hypoxemia is blunted in HPS.
• NITRIC OXIDE PLAYS A MAJOR ROLE IN VASODILATION .
• The main pathophysiologic event underlying hypoxemia is widespread
pulmonary precapillary and capillary vasodilatation.
• CLINICAL MANIFESTATIONS :- Cirrhosis , Cyanosis , Clubbing

53. TREATMENT -
• Oxygen supplementation .
• Embolization of the dilated blood vessels .
• Liver transplantation .
• Medical management - (tried )
• Indomethacin : To cause inhibition of prostaglandin production which
has a putative role of vasodilatation.
• Methylene blue: Is a potent inhibitor of NO and its intracellular
mediator, gunaylate cyclase and is potentially effective for treatment
of HPS although transiently.

54. THANK YOU . . .