CLD NON HEP B,C

1. CASE PRESENTATION
DR ALOK DHUNGEL
PGR (WMW)

2. PATIENT PROFILE
• Name: Zubaida Rafique
• Age: 48 years
• Sex: Female
• Marital status: married, house wife
• Address: Samnabad, Lahore
• History obtained from patient daughter
• Admitted from emergency department

3. CHIEF COMPLAINTS
• Yellowish discoloration of skin and sclera for last
four months
• Abdominal distension for last 1 months
• Constipation for last 4 days
• Per rectal bleeding for last 3 days
• Altered sensorium for last 1 day

4. HISTORY OF PRESENTING ILLNESS
• My patient was usual state of health 4 month back when
she noticed yellowish discoloration of sclera which was
gradual in onset, first appeared in sclera and then
progessed to face and then to whole body.
• Patient took medication from the local hospital after which
her yellow discoloration of body improved over next one
month but didn’t completely disappeared.Patient also took
hakeem medications for 2 weeks but wasn’t improved and
she quited hakeem medication

5. HOPI
• Jaundice was associated with anorexia, nausea,
malaise, lethargy and generalized body weakness.
Patient also complains of dark color urine and pale
stool .
• There is no history of fever, weight loss,lumps and
bumps in the body chronic abdominal pain,
arthalgia ,rash, pigmentation, bluish discolation of
hands ,recurrent abortions, acne, photosensitivity,
amenorrhea,early morning dark color urine or DVT,
drug/alcohol intake, or pruritis preceding or
following jaundice,blood transfusion or travel
abroad.

6. CONTD
• She also complained of abdominal distension for last
one month which was of gradual onset and progressive
in nature. Initially there was fullness of flank which
gradually progressed to whole abdomen and then to
the lower limbs. It was not associated with abdominal
pain, steatorhhea ,diarrhoea alternating with
constipation or fever.
• There is no history of orthopnea, PND, breathlessness
on exertion, arthralgias, rash or easy
bruisibility,frothing of urine,pluirisy.
•
• There is no history of dyspepsia.

7. CONTD
• She then developed constipation 4 days prior to
presentation but there is no history of hemetemesis
and malena.
• There is history of painless bleeding per rectum
which was fresh, 50-60 ml in amount, 3-4 episodes
per day for last three day.
• She developed altered state of consciousness which
was gradual. Patient initially became confuse,
drowsy and was not easily arousable.

8. SYSTEMIC INQUIRY
• No history of chronic headache,migraine, fits,
visual disturbances, blackouts, abnormal behavior,
psychosis, numbness or tingling sensations.
• No history of exertional dyspnoea, chest pain, body
swelling, orthopnea, PND, peripheral vascular
disease.
• No history of cough ,dyspnoea, orthodexia,
pleurisy, wheezing or nasal discharge
• There is no history of dysuria, urgency, hesitancy
and no history of polyuria or hematuria or renal
colic or genitourinary ulcers

9. PAST HISTORY
• She is a known hypertensive for last 5 years and
was non compliant to medicaton.
• She had prior history of IHD(ACS) 2 yrs back
and left medication by herself after taking it for
just 6 months.
• Diabetic for last 1 year and was taking
sulphonylurea (Diamicron).
• s/p cholecystectomy 1 yrs back
• There is no history of Tuberculosis

10. MENSTRUATION HISTORY
• Patient had regular menstrual cycle…
• She had menopause 2 yrs back

11. TREATMENT HISTORY
• She was under treatment for hypertension
,ischemic heart disease and diabetes but she was
not taking her medications regularly
• She was taking treatment for jaundice for last 3-
4 mth (vitamins ,hepamerz and risek)

12. FAMILY HISTORY
• No history of similar illness in her family
• Her father had ischemic heart disease ..he died
of stroke at the age of sixty.

13. PERSONAL HISTORY
• Widow with three children (one son and two
daughter)
• House wife

14. Drug history
• No known allergy to any drugs

15. Summary of hx
• 48 years female
• Jaundice for last 4 mth
• Abdominal distension for last 1 mth
• Constipation for 4-5 days
• Lower GI bleeding 3-4 days
• Asoc for one day
• History of lethargy,fatigue,malaise ,nausea, anorexia
and generalized body weakness
• Weight loss
• No history of orthopnea,PND,frothing of
urine,hematuria or any chronic chest illness
• history of Diabetes ,HTN ,ACS

16. Differential diagnosis after History
• Acute on chronic Decompensated Liver disease with portal hypertension
• Primary biliary cirrhosis
• Venoocclusive disease(budd-chiari syndrome)
• abdominal malignancy(CA head of pancreas ,lymphoma,HCC)
• Non alcohalic fatty liver disease progressing to cirrhosis
• Hemochromatosis
• Primary sclerosing cholangitis

17. Clinical examinations
General physical examination
• A middle aged lady lying on bed having
branula on left arm ,nasogastric tube and foleys
in situ and not oriented to TPP with following
vitals:
• Pulse-68/minute regular
• BP-100/60
• T-Afebrile
• RR-20/min

18. • Pallor+
• Icterus+++
• Pedal Edema+
• Lymhadenopathy -
• Cyanosis-
• Bruises –
• palmer erythema -
• Spider naevi -
• Duputyen’s contracture-
• Parotid enlargement
• Loss of body hair –
• JVP not raised
• Rash –
• Xanthalesma and xanthomas-
• Pigmentations-
• Shiny nails-
• Scratch marks -

19. Systemic examination
• Abdominal Examination-
• Inspection- abdomen was distended, moving with
repiration, peristalsis is not visible, umbilicus
central and horizontally slit, no scar, stria or
prominent veins. Hernial orifices intact.
• Palpation- No rigidity or tenderness. Spleen is
palpable 1 finger below the left costal margin. Liver
not palpable
• Percussion- Shifting dullness present but fluid
thrill abscent
• Ausultation- Bowel sounds 3 per minute of normal
intensity,no audible bruits or rubs

20. Systemic examination
• CHEST- Abdomino thoracic respiration, equal expansion,
trachea central. Normo vesicular breath sounds bilaterally
with no added sounds heard
• CVS: Apex beat in fifth intercostal space in mid clavicular
line
• 1st and 2nd heart sound heard with normal intensity and
character.
• No added sounds or murmur heard
• CNS EXAMINATION:GCS E3V3M4 10/15……..No motor n
sensory abnormality

21. Per rectal Examination, proctoscopy
• 2° Haemorrhoids were present at 3,9,11 O clock
position

22. HISTORY IN SHORT
ON HISTORY ON EXAMINATIONS
• 48 years female
• Jaundice for last 4 mth
• Abdominal distension for last 1 mth
• Constipation for 4-5 days
• Lower GI bleeding 3-4 days
• Asoc for one day
• Nasal bleeding for last 2-3 days
• History of lethargy malaise fatigue
and generalized body weakness
,nausea, anorexia
• Weight loss
• Cholecystectomy
• history of Diabetes ,HTN ,IHD
• Pallor
• Icterus
• Edema
• Ascites
• Hemorrhoids
• Splenomegaly

23. Differentials after HX and PE
• Acute on chronic Decompensated Liver disease
with portal hypertension
• Primary biliary cirrhosis
• Venoocclusive disease(budd-chiari syndrome)
• Hemochromatosis
• NAFLD progressing to cirrhosis
• Primary sclerosing cholangitis

24. Investigations
Cbc lfts
• WBC-5.5-- 5.7
• HB- 6.9--12
• Hct- 18--36.5
• MCV- 74-- 82
• MCH- 27--27
• MCHC-37--33
• Plt- 114—101
• ESR-120(outside)
• Bil- 3.6—15.2
• Conjugated 9.3
• Uncon- 5.9
• ALT- 111-155
• AST-92-122
• ALP-487-280
• Prot- 6.4
• Alb- 3.3

25. Rfts PT /APTT
• Urea-20--26
• Cret-1.0– 0.5
• Na-136--136
• K-4—3.5
• PT /CONTROL-12/13
• APTT/CONTROL-32/33

26. ECG Chest xray
• NORMAL • NORMAL

27. Urine RME Hepatitis profile
• COLOR- pale yellow
• Sp Gravity- 1.025
• Ph- 6.0
• Protein- +
• Blood +++
• Pus Cell 15-20
• Red Cell- 25-30
• Epithelial Cell 2-3
• Hepatitis B- Neg
• Hep C- Neg
• Hep A- Neg
• Hep E- Neg

28. Usg abdomen and pelvis AFP
• Liver 14 cm
• Texure slightly Coarse
• Portal Vein 17 cm
• CBD Normal
• GB- Absent
• Spleen 15 Cm
• Splenic Varices seen
• Ascites present (moderate )
• 13 ng/ml (Normal upto 15)

29. Antibody tests send Fundoscopy
• ANA-
• ASMA-
• AMA-
• GAMMA GT- IU/ml
• No papilloedema

30. Final diagnosis
• Acute on chronic Decompensated Liver disease
with portal hypertension with portosystemic
encephalopathy grade III ( child pugh-C)
??cause

31. Common cause of CLD
• Chronic viral infections(B and C)
• Chronic alcoh0lism
• Non alcoh0lic fatty liver disease
• Immunological(autoimmune liver disease and
primary sclerosing cholangitis)
• Biliary(PBC and cystic fibrosis)
• Genetic(wilson,hemochromatosis,alpha
antitrypsin deficiency)
• Budd chiari syndrome
• cryptogenic

32. Further work up
• Ascites fluid analysis
• CT abdomen with contrast/biphasic CT scan
• Usg doppler
• MRI
• Iron studies(serum iron ,TIBC and ferritin)
• Serum ceruloplasmin level,s copper level and urinary copper
• Alpha 1 antitrypsin level
• Immunoglobulin levels
• Anti thyroid antibodies level
• ENA profile
• Dexa scan
• Calcium phosphate ,vit d levels
• Fat soluble vitamins level
• Opthalmologic examinations
• Lipid profile

33. Primary biliary cirrhosis
• autoimmune disease
• antimitochondrial antibody (a highly disease-specific
autoantibody found in 90%-95%)
• Fewer than 5% of patients with PBC are AMA-negative.
• Present in 4th to 6th decades
• Involvement of the small intrahepatic bile ducts
• Female male ratio=9:1

34. pathophysiology
• The exact mechanism of the liver damage is unknown,
although evidence indicates that it can be of autoimmune
origin.
• The data supporting this hypothesis are as follows:
• (1) abnormalities of the humoral and cellular immune
systems (ie, elevated serum levels of immunoglobulins,
mainly immunoglobulin M [IgM]),
• (2) multiple circulating autoantibodies,
• (3) granulomas in the liver and regional lymph nodes,

35. Contd..
• (4) impaired regulation of both B and T
lymphocytes, and
• (5) the association of this disease with a variety of
autoimmune-mediated diseases (eg, autoimmune
thyroiditis; keratoconjunctivitis sicca; scleroderma;
calcinosis cutis, Raynaud phenomenon, esophageal
motility disorder, sclerodactyly, and telangiectasia
[CREST] syndrome).

36. Clinical presentations
• Of patients with primary biliary cirrhosis, 25% are
incidentally diagnosed during a routine blood
evaluation.
• Fatigue (65%) Fatigue is the first reported symptom.
It can cause disability in some patients and has been
associated with depression and obsessive-compulsive
behavior. The etiology is unknown;
however, a sleep abnormality, particularly excessive
daytime somnolence, has been identified in a
significant proportion of patients and has been
associated with the degree of fatigue.

37. • Pruritus (55%)According to estimates, 10% of patients
experience severe pruritus.
• The cause of this symptom is not known.
• Pruritus appears unrelated to the deposition of bile acids
in the skin.
• Increased opioidergic tone (ie, increased production of
endogenous opioid peptides, up-regulation of
endogenous opioid receptors) appears to be the major
mechanism. The height of the bilirubin level is
proportionally related to the production of these
peptides.
• Right upper quadrant discomfort occurs in 8-17% of
patients.

38. Physical findings
• Physical examination findings depend on the stage of the disease. In
the early stages, examination findings are normal. As the disease
advances, excoriations of the skin, xanthelasmata, or findings
of cirrhosis may be present.
• Hepatomegaly (25%)
• Hyperpigmentation (25%)
• Splenomegaly (15%)
• Jaundice (10%)
• Xanthelasmata (10%) - In late stages of the disease
• Sicca syndrome (50-75%) - Xerophthalmia (ie, dry eyes), xerostomia
(ie, dry mouth)
• Kayser-Fleischer rings (extremely rare)
• Stigmata of advanced liver disease (ie, cirrhosis), such as spider
nevi, palmar erythema, ascites, temporal and proximal muscle
wasting, and peripheral edema

39. Criteria for diagnosis
1. The diagnosis of PBC can be established when
two of the following three criteria are met:
• ● Biochemical evidence of cholestasis based
mainly on alkaline phosphatase elevation.
• ● Presence of AMA.
• ● Histologic evidence of nonsuppurative
destructive cholangitis and destruction of
interlobular bile ducts

40. ddx
• Autoimmune Hepatitis
• Biliary Obstruction
• Graft Versus Host Disease
• Primary Sclerosing Cholangitis
• Sarcoidosis

41. Antimitochondrial antibodies
• The hallmark of this disease is the presence of
antimitochondrial antibodies (AMAs) in the
sera.AMAs can be found in 90-95% of patients
with primary biliary cirrhosis, and they have a
specificity of 98% for this disease.
• These antibodies target different components,
mainly enzymes, in the mitochondria.
• The presence of anti-M2, anti-M4, anti-M8, and
anti-M9 has been associated with the severity of
primary biliary cirrhosis.

42. Lab investigations
• Lfts-cholestatic picture .increase gamma –GT,alkaline
phosphatase ,AST and ALT
• Lipid profile –high cholesterol ,TG and HDL
• Auto antibody profile- A)AMA type -2 ,most specific and
sensitive present in 90-95 %
• B)ANA-present in 15 -20 percent of the cases
• C)ASMA-present in 50%
• CBC- thrombocytopenia(indicates portal HTN)

43. Labs
• ESR- raised
• Calcium and vit-d levels-low
• PT/APTT – high in advanced disease
• Serum albumin-low
• Immunoglobulins-high esp IgM
• Serum bile acid level and ceruloplasmin level -
high

44. imaging
• Abdominal ultrasonography, computed tomography
(CT) scanning, or magnetic resonance imaging
(MRI) are important to exclude biliary obstruction.
• Once patients are cirrhotic, findings compatible
with portal hypertension (eg, nodular appearance of
the liver, splenomegaly, intra-abdominal varices,
ascites) can be observed.
• At this stage, follow-up imaging every 6 months with
abdominal ultrasonography is suggested for early
detection of hepatic malignancy.

45. treatment
• The goals of treatment are to slow the progression
rate of the disease and to alleviate the symptoms
(eg, pruritus, osteoporosis, sicca syndrome). Liver
transplantation appears to be the only life-saving
procedure.
• A.Ursodeoxycholic acid (UDCA) (13-15 mg per kg
per day) is the major medication used to slow the
progression of the disease. Patients with early
disease have clinical, biochemical, and histologic
improvement. Reports suggest that UDCA delays the
need for transplantation or delays death. The
efficacy of this medication in late stages (ie,
cirrhosis) is questionable..

46. Treatment continued
• B.Immunosuppressive agents inhibit immune reactions
that mediate the progression of the disease.
• Methotrexate: Results of various trials suggest
improvement in biochemical and histologic findings
after treatment.
• Corticosteroids may alleviate symptoms and improve
biochemical and histologic findings. Corticosteroid-induced
osteoporosis is of great concern. The dangers of
using bisphosphonates requires further study.[11]
• Cyclosporine has some therapeutic potential.
• Colchicine has been used to limited effect.

47. Treatment continued
• C.Antipruritic treatment
• Antihistamines are first-line agents to relieve
pruritus in early stages and are the first line of
medication for patients with mild-to-moderate
pruritus. Use caution in patients with cirrhosis
and signs of encephalopathy because
antihistamines can further depress brain
function.
• Cholestyramine (8-16 gm per day)and colestipol
are effective in sequestering bile salts in the
enteric lumen. A 1- to 4-day delay is expected
before the itching remits.

48. • Rifampin (150-300mg bd)can also be used, but
the precise mechanism of action is unclear .
Rifampin is used in patients whose conditions
are not responding to cholestyramine.
• Some evidence suggests that dronabinol
(Marinol) can be used to good effect.
• Ondansetron- 8mg tds
• Sertraline-25 mg -50mg hs
• Plasmapheresis has also been implemented for
patients with severe pruritus intractable to
medical treatment. Results have been good.

49. Surgical tx
• Liver transplantation

50. Follow up
• ● Liver tests every 3-6 months
• ● Thyroid status (TSH) annually
• ● Bone mineral densitometry every 2-4 years
• ● Vitamins A, D, K annually if bilirubin greater
than 2.0
• ● Upper endoscopy every 1-3 years if cirrhotic
• ● Ultrasound and alpha fetoprotein in patients
with known or suspected cirrhosis†

51. Associated autoimmune diseases
• Sicca syndromes 80%
• Systemic sclerosis 20%
• Coeliac disease
• Thyroid disease 20%
• Addison disease less than 5%
• Raynaud syndrome less than 5%
• SLE
• Mysthenia gravis
• vitiligo