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PRIMARY BILIARY CIRRHOSIS : A Report of Six Cases

Amarapurkar Deepak, Baijal R, Agal S, Kulshreshta P, Mehta N, Desai H G
Dept. of Gastroenterology, Bombay Hospital and Medical Research Centre, Jagjivanram Western Railway Hospital and Bhatia Hospital, Mumbai.

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Primary biliary cirrhosis (PBC) is a rare cause of chronic liver disease in India [1-4] in contrast to its prevalence in Western countries. We present 6 cases of this uncommon disease.

CASE 1

A 30-year-old woman presented with generalized itching for the 2 1/2 years, persistent jaundice for 2 years and weakness for 4 months. There was no associated urticarial rash, fever, abdominal pain, anorexia or vomiting. There was no past history of ingestion of oral contraceptive pills, drugs, alcohol or any chronic illness. The patient had three uneventful pregnancies with no complaints of jaundice or pruritus. None of the family members suffered from a similar illness.

Physical examination showed mild icterus and the liver was palpable 6 cm below the right costal margin with span of 15 cm. splenomegaly and ascites were not present.

Investigations : haemoglobin 10.4 g%, total leucocyte count 8100/cu.mm, polymorphs 57%, lymphocytes 43%, EST 40 mm after 1 hr. Prothrombin time (PT) : 15 seconds (control 14), serum bilirubin total 1.7 mg% (direct 1.3), SGPT 43 u/l, SGOT 38 u/l, alkaline phosphatase 731 u/l, albumin 4.6 g/dl, globulin 3.4 g/dl, cholesterol 467 mg%, GGT 169 u/l, serum protein electrophoresis (SPE) was normal. Antinuclear antibody (ANA) and antimitochondrial antibody (AMA) were positive while HBsAg, anti HCV, LE cell and antismooth muscle antibody (ASA) were all negative. AMA was estimated by ELISA.

Abdominal ultrasonography revealed a normal liver, gall bladder and biliary tree. Hepatobiliary scan was suggestive of diffuse hepatocellular disease. Oesophagogastroduodenoscopy (OGD) and sigmoidoscopy were normal. Endoscopic retrograde cholangiopancreatography was normal. Liver biopsy showed loss of lobular architecture, ductopenia, lymphocytic infiltration and fibrosis around the portal triad, central vein and hepatic lobules.

The diagnosis of PBC was made on the basis of clinical presentation, biochemical parameters suggestive of cholestasis, normal biliary tree on cholangiography, absence of viral markers, positive AMA and liver biopsy suggestive of PBC.

On starting ursodeoxycholic acid (UDCA) there was marked reduction in itching and her serum bilirubin and alkaline phosphatase levels also decreased. At 1 year of follow-up, patient was free of itching and her alkaline phosphatase dropped to 176 u/l. There is no evidence of decompensation also.

CASE 2

A 36-year-old woman presented with low-grade fever and generalised itching for 2 years and jaundice and ascites for 10 months. She had been treated for malaria, typhoid and was receiving antitubercular therapy for 7 months for suspected abdominal tuberculosis but with no improvement.

Physical examination revealed mild pallor, icterus and minimal pedal oedema. On abdominal examination the liver was palpable 5 cm below the right costal margin. Spleen was palpable 10 cm below the left costal margin and marked ascites was present.

Investigations : Haemoglobin 10 g%, total leucocyte count 3600/cu.mm, polymorphs 60%, lymphocytes 40%, ESR 35 mm after 1 hr. PT : 12.5 seconds (control 11.5), serum bilirubin total 2.2 mg% (direct (1.1)), SGPT 127 u/l, SGOT 172 u/l, alkaline phosphatase 736 u/l, albumin 3.6 g/dl, globulin 3.1 g/dl, LDH 344 u/l, GGT 265 u/l, SPE was normal. ANA and AMA were positive. HBsAg, anti HCV, anti HIV. Rheumatoid factor, LE cells and ASA were all negative. Ascitic fluid examination showed proteins 2 g/dl and normal cell count.

Abdominal ultrasonography revealed a nodular liver with coarse echotexture, splenomegaly and ascites with normal gall bladder and biliary tree. Liver scan showed a diffuse hepatic tracer uptake with splenomegaly but bone marrow was not visualized. OGD revealed grade III oesophageal varices. Histological features were consistent with the diagnosis of PBC. The patient was given UDCA and diuretics and showed improvement.

TABLE 1 Clinical features and biochemical investigations
No.	Age	Sex	Complaints	Duration	Associated illness	S.Bil. (mg%)	Alk. Phos (u/l)	GGT (u/l)
1.	30	F	Itching	2.5 yrs	Nil	1.7	731	169
			Jaundice	2 years
			Fatiguability	4 months
2.	36	F	Low grade fever	2 years	Nil	2.2	736	265
			Itching	2 years
			Jaundice	10 months
			Ascites	10 months
3.	42	F	Itching	4 months	Nil	2.3	720	380
			Anorexia	3 months
			Jaundice	3 months
4.	41	F	Itching	2.5 years	Hypothyroidism	2.3	347	246
			Jaundice	2 years	Psoriasis
5.	52	F	Itching	3 years	Nil	1.1	743	206
			Pedal oedema	1 month
			Haematemesis	1 day
6.	42	F	Itching	2 years	Hypothyroidism	3.4	4990	927
			Skin	2 years
			pigmentation	2 years
			Weight loss	5 days
			Jaundice

CASE 3

A 42-year-old woman presented with generalised itching for the past 4 months. She also had anorexia, weight loss and mild jaundice for the past 3 months. Physical examination showed mild icterus and the liver was palpable 4 cm below the right costal margin. The spleen was palpable 2 cm below the left costal margin and there was minimal ascites.

Investigations : Haemoglobin 9.8 g%, total leucocyte count 7900/cu.mm, polymorphs 55%, lymphocytes 45%, ESR 102 mm after 1 hr. PT : 11.5 seconds (control 11.5), serum bilirubin total 2.3 mg% (direct 1.3), SGOT 87 u/l, SGPT 139 u/l alkaline phosphatase 720 u/l, albumin 2.8 g/dl, globulin 5.2 g/dl, GGT 380 u/l, LDH 386 u/l, SPE showed hypergammaglobulinaemia with raised IgM levels. ANA and AMA were positive. HBsAg, anti HCV and ASA were all-negative. Abdominal ultrasonography revealed mild splenomegaly and ascites with normal gall bladder and biliary tree. Histological features were consistent with the diagnosis of PBC.

The patient was treated with UDCA and diuretics with improvement in itching and biochemical parameters.

CASE 4

A 41-year-old woman presented with generalised itching for 2 1/2 years. She also had 4 episodes of jaundice in the past 2 years each lasting for about 1 month. She was diagnosed to have hypothyroidism 2 1/2 years back for which she was given oral thyroxine. She also had psoriasis for 2 years for which she was treated with cyclosporin.

Physical examination apart from icterus and psoriatic skin lesions was essentially normal. On abdominal examination the liver was palpable 2 cm below the right costal margin. Splenomegaly and ascites were not present.

Investigations : Haemoglobin 11.8 g%, total leucocyte count 8800/cu.mm, polymorphs 60%, lymphocytes 40%, ESR 60 mm after 1 hr. PT : 14 seconds (control 13), serum bilirubin total 2.3 mg%, (direct 2.1), SGPT 25 u/l, SGOT 60 u/l, alkaline phosphatase 347 u/l, albumin 3.9 g/dl, globulin 4.7 g/dl, LDH 420 u/l, GGT 246 u/l ANA, AMA and ASA were all positive, HBsAg, anti HCV, anti HEV, and anti LKM1 and anti HIV were all negative. T3 30 ng/dl, T4 0.5 ug/dl and TSH 150 mu/l.

Abdominal ultrasonography revealed a normal liver, gall bladder and biliary tree. OGD and colonoscopy were normal. Liver scan showed a diffuse homogeneous uptake in the liver. Histological features were consistent with the diagnosis of PBC.

Patient was treated with UDCA and cyclosporin with excellent improvement.

CASE 5

A 52-year-old woman presented with haematemesis due to oesophageal varices and was treated with sclerotherapy. The patient had generalised itching for 10 years and oedema feet for one month. There was no other significant illness in the past. Physical examination revealed mild pallor, pedal oedema and the spleen was palpable 5 cm below the left costal margin. There was no hepatomegaly or ascites.

Investigations : Haemoglobin 9.5 g%, total leucocyte count 6000/cu.mm, polymorphs 52%, lymphocytes 48%, ESR 40 mm after 1 hr. PT : 11.5 seconds (control 11.5), serum bilirubin total 1.1 mg% (direct 0.3), SGPT 103 u/l, SGOT 161 u/l, alkaline phosphatase 743 u/l, albumin 3.7 g/dl. Globulin 4.1 g/dl, LDH 400 u/l, GGT 206 u/l. ANA and AMA were positive while HBsAg and anti HCV were negative.

Abdominal ultrasonography revealed a nodular liver with coarse echotexture and splenomegaly. OGD showed grade III oesophageal varices with portal hypertensive gastropathy.

Patient was treated with UDCA with significant improvement.

CASE 6

A 42-year-old female was operated in October 1996 for abdominal and pelvic adhesions. Subsequently she developed wound infection and jaundice was noticed after 5 days of surgery. She had history of generalised itching, change in colour of the skin and significant weight loss over the last 2 years. She also had history of cold intolerance, dry skin, oedema feet and constipation for 2 years. She was diagnosed as case of hypothyroidism and treated with oral thyroxine (0.1 mg daily). She did not give history of bone pain, steatorrhoea, ascites, haematemesis, melaena, encephalopathy or blood transfusion. Features suggestive of septicaemia were absent and the patient was given antibiotics for control of wound infection. On examination she had hepatomegaly, skin discoloration and an infected wound.

Investigations : Haemoglobin 10.5 g%, total leucocyte count 11000/cu.mm, polymorphs 70%, lymphocytes 30%, ESR 40 mm after 1 hr. PT 15 seconds (Control 13). Serum bilirubin total 3.5 mg% (direct 2.2) SGPT 173 u/l, SGOT 194 u/l alkaline phosphatase 4990 u/l, albumin 2.6 g/dl, globulin 4.2 g/dl, gamma globulin 2.2 g/dl, GGT 927 u/l, serum cholesterol 388 mg%, triglycerides 150 mg%, HBsAg and anti HCV were negative. AMA was positive.

Abdominal ultrasonography revealed hepatomegaly with small paraaortic lymph nodes and no ascites. CT scan of the abdomen did not reveal any mass or liver abscess. Liver scan was suggestive of chronic liver disease with hot enlarged spleen. OGD did not reveal any varices. Histological features were consistent with diagnosis of PBC.

DISCUSSION

Ninety per cent of patients of PBC are females, usually between the ages of 40 and 60 years. The disease starts insidiously, most frequently as pruritus without jaundice. Jaundice usually appears 6 months to 2 years after the onset of pruritus. In about 25% of patients’ jaundice and pruritus start simultaneously. [7] Jaundice without pruritus is extremely rare. [8]

Recently, 6 first generation migrant SouthAsian patients with PBC were reported from England over a period of 14 years from 1982-94,6 indicating the rarity of the disease.

Till date, only 8 cases of PBC have been reported from India, out of which 3 cases did not have pruritus [3-5] which is classical symptom in the West.

All 6 of our cases had the classical symptom of pruritus prior to the development of other signs of chronic liver disease. Two patients had associated autoimmune disease in the form of hypothyroidism and psoriasis. These cases emphasize that the classical presentation of PBC does occur in Indian patients and should be looked for carefully.

REFERENCES

1. Samanta AKS, Bhagwat AG, Gupta NM, Sehgal S, Datta DV. Primary biliary cirrhosis in India. Gut 1973; 14 : 448-50.
2. Desai HG. Persistent jaundice in a young female. J Assoc Physc India 1983; 31 : 309-10.
3. Raman G, Kakkar B, Desai HG. Primary biliary cirrhosis - reports of two cases. Bull Jaslok Hosp Res Centre 1983; 7 : 145-6.
4. Contractor QQ, Kalro RH, Vadgaonkar DM, Desai HG. Primary biliary cirrhosis; a case report. Indian J Gastroenterol 1985; 4 : 273-4.
5. Sharma BC, Saraswat VA, Choudhuri G, et al. Primary biliary cirrhosis without pruritus - an Indian variant. Trop Gastroenterol 1996; 17 : 176-7.
6. Anand AC, Elias E. End stage primary biliary cirrhosis in a first generation migrant South Asian population. Eur J Gastroenterol Hepatology 1996; 8 (7) : 663-6.
7. Sherlock S, Dooley J. Diseases of liver and biliary system. Blackwell Scientific Publications. 1993; 236-45.
8. Sherlock S, Scheuer PJ. The presentation and diagnosis of 100 patients with primary biliary cirrhosis. N Engl J Med 1973; 289 : 674-8.

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