Pediatrics International

(2002)

44

, 456–459

Patient Report

Hepatic glomerulosclerosis in a child with extrahepatic portal vein obstruction

TORU WATANABE

1

AND KOJU NITTA

2

Departments of

1

Pediatrics and

2

Pediatric Surgery, Niigata City General Hospital, Niigata, Japan

Key words

extrahepatic portal vein obstruction, glomerulonephritis, hepatic glomerulosclerosis.

Glomerular abnormalities in liver cirrhosis, termed as hepaticor cirrhotic glomerulonephritis, have been well described inpublished reports.

1

Crawford

et al

. classified them into fourpatterns of glomerular histological changes: minor glomerularabnormalities, hepatic glomerulosclerosis, mesangiocapillaryglomerulonephritis and IgA nephropathy.

2

There is a trendtoward better hepatic function in patients with minor abnor-malities than in those with other forms of glomerular injuryand it is possible that the lesion can progress into one of theother forms as liver function degrades.

2

In these lesions,hepatic glomerulosclerosis is the most prominent of glomerularchanges in liver cirrhosis.

2

While almost all the patients withhepatic glomerulosclerosis reported in the published documentswere adults, the same glomerular abnormalities were alsopresent in children.

3

Extrahepatic portal vein obstruction (EHPO) is animportant cause of portal hypertension in children.

4

Whilesome patients die from variceal hemorrhage or infection, ingeneral, EHPO is a relatively benign disease, which usuallydoes not lead to liver cirrhosis.

4

Glomerular abnormalities in EHPO are extremely rare.Only two cases of glomerulonephritis in EHPO have beenreported.

4,5

We describe a patient with EHPO, developinghepatic glomerulosclerosis after bacterial colitis and portal-systemic encephalopathy.

Case report

A 7-year-old Japanese girl was admitted to Niigata CityGeneral Hospital on December 1992 because of hemato-emesis, splenomegaly and pancytopenia. She was diagnosedas having EHPO from the clinical and angiographic findings.

Aortoportogram and abdominal computed tomography (CT)showed a tortuous,

η

-shaped extrahepatic portal vein withcavernous transformation of collateral vessels, suggesting thather EHPO was caused by congenital malformation (Fig. 1).

6

As massive hemorrhage from esophageal varices recurredseveral times, she underwent esophageal transection, splenec-tomy and gastric devascularization. Thereafter, she becamewell and had no abnormal findings of urine until the reportedpresent illness. On 7 October 1998, she was transferred to ourhospital with a fever, diarrhea, unconsciousness and anasarca.

Physical examinations revealed coma, generalized edema,massive ascites and coarse crackles of the bilateral lungs. Herblood pressure was 120/60 mmHg, her temperature 38.1

°

Cand her pulse rate 128/min. Jaundice or vascular spiders wereabsent.

Laboratory studies revealed the following: leukocytecount 21 000/

µ

L, C-reactive protein 8.19 mg/dL, total protein3.2 g/dL, albumin 1.65 g/dL and ammonia level 233

µ

g/dL.An indocianine green retention rate at 15 min (ICG-R15) andan indocianine green elimination constant (ICG-K) were20.6% (normal, 0–10%) and 0.087 (normal, 0.168–0.206),respectively. Serum liver enzymes, total and direct bilirubin,glucose, electrolytes and renal function were normal. Thefollowing data were also within normal ranges: serum IgG,IgA, IgM, C3, C4, activated partial thromboplastin time,prothrombin time and hepaplastin test. Hepatitis B surfaceantigen, hepatitic C antibody, antinuclear antibody and rheu-matoid factor were negative. Cerebrospinal fluid was clearand had no pleocytosis. A urinalysis disclosed 43 mg/dL(0.5 g/day) protein, 3+ blood, many red blood cells and20–29 white blood cells/high power field and a few granularand hyaline casts. Creatinine clearance was 133.3 mL/minper 1.73m

2

. Two stool cultures were positive for heavygrowth of

Pseudomonas aeruginosa

. No other pathogenicagents grew from the bacterial cultures of blood, sputa, urineand cerebrospinal fluid. A chest X-ray film revealed cardio-megaly and pulmonary congestion. The CT films of the brainhad no abnormality. Electroencephalogram showed diffusehigh voltage slow waves.

Correspondence: Toru Watanabe MD, Department of Pediatrics,Niigata City General Hospital 2-6-1 Shichikuyama, Niigata 950-8739, Japan. Email: twata@hosp.niigata.niigata.jp

Received 2 February 2001; revised 2 May 2001; accepted 25 June2001.

Hepatic glomerulosclerosis in EHPO 457

From the clinical and laboratory findings, she wasdiagnosed with bacterial colitis and portal-systemic encephalo-pathy. Intravenous administration of antibiotics, albumin andfurosemide, and oral lactulose improved her condition andlaboratory data except for urinalysis, serum protein level(5.0 g/dL) and plasma ammonia levels (80–120

µ

g/mL). Shewas discharged on 16 November, 1998 with mild edema of theeyelids and lower extremities, ascites and urinary abnormalities.

On 28 March 1999, she underwent renal needle biopsybecause of the persistence of urinary abnormalities (urinaryprotein 0.6 g/day, urine red blood cells many/high powerfield), hypoproteinemia (serum total protein 5.2 g/dL, serumalbumin 2.3 g/dL), pretibial edema and ascites. Creatinineclearance was 109.3 mL/min per 1.73m

2

.Fifteen glomeruli were obtained by needle renal biopsy.

Light microscopy showed diffuse and global mesangial cellproliferation and excess amounts of matrix, glomerularadhesion to Bowman’s capsule and segmental double contours(Fig. 2a). Immunofluorescence showed granular deposits ofIgM (2+), IgA (1+), C3 (1+) and fibrinogen (1+) in themesangium and along the capillary walls (Fig. 2b). Electronmicroscopy revealed endothelial cell hypertrophy, mesangialcell proliferation, an increase of mesangial matrix (Fig. 2c)and mesangial dense deposits (Fig. 2d). These findings werecompatible with hepatic glomerulosclerosis.

On 15 November 1999, the pretibial edema, ascites andurinary abnormalities disappeared. Serum total protein (6.3 g/dL),ICG-R15 (6.0%) and ICG-K (0.168) returned to within thenormal ranges. The CT of the liver showed no abnormalitiesexcept for extrahepatic portal vein obstruction. While she didnot undergo liver biopsy, she was diagnosed as having non-cirrhotic portal vein obstruction because of normal liverfunction tests and normal findings of CT of the liver.

Discussion

Extrahepatic portal vein obstruction is an important cause ofportal hypertension in children.

4

The most serious complica-tion is severe bleeding from gastro-esophageal varices, whichhas recently been well controlled by endoscopic sclerother-apy or surgical intervention.

7

As portal venous pressure doesnot affect the liver directly in this disease, EHPO usuallydoes not develop into liver cirrhosis. However, some degreeof portal-systemic shunting through the collateral vessels ispresent and it may cause portal-systemic encephalopathy ifsuch critical exacerbations as infection are added.

4

Glomerular alterations in liver disease, especially incirrhosis, have been well described in published reports.

1–3

According to the studies with renal biopsy, almost all thepatients with liver cirrhosis had glomerular lesions.

2,3

However, a majority of them did not have significant clinicaland biochemical evidence of renal dysfunction.

Although exact pathogenesis of glomerular lesions in livercirrhosis remains obscure, it was suggested that hepaticglomerulosclerosis was an immune complex-mediateddisease because of immunofluorescence findings andfrequent presence of circulating immune complexes.

2

As theliver and spleen are the principal sites for clearing circulatingimmune complexes, their dysfunctions and/or portal-systemicshunting result in an increase of circulating immunecomplexes. The antibodies in the circulating immunecomplexes found in patients with cirrhosis are directedagainst antigens arising from the digestive tract.

8

Crawford

et al

. showed IgM immunofluorescence was present in allrenal biopsies and IgM-containing circulating immunecomplexes occurred in five out of 18 patients with cirrhosisreceiving liver transplantation, suggesting a pathogenic rolefor IgM immune complex deposition.

2

However, IgA immuno-fluorescence was present only in 11 out of 18 patients,therefore, they suggested that IgA deposition was notnecessary for the development of hepatic lesions accompany-ing cirrhosis.

2

Glomerular abnormalities in EHPO are extremely rare andonly two cases have been reported. Webb

et al

. reported thatone out of 97 patients with EHPO had glomerulonephritis,which was not described in detail.

4

Babbs

et al

. reported a4-year-old boy with EHPO who developed IgA nephropathyand a nephrotic syndrome, which resulted in remission bysplenectomy with resection of a splenic artery aneurysm.

5

However, hepatic glomerulosclerosis in EHPO has never beenreported. Recently, Karashima

et al

. reported two patients ofmembranoproliferative glomerulonephritis in congenital porto-systemic shunt without liver cirrhosis.

9

Their patients were notEHPO; however, their cases presented that portosystemicshunt without cirrhosis could induce renal injuries.

Our patient developed hepatic glomerulosclerosis;however, the urinary abnormalities improved without any

Fig. 1

Post-contrast computed tomogram of the abdomenshowing a tortuous extrahepatic portal vein in the portal area ofthe liver. The pancreas shifts to the back due to splenectomy.

458 T Watanabe and K Nitta

specific therapies when ICG clearance returned into the normalrange. As ICG clearance is dependent on hepatic blood flowand/or hepatocyte function, its decrease means liver hypoper-fusion and/or hepatic dysfunction.

10

Therefore, in this patient,it was suggested that bacterial infection in the colon stimulatedproduction of immune complexes, exacerbated portal-systemicshunting and impaired clearance of immune complexes by theliver due to transient hepatic hypoperfusion and/or hepaticdysfunction. As our patient had undergone splenectomy,

further impaired clearance of circulating immune complexesmay be present. These changes led to an increase of circulatingimmune complexes, which resulted in hepatic glomerulo-sclerosis. Unlike liver cirrhosis, antigenic supply from thecolon and hepatic dysfunction did not continue when infectionsubsided, therefore urinary abnormalities disappeared in thepatient. As recurrence of such exacerbations may induce moresevere or irreversible glomerular lesions, caution should beneeded for gastrointestinal tract infection in EHPO.

Fig. 2

(a) Light microscopic findings. Arrows indicate segmental double contours (Periodic acid-Schiff methenamine silver,

×

400).(b) Immunofluorescence for IgM (

×

400). (c,d) Electron microscope findings (

×

2400).

Hepatic glomerulosclerosis in EHPO 459

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