Case Report

Color Doppler Demonstration of Segmental Portal Flow Reversal An Early Sign of Hepatic Veno-occlusive Disease in an Infant Eduard Ghersin, MD, Olga R. Brook, MD, Diana Gaitini, MD, Ahuva Engel, MD

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epatic veno-occlusive disease (HVOD) is a relatively frequent complication of bone marrow transplantation (BMT), with a reported prevalence of 1% to 54%.1 The role of color duplex ultrasonography (CDU) in the diagnosis and monitoring of HVOD is controversial; some authors advocate its use,2–4 whereas others find it insensitive and nonspecific.5–7 Hepatofugal flow in the main portal vein is regarded as a relatively specific finding of severe HVOD; however, it is of limited value because it seldom occurs.6 Here we report HVOD in an infant who previously underwent BMT. The HVOD was diagnosed early by demonstration of hepatofugal flow in only 1 segmental portal vein. After treatment with high-dose methylprednisolone and defibrotide, CDU showed reversal to hepatopetal flow accompanied by marked clinical improvement.

Case Report

Abbreviations BMT, bone marrow transplantation; CDU, color duplex ultrasonography; HVOD, hepatic veno-occlusive disease

Received May 16, 2003, from the Department of Diagnostic Radiology, Rambam Medical Center, Haifa, Israel. Manuscript accepted for publication May 22, 2003. Address correspondence and reprint requests to Eduard Ghersin, MD, Department of Diagnostic Radiology, Rambam Medical Center, PO Box 9602, Haifa 31096, Israel. E-mail: [email protected].

A 3.5-month female infant had familial hemophagocytic lymphohistiocytosis, a uniformly fatal disease usually seen in infancy, characterized by fever, hepatosplenomegaly, and pancytopenia.8 The patient underwent BMT with partial T-cell depletion from her HLA antigen–identical sibling, which is the only known cure for this disorder. The patient’s marrow was conditioned with busulfan, fludarabine, and cyclophosphamide. She received heparin and ursodeoxycholic acid for prevention of HVOD. Platelet engraftment occurred on day 9 and leukocyte engraftment on day 12 after BMT. On day 9 after BMT, the patient began to gain weight and retain fluids, and thrombocytopenia became refractory. We suspected HVOD and performed bedside CDU with an HDI 5000 ultrasonographic scanner and a 7-4 40R broadband frequency curved array transducer (Philips Medical Systems, Bothell, WA). Gray scale ultrasonography showed moderate ascites in all peritoneal compartments (Fig. 1A). Color duplex ultrasonography showed normal-appearing hepatic veins

© 2003 by the American Institute of Ultrasound in Medicine • J Ultrasound Med 22:1103–1106, 2003 • 0278-4297/03/$3.50

Segmental Portal Flow Reversal in Hepatic Veno-occlusive Disease

with normal triphasic flow toward the inferior vena cava (Fig. 1B) and a normal-appearing main portal vein with hepatopetal flow (Fig. 1, C and D). Careful evaluation of the segmental portal veins disclosed hepatofugal flow only in the portal vein of segment 8. The finding could be recognized on color Doppler ultrasonography by noting opposite flow directions in the segmental portal vein and the corresponding segmental hepatic artery (Fig. 2, A and B). Because the diagnosis of HVOD was established on the basis of the CDU findings, medical treatment with high-dose methylprednisolone and defibrotide was initiated. Between days 9 and 10 after BMT, the patient’s condition continued to deteriorate, with a further increase in abdominal girth, shortness of breath, a decrease

in urinary output, and hyperbilirubinemia reaching a value of 4.1 mg/dL. The patient received additional treatment with furosemide in a continuous drip and underwent midline paracentesis. After this treatment, gradual clinical improvement was noted by day 14 after BMT, with a decrease in abdominal girth, hepatomegaly, and a drop of the bilirubin level to 1.8 mg/dL. At this point, CDU was repeated. Gray scale ultrasonography showed small residual ascites in the pelvis. Color duplex ultrasonography showed normal-appearing hepatic veins with normal triphasic flow toward the inferior vena cava and a normal-appearing main portal vein with hepatopetal flow. Careful reexamination of the portal vein of segment 8 disclosed hepatopetal flow (Fig. 2, C and D).

Figure 1. A, Longitudinal sonogram of the right upper abdomen showing moderate ascites. B, Axial color Doppler image of the right upper abdomen showing normal-appearing hepatic veins (dotted arrows) with normal flow toward the inferior vena cava. C and D, Longitudinal color Duplex images of the right upper abdomen showing a normal-appearing main portal vein (arrow) with hepatopetal flow.

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Later, the therapy with high-dose methylprednisolone and defibrotide was discontinued for 2 days because of a transient respiratory distress episode accompanied by pulmonary infiltrates on chest computed tomography. Because pulmonary hemorrhage was eventually excluded, the treatment with high-dose methylprednisolone and defibrotide was renewed, resulting in complete clinical recovery within 29 days after BMT.

Discussion Hepatic veno-occlusive disease is a serious illness usually caused by intensive myeloablative

chemotherapy or radiation therapy before BMT.9 It usually develops before day 20 after BMT and is characterized by jaundice, painful hepatomegaly, and fluid retention. According to McDonald et al,10,11 the presence of 2 of the above-mentioned clinical manifestations establishes the diagnosis of HVOD. No optimal treatment for HVOD has been established at present. Anticoagulant agents (prostaglandin E1, tissue plasminogen activator, and heparin), defibrotide, and high-dose methylprednisolone are among the commonly used therapeutic agents.12 On histopathology there is concentric narrowing or fibrous obliteration of terminal hepatic

Figure 2. A and B, Ultrasonography on day 9 after BMT. A, Axial color Doppler image of the right lobe of the liver showing hepatofugal flow in the portal vein of segment 8 in blue (arrows) and hepatopetal flow in the corresponding hepatic artery of segment 8 in red (dotted arrows). B, Spectral display of the portal vein of segment 8 showing hepatofugal flow with a maximal flow velocity of 15 cm/s. C and D, Ultrasonography on day 14 after BMT. C, Axial color Doppler image of the right lobe of the liver showing hepatopetal flow in the portal vein and corresponding hepatic artery of segment 8 in red (arrows). D, Spectral display of the portal vein of segment 8 showing hepatopetal flow with a maximal flow velocity of 15 cm/s. Note the normal velocity variations with breathing.

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venules and sublobular veins, dilatation followed by fibrosis of centrilobular sinusoids, and necrosis of zone 3 hepatocytes.1 The sonographic appearance of HVOD after BMT is variable and sometimes nonspecific. The spectrum of findings includes ascites, hepatomegaly, thickening of the gallbladder wall, an increased mean hepatic artery resistive index, and decreased or reversed portal venous flow.1 According to some authors, reversed portal venous flow is a relatively specific finding of HVOD but occurs rarely and only in late stages of the disease, when the clinical picture is obvious.1,6 The importance of our case lies in the demonstration of another CDU finding of HVOD, that of segmental portal flow reversal, which occurs in early stages of the disease, when the clinical picture may be vague. Flow reversal in only 1 segmental portal vein was reported previously by Yoshimoto et al.12 They reported 2 adult patients with a diagnosis of HVOD based on CDU findings of segmental portal vein flow reversal. The CDU findings preceded the clinical diagnosis by 5 to 6 days and enabled institution of early anticoagulant therapy. Our case’s uniqueness is the demonstration of segmental portal vein flow reversal in an infant treated with BMT. In our case, portal vein flow reversal preceded hyperbilirubinemia by 1 day and evolved to hepatopetal in only 5 days after treatment with highdose methylprednisolone and defibrotide. The reinstitution of hepatopetal flow in the affected segmental portal vein was accompanied by marked clinical improvement. On the basis of our report and the report of Yoshimoto et al,12 we suggest that CDU evaluation of both pediatric and adult patients with suspected HVOD should include meticulous evaluation of all segmental portal veins in addition to the main portal vein branches. We also propose that once segmental portal vein flow reversal is detected, CDU should be repeated routinely in short intervals of 1 to 2 days to monitor the effectiveness of the medical treatment. Although yet to be proved, such a perseverant approach may increase the efficacy of CDU as a noninvasive diagnostic and monitoring tool in HVOD.

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10. McDonald GB, Sharma P, Matthews DE, Shulman HM, Thomas ED. Venoocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence, and predisposing factors. Hepatology 1984; 4:116– 122. 11. McDonald GB, Hinds MS, Fisher LD, et al. Venoocclusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med 1993; 118:255–267. 12. Yoshimoto K, Yakushiji K, Ijuin H, et al. Colour Doppler ultrasonography of a segmental branch of the portal vein is useful for early diagnosis and monitoring of the therapeutic course of veno-occlusive disease after allogenic haematopoietic stem cell transplantation. Br J Haematol 2001; 115:945–948. J Ultrasound Med 22:1103–1106, 2003