CASE 14451 Published on 12.02.2017

Beware of hepatocellular carcinoma in HIV-infected patients !

Section

Abdominal imaging

Case Type

Clinical Cases

Authors

Tonolini Massimo, MD.

"Luigi Sacco" University Hospital,Radiology Department; Via G.B. Grassi 74 20157 Milan, Italy; Email:mtonolini@sirm.org

Patient

54 years, male

Categories

Area of Interest Liver ; Imaging Technique CT, MR

Procedure Diagnostic procedure ; Special Focus Metastases, Neoplasia ;

Show more Show less

Download as PDF Print Show related cases Notify admin

Clinical History

A middle-aged male with a long-standing history of human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV)-related liver disease presented to our department. Until recently the patient was in in acceptable clinical and immunological (CD4+ count 135 cells/mmc, suppressed viral load) condition on combined antiretroviral therapy, and now manifests with sudden liver failure with jaundice and ascites.

Imaging Findings

Urgent quadriphasic CT (Fig.1) confirmed multicompartmental ascites and advanced-stage cirrhotic liver with caudate and left lobe hypertrophy. The portal bifurcation and left intrahepatic branch showed an expansile, solid and enhancing thrombus. Parts of the left liver lobe showed faint patchy hyperenhancement with subsequent inhomogeneous contrast washout without clear evidence of focal neoplastic mass. The suspicion of hepatocellular carcinoma with predominant portal involvement was confirmed by marked elevation of serum alpha-fetoprotein (900 U/l). The main portal trunk showed partial bland thrombosis.
Despite paracentesis (with negative microscopy and cultures), diuretics and anticoagulation, MRI (Figs.2, 3) showed increased ascites. Albeit with poor patchy enhancement, the true extent of neoplastic involvement of the left liver lobe including satellite nodules was effectively demonstrated by diffusion-weighted images, with low apparent diffusion coefficient (ADC) of the intrahepatic malignant thrombus.
The patient received only supportive care. Two months later, progressive disease was heralded by development of aggressive costal metastasis (Fig.4).

Discussion

During the last two decades, antiretroviral therapy dramatically changed the natural history and outcome of Human Immunodeficiency Virus (HIV)-infected people by suppressing HIV, improving immune function, decreasing opportunistic infections and Acquired Immunodeficiency Syndrome (AIDS)-defining cancers, and ultimately resulted in increased survival with better quality of life. However, in patients with long-standing HIV disease the combination of increased lifespan, prolonged exposure to environmental and lifestyle cancer risk factors, and coinfection with oncogenic viruses progressively led to the emergence of several non-AIDS-defining neoplasms such as squamocellular anal carcinoma, Hodgkin lymphoma, lung and colorectal cancers, melanoma and basal cell skin tumours [1-7].
Because of shared transmission route, coinfection with hepatitis C virus (HCV) is very common (almost 30%): HIV+HCV coinfection is present in two-thirds of patients with cirrhosis and represents the key risk factor for developing HCC along with increasing age and low CD4 cell count. As a result, cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC) currently represent the leading (approximately 50%) cause of mortality [1-7].
Albeit the mechanisms of accelerated hepatocarcinogenesis are still unclear, HCC represents a growing concern in HIV-positive individuals, with a 4-fold increased risk compared to the general population and 6.72 cases/1000 person-years incidence rate. Compared to non-HIV cohorts, HIV-positive patients with HCC are younger, more likely males, with fewer comorbidities [3-5, 8-10].
Imaging surveillance is crucial to allow HCC detection at an early stage and timely treatment with chemoembolization, biological drugs and liver transplantation: the latter is feasible, without differences in outcome and recurrence rates compared to non-HIV patients [11].
In the HIV setting the otherwise rare infiltrative growth pattern and portal obstructing tumour are relatively common (23-30% of cases): HCC is often challenging to discern from the markedly heterogeneous cirrhotic background not only sonographically but also at cross-sectional CT and MR imaging. Albeit permeative growth and hypovascularity cause decreased conspicuity on dynamic contrast-enhanced studies, aware radiologists should suspect HCC when faced with irregular, heterogeneous venous- and equilibrium-phase hypoattenuation compared to the remaining parenchyma, despite inconsistent arterial enhancement. Conversely, the true extent of the tumour is generally best assessed on unenhanced T1-, T2- and diffusion-weighted MR images. The presence of expansile or vascularised portal thrombus represents a red-flag sign [12-14]
Despite younger age, median survival is shorter (grossly half, 40% one-year survival) than that of non-HIV counterparts. Adverse prognostic factors include advanced HCC stage, tumour size over 3 cm, diagnosis outside screening program, and portal thrombosis [2-4, 7, 10].

Differential Diagnosis List

Hepatocellular carcinoma with portal thrombosis in HIV disease.

Non-malignant portal thrombosis

Focal confluent fibrosis

Cholangiocarcinoma

Final Diagnosis

Hepatocellular carcinoma with portal thrombosis in HIV disease.

References

[1] Rosenthal E, Salmon-Ceron D, Lewden C, et al (2009) Liver-related deaths in HIV-infected patients between 1995 and 2005 in the French GERMIVIC Joint Study Group Network (Mortavic 2005 study in collaboration with the Mortalite 2005 survey, ANRS EN19). HIV Med 10:282-289 (PMID: 19226410)

[2] Nunnari G, Berretta M, Pinzone MR, et al (2012) Hepatocellular carcinoma in HIV positive patients. Eur. Rev Med Pharmacol Sci 16:1257-1270. (PMID: 23047511)

[3] Merchante N, Merino E, Lopez-Aldeguer J, et al (2013) Increasing incidence of hepatocellular carcinoma in HIV-infected patients in Spain. Clin Infect Dis 56:143-150 (PMID: 22955438)

[4] Yopp AC, Subramanian M, Jain MK, et al (2012) Presentation, treatment, and clinical outcomes of patients with hepatocellular carcinoma, with and without human immunodeficiency virus infection. Clin Gastroenterol Hepatol 10:1284-1290. (PMID: 22902759)

[5] Ioannou GN, Bryson CL, Weiss NS, et al (2013) The prevalence of cirrhosis and hepatocellular carcinoma in patients with human immunodeficiency virus infection. Hepatology 57:249-257 (PMID: 22532055)

[6] Puoti M, Rossotti R, Garlaschelli A, et al (2011) Hepatocellular carcinoma in HIV hepatitis C virus. Curr Opin HIV AIDS 6:534-538. (PMID: 21934618)

[7] Berretta M, Garlassi E, Cacopardo B, et al (2011) Hepatocellular carcinoma in HIV-infected patients: check early, treat hard. Oncologist 16:1258-1269 (PMID: 21868692)

[8] Montes Ramirez ML, Miro JM, Quereda C, et al (2014) Incidence of hepatocellular carcinoma in HIV-infected patients with cirrhosis: a prospective study. J Acquir Immune Defic Syndr 65:82-86 (PMID: 24419065)

[9] Sahasrabuddhe VV, Shiels MS, McGlynn KA, et al (2012) The risk of hepatocellular carcinoma among individuals with acquired immunodeficiency syndrome in the United States. Cancer 118:6226-6233 (PMID: 22736272)

[10] Galia M, Taibbi A, Marin D, et al (2014) Focal lesions in cirrhotic liver: what else beyond hepatocellular carcinoma?. Diagn Interv Radiol 20:222-228 (PMID: 24509186)

[11] Gramenzi A, Tedeschi S, Cantarini MC, et al (2013) Outcome of hepatocellular carcinoma in human immunodeficiency virus-infected patients. Dig Liver Dis 45:516-522. (PMID: 23332770)

[12] Di Benedetto F, Tarantino G, Ercolani G, et al (2013) Multicenter italian experience in liver transplantation for hepatocellular carcinoma in HIV-infected patients. Oncologist 18:592-599 (PMID: 23666950)

[13] Lewin M, Gelu-Simeon M, Ostos M, et al (2015) Imaging Features and Prognosis of Hepatocellular Carcinoma in Patients with Cirrhosis Who Are Coinfected with Human Immunodeficiency Virus and Hepatitis C Virus. Radiology 277:443-453 (PMID: 25961631)

[14] Reynolds AR, Furlan A, Fetzer DT, et al (2015) Infiltrative hepatocellular carcinoma: what radiologists need to know. Radiographics 35:371-386

Case information

URL:	https://eurorad.org/case/14451
DOI:	10.1594/EURORAD/CASE.14451
ISSN:	1563-4086

License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Figure 1

Unenhanced and post-contrast CT (quadriphasic technique)

Precontrast images (a,b) showed multicompartmental ascites (+), advanced-stage cirrhotic liver with caudate and left lobe hypertrophy, solid-attenuation thrombosis (*) of portal bifurcation and left branch.

Arterial-phase acquisition (c,d) showed expansile, enhancing thrombosis (*) of portal bifurcation and left branch, ascites (+), faint patchy hyperenhancement along ventromedial and dorsal aspect of left liver lobe (arrowheads in d).

Portal venous phase (e,f) confirmed solid thrombosis (*) of portal bifurcation and left branch, hypoattenuating nonenhancing partial bland thrombosis of portal trunk (arrows), and multicompartmental ascites (+).

Portal venous phase (e,f) confirmed solid thrombosis (*) of portal bifurcation and left branch, inhomogeneous washout (arrowheads) involving most of left liver lobe, and multicompartmental ascites (+).

Equilibrium phase images (g,h) showed contrast washout of intrahepatic portal thrombosis (*), inhomogeneous washout (arrowheads) involving most of the left liver lobe, including a roundish mass in the dorsal 3rd segment (h). Note ascites (+).

Figure 2

Liver MRI - precontrast T2- and diffusion-weighted images

Coronal (a) and axial (b,c) T2-weighted images showed increased ascites (+), faint hyperintensities along ventromedial and dorsal aspects of left liver lobe (arrowheads), moderately high signal of intrahepatic portal thrombus (*).

T2-weighted images showed faint hyperintensities along ventromedial and dorsal aspects of left liver lobe (arrowheads) plus a centimetric nodule (thin arrow), moderately high signal of intrahepatic portal thrombus (*).

T2-weighted images showed increased ascites (+), faint hyperintensities along ventromedial and dorsal aspects of left liver lobe (arrowheads), moderately high signal of intrahepatic portal thrombus (*) compared to hypointense bland extrahepatic thrombus (arrow).

High b-value (800) diffusion-weighted images showed hyperintensities at the expansile intrahepatic thrombus (*) and extensive part of the left liver lobe (arrowheads).

High b-value (800) diffusion-weighted images showed hyperintensities at the expansile intrahepatic thrombus (*) and extensive part of the left liver lobe (arrowheads). Note satellite tumour nodule (thin arrow).

On corresponding apparent diffusion coefficient (ADC) map image, the intrahepatic thrombus (*) showed low signal with ADC values 1.1 ×10−3 mm2/s.

Figure 3

Liver MRI - Dynamic study (1 molar Gadobutrol 1ml/kg)

Hampered by limited breath-hold due to increased ascites (+), arterial-phase MRI showed mottled hyperenhancement at dorsal 3rd segment (arrowhead) and ventral nodule (thin arrow). Note intrahepatic portal thrombus (*).

Portal venous (b) and equilibrium (c,d) phase images showed progressive contrast washout at involved areas of left liver lobe (arrowheads) and satellite nodule (thin arrow). Note ascites (+), intrahepatic portal thrombosis (*).

Nonenhancing partial bland thrombosis of the main portal trunk (arrows) persisted despite anticoagulation. Note increased ascites (+).

Figure 4

Follow-up thoracic CT

Two months later, focused CT confirmed the development of a large (10x4.5 cm) solid mass at the dorsal right thoracic wall (thick arrows) causing aggressive costal osteolysis.