Focal nodular hyperplasia-like nodule with reduced expression of organic anion transporter 1B3 in alcoholic liver cirrhosis

We report a patient with alcoholic liver cirrhosis who had a 15 mm focal nodular hyperplasia (FNH)-like nodule in the liver. This FNH-like nodule was diagnosed as hepatocellular carcinoma (HCC) mainly based on hypervascularity during the hepatic arterial phase, washout pattern during the equilibrium phase and low signal intensity during the hepatobiliary phase in gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI; it was surgically resected. Its histology exhibited hepatocyte hyperplasia, fibrous septa containing unpaired small arteries accompanied by reactive bile ductules, remarkable iron deposits and sinusoidal capillarization, and was compatible with the diagnosis of an FNH-like nodule. When we analyzed the images of the present nodule retrospectively, low signal intensity on in-phase and isosignal intensity on opposed-phase T1-weighted MRI may have reflected iron deposits in the FNH-like nodule. In addition, a low signal intensity on T2-weighted MRI and no detection in diffusion-weighted MRI may help in distinguishing FNH-like nodules from HCC, since these image findings are inconsistent with typical HCC. Immunohistochemical analysis revealed a markedly reduced expression of organic anion transporter (OATP) 1B3 in this nodule, which implied decreased Gd-EOB-DTPA uptake by hepatocytes and accounted for the low signal intensity during the hepatobiliary phase on Gd-EOB-DTPA-enhanced MRI. To the best of our knowledge this is the first report in which an FNH-like nodule was assessed for OATP1B3 expression.     

Multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated hepatocellular carcinoma in a patient with alcohol-related liver cirrhosis

We describe a rare case of the transformation of a dysplastic nodule into well-differentiated hepato- cellular carcinoma (HCC) in a 56-year-old man with alcoholrelated liver cirrhosis. Ultrasound (US) disclosed a 10 mm hypoechoic nodule and contrast enhanced US revealed a hypovascular nodule, both in segment seven. US-guided biopsy revealed a high-grade dysplastic nodule characterized by enhanced cellularity with a high N/C ratio, increased cytoplasmic eosinophilia, and slight cell atypia. One year later, the US pattern of the nodule changed from hypoechoic to hyperechoic without any change in size or hypovascularity. US-guided biopsy revealed well-differentiated HCC of the same features as shown in the first biopsy, but with additional pseudoglandular formation and moderate cell atypia. Moreover, immunohistochemical staining of cyclase- associated protein 2, a new molecular marker of well- differentiated HCC, turned positive. This is the first case of multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated HCC within one year in alcohol-related liver cirrhosis.     

Des-gamma-carboxyprothrombin in patients with hepatocellular carcinoma and liver cirrhosis

OBJECTIVES: To ascertain serum and tissue expression of des‐gamma‐carboxyprothrombin (DCP) in patients with hepatocellular carcinoma (HCC) and liver cirrhosis and clarify the relationship between DCP expression and prognosis. METHODS: Expression of DCP in tissues was evaluated with immunohistochemical staining using anti‐DCP antibody in 74 patients with a single primary HCC nodule and liver cirrhosis. Their serum DCP levels were determined using an enzyme immunoassay with a double antibody sandwich system. RESULTS: Positive DCP expression in cancerous and non‐cancerous tissues was related to a worse prognosis for patients with HCC and liver cirrhosis. The combined evaluation of tissue DCP expression and serum DCP level showed that prognosis was the worst for patients with positive tissue DCP expression and a high serum DCP level. Univariate analysis indicated that a lower 5‐year survival rate was significantly correlated with positive tissue DCP expression, a high serum DCP level and the combined factor of positive tissue DCP expression and a high serum DCP level. Multivariate analysis indicated that the combined factor of positive tissue DCP expression and a high serum DCP level was a significant prognostic factor. CONCLUSION: The combined evaluation of tissue DCP expression and serum DCP level is more useful than either factor alone in predicting prognosis for patients with HCC and liver cirrhosis.     

Focal nodular hyperplasia or focal nodular hyperplasia-like lesions of the liver: a special emphasis on diagnosis

Background and Aim: Focal nodular hyperplasia (FNH) and FNH‐like lesions are hypervascular masses that can mimic hepatocellular carcinoma (HCC). We have investigated the clinical, radiological and pathological features of FNH and FNH‐like lesions of the liver, with particular focus on the aspect of diagnosis. Methods: A total of 84 patients, 77 with pathologically‐proven FNH and seven with FNH‐like lesions of the liver, were analyzed retrospectively. Results: Of the 84 patients, seven had underlying liver cirrhosis, including two with Budd‐Chiari syndrome and one with cardiac cirrhosis. These cases were therefore classified as having FNH‐like lesions. Two of the remaining 77 patients without underlying liver cirrhosis were positive for hepatitis B surface antigen. Seven of 50 (14.0%) patients evaluated by four‐phase computed tomography (CT) showed portal or delayed washout, and three of 28 (10.7%) patients analyzed by three‐phase CT showed washout on the portal phase. Collectively, three of nine (33.3%) patients with risk factors for HCC could have been wrongly diagnosed with HCC based on the non‐invasive diagnostic criteria for HCC. A central scar was observed in 30 patients (35.7%) radiologically. Among 62 patients who underwent percutaneous needle biopsy, four patients (6.5%) were misdiagnosed as having HCC and two patients (3.2%) had inconclusive results by a first needle biopsy. Conclusions: The presence of a hepatic lesion with arterial hypervascularity and/or portal/delayed washout is not necessarily diagnostic of HCC, particularly in patients without risk factors for HCC. These radiological findings can also occur in cirrhotic patients with FNH‐like lesions, including those with hepatic outflow obstruction.     

Scirrhous hepatocellular carcinoma displaying atypical findings on imaging studies

We describe a 15-mm scirrhous hepatocellular carcinoma （HCC） in a 60-year-old man with B-type cirrhosis. Ultrasound disclosed a 15-mm hypoechoic nodule in segment 7. Contrast-enhanced US revealed heterogeneous, not diffuse, hypervascularity in the early phase and a defect in the Kupffer phase.Contrast-enhanced computed tomography （CT） revealed a heterogeneous hypervascular nodule in the early phase and a low-density area in the late phase.Magnetic resonance imaging （MRI） revealed iso- to hypointensity at T1 and high intensity at T2-weighted sequences. Contrast-enhanced MRI also revealed a heterogeneous hypervascular nodule in the early phase and washout in the late phase. Super-paramagnetic iron oxide-MRI revealed a hvoerintense nodule. CT during hepatic arteriography and CT during arterial portography revealed heterogeneous hyperattenuation and a perfusion defect, respectively. Based on these imaging findings the nodule was diagnosed as a mixed well-differentiated and moderately-differentiated HCC.Histologically, the nodule was moderately-differentiated HCC characterized by typical cytological and structural atypia with dense fibrosis. Immunohistochemically,the nodule was positive for heterochromatin protein 1 and alpha-smooth muscle actin, and negative for cytokeratin 19. From the above findings, the nodule was diagnosed as scirrhous HCC. Clinicians engaged in hepatology should exercise caution with suspected scirrhous HCC when imaging studies reveal atypical findings, as shown in our case on the basis of chronic liver disease.     

Well-to moderately-differentiated HCC manifesting hyperattenuation on both CT during arteriography and arterial portography

We present a rare case of well- to moderatelydifferentiated hepatocellular carcinoma （HCC） in a 71-year-old woman with hepatitis C virus-related cirrhosis and unusual radiologic features. A 20-mm hypoechoic nodule disclosed by ultrasound in segment two showed hyperattenuation on both computed tomography hepatic arteriography and computed tomography during arterial portography. Contrast-enhanced ultrasound revealed hypervascularity in the early vascular phase and defect in the post-vascular phase, with the same pattern detected by the two imaging techniques. SPIO-MRI revealed a hyperintense nodule. These findings were compatible with those of moderately-differentiated HCC. An ultrasound-guided biopsy showed histological features of well- to moderately-differentiated HCC characterized by more than two-fold the cellularity of the non-tumorous area, fatty change, clear cell change and mild cell atypia with a thin to mid-trabecular pattern. Further studies may provide insights into the correlation between tumor neovascularity in multistep hepatocarcinogenesis and dual hemodynamics, including the artery and the portal vein.     

Hepatocellular carcinoma with extensive peliotic change

Peliosis hepatis is a rare lesion histologically characterized by multiple cavities representing dilated sinusoids filled with blood in the liver. Although it has been observed in the liver parenchyma in association with several diseases and medications, there are few reports of nodules of hepatocellular carcinoma (HCC) showing extensive peliotic change. We describe a case of HCC showing extensive peliotic change in the cancer nodule. A 73-year-old man with a liver tumor was referred to our hospital for further investigation. Abdominal ultrasonography revealed an 8-cm hyperechoic lesion with a halo and mosaic pattern in segment 8 (S8) of the liver. Dynamic magnetic resonance imaging of the liver showed early irregular enhancement of the peripheral part of the lesion, and the effect persisted into the late phase, spreading into the central part of the nodule. Hepatic arteriography showed the “cotton–wool” sign, usually observed in cavernous hemangiomas. Fine-needle aspiration biopsy revealed the diagnosis of HCC. Anterior sectionectomy of the liver was conducted. Histological examination of the resected specimen showed that the tumor was a well-differentiated HCC with extensive dilated sinusoid-like structures in the main portion of the nodule, suggestive of peliotic change.     

Role of serum C-reactive protein as a marker of hepatocellular carcinoma in patients with cirrhosis

BACKGROUND: The usefulness of C-reactive protein (CRP) as a tumour marker in patients with hepatocellular carcinoma (HCC) is controversial. The purpose of this study was to determine whether CRP estimation could be used to identify patients with HCC among those with cirrhosis. METHODS: Serum levels of CRP and alpha-fetoprotein (AFP) were investigated in 122 previously untreated patients with cirrhosis and HCC. Another 76 patients with cirrhosis alone were also investigated as controls. RESULTS: Of the subjects tested, 47.5% of patients with HCC and 39.5% of controls had elevated CRP values (> 6 microg/mL). Although using elevated CRP and/or AFP (> 20 ng/mL) as a criterion showed a significant difference between controls and patients with multiple nodular, massive, or diffuse type HCC (all P < 0.005), the clinical application of this criterion was limited because of low specificity (58%) and accuracy (all < 73%). By using receiver-operating characteristic curves no valuable threshold value of CRP was found to discriminate various types of HCC, except for distinguishing the diffuse type from controls. The CRP value of 12 microg/mL could be used as the cut-off value to differentiate diffuse-type HCC from controls (sensitivity 82.4%, specificity 82%, accuracy 82.1%, P<0.005). CONCLUSIONS: Serum CRP is not a good marker for HCC. However, very high values of CRP in patients with cirrhosis may suggest the presence of a diffuse-type HCC.     

Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma

This study prospectively evaluates the accuracy of contrast-enhanced ultrasound (CEUS) and dynamic magnetic resonance imaging (MRI) for the diagnosis of nodules 20 mm or smaller detected during ultrasound (US) surveillance. We included 89 patients with cirrhosis [median age, 65 years; male 53, hepatitis C virus 68, Child-Pugh A 80] without prior hepatocellular carcinoma (HCC) in whom US detected a small solitary nodule (mean diameter, 14 mm). Hepatic MRI, CEUS, and fine-needle biopsy (gold standard) (FNB) were performed at baseline. Non-HCC cases were followed (median 23 months) by CEUS/3 months and MRI/6 months. FNB was repeated up to 3 times and on detection of change in aspect/size. Intense arterial contrast uptake followed by washout in the delayed/venous phase was registered as conclusive for HCC. Final diagnoses were: HCC (n = 60), cholangiocarcinoma (n = 1), and benign lesions (regenerative/dysplastic nodule, hemangioma, focal nodular hyperplasia) (n = 28). Sex, cirrhosis cause, liver function, and alpha-fetoprotein (AFP) levels were similar between HCC and non-HCC groups. HCC patients were older and their nodules significantly larger (P < 0.0001). First biopsy was positive in 42 of 60 HCC patients. Sensitivity, specificity, and positive and negative predictive values of conclusive profile were 61.7%, 96.6%, 97.4%, and 54.9%, for MRI, 51.7%, 93.1%, 93.9%, and 50.9%, for CEUS. Values for coincidental conclusive findings in both techniques were 33.3%, 100%, 100%, and 42%. Thus, diagnosis of HCC 20 mm or smaller can be established without a positive biopsy if both CEUS and MRI are conclusive. However, sensitivity of these noninvasive criteria is 33% and, as occurs with biopsy, absence of a conclusive pattern does not rule out malignancy. These results validate the American Association for the Study of Liver Disease (AASLD) guidelines.     

Hepatic resection for inflammatory hepatocellular adenomas: pathological identification of micronodules expressing inflammatory proteins

Background: Inflammatory hepatocellular adenoma (IHCA) defines a subgroup of hepatocellular adenomas characterized by the expression of members of the acute‐phase inflammatory response [(serum amyloid A protein (SAA) and C‐reactive protein (CRP)]. IHCA are unique or multiple as defined by the presence of several nodule(s) larger than 10 mm using both imaging and macroscopic observation. Frequently, additional micronodules (<10 mm), previously undetected by imaging, can be observed in resected specimens. Aims: To analyse micronodules in multiple (group 1, nine patients) and single (group 2, eight patients) IHCA cases, immunohistochemistry using SAA and CRP antibodies was performed on all nodules detected under macroscopic examination as well as on surrounding tissue with no visible nodules. Results: Nodules of different sizes (>5≤10 mm, ≥1≤5 mm) were found in group 1, whereas only rare nodules in the mm range were found in group 2. Micronodules shared the characteristics of large nodules, which justified surgery such as inflammatory infiltrates, abnormal arteries, sinusoidal dilatation or peliosis. However, the number of these characteristics was proportional to the size of the nodules. Conclusion: This study demonstrates that the real number of IHCA is greater than that predicted from imaging‐based analyses. In addition, we show that patients with more than one nodule present a greater chance to display more and larger undetected micronodules than patients with a single nodule.     

Imaging of focal nodular hyperplastic-like nodules in alcoholic liver cirrhosis patients using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging

We report on two patients with a history of alcohol abuse who presented with multiple hepatic nodules. Dynamic computed tomography revealed multiple nodular lesions, which were enhanced at the early contrast phase and washed out at the portal phase. In the hepatobiliary phase using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (Gd-EOB-DTPA MRI), these tumors did not show any uptake, thus suggesting the presence of hepatocellular carcinoma. An ultrasound-guided biopsy revealed a slight increase in cell density, sinusoidal dilatation, and contained unpaired small arteries. According to immunohistochemical analyses, these arteries were positive for CD34 and alpha-smooth muscle actin. From these findings, the nodules were diagnosed to be focal nodular hyperplastic (FNH)-like nodules arising in alcoholic-cirrhosed livers. The differential diagnosis of FNH-like nodules arising in alcoholic liver cirrhosis and hepatocellular carcinoma is difficult with Gd-EOB-DTPA MRI, and therefore histological confirmation is necessary.     

Case report of a focal nodular hyperplasia-like nodule present in cirrhotic liver

An 81-year-old female was referred to Sapporo Medical University Hospital because of a nodular lesion 20 mm in diameter found in the liver S8 during follow-up for type C liver cirrhosis. Abdominal ultrasonography showed a capsule-like structure, and contrast computed tomography revealed hypervascularity at the early phase and inner pooling of the contrast medium with ring enhancement at the late phase. Magnetic resonance T2-weighted imaging (T2WI) demonstrated a hyperintensity nodule with further hyperintensity signals in some parts of the nodule, and the signal pattern differed from that of typical fibrosis. SPIO-magnetic resonance imaging showed partial hypointensity signals by T2WI, which indicated the presence of Kupffer cells. Angiography did not show a spoke-wheel pattern. The results by imaging modalities indicated that the nodule was atypical for hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH), and liver nodule biopsy was performed for histological diagnosis. Compared with the background liver, the nodule revealed high cellular density, cellular dysplasia at the periphery, a pseudo-crypt structure and irregular hepatic cord arrangement in some parts of the nodule. Among them, there was immature fibrous tissue containing arterioles with muscular hypertrophy. There has been no report of well-differentiated HCC with a central scar, and this case was presumed to be an FNH-like nodule with dysplasia physically associated with cirrhotic tissue.     

Hepatocellular carcinoma with nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) was originally believed to be a benign disease. However, it has been recently revealed that NASH could lead to irreversible liver disease in some patients. We report an unusual case of hepatocellular carcinoma (HCC) in a 76-year-old man with NASH. He had no history of alcohol consumption, drug use, or blood transfusion. He was negative for all serological viral markers and autoantibodies. In addition, he was obese (body mass index [BMI], 30.75kg/m²) and had type 2 diabetes mellitus. A liver biopsy specimen showed moderate steatosis with necroinflammatory changes, ballooning degeneration, Mallory bodies, pericellular fibrosis, and evidence of nodular regeneration. He was diagnosed with NASH with cirrhosis. Simultaneously, a liver tumor, measuring 19mm in diameter, was detected in segment 6. A tumor biopsy specimen revealed well-differentiated HCC, and imaging modalities confirmed the characteristics of HCC. To our knowledge, ten patients who had HCC with NASH were reported. In all patients with NASH and HCC, cirrhosis was present. Patients with NASH and cirrhosis may progress to HCC, and regular screening, based on tumor markers and imaging modalities, is needed to detect HCC in patients with NASH and cirrhosis.     

Hepatocellular carcinoma appearance in patients with hepatitis C virus‐related chronic liver disease 90 and 70 months after sustained virological response to interferon and ribavirin

We report here two cases of hepatocellular carcinoma (HCC) 90 and 70 months, respectively, after successful treatment with interferon (IFN) and ribavirin for hepatitis C virus (HCV)‐related cirrhosis. A 50‐year‐old Caucasian man and a 66‐year‐old Caucasian woman with HCV‐related cirrhosis were treated with IFN and ribavirin and in both cases a sustained virological response (SVR) was obtained with persistent normalization of serum aminotransferases and continuous disappearance of serum HCV‐RNA. Both patients were subsequently followed up within an HCC surveillance programme based on biochemical and ultrasound (US) evaluation every 6 months and the appearance of HCC was detected 90 and 70 months, respectively, after discontinuation of therapy. We introduce these two cases to call attention to the importance of not underestimating the risk of HCC development even many years after complete HCV eradication, especially in the presence of established cirrhosis and concomitance of other risk factors for HCC.     

Noninvasive diagnostic criteria for hepatocellular carcinoma in hepatic masses >2 cm in a hepatitis B virus‐endemic area

Background: Noninvasive criteria for diagnosing hepatocellular carcinoma (HCC) suggested by the American Association for the Study of Liver Diseases (AASLD) in 2005 consisted of serum α‐fetoprotein (AFP) level >200 ng/ml or a typical enhancement pattern (arterial enhancement and portal/delayed washed out) on dynamic imaging of hepatic mass(es) >2 cm in a cirrhotic liver. Aims: To validate these criteria in a Korean population and to evaluate whether these criteria are applicable to patients without cirrhosis at a high risk of developing HCC. Methods: We prospectively investigated 206 consecutive patients with hepatic mass(es) >2 cm who underwent biopsy or surgical resection. Patients were evaluated by four‐phase dynamic computed tomography (CT) and by assays of serum AFP concentrations at baseline. Patients were classified according to the presence of risk factors or cirrhosis, and the diagnostic accuracy of each test was determined. Results: The positive predictive values (PPV) of typical CT findings or serum AFP >200 ng/ml were 97.8% in cirrhotic patients, 89.6% in high‐risk patients without cirrhosis and 82.4% in low‐risk patients. The PPVs of typical CT findings alone in these groups were 98.8, 97.6 and 87.5% respectively. In high‐risk patients without cirrhosis, the addition of serum AFP levels to typical CT findings minimally increased the diagnostic sensitivity from 81.6 to 87.8% but reduced the PPV from 97.6 to 89.6%. Conclusions: Serum AFP concentration is not a suitable diagnostic criterion for HCC. Typical CT findings can be used to diagnose HCC >2 cm both in cirrhotic patients and in high‐risk patients without cirrhosis.     

Small hepatic nodules (< or =2 cm) in cirrhosis patients: characterization with contrast-enhanced ultrasonography.

AIM: We evaluated the efficacy of contrast-enhanced ultrasonography (CEUS) for the characterization of small hepatic nodules (< or =2 cm) in cirrhosis patients. PATIENTS AND METHODS: Thirty cirrhosis patients with 30 hepatic nodules (1-2 cm) were enrolled in this study. Eighteen hepatic nodules were hepatocellular carcinomas (HCC) and 12 were benign lesions. CEUS was performed using microbubble contrast (Levovist). With surrounding hepatic parenchyma as a reference, two characteristics of hepatic nodules, including arterial phase enhancement (AE) and the absence of delayed phase enhancement (ADE), were evaluated as criteria for the diagnosis of HCC. A radiologist independently reviewed the dynamic computed tomographies (CT) of 26 hepatic nodules. RESULTS: CEUS showed AE in 15 nodules (13 HCC and two benign) and ADE in 17 lesions (14 HCC and three benign). For HCC, the coincidental AE of both CEUS and dynamic CT was 40%. Using both AE and ADE for HCC diagnosis, the sensitivity, specificity, accuracy, positive predictive value and negative predictive values were 55.6%, 91.7%, 70%, 90.9% and 57.9%, respectively. When using either AE or ADE for HCC diagnosis, the same parameters were 94.4%, 66.7%, 83.3%, 81% and 88.9%, respectively. One benign hepatic nodule with both AE and ADE was diagnosed as HCC 29 months after the CEUS study. CONCLUSIONS: A combination of characteristics of AE and ADE as determined by CEUS was highly specific for small HCCs in cirrhosis patients. Concurrent delayed phase imaging is useful in the diagnosis of small hypovascular HCCs.     

Peroral direct cholangioscopic-guided biopsy and photodynamic therapy using an ultraslim upper endoscope for recurrent hepatocellular carcinoma with intraductal tiny nodular tumor growth

Bile-duct invasion is rare in patients with hepatocellular carcinoma (HCC). We report a case that received peroral direct cholangioscopy (PDCS)-guided endoscopic biopsy and photodynamic treatment (PDT) for recurrent HCC with intraductal tiny nodular tumor growth. A 64-year-old woman presented with recurrent right upper-quadrant pain. Six months previously she had been diagnosed with HCC with bile-duct invasion in the right anterior segment and had received right anterior segmentectomy. On pathological examination, the margin of resection was clear, but macroscopic bile-duct invasion was noted. On admission, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) revealed a 0.5-cm-sized polypoid mass at the hilar portion. ERCP-guided biopsy failed, and an ampullary stricture was noted. PDCS-guided endoscopic biopsy was thus performed, and histopathology of the retrieved specimen revealed HCC. The patient submitted to PDT. There was no procedure-related complication. After 1 month of PDT the polypoid lesion and scar change at the hilar lesion had disappeared.     

Validation of an extension of the international non-invasive criteria for the diagnosis of hepatocellular carcinoma to the characterization of macroscopic portal vein thrombosis

Background and Aim: We aimed to validate the non‐invasive criteria for the characterization of portal vein thrombosis (PVT) in patients with cirrhosis and hepatocellular carcinoma (HCC). In a prospective study, we examined the impact of arterial hypervascularity, as established by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases recommendations for the non‐invasive diagnosis of HCC, as a criterion for characterizing macroscopic PVT (EASL/AASLD extension criteria). Methods: A total of 96 cases of PVT detected using ultrasonography in patients with cirrhosis and HCC were included in the study. When coincidental arterial hypervascularity was detected by contrast perfusional ultrasonography and helical computed tomography, the thrombus was considered malignant according to our EASL/AASLD extension criteria. In all cases, an ultrasound‐guided biopsy examination of the thrombus was performed. Results: Coincidental hypervascularity was found in 54 of 96 nodules (56.2%), and all were malignant upon biopsy (100% positive predictive value). Twenty‐four (25%) had negative results with both techniques (non‐vascular thrombus). Biopsies showed HCC in five non‐vascular thrombi (5.3% of all thrombi) and in 13 of 18 thrombi with a hypervascularity result from only one technique. Conclusions: The EASL/AASLD extension criteria for non‐invasive diagnosis of malignant thrombosis were satisfied in 75.2% of malignant thrombi; thus, a biopsy is frequently required in this setting. However, in the presence of coincidental hypervascularity of a thrombus with both techniques, a biopsy is not required (absolute positive predictive value for malignancy). Relying on imaging techniques in thrombi could miss the diagnosis of malignant portal invasion in up to 24.9% of cases.     

Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma

Background  Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) is an MRI contrast agent with perfusion and hepatoselective properties. The purpose of the study was to examine uptake of Gd-EOB-DTPA in the hepatobiliary phase in hepatocellular carcinoma (HCC). Methods  A retrospective analysis of 22 patients with HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI was performed. Enhancement ratios (ERs) and expression levels of the organic anion transporter (OATP) 1B3 protein were examined. Results  Gd-EOB-DTPA accumulated in the hepatobiliary phase in 6 of the 22 cases. All 6 Gd-EOB-DTPA-positive cases were moderately differentiated HCC, but 11 other moderately differentiated HCCs did not show Gd-EOB-DTPA uptake. Histopathologically, 4 Gd-EOB-DTPA-positive HCCs and 5 Gd-EOB-DTPA-negative HCCs produced bile. HCCs with Gd-EOB-DTPA uptake overexpressed OATP1B3 compared with HCCs without Gd-EOB-DTPA uptake, and OATP1B3 levels were significantly correlated with ERs (r = 0.91, P < 0.0001). Conclusions  Uptake of Gd-EOB-DTPA in HCC is determined by expression of OATP1B3 rather than by tumor differentiation or bile production.     

Hyperinsulinaemia and insulin signalling in the pathogenesis and the clinical course of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and is one of the leading causes of cancer‐related death. The risk factors for HCC include cirrhosis, chronic viral hepatitis, heavy alcohol intake and metabolic diseases such as obesity, type 2 diabetes and metabolic syndrome. Insulin resistance is a common denominator of all of these conditions and is tethered to hyperinsulinaemia. Here, we give an overview of the recent advances linking hyperinsulinaemia to HCC development and progression. In particular, we summarise the underlying causes of hyperinsulinaemia in the setting of chronic liver diseases. We present epidemiological evidence linking metabolic diseases to HCC risk and HCC‐related mortality, as well as the pathogenic cellular and molecular mechanisms explaining this relation. A better understanding of the mechanisms by which insulin participates in HCC biology might ultimately provide novel opportunities for prevention and treatment.