Diagnosing Nodular Regenerative Hyperplasia of the Liver Is Thwarted by Low Interobserver Agreement.

BACKGROUND AND AIMS: Nodular regenerative hyperplasia (NRH) of the liver is associated with several diseases and drugs. Clinical symptoms of NRH may vary from absence of symptoms to full-blown (non-cirrhotic) portal hypertension. However, diagnosing NRH is challenging. The objective of this study was to determine inter- and intraobserver agreement on the histopathologic diagnosis of NRH. METHODS: Liver specimens (n=48) previously diagnosed as NRH, were reviewed for the presence of NRH by seven pathologists without prior knowledge of the original diagnosis or clinical background. The majority of the liver specimens were from thiopurine using inflammatory bowel disease patients. Histopathologic features contributing to NRH were also assessed. Criteria for NRH were modified by consensus and subsequently validated. Interobserver agreement was evaluated by using the standard kappa index. RESULTS: After review, definite NRH, inconclusive NRH and no NRH were found in 35% (23-40%), 21% (13-27%) and 44% (38-56%), respectively (median, IQR). The median interobserver agreement for NRH was poor (κ = 0.20, IQR 0.14-0.28). The intraobserver variability on NRH ranged between 14% and 71%. After modification of the criteria and exclusion of biopsies with technical shortcomings, the interobserver agreement on the diagnosis NRH was fair (κ = 0.45). CONCLUSIONS: The interobserver agreement on the histopathologic diagnosis of NRH was poor, even when assessed by well-experienced liver pathologists. Modification of the criteria of NRH based on consensus effort and exclusion of biopsies of poor quality led to a fairly increased interobserver agreement. The main conclusion of this study is that NRH is a clinicopathologic diagnosis that cannot reliably be based on histopathology alone.

Relationship between the histological appearance of the portal vein and development of ischemic-type biliary lesions after liver transplantation.

Ischemic-type biliary lesions (ITBLs) are a major cause of morbidity after liver transplantation (LT). Their assumed underlying pathophysiological mechanism is ischemia/reperfusion injury of the biliary tree, in which the portal circulation has been proposed recently to have a role. The aim of this study was to investigate whether early histological changes, particularly in the portal vein, predispose patients to ITBLs. A case-control study of 22 LT recipients was performed through a retrospective assessment of more than 30 histological parameters in 44 intraoperative liver biopsy samples taken after cold ischemia (time 0) and portal reperfusion (time 1). Eleven grafts developed ITBLs requiring retransplantation (the ITBL group), and 11 matched controls had normally functioning grafts 11 years after LT on average (the non-ITBL group). Additionally, 11 liver biopsy samples from hemihepatectomies performed for metastases of colorectal cancer (CRC) were assessed similarly. Analyses showed no significant histological differences at time 0 between the ITBL and non-ITBL groups. However, the time 1 biopsy samples from the ITBL group showed smaller portal vein branches (PVBs) significantly more often than the samples from the non-ITBL group, which also showed persisting paraportal collateral vessels. Larger PVBs and paraportal collateral vessels were also found in the CRC group. A morphometric analysis confirmed these findings and showed that PVB measurements were significantly lower for the ITBL group at time 1 versus the ITBL group at time 0 and the non-ITBL and CRC groups (they were largest in the CRC group). Thus, the PVB dimensions decreased in the ITBL group in comparison with the time 0 biopsy samples, and they were significantly smaller at time 1 in comparison with the dimensions for the non-ITBL and CRC groups. In conclusion, a smaller PVB lumen size in postreperfusion biopsy samples from liver grafts, suggesting a relatively decreased portal blood flow, is associated with a higher incidence of ITBLs. These findings support recent clinical studies suggesting a possible pathophysiological role of portal blood flow in the oxygenation of the biliary tree after LT.

Evaluation of transient elastography for fibrosis assessment compared with large biopsies in chronic hepatitis B and C.

BACKGROUND: Fibrosis determines prognosis and management in patients with chronic hepatitis B and C (CHB and CHC). Transient elastography (TE) is a promising non-invasive method to assess fibrosis. We prospectively studied the performance of TE compared to histology and also whether there are differences between CHB and CHC. Only large biopsies (≥ 25 mm) were used. METHODS: We included 241 patients with CHB (n = 125) and CHC (n = 116), of whom we acquired 257 liver biopsies, all preceded by elastography. We correlated liver stiffness with fibrosis stage according to the METAVIR system, inflammation (Histology Activity Index), steatosis and iron. The impact of gender, age, body mass index, alcohol, alanine aminotransferase levels, platelet count, viral load and genotype on liver stiffness was evaluated. RESULTS: The AUROC's for F ≥ 2 were 0.85 for CHB and 0.76 for CHC. AUROC's for F ≥ 3 were 0.91 for CHB and 0.87 for CHC and 0.90 and 0.91 for F4 for CHB and CHC respectively. For F ≥ 2 the cut-off value was 6.0 kPa for CHB and 5.0 kPa for CHC. The cut-off values for ≥ F3 were 9.0 and 8.0 kPa for CHB and CHC, respectively, and 13.0 kPa for F4 in both CHB and CHC patients. Besides inflammation, all other remaining factors do not influence liver stiffness. CONCLUSION: For the diagnosis of fibrosis stages F ≤ 2 TE is suboptimal, and inflammation may induce higher values. For stages F ≥ 3 TE performance is good and equal in both CHB and CHC patients.

Comparison of macroscopic pathology measurements with magnetic resonance imaging and assessment of microscopic pathology extension for colorectal liver metastases.

PURPOSE: To compare pathology macroscopic tumor dimensions with magnetic resonance imaging (MRI) measurements and to establish the microscopic tumor extension of colorectal liver metastases. METHODS AND MATERIALS: In a prospective pilot study we included patients with colorectal liver metastases planned for surgery and eligible for MRI. A liver MRI was performed within 48 hours before surgery. Directly after surgery, an MRI of the specimen was acquired to measure the degree of tumor shrinkage. The specimen was fixed in formalin for 48 hours, and another MRI was performed to assess the specimen/tumor shrinkage. All MRI sequences were imported into our radiotherapy treatment planning system, where the tumor and the specimen were delineated. For the macroscopic pathology analyses, photographs of the sliced specimens were used to delineate and reconstruct the tumor and the specimen volumes. Microscopic pathology analyses were conducted to assess the infiltration depth of tumor cell nests. RESULTS: Between February 2009 and January 2010 we included 13 patients for analysis with 21 colorectal liver metastases. Specimen and tumor shrinkage after resection and fixation was negligible. The best tumor volume correlations between MRI and pathology were found for T1-weighted (w) echo gradient sequence (r(s) = 0.99, slope = 1.06), and the T2-w fast spin echo (FSE) single-shot sequence (r(s) = 0.99, slope = 1.08), followed by the T2-w FSE fat saturation sequence (r(s) = 0.99, slope = 1.23), and the T1-w gadolinium-enhanced sequence (r(s) = 0.98, slope = 1.24). We observed 39 tumor cell nests beyond the tumor border in 12 metastases. Microscopic extension was found between 0.2 and 10 mm from the main tumor, with 90% of the cases within 6 mm. CONCLUSIONS: MRI tumor dimensions showed a good agreement with the macroscopic pathology suggesting that MRI can be used for accurate tumor delineation. However, microscopic extensions found beyond the tumor border indicate that caution is needed in selecting appropriate tumor margins.

Comparison of non-invasive assessment to diagnose liver fibrosis in chronic hepatitis B and C patients.

OBJECTIVE: Chronic viral hepatitis B and C cause liver fibrosis, leading to cirrhosis. Fibrosis assessment is essential to establish prognosis and treatment indication. We compared seven non-invasive tests, separately and in combination, in chronic hepatitis patients to detect early stages of fibrosis according to the Metavir score in liver biopsy. MATERIAL AND METHODS: Galactose and methacetin breath tests (GBT and MBT), biomarkers (hyaluronic acid (HA), aspartate aminotransferase platelet ratio index (APRI), FibroTest, and Fib-4) and transient elastography (TE) were evaluated in 89 patients. Additionally, 31 healthy controls were included for evaluation of breath tests and biomarkers. RESULTS: Serum markers (HA, APRI, FibroTest, and Fib-4) and elastography significantly distinguished non-cirrhotic (F0123) from cirrhotic (F4) patients (p < 0.001, p = 0.015, p < 0.001, p = 0.005, p = 0.006, respectively). GBT, HA, APRI, FibroTest, Fib-4, and TE detected F01 from F234 (p = 0.04, p = 0.011, p = 0.009, p < 0.001, p < 0.001, and p < 0.001, respectively). A combination of different tests (TE, HA, and FibroTest) improved the performance statistically, area under the curve (AUC) = 0.87 for F234, 0.92 for F34, and 0.90 for F4. CONCLUSION: HA, APRI, FibroTest, Fib-4, and TE reliably distinguish non-cirrhotic and cirrhotic patients. Except for MBT, all tests discriminate between mild and moderate fibrosis. As single tests: FibroTest, Fib-4, and TE were the most accurate for detecting early fibrosis; combining different non-invasive tests increased the accuracy for detection of liver fibrosis to such an extent and thus might be acceptable to replace liver biopsy.

[Hepatocellular carcinoma: the significance of cirrhosis for treatment and prognosis--retrospective study]. / Hepatocellulair carcinoom: de betekenis van cirrose voor beleid en prognose--retrospectief onderzoek.

OBJECTIVE: To determine whether the presence of liver cirrhosis was related to the treatment options and survival of patients with hepatocellular carcinoma (HCC). DESIGN: Retrospective. METHOD: A status investigation of all HCC patients who were treated in the period 2000-2007 at the Erasmus MC Hospital, Rotterdam, was performed. The treatments were analysed and the disease-free and total survival rate were calculated. RESULTS: HCC was diagnosed in 461 patients during the study period. Cirrhosis was present in 295 patients (64%). Treatment with curative intent was pursued in 184 patients through partial liver resection, orthotopic liver transplantation or radiofrequency ablation. The group of patients without cirrhosis contained significantly more women (38% versus 18%) (p < 0.001), showed less hepatitis B or C infection (34% versus 74%) (p < 0.001) and had a larger median tumour size (80 mm (range: 3-227) versus 35 mm (range: 8-200)) (p < 0.001). Patients without cirrhosis were mainly treated by partial liver resection (37% versus 10%) (p < 0.001) and less by liver transplantation (1% versus 13%) (p < 0.001) or radiofrequency ablation (5% versus 16%) (p = 0.001). Median follow-up was 31 months (range: 1-108). Without stratification according to treatment, the overall 3-year survival in patients with non-cirrhotic and cirrhotic HCC was 30% and 32%, respectively (difference not significant). Patients who had undergone potential curative treatment in cirrhotic or non-cirrhotic livers had a 3-year survival rate of 54% and 59%, respectively (difference not significant). The recurrence rate of HCC without cirrhosis was 39%, of which 31% in the first year. The recurrence rate with cirrhosis was 37%, of which 23% in the first year (difference not significant). CONCLUSION: The presence of liver cirrhosis was strongly associated with treatment options for patients with HCC but not with the prognosis for a recurrence of HCC or the survival rate following potential curative treatment.

A randomized trial of peginterferon alpha-2a with or without ribavirin for HBeAg-negative chronic hepatitis B.

OBJECTIVES: Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients are at high risk of treatment relapse after any antiviral therapy. Combining peginterferon alpha-2a with ribavirin might improve sustained response rates. METHODS: Overall, 138 HBeAg-negative chronic hepatitis B patients were randomized to receive monotherapy (peginterferon alpha-2a 180 microg weekly plus placebo) or combination therapy (peginterferon alpha-2a weekly plus ribavirin 1,000 or 1,200 mg daily, depending on body weight) for 48 weeks. Post-treatment follow-up lasted 24 weeks. Analyses were based on the modified intention-to-treat population after exclusion of five patients. RESULTS: At the end of follow-up, 14 (20%) of 69 patients assigned to monotherapy and 10 (16%) of 64 assigned to combination therapy had a combined response (hepatitis B virus (HBV) DNA <10,000 copies/ml (<1,714 IU/ml) and a normal alanine aminotransferase level, P=0.49). At the end of treatment, more patients had a combined response (25 (36%) vs. 26 (41%) in the monotherapy and combination therapy group, respectively, P=0.60), but subsequently relapsed during follow-up. Serum HBV DNA and hepatitis B surface antigen (HBsAg) levels decreased during treatment (mean change at week 48 compared with baseline -3.9 vs. -2.6 log copies/ml, P<0.001 and -0.56 vs. -0.34 log IU/ml, P=0.23, respectively). HBV DNA levels relapsed after treatment discontinuation; HBsAg remained at end-of-treatment levels. In general, combination therapy was well tolerated, although it was associated with a higher risk of anemia and neutropenia. CONCLUSIONS: Treatment with peginterferon alpha-2a resulted in a limited sustained response rate in HBeAg-negative chronic hepatitis B patients. Addition of ribavirin did not improve response to therapy.

Paris criteria are effective in diagnosis of primary biliary cirrhosis and autoimmune hepatitis overlap syndrome.

BACKGROUND & AIMS: Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) differ in clinical, laboratory, and histologic features as well as in response to therapy. A small subgroup of patients have an overlap syndrome with features of both diseases, although there is no consensus on its definition or diagnostic criteria. We evaluated the significance of the criteria used to diagnose PBC-AIH overlap syndrome. METHODS: This retrospective, single-center study included all patients diagnosed with PBC, AIH, or PBC-AIH overlap syndrome, based on the Paris criteria, since January 1990 (n = 134); patients were followed up for 9.7 +/- 3.7 years. The 3 groups were compared for their clinical, laboratory, and histologic features. Patients with overlap syndrome or PBC were graded by the revised and simplified AIH scoring systems to assess the ability of this system to identify AIH cases properly. RESULTS: The sensitivity and specificity of the Paris criteria for diagnosing the overlap syndrome were 92% and 97%, respectively. The sensitivity and specificity of the AIH scoring systems were considerably lower. Among patients with the overlap syndrome, the 10-year, transplantation-free survival rate was 92%. CONCLUSIONS: The Paris diagnostic criteria detect overlap syndrome (PBC and AIH) with high levels of sensitivity and specificity. The clinical value of the revised and simplified AIH scoring system is not as reliable. Patients with PBC-AIH overlap syndrome have a 92% rate of 10-year, transplantation-free survival.

[A patient with an alpha-foetoprotein producing tumour]. / Een patiënt met een alfafoetoproteïneproducerende tumor.

A 45-year-old Turkish man presented with a chronic hepatitis B virus infection, a nodular lesion in the liver and a highly elevated serum alpha-foetoprotein (AFP) concentration. Ultrasound and MRI showed multiple focal liver lesions and a thickened wall of the gastro-oesophageal junction. Biopsies taken from both sites showed stomach type mucosa with a poorly differentiated adenocarcinoma and AFP positive tumour cells. The diagnosis was hepatoid adenocarcinoma of the stomach. The authors' conclusion is that an elevated serum AFP concentration in a patient with chronic hepatitis B and a nodular lesion in the liver is not diagnostic for a hepatocellular carcinoma. AFP measurement should not be used as a screening method for this type of cancer.

The Ross procedure: a systematic review and meta-analysis.

BACKGROUND: Reports on outcome after the Ross procedure are limited by small study size and show variable durability results. A systematic review of evidence on outcome after the Ross procedure may improve insight into outcome and potential determinants. METHODS AND RESULTS: A systematic review of reports published from January 2000 to January 2008 on outcome after the Ross procedure was undertaken. Thirty-nine articles meeting the inclusion criteria were allocated to 3 categories: (1) consecutive series, (2) adult patient series, and (3) pediatric patient series. With the use of an inverse variance approach, pooled morbidity and mortality rates were obtained. Pooled early mortality for consecutive, adult, and pediatric patients series was 3.0% (95% confidence interval [CI], 1.8 to 4.9), 3.2% (95% CI, 1.5 to 6.6), and 4.2% (95% CI, 1.4 to 11.5). Autograft deterioration rates were 1.15% (95% CI, 1.06 to 2.06), 0.78% (95% CI, 0.43 to 1.40), and 1.38%/patient-year (95% CI, 0.68 to 2.80), respectively, and for right ventricular outflow tract conduit were 0.91% (95% CI, 0.56 to 1.47), 0.55% (95% CI, 0.26 to 1.17), and 1.60%/patient-year (95% CI, 0.84 to 3.05), respectively. For studies with mean patient age >18 years versus mean patient age < or =18 years, pooled autograft and right ventricular outflow tract deterioration rates were 1.14% (95% CI, 0.83 to 1.57) versus 1.69% (95% CI, 1.02 to 2.79) and 0.65% (95% CI, 0.41 to 1.02) versus 1.66%/patient-year (95% CI, 0.98 to 2.82), respectively. CONCLUSIONS: The Ross procedure provides satisfactory results for both children and young adults. Durability limitations become apparent by the end of the first postoperative decade, in particular in younger patients.

The angiogenic makeup of human hepatocellular carcinoma does not favor vascular endothelial growth factor/angiopoietin-driven sprouting neovascularization.

UNLABELLED: Quantitative data on the expression of multiple factors that control angiogenesis in hepatocellular carcinoma (HCC) are limited. A better understanding of the mechanisms underlying angiogenesis in HCC will improve the rational choice of anti-angiogenic treatment. We quantified gene and protein expression of members of the vascular endothelial growth factor (VEGF) and angiopoietin systems and studied localization of VEGF, its receptors VEGFR-1 and VEGFR-2, Angiopoietin (Ang)-1 and Ang-2, and their receptor, in HCC in noncirrhotic and cirrhotic livers. We employed real-time reverse transcription polymerase chain reaction (RT-PCR), western blot, and immunohistology, and compared the outcome with highly angiogenic human renal cell carcinoma (RCC). HCC in noncirrhotic and cirrhotic livers expressed VEGF and its receptors to a similar extent as normal liver, although in cirrhotic background, VEGFR-2 levels in both tumor and adjacent tissue were decreased. Ang-1 expression was slightly increased compared with normal liver, whereas Tie-2 was strongly down-regulated in the tumor vasculature. Ang-2 messenger RNA (mRNA) levels were also low in HCCs of both noncirrhotic and cirrhotic livers, implying that VEGF-driven angiogenic sprouting accompanied by angiopoietin-driven vascular destabilization is not pronounced. In RCC, VEGF-A levels were one order of magnitude higher. At the same time, endothelially expressed Ang-2 was over 30-fold increased compared with expression in normal kidney, whereas Ang-1 expression was decreased. CONCLUSION: In hepatocellular carcinoma, tumor vascularization is not per se VEGF/angiopoietin driven. However, increased CD31 expression and morphological changes representative of sinusoidal capillarization in tumor vasculature indicate that vascular remodeling is taking place. This portends that therapeutic intervention of HCC at the level of the vasculature is optional, and that further studies into the molecular control thereof are warranted.

Magnetic resonance imaging of liver lesions: exceptions and atypical lesions.

On state-of-the-art magnetic resonance imaging, most lesions can be detected and characterized with confidence according to well-known criteria. However, atypical characteristics in some common lesions and the incidental encounter with rare lesions may pose diagnostic difficulties. In this article, six challenging hepatic lesions will be discussed and evaluated on the most important magnetic resonance imaging sequences, with histological correlation when available. In addition, the background information concerning these lesions will be described based on the most recent available literature. By reading this article, the reader will be able to (1) categorize the lesion in solid and fluid-containing lesions, based on the T2 signal intensity; and (2) define the benign or malignant nature of the lesion, in relation to the signal intensity and dynamic enhancement pattern, despite the presence of atypical characteristics of some lesions.

Primary hepatocellular lesions: imaging findings on state-of-the-art magnetic resonance imaging, with pathologic correlation.

Magnetic resonance imaging is routinely used for the workup of patients with focal or diffuse liver disease, including primary hepatocellular lesions, storage diseases, metastatic liver disease, and diseases of the hepatobiliary tree. The most important magnetic resonance imaging sequences used for diagnostic imaging of the liver consist of T1-weighted sequences, T2-weighted sequences, and at least the arterial and delayed phases of dynamic gadolinium-enhanced imaging. This article provides an overview of magnetic resonance imaging of primary hepatocellular lesions and will describe the following: (1) the classification and etiology of primary hepatocellular lesions, including focal nodular hyperplasia, hepatocellular adenoma, and hepatocellular carcinoma; (2) the stepwise carcinogenesis of hepatocellular carcinoma in cirrhosis on magnetic resonance imaging; and (3) the typical imaging findings of primary hepatocellular lesions on magnetic resonance imaging, with differential diagnoses.

Hepatocellular carcinoma complicating biliary atresia after Kasai portoenterostomy.

Kasai portoenterostomy (PE) increases the survival for children with biliary atresia (BA) and consequently postpones subsequential liver transplantation. All long-term survivors, however, develop complications of biliary cirrhosis. We report a case of hepatocellular carcinoma (HCC) in a 19-year-old male patient with BA and Kasai PE. The preoperative abdominal ultrasound and magnetic resonance imaging showed a large hepatic mass (diameter 10 cm). The serum alpha-fetoprotein level was within normal range. Pathologic findings of the mass, after orthotopic liver transplantation, demonstrated a well-differentiated HCC (T1N0M0). HCC is a rare complication of BA, but will intensively impair the survival. Therefore, clinicians should be alert to the development of HCC in this very young patient group. Repeated sequential magnetic resonance imaging of the native liver in patients with Kasai PE is necessary to monitor possible malignant transformation of liver nodules that may potentially develop as a result of chronic cholestatic liver disease.

Severe jaundice, due to vanishing bile duct syndrome, as presenting symptom of Hodgkin's lymphoma, fully reversible after chemotherapy.

Liver involvement in Hodgkin's lymphoma is common and is caused by hepatic infiltration, biliary obstruction by lymphoma, hepatitis, sepsis or complications of chemotherapeutic treatment. Jaundice caused by the vanishing bile duct syndrome related to Hodgkin's lymphoma is very rare. The mechanism is poorly understood but a paraneoplastic effect seems most likely as liver biopsy samples show cholestasis in the absence of lymphoma cells. Despite adequate treatment almost all reported patients died of liver failure or disease progression. Disease progression is explained partly by the difficulties encountered in the administration of potential hepatotoxic chemotherapy in severely cholestatic patients. We describe a 17-year-old man with vanishing bile duct syndrome and Hodgkin's lymphoma who was treated successfully with chemotherapy. The markedly elevated serum bilirubin levels completely normalized. Our case demonstrates that although dosing of chemotherapy in this situation can be very difficult, a good clinical outcome is possible, which makes the attempt at curative treatment worthwhile.

Thiopurine-methyltransferase and inosine triphosphate pyrophosphatase polymorphism in a liver transplant recipient developing nodular regenerative hyperplasia on low-dose azathioprine.

The enzymes thiopurine-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) are involved in thiopurine metabolism. We describe a liver transplant recipient who presented with liver enzyme abnormalities after 78 months of low-dose azathioprine (AZA) therapy (less than 1 mg/kg). No underlying etiology of these abnormalities was identified after extensive analysis including repeated liver biopsy. Fifteen years after transplantation, the patient presented with variceal bleeding, liver biopsy showed nodular regenerative hyperplasia (NRH). TPMT*3C genotype was found in the patient's lymphocytes and heterozygous ITPA (94C>A) genotype was found in both patient and donor liver. These findings further emphasize the importance of pharmacogenetics in predicting NRH and other adverse events during AZA therapy. Furthermore, a high index of suspicion with early detection of NRH is crucial, as improvement seems only to occur in patients with compensated liver disease. Liver biopsy and discontinuation of AZA are recommended in case of liver enzyme abnormalities or signs of portal hypertension.

Early changes of the portal tract on microcomputed tomography images in a newly-developed rat model for Budd-Chiari syndrome.

BACKGROUND AND AIM: The effect of increased sinusoidal pressure on the portal tract in Budd-Chiari syndrome (BCS) is as yet not elucidated. Our aim was to investigate portal changes in a newly-developed rat model for BCS. METHODS: We created an outflow obstruction in Sprague-Dawley rats (n = 6) by diameter reduction of the inferior vena cava. Left and right liver lobes with portal vein contrast were scanned using microcomputed tomography, and volumes of the portal tree and liver parenchyma were computed by the ANALYZE software program. RESULTS: Portal branching density was significantly lower in BCS than the shams, and decreased over time (P < 0.01). There was a significant drop in volume of both parenchyma and the portal tree in the left but not right lobes. At 6 weeks post-surgery, the perfusion index (i.e. ratio between both volumes) became equal to (left) or even higher than (right) the shams, suggesting a new equilibrium with preserved portal perfusion. Histological findings were consistent with those observed in humans. CONCLUSION: As early as day 2, a significant loss of peripheral portal branches was seen, which progressed over time. Inter-lobar differences in vascular abnormalities suggest compensatory mechanisms. Despite a decrease in both liver and portal vein volume, relative portal perfusion appeared spared.

FOXP3 mRNA expression analysis in the peripheral blood and allograft of heart transplant patients.

Previously, we demonstrated in heart transplant patients that FOXP3, a gene required for the development and function of regulatory T cells, was highly expressed in the graft during an acute cellular rejection. In this study, we analyzed whether the FOXP3 gene expression in the peripheral blood also reflects anti-donor immune responses, and therefore may provide clues for non-invasive detection of non-responsiveness or acute rejection. We examined the FOXP3 expression patterns of peripheral blood mononuclear cells (PBMC; n=69) of 19 heart transplant patients during quiescence and rejection in comparison with those of endomyocardial biopsies (EMB; n=75) of 24 heart transplant patients. While the FOXP3 mRNA levels were abundantly expressed in rejecting EMB (ISHLT rejection grade>1R) compared with EMB without histological evidence of myocardial damage (ISHLT rejection grade 0R-1R; p=0.003), no association with rejection or non-responsiveness was found for the FOXP3 mRNA levels in the peripheral blood. Thus, in contrast to intragraft FOXP3 gene expression, the peripheral FOXP3 mRNA levels lack correlation with anti-donor immune responses in the graft, and, consequently, FOXP3 does not appear to be a potential candidate gene for non-invasive diagnosis of non-responsiveness or rejection.

MR imaging of hepatocellular carcinoma: relationship between lesion size and imaging findings, including signal intensity and dynamic enhancement patterns.

PURPOSE: To assess the relationship between lesion size and MR imaging findings of pathologically-proven hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In a retrospective, single-center study, 37 consecutive patients were identified between 1999 and 2005 that underwent preoperative MRI and surgical resection of HCC. A total of 47 lesions (mean size = 6.85 cm, range = 1-25 cm) were assessed for signal intensity (SI), enhancement patterns, and secondary morphologic features. Interobserver rating, percentage enhancement, and contrast-to-noise-ratio (CNR) were determined. Lesions were assessed for combinations of typical MRI features. Regression analysis was used to assess relations between MRI findings and tumor size. RESULTS: On fat-suppressed T2-weighted (T2w) fast-spin-echo, smaller lesions had lower SI compared to larger lesions (P < 0.05). In the arterial phase, smaller lesions showed significantly higher percentage enhancement compared to larger lesions (P < 0.05). In the delayed phase, smaller lesions showed less pronounced washout (P < 0.05). Heterogeneity of the lesions, including fatty infiltration, internal nodules, or mosaic pattern, was observed significantly more frequently in larger lesions (P < 0.001). The classic combination of high T2w signal, strong arterial enhancement, and delayed phase washout was present in 23 of 44 lesions (52%). CONCLUSION: Smaller HCC often showed lower SI on T2w, more intense arterial enhancement, and less pronounced delayed washout compared to larger HCC.

Peginterferon alpha-2b is safe and effective in HBeAg-positive chronic hepatitis B patients with advanced fibrosis.

UNLABELLED: Chronic hepatitis B (CHB) patients with advanced fibrosis are often not considered for treatment with peginterferon (PEG-IFN) because IFN therapy may precipitate immunological flares, potentially inducing hepatic decompensation. We investigated the efficacy and safety of treating hepatitis B e antigen (HBeAg)-positive CHB patients with 52 weeks of PEG-IFN-alpha-2b (100 microg weekly) alone or in combination with lamivudine (100 mg daily). Seventy patients with advanced fibrosis (Ishak fibrosis score 4-6) and 169 patients without advanced fibrosis, all with compensated liver disease, participated in the study. Virologic response, defined as HBeAg seroconversion and hepatitis B virus (HBV) DNA < 10,000 copies/ml at week 78, occurred significantly more often in patients with advanced fibrosis than in those without (25% versus 12%, respectively; P = 0.02). Also patients with cirrhosis (n = 24) exhibited a virologic response more frequently than did patients without cirrhosis (30% versus 14%, respectively; P = 0.02). Improvement in liver fibrosis occurred more frequently in patients with advanced fibrosis (66% versus 26%, P < 0.001). HBV genotype A was more prevalent among patients with advanced fibrosis than among those without (57% versus 24%, P < 0.001). Most adverse events, including serious adverse events, were observed equally as frequently in patients with advanced fibrosis and those without. Fatigue, anorexia, and thrombocytopenia occurred more often in patients with advanced fibrosis than in those without (P < 0.01). Necessary dose reduction or discontinuation of therapy was comparable for both patient groups (P = 0.92 and P = 0.47, respectively). CONCLUSION: PEG-IFN is effective and safe for HBeAg-positive patients with advanced fibrosis. Because PEG-IFN therapy results in a high rate of sustained off-therapy response, patients with advanced fibrosis or cirrhosis but compensated liver disease should not be excluded from PEG-IFN treatment.