Hepatic Parenchymal Changes Research Articles

HCV treatment outcome depends on SNPs of IFNL3-Gene polymorphisms (rs12979860) and cirrhotic changes in liver parenchyma

Background and objectiveThe allelic discrimination of IFNL3-(rs12979860 C > T) polymorphism reveals ambiguous associations with the effectiveness of oral HCV treatment. Solitary intra peripheral-blood-mononuclear-cells (PBMCs) HCV-RNA antisense-strands are independently detected in naïve and experienced cases regardless of viremia or hepatic-parenchymal alterations. We examined the frequencies of IFNL3-genetic variants with chronic-HCV-induced liver changes during the sustained virologic response (SVR) by evaluating the PBMCs- HCV-PCR after oral antiviral therapy. Methods: Twelve weeks after finishing oral antiviral therapy, the effects of IFNL3-genetic variants were evaluated in three groups of patients: Group-I (n = 25) showed HCV-RNA negativity in both serum and PBMCs-, group II (n = 52) showed positivity of HCV-RNA in PBMCs, and group-III (n = 25) had positive HCV-RNA in serum. The genetic variants of the IFNL3-gene were estimated for all the enrolled cases and correlated with their hepatic image changes. Results: IFNL3-(rs12979860) genotyping in post-direct acting antivirals (DAAs) SVR and HCV-relapse revealed: a) high frequency of CC-genotype and C-allele in group I compared to group II (P < 0.005) and group III(P ≤ 0.05) when hepatic-parenchyma looks normal by ultrasound b) frequent CT-genotype and T-allele in group II compared with I(P < 0.01) and III(P < 0.05) when liver tissues are bright (early cirrhotic-changes) c) frequent TT-genotype and T-allele in group III relative to I (P < 0.05) and II (P ≤ 0.08) when liver-tissues appear coarse by ultrasound. Conclusion: Outcomes of HCV treatment depend on host IFNL3-gene polymorphism and hepatic-parenchymal changes. A high frequency of wild-CC-genotype and C-allele is observed in patients with normal hepatic parenchyma and that achieved SVR. Solitary relapse in PBMCs occurs on increasing CT-genotype frequency when liver tissues are bright. Serologic relapse is detected when TT-genotype and T-allele are dominant in association with the cirrhotic liver. Therefore, IFNL3-gene-SNP analysis as a genetic predictor in relation to ultra-sonographic hepatic-parenchymal changes could be valuable for selecting the patients with the highest priority for treatment.

Evaluation of Morphological Changes in Hepatic Parenchyma, Bile Ducts, and Hepatic Vasculature in Patients with Oriental Cholangiohepatitis using Ultrasonography

Objective: The objective of this study is to study the morphological changes in hepatic parenchyma, to characterize the intra and extrahepatic ductal changes and to study the morphological changes in vasculature of the liver in patients with oriental cholangiohepatitits (OCH). Materials and Methods: All documented or newly diagnosed cases of OCH, referred to the department of radiodiagnosis and imaging from Departments of Surgical Gastroenterology and Medical Gastroenterology were evaluated by ultrasonography (USG) and color Doppler study. The dilatation of the intrahepatic as well as extra-hepatic ducts was noted. The morphological changes in the liver parenchyma as well as hepatic vasculature were studied. Results: USG showed calculi in 53 (98.1%) cases, ductal dilatation in 52 (96.3%), and worms within biliary ducts in 10 cases (18.5%). Among parenchymal changes, atrophy was seen in 9 cases (16.6%), space-occupying lesion was seen in seven cases (12.9%), and peri-portal echogenicity in 10 cases (18.5%). Significant association was found between atrophic segments and reduced/absent blood flow in the affected segmental portal venous branches. Conclusion: USG is the preferred primary examination. Further imaging depends on the USG findings, the patient's symptomatology, the clinical problems, and the intended mode of treatment. Advances in Knowledge: USG plays a pivotal role in the evaluation of oriental cholangiohepatitis in the low resource settings where higher modalities like MRI are not available, especially in the remote areas of developing countries, as it has high degree of accuracy in the diagnosis of OCH.

Simulation of prehepatic portal hypertension and impact of hepatic deportalization on its tissue

Objective. On the prehepatic portal hypertension pattern, created by partial ligature of venae portae in rats, to estimate the impact of partial hepatic deportalization on its tissue.&#x0D; Materials and methods. The investigation was conducted on 35 male rats of a Wistar line, aged 4–6 weeks. In 15 laboratory animals the partial ligature of vena porta with formation of stenosis was conducted, and in 15 –false ligature, while the control group consisted of 5 intact laboratory animals.&#x0D; Results. There were revealed certain connections between conduction of partial ligature of vena porta and critical (lethal) lowering of portohepatic perfusion.&#x0D; The model of prehepatic portal hypertension, using partial ligature of vena porta, leading to partial lowering of portohepatic perfusion with development of cavernous transformation of vena porta and dystrophic changes in hepatocytes with further fibrous changes in hepatic parenchyma, was applied.&#x0D; Conclusion. The portal vein narrowing grade in range 52 – 59% constitutes the optimal one for the prehepatic portal hypertension formation with development of zonal adipose parenchymatous hepatic dystrophy and the balloon degeneration of hepatocytes with further development of fibroses in rats of a Wistar line aged 4 – 6 weeks.

S3164 Successful Use of Ribavirin in an Immunocompetent Patient With Severe Hepatitis E

Introduction: Hepatitis E is usually a self-limited disease that does not require antiviral therapy. Limited use of Ribavirin has been described in immunocompromised patients with chronic hepatitis E virus (HEV) infection. We present a rare case of acute hepatitis E in an immunocompetent patient who was successfully treated with Ribavirin, highlighting its potential use in severe cases. Case Description/Methods: A 23-year-old man presented with 5 days of abdominal pain and jaundice 1 month after returning from South Asia. History was negative for liver disease, unprotected sexual activity, or toxic ingestion. Liver chemistries were abnormal with AST 1684, ALT 3001, T bili 6.6, and ALP 188. Initial CBC, BMP, and coagulation studies were at baseline. Abdominal imaging was also unremarkable except for evidence of hepatic parenchymal changes. An extensive viral, toxicological, and autoimmune workup revealed acute HEV infection with a viral load of 1.8 million IU/ml. He was initially managed conservatively but required admission to the liver service by day 4 due to persistently abnormal liver studies and a worsening INR to 1.7. A trial of Ribavirin 200mg BID was initiated and the patient’s transaminases and INR started to downtrend by day 5. By day 6, his symptoms improved and viral load decreased to 23,700 IU/mL. He was discharged on day 8 with a 12-week course of Ribavirin 400mg BID. Liver studies had completely resolved at follow-up 35 days after presentation. Discussion: HEV is a common source of liver failure in regions with high endemicity but is typically self-limited in developed nations. No therapy has been approved for acute hepatitis E, however, ribavirin, a nucleoside inhibitor used for hepatitis C, has been administered effectively in immunocompromised patients with chronic HEV. Limited instances of it being used in healthy patients with acute hepatitis E have also been reported but no clear guidance exists on its use in such rare, severe cases. Although our patient was young and healthy, we chose to trial Ribavirin in light of worsening synthetic liver function and to forestall impending fulminant liver failure. Various regimens have been previously described, ranging from 600-1200mg/day, but we found that a dose of 400-800mg/day was sufficient to induce a 76-fold decrease in viral load within days of Ribavirin initiation. This case provides yet another example of Ribavirin’s effectiveness in the treatment of severe hepatitis E and raises the need for further evaluation for use in such cases.

Imaging features of COVID-19-associated secondary sclerosing cholangitis on magnetic resonance cholangiopancreatography: a retrospective analysis

BackgroundDespite emerging reports of secondary sclerosing cholangitis (SSC) in critically ill COVID-19 patients little is known about its imaging findings. It presents as delayed progressive cholestatic liver injury with risk of progression to cirrhosis. Diagnosis cannot be made based on clinical presentation and laboratory markers alone. Magnetic resonance imaging (MRI) and magnetic resonance cholangiopancreatography (MRCP) can aid in the diagnosis. The aim of this study was to describe MRI/MRCP imaging features of COVID-19-associated SSC.ResultsSeventeen patients (mean age 60.5 years, 15 male) who underwent MRI/MRCP were included. All had been admitted to intensive care unit (ICU) (median duration of ICU stay 10 weeks, range, 2–28 weeks) and developed acute respiratory distress syndrome requiring mechanical ventilation. On imaging, all patients had intrahepatic bile duct strictures and 10 (58.8%) had associated upstream dilatation. Intrahepatic bile duct beading was seen in 14 cases (82.3%). Only one patient (5.9%) had extrahepatic bile duct stricturing. Patchy arterial phase hyperenhancement and high signal on T2- and diffusion-weighted images were seen in 7 cases (53.8%) and 9 cases (52.9%), respectively. Biliary casts were seen in 2 cases (11.8%). Periportal lymphadenopathy and vascular complications were not seen.ConclusionOn MRI/MRCP, COVID-19-associated SSC presents with multiple intrahepatic bile duct strictures with or without upstream dilatation and intrahepatic bile duct beading. Surrounding hepatic parenchymal changes including alterations in enhancement and T2 signal are common. The extrahepatic biliary tree was typically spared and periportal lymphadenopathy was missing in all patients.

Treatment of hepatitis C virus infection with direct-acting antivirals plus ribavirin eliminates viral RNA from peripheral blood mononuclear cells and reduces virologic relapse in diverse hepatic parenchymal changes.

Elimination of hepatitis C virus (HCV) may fail, leading to a non-response outcome because of inappropriate testing for viral RNA in peripheral blood mononuclear cells (PBMCs). Sequelae of HCV genotype 4 therapy with sofosbuvir and daclatasvir ± ribavirin were assessed in our study at the 12th week after end of treatment (EOT) by screening for viral genomic RNA in serum and PBMCs with correlation to hepatic parenchymal changes. We recruited 102 out of 2165 patients who had received sofosbuvir/daclatasvir, either alone (n = 1573) or together with ribavirin (n = 592). Subjects were classified into three groups based on testing by single-step reverse transcription PCR: group I, HCV negative in both serum and PBMCs (n = 25); group II, HCV positive in PBMCs only (n = 52); and group III, HCV positive in both serum and PBMCs (n = 25). Groups I and II (n = 77) were selected out of 2102 (every 27th subject), while group III (n = 25) were selected from every second or third serologic relapse (n = 63). The pre-sampling population (n = 2165) showed sustained virologic response (SVR) in 33.21%; serologic relapse in 2.91%; HCV RNA only in PBMCs (66.79%) compared to serologic relapses and potential cure (P < 0.0001); higher serologic (38 out of 63, P = 0.03210) and cellular (36 out of 52, P = 0.0002) relapses in dual therapy than in triple therapy. The post-sampling population (n = 102) showed more HCV relapses in dual (50 out of 60) than in triple (27 out of 42) therapy (P = 0.0351); increased HCV antisense RNA strand in relapses compared to positive-sense strands alone (P < 0.001); and significant SVR events in undetectable (15 out of 31) compared to early (10 out of 55, P = 0.0058) and cirrhotic liver tissue changes (0 out of 16, P = 0.0006). In summary, HCV treatment with sofosbuvir/daclatasvir is followed by higher rates of serologic and intracellular viral RNA relapse than treatment with sofosbuvir/daclatasvir plus ribavirin. Cellular and serum viral RNA relapses are accompanied by HCV-induced hepatic pathology. An increased SVR with no detectable liver tissue changes was observed after triple therapy due to elimination of HCV RNA from PBMCs.

Evaluation of IL28B Gene Sequence Variations in the Diagnosed Null-Response to DAAs Therapy by Intra PBMCs Nested HCV RNA PCR

Background: Single nucleotide polymorphisms (SNPs) of the IL-28B gene are reliable predictors of chronic HCV disease course after treatment with Peg-IFN and Ribavirin (RBV). Aims, Subjects and Methods: Impacts of IL-28B-SNPs on the response to direct acting antivirals (DAAs) were evaluated in posttreatment negative serum and cellular HCV-PCR (group I), solitary intra-PBMCs viral infections (group II), and positive HCV-RNA serology (group III). Twelve weeks after completing DAAs-therapy, 45 patients were recruited and divided into three groups (n=15each), as afro-mentioned. IL-28B gene sequencing was done to detect SNPs in relation to hepatic parenchymal changes in the selected study populations. Results and conclusion: Changes in liver parenchyma of group III (46.7%) and II (26.6%) were associated with higher HCV-relapse compared to I (P

Toxicological Investigations of Aristolochia longa Root Extracts

Aristolochia longa L. (Aristolochiaceae) is an herbaceous plant recognized in alternative medicine for its many therapeutic virtues. The aim of this study was to determine the pharmacotoxicological effects of this plant in order to ensure safe clinical use. The oral toxicity of the aqueous extract of A. longa roots was performed in vivo on Wistar rats at doses of 0.8, 1.25, 2, 2.5, and 5 g/kg/day for 21 days. Clinical signs were observed throughout the experimental period, followed by measurement of body weight change, while selected biochemical parameters, as well as relative organ weights and the histology of liver, kidney, and intestinal tissues, were evaluated after 6, 11, and 16 days and then at the end of 21 days of daily administration. At repeated doses for 21 days, the extract contributed to significant weight gain, in both control and treated rats. The global analysis of hepatic and renal biomarkers showed a significant increase between control and different doses of the extract, from the first to the third week of treatment, indicating the likely toxic effect of the extract on liver and kidney function. Organ toxicity was confirmed by histopathological examination, which revealed greater renal and hepatic parenchymal changes in animals treated with a high dose beyond the 16th day. At the end of the treatment, relatively small size of intestinal villi was also observed. It was concluded that ALAE has a low toxicity potential in nonprolonged oral administrations. However, at high chronic oral doses, A. longa appears to have significant toxicity on the organs tested.

Severity of Fontan-Associated Liver Disease Correlates with Fontan Hemodynamics

Fontan-palliated patients are at risk for the development of Fontan-associated liver disease (FALD). In this study, we performed a detailed hemodynamic and hepatic assessment to analyze the incidence and spectrum of FALD and its association with patients' hemodynamics. From 2017 to 2019, 145 patients underwent a detailed, age-adjusted hepatic examination including laboratory analysis (FibroTest®, n = 101), liver ultrasound (n = 117) and transient elastography (FibroScan®, n = 61). The median patient age was 16.0 years [IQR 14.2], and the median duration of the Fontan circulation was 10.3 years [IQR 14.7]. Hemodynamic assessment was performed using echocardiography, cardiopulmonary exercise capacity testing and cardiac catheterization. Liver ultrasound revealed hepatic parenchymal changes in 83 patients (70.9%). Severe liver cirrhosis was detectable in 20 patients (17.1%). Median liver stiffness measured by FibroScan® was 27.7 kPa [IQR 14.5], and the median Fibrotest® score was 0.5 [IQR 0.3], corresponding to fibrosis stage ≥ 2. Liver stiffness values and Fibrotest® scores correlated significantly with Fontan duration (P1 = 0.013, P2 = 0.012). Exercise performance was significantly impaired in patients with severe liver cirrhosis (P = 0.003). Pulmonary artery pressure and end-diastolic pressure were highly elevated in cirrhotic patients (P1 = 0.008, P2 = 0.003). Multivariable risk factor analysis revealed Fontan duration to be a major risk factor for the development of FALD (P < 0.001, OR 0.77, CI 0.68–0.87). In the majority of patients, hepatic abnormalities suggestive of FALD were detectable by liver ultrasound, transient elastography and laboratory analysis. The severity of FALD correlated significantly with Fontan duration and impaired Fontan hemodynamics. A detailed hepatic assessment is indispensable for long-term surveillance of Fontan patients.

Assessment of Diffusion Tensor Imaging Parameters of Hepatic Parenchyma for Differentiation of Biliary Atresia from Alagille Syndrome.

ObjectiveTo assess diffusion tensor imaging (DTI) parameters of the hepatic parenchyma for the differentiation of biliary atresia (BA) from Alagille syndrome (ALGS).Materials and MethodsThis study included 32 infants with BA and 12 infants with ALGS groups who had undergone DTI. Fractional anisotropy (FA) and mean diffusivity (MD) of the liver were calculated twice by two separate readers and hepatic tissue was biopsied. Statistical analyses were performed to determine the mean values of the two groups. The optimum cut-off values for DTI differentiation of BA and ALGS were calculated by receiver operating characteristic (ROC) analysis.ResultsThe mean hepatic MD of BA (1.56 ± 0.20 and 1.63 ± 0.2 × 10−3 mm2/s) was significantly lower than that of ALGS (1.84 ± 0.04 and 1.79 ± 0.03 × 10−3 mm2/s) for both readers (r = 0.8, p = 0.001). Hepatic MD values of 1.77 and 1.79 × 10−3 mm2/s as a threshold for differentiating BA from ALGS showed accuracies of 82 and 79% and area under the curves (AUCs) of 0.90 and 0.91 for both readers, respectively. The mean hepatic FA of BA (0.34 ± 0.04 and 0.36 ± 0.04) was significantly higher (p = 0.01, 0.02) than that of ALGS (0.30 ± 0.06 and 0.31 ± 0.05) for both readers (r = 0.80, p = 0.001). FA values of 0.30 and 0.28 as a threshold for differentiating BA from ALGS showed accuracies of 75% and 82% and AUCs of 0.69 and 0.68 for both readers, respectively.ConclusionHepatic DTI parameters are promising quantitative imaging parameters for the detection of hepatic parenchymal changes in BA and ALGS and may be an additional noninvasive imaging tool for the differentiation of BA from ALGS.

CT and MR imaging of chemotherapy-induced hepatopathy.

Chemotherapy-induced hepatopathy includes a wide variety of parenchymal and vascular hepatic changes on imaging, including diffuse or focal hepatopathies (i.e. hepatitis, steatosis, fibrosis, pseudocirrhosis, or sinusoidal obstruction). These changes can profoundly alter the hepatic parenchyma on imaging and result in both false negative and false-positive diagnoses of hepatic metastases and lead to errors in patient management strategies. It is therefore important for radiologists to have a comprehensive knowledge of the imaging patterns that may develop following chemotherapy. The purpose of this review is to explore the broad spectrum of hepatic parenchymal and vascular chemotherapy-induced changes on CT and MR imaging.

Targeting Accuracy of Image-Guided Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma in Real-Life Clinical Practice: In Vivo Assessment Using Hepatic Parenchymal Changes on Gd-EOB-DTPA–Enhanced Magnetic Resonance Images

Stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) has emerged as an alternative treatment option when curative treatment modalities cannot be applied. Although excellent local tumor control has been achieved with SBRT, the targeting accuracy in real-life practice remains poorly understood. We proposed an invivo assessment of targeting accuracy using hepatic parenchymal changes observed on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) images and applied this method to investigate the "real-life" targeting accuracy of image-guided SBRT. We selected 29 patients with available follow-up MR images acquired 2 to 4months after completion of SBRT. All patients were administered 45Gy in 3 fractions. The treated HCC and the region of hepatic parenchymal changes in the hepatobiliary phase of MR images were delineated. We evaluated the discrepancies between the center of the HCC and that of the parenchymal change area (intercenter discrepancy [ICD]). We also analyzed the difference in ICDs between those who underwent SBRT with intrahepatic marker guidance and those with diaphragm guidance. The median ICD in the 3-dimensional direction was 6.81mm (interquartile range [IQR], 4.27-9.61mm). Those for the craniocaudal, left-right, and anteroposterior components were 2.70mm (IQR, 1.83-4.06mm), 1.63mm (IQR, 0.76-3.49), and 4.12mm (IQR, 1.20-6.96mm), respectively. The median ICD for patients who underwent treatment with intrahepatic marker guidance and those with diaphragm guidance was 7.53mm (IQR, 6.63-10.86mm) and 5.60mm (IQR, 4.28-8.18mm), respectively. There was no significant difference in ICD between those who underwent treatment with intrahepatic marker guidance and those with diaphragm guidance (P=.296). The hepatic parenchymal changes observed on Gd-EOB-DTPA-enhanced MR images can be used to assess the targeting accuracy after SBRT for HCC.

PATHOLOGICAL AND PARASITOLOGICAL STUDIES ON SOME EIMERIA SPECIES IN RABBITS USING LIGHT AND ELECTRON MICROSCOPE

The prevalence of Eimeria in 50 examined rabbits was 84% (42/50). The prevalence was 92.6% in male rabbits while it was73.9% in female rabbits. According to age, the prevalence was determined 88% in rabbits less than 4 months of age while it was 80% in rabbits 4 months of age or more. No significant difference was recorded between rabbits in correlation to age and sex. Ten species of Eimeria infecting rabbits were isolated in Assiut by parasitological examination. The prevalence of Eimeria species were E. perforans (66.7%) followed by E. exigua (26.2%), E. media (26.2%), E. magna (21.4%), E. intestinalis (19%), E. coecicola (19%), E. irresidua (19%), E. piriformis (14.3%), E. flavescens (7.1%) and E. stiedae (7.1%). Single infection of Eimeria spp. was found in 23.8% of the infected rabbits, where as mixed infection involved two, three or four Eimeria spp. was observed in 76.2% of the infected rabbits. Clinical signs were depression, anorexia, diarrhea while postmortem examination revealed hepatomegaly with presence of separate yellowish-white nodules of varying sizes spread over the surface with distended gall bladder. The intestinal lesions revealed varying degree of congestion, thickening of intestinal wall. Histopathological examination of the liver revealed dilated bile ducts and formation of papilliform projections of epithelium containing different developmental stages of Eimeria, associated with degeneration and pathological changes in hepatic parenchyma. The intestinal coccidiosis revealed hyperplasia of the epithelial cells and presence of Eimeria oocytes and gametocytes within the epithelial cells of the villi associated with lymphocytic infiltration in the lamina propria of the villi. The transmission electron microscope showed asexual and sexual developmental stages of rabbit Eimeria including developing schizont and macrogametocyte.

Different combinations of maternal and postnatal diet are reflected in changes of hepatic parenchyma and hepatic TNF-alpha expression in male rat offspring

Obesity is related to increased TNF-alpha production in different tissues. TNF-alpha is connected to mitochondrial dysfunction in the liver and also development of fatty infiltration of the liver. Also, postnatal change from normal to high-fat diet causes a significant increase in TNF-alpha serum levels. The aim of this research was to determine how maternal diet and switching male offspring to a different dietary regime after lactation influences rat liver. Ten female Sprague Dawley rats at nine weeks of age were randomly divided in two groups and fed either standard laboratory chow or high-fat diet during six weeks, and then mated with the same male subject. After birth and lactation male offspring from both groups were further divided into four subgroups depending on their subsequent diet. At 22 weeks of age, the animals were weighted, sacrificed and major organs were collected and weighted. Immunohistochemistry for TNF-alpha was performed on liver, and liver samples were analyzed for pathohistological changes. The group in which mothers were fed standard chow and offspring high-fat diet had the most pronounced changes: heaviest liver, poorest histopathological findings and strongest TNF-alpha immunohistochemical staining of liver parenchyma. High-fat diet during pregnancy and lactation and switching to high-fat diet postnatally affects liver weight, histological structure and TNF-alpha expression in male offspring.

Alagille Syndrome Candidates for Liver Transplantation: Differentiation from End-Stage Biliary Atresia Using Preoperative CT.

PurposeTo compare preoperative CT findings before liver transplantation between patients with Alagille syndrome (AGS) and those with end-stage biliary atresia (BA).Materials and MethodsThe institutional review board approved this retrospective study. Eleven children with AGS (median age, 19.0 ± 13.0 months; male to female ratio, 3:8) and 109 children with end-stage BA (median age, 17.9 ± 25.8 months; male to female ratio, 37:72) who underwent abdomen CT as candidates for liver transplant were included. CT images were reviewed focusing on hepatic parenchymal changes, vascular changes, presence of focal lesions, and signs of portal hypertension.ResultsHepatic parenchymal changes were present in 27% (3/11) of AGS patients and 100% (109/109) of end-stage BA patients (P < .001). The hepatic artery diameter was significantly smaller (1.9 mm versus 3.6 mm, P = 008), whereas portal vein diameter was larger (6.8 mm versus 5.0 mm, P < .001) in patients with AGS compared with patients with end-stage BA. No focal lesion was seen in patients with AGS, whereas 44% (48/109) of patients with end-stage BA had intrahepatic biliary cysts (39%, 43/109) and hepatic tumors (8%, 9/109) (P = .008). Splenomegaly was commonly seen in both groups (P = .082), and ascites (9% [1/11] versus 50% [54/109], P = .010) and gastroesophageal varix (0% [0/11] versus 80% [87/109], P < .001) were less common in patients with AGS than in patients with end-stage BA.ConclusionFibrotic or cirrhotic changes of the liver, presence of focal lesions, and relevant portal hypertension were less common in patients with AGS than in patients with end-stage BA.

Fontan-associated liver disease: Spectrum of US findings

PurposeTo describe ultrasonography (US) findings of Fontan-associated liver disease (FALD) and to determine whether screening US examinations can identify FALD before biochemical hepatic dysfunction. MethodsThis retrospective study included 55 patients who underwent Fontan procedure over a 20-year period. Hepatobiliary US findings (n=55), CT or MRI findings (n=19), biochemical hepatic function tests (n=49), and histopathological results (n=4) were analyzed. Images were reviewed focusing on the hepatic parenchymal changes, presence of focal lesions, and signs of portal hypertension. ResultsHepatic parenchymal changes (either heterogeneous echotexture or surface nodularity) evident on US were present in 67% (37/55) and showed positive correlation with the Fontan duration. Hyper-echoic lesions were noted in 35% (19/55) and showed a predilection for multiplicity, small size, right lobe location, and irregular margin on high-frequency transducer. These lesions were not demonstrated by CT or MRI or by low-frequency transducer. Histopathological results of targeted biopsy for hyper-echoic lesions revealed lesser degree of patchy sinusoidal and portal fibrosis than seen in cases with surface nodularity. Abnormal parenchymal enhancement was commonly seen with CT or MRI in 63% (12/19) and hypervascular nodules in 21% (4/19). Most patients (82%, 40/49) showed normal biochemical hepatic function tests, despite the presence of hepatic parenchymal changes on imaging. ConclusionThe common US findings of FALD included heterogeneous parenchymal echotexture, surface nodularity, and hyper-echoic lesions. We suggest that hyper-echoic lesions without surface nodularity detected by high-frequency transducer may represent the early stage of fibrosis. US examination may be useful for identifying the progression of FALD before biochemical hepatic dysfunction.

Hepatic reaction dose for parenchymal changes on Gd-EOB-DTPA-enhanced magnetic resonance images after stereotactic body radiation therapy for hepatocellular carcinoma.

The present study evaluated the threshold dose for hepatic parenchymal changes on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) images after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC). Twenty patients with available data of follow-up MR images acquired 2-4 months after completion of SBRT were selected among the registered patients. SBRT was performed using multiple coplanar and non-coplanar beams with energies of 6 or 15 MV. All patients were treated with doses of 45 Gy administered in three fractions over 3 consecutive days. For image registration between planning computed tomography (CT) and MR images, landmark-based rigid body registration was performed using MIM software. Seventeen patients were included in the analysis. The median discrepancies between planning CT and MR images in the left-right, anterior-posterior and superior-inferior directions were 1.38 mm, 1.24 mm and 1.72 mm, respectively. The median D50 value for the defect in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MR images after SBRT was 19.8 Gy (range, 14.2-28.7 Gy), with R(2) values ranging from 0.76 to 0.99. The threshold dose for parenchymal changes in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MR images performed 2-4 months after 45 Gy of SBRT in three fractions was approximately 20 Gy. Our results provide the basis for further research on the functional loss of liver parenchyma after SBRT.

Combined Protein C and Protein S Deficiency Presenting as Primary Budd-Chiari Syndrome in a 23-Year-Old Filipino Woman

Budd - Chiari Syndrome (BCS) is an uncommon hepatic vascular disorder affecting approximately 1 in every 2.5 million people worldwide often presenting as a sub - acute to chronic hepatic failure. Primary BCS, an even rarer subset of BCS, is described as the presence of intrinsic hepatic venous compression and occurs in 1 in every 6 million population. Primary BCS has often been attributed to hematologic disorders, more commonly myeloproliferative disorders, such as Polycythemia Vera, and in fewer cases, inherited thrombophilias, such as Protein C (PC) and Protein S (PS) deficiency, of which such cases are noted to be exceedingly rare. The authors describe a case of a 23-year-old Filipino female who was admitted on multiple occasions at a tertiary private hospital for over the course of a year, initially for complaints of epigastric pain and increasing abdominal girth. A review of the patient's past medical history was largely unremarkable with no familial cancers nor hepatitis infections noted, with the absence of oral contraceptive use. Initial workup consisted of serum chemistries and serology which yielded non specific and unremarkable findings. A series of imaging studies were then conducted - an initial screening abdominal ultrasound revealed an unremarkable biliary system and non specific structural hepatic parenchymal changes. A biopsy of the liver was taken revealing non specific venous congestion. The patient was then subjected to serial abdominal CT scans over the course of 6 months, which finally revealed complete absence of opacification of hepatic veins with a pattern suspicious for the presence of a thrombus, further mottled enhancement of the liver and splenic parenchyma due to congestion, all of which werefindings compatible with a Budd - Chiari Syndrome. Referral to a hematologist was carried out with thrombophilia workup done revealing decreased Protein C (Results: 32.2%,[Ref. Range: 70-140%]) and decreased Protein S (Results: 56%[Ref. Range: 60-140%]) results. The patient was then appraised of the eventual need for hepatic transplantation with a DIPS procedure contemplated.However, the patient eventually died from complications. This clinical case report documents an ethnic Filipino patient diagnosed with Primary BCS secondary to combined PC and PS deficiency, a subset of BCS that is both extremely rare and is not known to have previously occured in this population group. The authors cite this case to highlight both the need for diagnostic suspicion in cases of fulminant hepatic failure in the young and intend for it to be an early contribution to potential population based studies on BCS.Figure 1Figure 2

Hepatic Parenchymal Changes following Transcatheter Embolization and Chemoembolization in a Rabbit Tumor Model

ObjectiveTo compare the effects of transcatheter arterial chemoembolization (TACE) with transcatheter arterial embolization (TAE) on liver function, hepatic damage, and hepatic fibrogenesis in a rabbit tumor model.Materials and MethodsThirty-nine New Zealand white rabbits implanted with VX2 tumors in the left liver lobes were randomly divided into three groups: TAE, TACE, and control group. In the TAE group (n = 15), polyvinyl alcohol particles (PVAs) were used for left hepatic artery embolization. In the TACE group (n = 15), the tumors were treated with left hepatic arterial infusions of a suspension of 10-hydroxycamptothecin and lipiodol, followed by embolization with PVAs. In the control group (n = 9), the animals received sham treatment with distilled water. Serum and liver samples were collected at 6 hours, 3 days and 7 days after treatment. Liver damage was measured using a liver function test and histological analyses. Liver fibrogenesis and hepatic stellate cell (HSC) activation were evaluated using Sirius Red and anti-alpha-smooth muscle actin (α-SMA) immunohistochemical stains.ResultsTACE caused liver injury with greater increases in serum alanine aminotransferase and aspartate aminotransferase levels on day 3 (P<0.05). Histological analyses revealed increased hepatic necrosis in adjacent non-tumorous liver tissue from day 3 compared to the TAE group (Suzuki score of 2.33±1.29 versus 1.13±1.18, P = 0.001). HSC activation and proliferation were significantly increased in the TACE group compared to the control group at 3 and 7 days after treatment (0.074±0.014 vs. 0.010±0.006, and 0.088±0.023 vs. 0.017±0.009, P<0.05). Sirius Red staining demonstrated a statistically significant increase in collagen deposition in the livers in the TACE group 7 days after embolization compared to the control group (0.118±0.012 vs. 0.060±0.017, P = 0.05).ConclusionThe results of this animal study revealed that TACE induced prominent hepatocellular damage and hepatic fibrogenesis, which compromised liver function and may be responsible for chronic liver decompensation.

MR imaging in diffuse-type hepatocellular carcinoma with synchronous portal vein thrombi

Diffuse or continuous multifocal tumors with accompanying portal vein thrombosis yield considerable changes in the magnetic resonance imaging findings of hepatocellular carcinoma. The overlapped imaging findings of these two co-existing pathologies may be confusing. We aimed to evaluate the magnetic resonance imaging findings of widespread hepatocellular carcinoma lesions complicated with portal vein thrombosis. Twenty-two patients (20 male, 2 female; mean age: 57 years) with portal vein thrombosis and diffuse-type hepatocellular carcinoma who underwent contrast-enhanced hepatic magnetic resonance imaging in our department between August 2001 and November 2008 were evaluated retrospectively. The unenhanced axial T1-weighted, T2-weighted, and post-contrast early- and late-phase images were reviewed in each patient. On T2-weighted magnetic resonance images, tumors were seen mildly hyperintense in 11 patients and heterogeneously hyperintense in 11 patients. Unenhanced T1-weighted images demonstrated homogeneous hypointensity in 15 patients and heterogeneous hypointensity in 7 patients. Post-contrast early-phase magnetic resonance images showed patchy enhancement in 12 patients, moth-eaten enhancement in 6 patients, strong enhancement in 1 patient, and minimal enhancement in 3 patients. Post-contrast late-phase magnetic resonance images demonstrated heterogeneous washout in all patients. Portal vein thrombosis was present in all patients. The mean diameter of main portal vein thrombi was 27 mm (range: 25-30 mm). Serum alpha-fetoprotein levels were elevated in all patients. In patients with chronic parenchymal liver disease, when portal vein thrombosis and high serum alpha-fetoprotein values co-exist, careful attention must be paid to the hepatic parenchymal changes, especially on contrast-enhanced images, in order to not overlook diffuse-type hepatocellular carcinoma.