Epidemiology, pathogenesis, diagnosis, surveillance, and management of hepatocellular carcinoma associated with vascular liver disease.

Vascular liver disease (VLD) presents special challenges in the diagnosis, surveillance, and treatment of hepatocellular carcinoma (HCC). HCC arising in the setting of vascular liver disease is often thought to be due to elevated hepatic arterial blood flow, rather than progressive fibrosis from chronic inflammation as with other chronic liver conditions such as viral hepatitis, autoimmune, and metabolic liver diseases. Vascular alteration inherent in VLD often impedes HCC non-invasive diagnosis and loco-regional treatment that depend on vascular properties found in typical liver environment. Benign and pre-malignant liver nodules such as focal nodular hyperplasia and hepatocellular adenoma are also more common in certain VLDs, further adding to surveillance and diagnostic challenges. In this synopsis, we aimed to review available literature on the epidemiology, surveillance, diagnosis, and management of HCC in patients with VLD and specifically Budd-Chiari syndrome, congenital porto-systemic shunts, Fontan-associated liver disease, hereditary hemorrhagic telangiectasia.

Diffusion behavior of cerebral metabolites of congenital portal systemic shunt mice assessed noninvasively by diffusion-weighted 1 H magnetic resonance spectroscopy.

Diffusion-weighted 1 H-MRS (DW-MRS) allows for noninvasive investigation of the cellular compartmentalization of cerebral metabolites. DW-MRS applied to the congenital portal systemic shunt (PSS) mouse brain may provide specific insight into alterations of cellular restrictions associated with PSS in humans. At 14.1 T, adult male PSS and their age-matched healthy (Ctrl) mice were studied using DW-MRS covering b-values ranging from 0 to 45 ms/µm2 to determine the diffusion behavior of abundant metabolites. The remarkable sensitivity and spectral resolution, in combination with very high diffusion weighting, allowed for precise measurement of the diffusion properties of endogenous N-acetyl-aspartate, total creatine, myo-inositol, total choline with extension to glutamine and glutamate in mouse brains, in vivo. Most metabolites had comparable diffusion properties in PSS and Ctrl mice, suggesting that intracellular distribution space for these metabolites was not affected in the model. The slightly different diffusivity of the slow decaying component of taurine (0.015 ± 0.003 µm2 /ms in PSS vs 0.021 ± 0.002 µm2 /ms in Ctrl, P < 0.05) might support a cellular redistribution of taurine in the PSS mouse brain.

Assessment of surgical portosystemic shunts and associated complications: The diagnostic and therapeutic role of radiologists.

Surgical portosystemic shunting, the formation of a vascular connection between the portal and systemic venous circulation, has been used as a treatment to reduce portal venous pressure. Although the use of portosystemic shunt surgery in the management of portal hypertension has declined during the past decade in favour of alternative therapies, and subsequently surgeons and radiologists became less familiar with the procedure, it remains a well-established treatment. Knowledge of different types of surgical portosystemic shunts, their pathophysiology and complications will help radiologists improve communication with surgeons and enhance their understanding of the diagnostic and therapeutic role of radiology in the assessment and management of these shunts. Optimal assessment of the shunt is essential to determine its patency and allow timely intervention. Both non-invasive and invasive imaging modalities complement each other in the evaluation of surgical portosystemic shunts. Interventional radiology plays an important role in the management of complications, such as shunt thrombosis and stenosis. This article describes the various types of surgical portosystemic shunts, explains the anatomy and pathophysiology of these shunts, illustrates the pearls and pitfalls of different imaging modalities in the assessment of these shunts and demonstrates the role of radiologists in the interventional management of complications.

Effect of surgical portosystemic shunt on prevalence of minimal hepatic encephalopathy in children with extrahepatic portal venous obstruction: assessment by magnetic resonance imaging and psychometry.

OBJECTIVE: The aim of this study was to evaluate the effect of surgical portosystemic shunt (PSS) on the prevalence of minimal hepatic encephalopathy (MHE) in patients with extrahepatic portal venous obstruction. PATIENTS AND METHODS: Forty-two children with extrahepatic portal venous obstruction (17 with surgical PSS, 25 without surgical shunt) and 20 healthy children were evaluated with blood ammonia (BA), psychometry, H magnetic resonance spectroscopy, critical flicker frequency (CFF), and diffusion tensor imaging. Serum tumor necrosis factor-α and interleukin-6 were measured in 10 patients and 8 controls. RESULTS: Patients with surgical PSS had significantly higher BA and glutamine/creatine on H-MR spectroscopy than those without surgical shunt. Both groups of patients had significantly higher BA and glutamate/creatine than controls. Myoinositol was reduced in patients with surgical PSS. MHE was present in 41% cases with and 32% cases without surgical PSS (p-ns). Raised mean diffusivity on diffusion tensor imaging signifying low-grade cerebral edema was seen only in MHE cases. Patients had significantly higher serum tumor necrosis factor-α and interleukin-6 levels than controls. CFF was abnormal in 5 of 15 patients with MHE. CONCLUSIONS: Patients with surgical PSS have significantly higher BA and Glx/creatine than those without surgical PSS. MHE prevalence was higher in surgically shunted than in the nonshunted patients, but the difference was not significant. Cerebral edema is present in patients with MHE. CFF has limited diagnostic utility for MHE in children.

In vivo assessment of the hepatic microcirculation after mesenterico-portal bypass (REX-shunt) using orthogonal polarization spectral imaging.

BACKGROUND: Extrahepatic portal vein thrombosis, not associated with cirrhosis or tumours, is the second most frequent cause of portal hypertension worldwide. Especially in children, anatomic mesenterico-portal interposition (REX-shunt) has become an established treatment. The changes in hepatic microcirculation after reperfusion of the shunt have not been investigated so far. AIMS: This study investigates the hepatic microcirculation before and after REX-shunt interposition using orthogonal polarization spectral imaging (OPS). PATIENTS AND METHODS: Since 2004, three consecutive patients with extrahepatic portal vein thrombosis underwent REX-shunt interposition. We measured the hepatic microcirculation by OPS before and directly after REX-shunt reperfusion and analysed the capillary vessel diameter, red blood cell velocity, functional capillary density and volumetric blood flow. Furthermore, we compared our values with the physiological values of the hepatic microcirculation defined previously by other investigators. RESULTS: All shunts showed an excellent function in the follow-up investigations. The intra-individual microcirculatory analysis revealed a reduction in the red blood cell velocity after shunt reperfusion in particular. CONCLUSIONS: Our results provide preliminary evidence for the reversal of the hepatic arterial buffer response following the restoration of the portal venous blood flow. This may be a short-term effect because of the restored portal venous blood flow.

Direct puncture of the recanalized paraumbilical vein for portal vein targeting during transjugular intrahepatic portosystemic shunt procedures: assessment of technical success and safety.

PURPOSE: To assess the success of direct percutaneous puncture of the recanalized paraumbilical vein (RPUV) for access and visualization of the portal vein (PV) to guide transhepatic puncture during transjugular intrahepatic portosystemic shunt (TIPS) creation. The predictive value of successful catheterization based on preprocedural vein diameter was analyzed. MATERIALS AND METHODS: A retrospective review of all TIPS procedures from 2002 to 2008 performed at a single institution was conducted, and a subset of procedures in which portal venography was attempted via the paraumbilical vein were identified. In this subset, TIPS outcomes and diameters of the RPUV near the skin puncture site and left PV junction were measured and analyzed with a two-tailed Student t test. RESULTS: During the study period, 114 TIPSs were created. RPUV punctures were found in 22 patients (19.3%) and portal venography was successful in 14 of the 22 patients (64%), all without complications. In the remainder (n = 8), access via the RPUV failed secondary to a small vein diameter (< 0.3 cm; n = 3), moderate to severe vessel tortuosity (n = 4), and distal thrombosis (n = 1). Puncture, catheterization, and portal venography was successful when the paraumbilical vein measured a mean of 0.75 cm at the skin and a mean of 0.84 cm at the junction with the left PV when analyzed against the failed attempts. CONCLUSIONS: Portal venography via the RPUV is a feasible and probably safe alternative to other methods of PV opacification during TIPS procedures.

Impact of hospital and surgeon volumes in the management of complicated portal hypertension: review of a statewide database in Florida.

Mortality after complex surgical procedures has been shown to be inversely related to hospital volume. The purpose of this study was to determine whether these findings are applicable to radiologic and surgical procedures for complicated portal hypertension. The Agency for Healthcare Administration for the State of Florida database was queried to determine outcomes after transjugular intrahepatic stent shunts (TIPS) or surgical shunts from 2000 to 2003. A total of 1486 patients underwent either TIPS (1321) or surgical shunts (165). Natural breakpoints occurred at two and six procedures per year were correlated with survival for surgical shunts but not TIPS. Overall mortality was not different between TIPS and surgical shunts (11.0 vs. 12.7%, P = 0.51); however, the cost of TIPS was significantly lower (62,000 +/- 58.5 vs. 107,000 +/- 97.8, P < 0.001) as well as the length of hospitalization (9 +/- 9.0 days vs. 15 days +/- 12.6 days, P < 0.001). Surgical procedures for complicated portal hypertension are rapidly being replaced by TIPS. Like with other complex procedures, outcomes are related to hospital volume.

Racial disparities in the management of hospitalized patients with cirrhosis and complications of portal hypertension: a national study.

UNLABELLED: Having complications of portal hypertension is a harbinger of decompensated cirrhosis and warrants consideration for liver transplantation (LT). Racial disparities in LT have been reported. We sought to characterize disparities in the performing of surgical and endoscopic procedures among hospitalized patients with complications of portal hypertension. We queried the Nationwide Inpatient Sample from 1998 to 2003 to identify patients with cirrhosis and complications of portal hypertension. Logistic regression controlling for confounders was used to evaluate race as a predictor of undergoing a portosystemic shunt and LT and of dying in the hospital. Compared to whites, the adjusted odds ratios of receiving a portosystemic shunt were 0.37 (95% CI: 0.27-0.51) and 0.69 (95% CI: 0.54-0.88) for African Americans (AAs) and Hispanics, respectively. AAs with variceal bleeding were more likely to have endoscopic variceal hemostasis delayed more than 24 hours after admission than were whites (OR 1.6; 95% CI: 1.2-2.1). The adjusted odds ratios of undergoing LT were 0.32 (95% CI:0.20-0.52) and 0.46 (95% CI: 0.25-0.83) for AAs and Hispanics, respectively. Compared to whites, AAs experienced higher in-hospital mortality (OR 1.12; 95% CI: 1.01-1.24), whereas Hispanics had a lower risk of death (OR 0.83; 95% CI: 0.75-0.92). Among variceal bleeders, the odds ratio of death for AAs was 1.7 (95% CI: 1.2-2.4) compared to whites. CONCLUSION: AAs and Hispanics hospitalized for complications of portal hypertension were less likely to undergo a palliative shunt or LT than whites, which may contribute to the higher in-hospital mortality of AAs. Further studies are warranted to elucidate the mechanisms of these exploratory findings.

Update on the classification, assessment of prognosis and therapy of Budd-Chiari syndrome.

Budd-Chiari syndrome (BCS) occurs as a result of obstruction of hepatic venous outflow at any level from the small hepatic veins to the junction of the inferior vena cava with the right atrium. Diagnosis can be difficult because of the wide spectrum of presentation of the disease and the varying severity of liver damage. The traditional classification of BCS--as fulminant, acute or chronic--is not prognostically useful. This makes assessing the benefit of therapy difficult, especially as there is no evidence from randomized studies. This article highlights advances in the prognosis and therapy of BCS. Identification of the site of venous obstruction has a major effect on prognosis. Portal-vein thrombosis occurs in 20-30% of cases, and acute presentation of BCS reflects an acute or chronic syndrome in 60% of BCS cases. BCS can be diagnosed and treated on a single occasion in the setting of the radiology department, with hepatic venography, transjugular liver biopsy, retrograde CO2 portography and inferior vena cava pressure measurements performed simultaneously with therapies such as dilation or stenting of webs in the inferior vena cava or hepatic veins, and placement of transjugular intrahepatic portosystemic shunts. Disruption of a portal vein thrombus can also be done during the same session. Surgical shunts have been superseded by the use of transjugular intrahepatic portosystemic shunts. Liver transplantation is reserved for fulminant and progressive chronic forms of BCS. Anticoagulation therapy must be used routinely, before and after specific therapy, regardless of whether a thrombophilic disorder is diagnosed.

Quantification of the electroencephalographic theta/alpha ratio for the assessment of portal-systemic encephalopathy following implantation of transjugular intrahepatic portosystemic stent shunt (TIPSS).

The aim of the study was the quantification of metabolically caused electroencephalographic changes of portal-systemic encephalopathy, a prototype of hepatic encephalopathy. We examined 12 patients with liver cirrhosis before and after implantation of a transjugular intrahepatic portosystemic stent shunt (TIPSS) by means of quantitative digital electroencephalography (EEG). One month after TIPSS implantation, all patients showed an increase in the power of the theta frequency band as well as a decrease in the power of the alpha frequency band. To reduce the error variance, we formed the quotient of the relative power of the theta and alpha frequency band. Theta/alpha quotient values over 0.7 indicate a general change of the EEG with a sensitivity of 93% and a specificity of 87%. The results we have to hand indicate a correlation between the albumin concentration and the theta/alpha quotient 1 and 3 months after TIPSS. No significant correlation was revealed with regard to the Child-Pugh score or the liver function parameters cholinesterase, bilirubin, and prothrombin time. Neither the arterial ammonia concentration nor the performance in the psychometric test showed significance in relation to the theta/alpha quotient. Substances with a high albumin bond and potential neurotoxicity may--in the case of lower albumin levels--be absorbed with increased frequency in the CNS and may be responsible for the observed EEG change.

The prognostic value of histology in the assessment of patients with Budd-Chiari syndrome.

BACKGROUND/AIMS: It is unclear whether treatment of patients with Budd-Chiari syndrome (BCS) should be based on liver histology, as large histopathological studies have not been performed. We investigated the relationship between the histopathological findings and survival. METHODS: We studied the clinical features and findings on biopsy specimens in 45 patients with BCS who were admitted to four tertiary referral medical centers. Histological findings, i.e. congestion, necrosis, inflammation and fibrosis, were graded. Survival was assessed in relation to histological findings and clinical features at the time of diagnosis as well as in relation to subsequent treatment with or without portosystemic shunting. RESULTS: Centrilobular congestion, centrilobular necrosis, lobular inflammation and portal inflammation were not significantly related to survival. In addition, there was no association between either pericentral or periportal fibrosis and survival. Univariate analysis revealed that the prothrombin time and Child-Pugh score were significantly related to survival (P = 0.005 and Ptrend = 0.02, respectively). Multivariate analysis yielded the Child-Pugh score, serum alanine aminotransferase (ALT) and treatment with portosystemic shunting as independent prognostic indicators. CONCLUSIONS: We found no evidence for a relationship between early liver pathology and survival. Child-Pugh score, serum ALT and portosystemic shunting appeared to be prognostic indicators for patients with BCS.

Transjugular intrahepatic portasystemic shunt vs surgical shunt in good-risk cirrhotic patients: a case-control comparison.

HYPOTHESIS: In good-risk patients with variceal bleeding undergoing portal decompression, surgical shunt is more effective, more durable, and less costly than angiographic shunt (transjugular intrahepatic portasystemic shunt [TIPS]). DESIGN: Retrospective case-control study. SETTING: Academic referral center for liver disease. PATIENTS: Patients with Child-Pugh class A or B cirrhosis with at least 1 prior episode of bleeding from portal hypertension (gastroesophageal varices, portal hypertensive gastropathy). INTERVENTION: Portal decompression by angiographic (TIPS) or surgical (portacaval, distal splenorenal) shunt. MAIN OUTCOME MEASURES: Thirty-day and long-term mortality, postintervention diagnostic procedures (endoscopic, ultrasonographic, and angiographic studies), hospital readmissions, variceal rebleeding episodes, blood transfusions, shunt revisions, and hospital and professional charges. RESULTS: Patients with Child-Pugh class A or B cirrhosis undergoing TIPS (n = 20) or surgical shunt (n = 20) were followed up for 385 and 456 patient-months, respectively. Thirty-day mortality was greater following TIPS compared with surgical shunt (20% vs 0%; P =.20); long-term mortality did not differ. Significantly more rebleeding episodes (P<.001); rehospitalizations (P<.05); diagnostic studies of all types (P<.001); shunt revisions (P<.001); and hospital (P<.005), professional (P<.05), and total (P<. 005) charges occurred following TIPS compared with surgical shunt. CONCLUSIONS: Operative portal decompression is more effective, more durable, and less costly than TIPS in Child-Pugh class A and B cirrhotic patients with variceal bleeding. Good-risk patients with portal hypertensive bleeding should be referred for surgical shunt.

Transjugular intrahepatic portosystemic shunt versus H-graft portacaval shunt in the management of bleeding varices: a cost-benefit analysis.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is popular in treating portal hypertension because of its perceived efficacy and cost benefits, although it has never been compared with surgical shunting in a cost-benefit analysis. This study was undertaken to determine the cost benefit of TIPS versus small-diameter prosthetic H-graft portacaval shunt (HGPCS). METHODS: Cost of care was determined in 80 patients prospectively randomized to receive TIPS or HGPCS as definitive treatment for bleeding varices, beginning with shunt placement and including subsequent admissions for complications or follow-up related to shunting. RESULTS: Patients were similar in age, gender, severity of illness/liver dysfunction, and urgency of shunting. After TIPS or HGPCS, variceal rehemorrhage (8 versus O, respectively; p = 0.03), shunt occlusion (13 versus 4; p = 0.03), shunt revision (16 versus 4; p < 0.005), and shunt failure (18 versus 10; p = 0.10) were compared; all were more common after TIPS. Through the index admission, TIPS cost $48,188 +/- $43,355 whereas HGPCS cost $61,552 +/- $47,615. With follow-up, TIPS cost $69,276 +/- $52,712 and HGPCS cost $66,034 +/- $49,118. CONCLUSIONS: Early cost of TIPS was less than, though not different from, cost of HGPCS. With follow-up, costs after TIPS mounted. The initially lower cost of TIPS is offset by higher rates of subsequent occlusion and rehemorrhage.

The cost of dying of end-stage liver disease.

BACKGROUND: The high cost of liver transplantation is well known. The cost of dying of complications of end-stage liver disease (ESLD) without transplant, however, has not been well documented. METHODS: For a 5-year period (1991-1995), in 153 patients, mean inpatient hospital charges and length of stay were analyzed in 6 groups of patients: (1) patients admitted with the primary diagnosis of esophageal varices, (1a) the subset of group 1 patients who died on this admission, (2) patients admitted to the liver team who died of complications from ESLD, (3) patients who underwent transjugular intrahepatic portosystemic shunts, (4) patients who underwent surgical shunt for bleeding varices, and (5) patients who underwent liver transplantation. RESULTS: One hundred twenty-nine patients with esophageal varices were hospitalized 13.7 days with a mean charge of $30,980 for each of 202 admissions. Of these, 38 died after 24 days with a mean charge of $67,091. Seven patients admitted to the liver team died of complications of ESLD at $110,576 per admission. Transjugular intrahepatic portosystemic shunt was performed in 17 patients with a mean charge of $43,209. Six patients underwent surgical shunt for $53,994. Mean charge for 7 liver transplantations was $222,968. During the study period, 36.7% of all charges were for patients who died. CONCLUSIONS: It is difficult to estimate the total cost of ESLD; however, in evaluating inpatient costs, we see that it is expensive and significant amounts are spent on patients who die. Further study is necessary to determine which factors can optimize the cost of ESLD.

Efficacy of Doppler ultrasonography for assessment of transjugular intrahepatic portosystemic shunt patency.

PURPOSE: To assess the efficacy of Doppler ultrasonography (US) as a noninvasive method for monitoring patency of the transjugular intrahepatic portosystemic shunt (TIPS). METHODS: Twenty-nine patients who had received TIPS for bleeding esophagogastric varices and/or refractory ascites with portal hypertension underwent Doppler US studies within 2 weeks after TIPS. Further studies were performed in 15 of them at 6 months, in 9 at 1 year, and in 4 at 2 years for a total of 57 US studies. The US findings were compared with the angiographic findings obtained at the same time. RESULTS: In 45 of the 57 studies, shunt patency was found by Doppler US, correlating to 44 patencies and one occlusion on angiography. Doppler signal in the shunt could not be detected in 12 studies resulting in the diagnosis of shunt occlusion. This correlated with angiographic occlusion in 8 studies and patency in the remaining 4. All angiographically patent shunts that were occluded by Doppler US had various degrees of stenosis. A number of technical factors were found to be responsible for Doppler US false-positive or false-negative diagnoses, some related to the type of stent used. The Doppler US sensitivity was therefore 92%, the specificity 89%. CONCLUSION: Doppler US is a reliable noninvasive method to evaluate patency of TIPS.

[Color Doppler sonographic assessment of intrahepatic hemodynamics and shunt patency after transjugular intrahepatic portosystemic shunt (TIPS)].

The usefulness of color Doppler sonography for the assessment of intrahepatic hemodynamics and shunt patency was evaluated in a total of eight patients in whom the intrahepatic hemodynamics before and after transjugular intrahepatic portosystemic shunt (TIPS) could be serially examined by color Doppler sonography. In six of these patients the serial sonographic examinations could be followed for more than one year after TIPS creation. Within one month after TIPS creation, Vmax in the shunt was ranged from 87 cm/sec to 242 cm/sec (mean: 142.5 cm/ sec), and the flow direction in the right anterior portal vein was reversed in all patients. More than 70% stenosis of the shunt could be diagnosed by color Doppler sonography. When the shunt was confirmed by angiography to be more than 70% stenotic or occluded, Vmax in the shunt was decreased to less than 50 cm/sec and the blood flow in the right anterior portal vein become hepatopetal. From three months before stenosis or occlusion of the shunt, it was confirmed that Vmax in the shunt was less than 70 cm/sec or the blood flow of right anterior portal vein was hepatopetal. Color Doppler sonography was useful for the assessment of intrahepatic hemodynamics, and shunt patency and prediction of shunt stenosis or occlusion following TIPS creation.

Ultrasonido endoluminal en la valoración de prótesis portosistémicas intrahepáticas: informe del primer caso en México / Intravascular ultrasound in portosistemic shunt evaluation: preliminary report

Con el advenimiento de transductores de ultrasonido endoluminal, se han logrado importantes avances diagnósticos y terapéuticos, especialmente en el campo cardiovascular y vascular periférico. Aunque su uso se ha extendido, no tenemos conocimiento de su utilidad en la evalucaión de prótesis portosistémicas intrahepáticas colocadas por vía transyugular (TIPS). Informamos sobre una mujer de 40 años de edad a quien se realizó ultrasonido endoluminal de la prótesis intrahepática a los seis meses de colocada ésta. Se documentó un diámetro interior en la prótesis de 8.6 mm y de téjido fibroso de neoformación de 1.4 milímetros

Diagnostic and therapeutic technology assessment. Transjugular intrahepatic portosystemic shunt (TIPS).

OBJECTIVE: To provide clinicians with a technology assessment of the safety and effectiveness of the use of a transjugular intrahepatic portosystemic shunt (TIPS) for reducing portal hypertension and its associated complications of esophageal varices and ascites. PARTICIPANTS: A literature review and a Diagnostic and Therapeutic Technology Assessment (DATTA) survey questionnaire were mailed to 72 physicians with expertise in gastrointestinal or abdominal surgery or interventional radiology and a special interest in liver disease or esophageal varices. These panelists had been nominated to the DATTA panel by appropriate specialty societies and medical schools. A total of 54 panelists (75%) responded. EVIDENCE: Assessment was based on the expert opinion of the panelists, as well as on published scientific literature (available as of January 2, 1995). Published studies were identified by a MEDLINE search using the terms transjugular intrahepatic portosystemic shunt, TIPS, and transjugular and by review of the references cited in these primary sources. CONSENSUS PROCESS: The respondents completed a DATTA survey questionnaire; the survey results were tabulated, analyzed, and interpreted by an American Medical Association staff physician. CONCLUSIONS: The safety of TIPS was considered to be established in the acute control of bleeding from esophageal varices in patients who had failed sclerotherapy. The safety of TIPS was considered to be promising for long-term control of bleeding from esophageal varices. In patients with end-stage liver disease and esophageal varices who are liver transplant candidates, the use of TIPS was considered to be an established therapy. The effectiveness of TIPS was considered to be (1) established in the acute control of bleeding in patients who failed sclerotherapy; (2) promising for long-term control of bleeding from esophageal varices; and (3) established in patients with end-stage liver disease and esophageal varices who are candidates for liver transplants.