Free Hepatic Venous Pressure Research Articles

Feasibility and safety of ultrasound-guided percutaneous transhepatic measurement of portal venous pressure.

The measurement of portal venous pressure (PVP) has been extensively studied, primarily through indirect methods. However, the potential of ultrasound-guided percutaneous transhepatic PVP measurement as a direct method has been largely unexplored. This study aimed to investigate the accuracy, safety, and feasibility of this approach. In vitro, the experiment aimed to select a needle that could accurately transmit pressure, had a small inner diameter and was suitable for liver puncture, and performed on 20 healthy New Zealand white rabbits. An ultrasound-guided percutaneous transhepatic portal vein puncture was undertaken to measure PVP. Additionally, free hepatic venous pressure (FHVP) and wedged hepatic venous pressure (WHVP) were measured under digital subtraction angiography (DSA). The correlation between the two methods was assessed. Enroll study participants from October 18, 2023 to November 11, 2023 with written informed consent. Five patients were measured the PVP under ultrasound guidance before surgery to determine the feasibility of this measurement method. There was no significant difference in the results obtained using 9 different types of needles (P > 0.05). This demonstrated a great repeatability (P < 0.05). The 22G chiba needle with small inner diameter, allowing for accurate pressure transmission and suitable for liver puncture, was utilized for percutaneous transhepatic PVP measurement. There were positive correlations between PVP and HVPG (r = 0.881), PVP and WHVP (r = 0.709), HVPG and WHVP (r = 0.729), IVCP and FHVP (r = 0.572). The PVP was accurately and safely measured in 5 patients with segmental hepatectomy. No complications could be identified during postoperative ultrasound. Percutaneous transhepatic portal venous puncture under ultrasound guidance is accurate, safe and feasible to measure portal venous pressure. This study has been registered in the Chinese Clinical Trial Registry with registration number ChiCTR2300076751.

Study on the correlation between PPG and HVPG in patients with portal hypertension

Objective: To explore the correlation between portal vein pressure gradient (PPG) and hepatic vein pressure gradient (HVPG) in patients with portal hypertension (PHT). Methods: 752 cases with portal hypertension (PHT) who underwent transjugular intrahepatic portosystemic shunt (TIPS) and met the enrollment criteria between January 2016 to December 2019 were analyzed for hepatic vein, inferior vena cava and portal vein pressure. Paired t-test was used for analysis. Pearson correlation test was used to estimate correlation coefficient and coefficient of determination. P<0.05 were considered statistically significant. Results: Wedged hepatic vein pressure (WHVP), portal vein pressure (PVP), correlation coefficient, and coefficient of determination were 27.98±8.95 mmHg, 33.85±7.33 mmHg, 0.329 (P<0.001), and 0.108, respectively. HVPG, PPG,correlation coefficient, and coefficient of determination were 16.84±7.97 mmHg, 25.11±6.95 mmHg (P<0.001), 0.145, and 0.021 (P<0.001), respectively. The difference between HVPG and PPG was greater than 5 mmHg in 524 cases, accounting for 69.7%. The difference between HVPG and PPG was within 5 mmHg or basically equal in 228 cases, accounting for 30.3%. The correlation coefficient between free hepatic venous pressure (FHVP) and inferior vena cava pressure (IVCP) was 0.568 (P<0.001), and the coefficient of determination was 0.323. According to the presence or absence of hepatic venous collaterals after balloon occluded hepatic angiography, they were divided into two groups: 157 (20.9%) cases in the group with hepatic venous collaterals, and 595 (79.1%) cases in the group without hepatic venous collaterals. The parameters of the two groups were compared: WHVP (15.73±3.63) mmHg vs. (31.22±6.90) mmHg, P<0.001; PVP (31.69±8.70) mmHg vs. (34.42±6.81) mmHg, P<0.001; HVPG (7.18±4.40) mmHg vs. (19.40±6.62) mmHg, P<0.001; PPG (24.24±8.11) mmHg vs. (25.34±6.60) mmHg, P<0.001; free hepatic venous pressure (FHVP) (8.58±3.37) mmHg vs. (11.82±5.07) mmHg , P<0.001; inferior vena cava pressure (IVCP) (7.45±3.29) mmHg vs. (9.09±4.14) mmHg, P<0.001. Conclusion: The overall correlation is poor between HVPG and PPG. HVPG of most patients is not an accurate representation of PPG, and the former is lower than the latter. Hepatic venous collateral formation is one of the important reasons for the serious underestimation of HVPG values.

Correlation of pressure gradient in three hepatic veins with portal pressure gradient.

BACKGROUNDThe liver is one of the most important organs in the human body, with functions such as detoxification, digestion, and blood coagulation. In terms of vascular anatomy, the liver is divided into the left and the right liver by the main portal vein, and there are three hepatic efferent veins (right, middle, and left) and two portal branches. Patients with impaired liver function have increased intrahepatic vascular resistance and splanchnic vasodilation, which may lead to an increase in the portal pressure gradient (PPG) and cause portal hypertension (PHT). In order to measure the increased pressure gradient of portal vein, the hepatic venous pressure gradient (HVPG) can be measured to reflect it in clinical practice. The accuracy of PPG measurements is directly related to patient prognosis.AIMTo analyze the correlation between HVPG of three hepatic veins and PPG in patients with PHT.METHODSFrom January 2017 to December 2019, 102 patients with PHT who met the inclusion criteria were evaluated during the transjugular intrahepatic portosystemic shunt procedure and analyzed.RESULTSThe mean HVPG of the middle hepatic vein was 17.47 ± 10.25 mmHg, and the mean HVPG of the right and left hepatic veins was 16.34 ± 7.60 and 16.52 ± 8.15 mmHg, respectively. The average PPG was 26.03 ± 9.24 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.15 and 0.02 (P = 0.164); 0.25 and 0.05 (P = 0.013); and 0.14 and 0.02 (P = 0.013), respectively. The mean wedged hepatic vein/venous pressure (WHVP) of the middle and left hepatic veins was similar at 29.71 ± 12.48 and 29.1 ± 10.91 mmHg, respectively, and the mean WHVP of the right hepatic vein was slightly lower at 28.01 ± 8.95 mmHg. The mean portal vein pressure was 34.11 ± 8.56 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.26 and 0.07 (P = 0.009); 0.38 and 0.15 (P < 0.001); and 0.26 and 0.07 (P = 0.008), respectively. The average free hepatic venous pressure (FHVP) of the right hepatic vein was lowest at 11.67 ± 5.34 mmHg, and the average FHVP of the middle and left hepatic veins was slightly higher at 12.19 ± 4.88 and 11.67 ± 5.34 mmHg, respectively. The average inferior vena cava pressure was 8.27 ± 4.04 mmHg. The correlation coefficient and coefficient of determination of the right hepatic vein, middle hepatic vein, and left hepatic vein were 0.30 and 0.09 (P = 0.002); 0.18 and 0.03 (P = 0.078); and 0.16 and 0.03 (P = 0.111), respectively.CONCLUSIONMeasurement of the middle hepatic vein HVPG could better represent PPG. Considering the high success rate of clinical measurement of the right hepatic vein, it can be the second choice.

Transjugular Liver Biopsy with Hemodynamic Evaluation: Correlation between Hepatic Venous Pressure Gradient and Histologic Diagnosis of Cirrhosis.

Objectives:Measurement of hepatic vein pressures is the accepted gold standard for the evaluation of portal hypertension. This study was conducted to evaluate the correlation between hepatic vein pressure measurements and histologic findings from transjugular liver biopsies. The hypothesis was that higher hepatic venous pressure gradients would correlate with a histologic diagnosis of cirrhosis.Material and Methods:We identified all patients who underwent transjugular liver biopsies at our institution between January 2015 and December 2019. Of these, 178 patients who had undergone hemodynamic evaluations during the biopsy procedure were included in the study. Demographic information and laboratory data were extracted from the patients’ electronic medical records. The hepatic vein pressure gradient (HVPG) was determined by subtracting the free hepatic venous pressure from the wedged hepatic venous pressure (WHVP), and the portosystemic gradient (PSG) was determined by subtracting the right atrial pressure from the WHVP. HVPG and PSG were compared by linear regression analysis and by calculating their receiver operating characteristics (ROC).Results:HVPG and PSG measurements were significantly associated with cirrhosis, with area under the ROC curve of 0.79 and 0.78, respectively. At the optimal cutoff of 9 mmHg, sensitivity and specificity for HVPG were 71% and 83% for HVPG and 67 % and 81% for PSG, respectively. No statistical difference was observed between the two measurements.Conclusion:A transhepatic venous pressure gradient above a cutoff of 9 mmHg is predictive of histologic cirrhosis, regardless of whether it is expressed as HVPG or PSG, with acceptable to excellent performance characteristics.

Degree of Portal and Systemic Hemodynamic Alterations Predict Recurrent AKI and Chronic Kidney Disease in Patients With Cirrhosis.

The relevance of hemodynamic derangements on the incidence of recurrent acute kidney injury (AKI) and chronic kidney disease (CKD) in patients with cirrhosis is largely unknown. Consecutive patients with cirrhosis with a complete record of baseline hemodynamics were followed for identifying risk factors for the development of recurrent AKI and CKD by using negative binomial regression and competing risk analysis, respectively. Consecutive patients with cirrhosis (n = 2013, age 50.1 ± 11.8 years, 80% male, Child A:B:C percentage 13.7:52.9:33.4, and mean Child‐Turcotte‐Pugh score 8.6 ± 1.8) were enrolled, 893 (44.3%) of whom received beta‐blockers, with 44.2% responders. Prior AKI was noted in 12.4% at enrollment. At a median follow‐up of 379 (interquartile range: 68‐869) days, AKI developed at a rate of 0.37 episodes per person‐year, and 26% patients developed CKD. A lower mean number of AKI episodes (0.05 ± 0.25 vs. 0.42 ± 0.868; P < 0.001), CKD (subdistribution hazard ratio 0.74 [0.54‐1.02]), and mortality (hazard ratio 0.21 [0.06‐0.73]) were observed in beta‐blocker responders. Albuminuria was an independent risk factor for recurrent AKI, CKD, and mortality (P < 0.05). Lower systemic vascular resistance index predicted hemodynamic response (odds ratio 2.04 [1.29‐3.22]), cumulative AKI episodes (ratio of means 0.10 [0.08‐0.14]), and development of CKD (subdistribution hazard ratio 0.70 [0.58‐0.83]). Higher hepatic venous pressure gradient (≥17 mm Hg) predicted AKI episodes (ratio of means 1.76 [1.32‐2.35]) but not CKD. Conclusion: High portal pressure and severe vasodilatation predispose patients with cirrhosis to repeated AKI episodes and development of CKD. Response to beta‐blockers and therapies targeting the vasodilatory state could prevent frequent AKI and the risk of CKD development. Albuminuria could serve as an early marker of renal dysfunction in patients with cirrhosis.

Partial splenic embolization is superior to intravenous somatostatin for decreasing portal pressure in cirrhotic patients: a dynamic self-controlled cohort study

Aims The efficacy of somatostatin in altering splanchnic hemodynamics in cirrhotic portal hypertension is still controversial. We aimed to establish the dynamic effect of somatostatin on portal pressure in cirrhotic patients and compared its effect with Partial Splenic Embolization (PSE). Methods Eighteen patients with cirrhotic portal hypertension were prospectively recruited. The wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) were repeatedly measured at baseline, 1-, 5-, 10- and 20-min after initiating somatostatin infusion. After somatostatin infusion cessation and washout, WHVP and FHVP were measured before and after PSE. The change in all the variables between time points was analyzed. Results Decreased hepatic venous pressure gradient (HVPG) 5-min after initiation of infusion was identified compared with baseline level (19.6%; p-value: .042), which was achieved through elevated FHVP (37.5%; p-value: 9.26e − 04). There was no significant decrease in WHVP at any time point during somatostatin infusion. The HVPG (17.4%; p-value: 1.27e − 04) and WHVP (10.4%; p-value: 3.00e − 03) post-PSE significantly decreased compared to the washout level. No significant distribution differences in the number of patients with HVPG decrease by a percentage relative to the baseline level were identified between the 5-min time point and post-PSE. Conclusion Our study indicates that somatostatin administration does not decrease WHVP within 20 min at clinically recommended doses. While somatostatin did decrease HVPG, this effect was achieved through increased FHVP, providing a possible explanation for its unclear efficacy. In contrast, PSE decreases both the WHVP and the HVPG.

Intrahepatic veno-venous collateralization and misrepresentative hepatic venous pressure gradients in children.

Accurate and reproducible means of measuring the portosystemic gradient are essential for risk stratification and treatment of portal hypertension. To report the reliability of hepatic venous pressure gradients in children with intrahepatic veno-venous collateralization. Between January 2012 and December 2019 (96months), 39 patients with native livers underwent wedge hepatic venography and hepatic venous pressure gradient measurements at a tertiary pediatric center. All archived images were reviewed for balloon isolation of the hepatic vein and hepatic vein-to-hepatic vein (HV-HV) collaterals. HV-HV collaterals were categorized as present on the basis of non-catheterized segmental venous opacification despite appropriate balloon isolation. Hepatic venous pressure gradient was defined as the difference of wedge and free hepatic venous pressures. Wedge portosystemic gradient was defined as the difference between wedge hepatic venous pressure and right atrial (RA) pressures. For patients subsequently undergoing portal venous catheterization, portosystemic gradient was defined as the difference between main portal vein and RA pressures. Thirteen of 39 (33.3%) patients demonstrated HV-HV collaterals on wedge hepatic venography. The mean hepatic venous pressure gradient was 5.2±3.8mmHg (range: 0-15mmHg). The mean hepatic venous pressure gradient was 3.6±2.6mmHg (range: 0-9mmHg) in the presence of HV-HV collaterals and 5.9±4.2mmHg (range: 1-15mmHg) in the absence of HV-HV collaterals (P=0.043). Twelve (30.8%) patients were found to have varices: 10 gastroesophageal, 1 rectal and 1 stomal. The mean hepatic venous pressure gradient in patients with varices was 5.4±47mmHg (range: 0-15mmHg). For patients with varices, mean hepatic venous pressure gradient was 3.0±2.7mmHg (range: 0-9mmHg) in the presence of HV-HV collaterals and 10.3±4.1mmHg (range: 5-15mmHg) in the absence of HV-HV collaterals (P=0.004). Four (10.3%) patients had extrahepatic portal vein occlusion: 3 with cavernous transformation and 1 with type Ib Abernethy malformation. All patients with extrahepatic portal vein occlusion demonstrated HV-HV collaterals compared with 8 of 35 (22.9%) patients without extrahepatic portal vein occlusion (P=0.002). Four of 39 (10.3%) patients underwent direct portal pressure measurements: 3 via transhepatic and 1 via trans-splenic portal access. All had demonstrated HV-HV collaterals on wedged imaging. One had extrahepatic portal vein occlusion. The mean time between wedge portosystemic gradient and portosystemic gradient measurement was 3.75days (range: 0-8days). The mean wedge portosystemic gradient was 4.5±3.1mmHg (range: 2-9mmHg) and the mean portosystemic gradient was 14.5±3.7mmHg (range: 12-20mmHg) (P=0.006). HV-HV collateralization is frequently observed in children undergoing wedged portal venography and leads to misrepresentative hepatic venous pressure gradients. All patients undergoing hepatic venous pressure gradient measurement should have wedged venography to identify HV-HV collaterals and to qualify measured pressures. Additional techniques to obtain representative pressures in the presence of HV-HV collaterals warrant further investigation.

Measurement of the Hepatic Venous Pressure Gradient and Transjugular Liver Biopsy.

Here we provide a detailed protocol describing the clinical procedure of hepatic venous pressure gradient (HVPG) measurement in patients with advanced chronic liver disease followed by an instruction for transjugular biopsy. Under local anesthesia and ultrasound guidance, a catheter introducer sheath is placed in the right internal jugular vein. Usingfluoroscopic guidance, a balloon catheter is advanced into the inferior vena cava (IVC) and inserted into a large hepatic vein. Correct and sufficient wedge position of the catheter is ensured by injecting contrast media while the balloon is blocking the outflow of the cannulated hepatic vein. After calibrating the external pressure transducer, continuous pressure recordings are obtained with triplicate recordings of the wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP). The difference between FHVP and WHVP is referred to as HVPG, with values ≥10 mm Hg indicating clinically significant portal hypertension (CSPH). Before removing the catheter, pressure readings obtained in the IVC at the same level, as well as the right atrial pressure are recorded. Finally, a transjugular liver biopsy can be obtained via the same vascular route. Different systems are available; however, core biopsy needles are preferred over aspiration needles, especially for cirrhotic livers. Again, under fluoroscopic guidance a biopsy needle introducer sheath is advanced into an hepatic vein. Next, the transjugular biopsy needle is gently advanced through the introducer sheath: (i) in case of aspiration biopsy, the needle is advanced into the liver parenchyma under aspiration and then removed quickly, or (ii) in case of a core biopsy, the cutting-mechanism is triggered inside the parenchyma. Several separate passages can be safely performed to obtain sufficient liver specimens via transjugular biopsy. In experienced hands, the combination of these procedures takes about 30-45 min.

2334 Dapagliflozin, Diabetes, Liver Disease: With New Medications Come New Responsibilities

INTRODUCTION: Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, is an oral hypoglycemic agent that was released in 2011. FDA approval was initially delayed due to concerns of hepatotoxicity. We present a case of drug induced liver injury (DILI) from dapagliflozin in a patient with newly diagnosed non-alcoholic fatty liver disease (NAFLD). CASE DESCRIPTION/METHODS: A 54-year-old Caucasian female with a history of obesity, diabetes mellitus, hyperlipidemia, and macular edema presented to the emergency room with new onset jaundice and intermittent episodes of confusion. She denied history of liver disease, recent travel, new or unusual foods, tattoos, incarcerations, previous blood transfusions, alcohol abuse, illicit substance use, or intake of herbal preparations. She started dapagliflozin one month prior for her diabetes. Her physical exam revealed scleral icterus and jaundice. Laboratory workup revealed total bilirubin 20.5, direct bilirubin 18.8, AST 228, ALT 222, alkaline phosphatase 1,145. She had a normal CBC, INR, ferritin, negative viral hepatitis panel, ASMA, AMA, and ANA. MRCP was unremarkable. Liver biopsy revealed a free hepatic venous pressure of 11 and wedged hepatic venous pressure of 14, and gradient was 3 mm Hg. Histology revealed cholestasis, several missing bile ducts, bile duct proliferation, portal edema from neutrophil related inflammation, and 35% steatosis with ballooning cells and stage 3-4 fibrosis. Dapagliflozin was stopped, and the patient's bilirubin and LFTs normalized over the next few months. DISCUSSION: With the incidence of type 2 diabetes mellitus projected to rise, novel medications are being introduced to treat patients. Obesity, metabolic syndrome, and diabetes are all risk factors for NAFLD, and currently the prevalence of NAFLD in this group is estimated at 75%. As patients with chronic liver disease have less hepatic reserve, physicians must identify signs of NAFLD or other chronic liver diseases prior to starting potentially hepatotoxic medications. Dapagliflozin is 1,200 times more specific for SGLT-2, but also has some inhibitory effects on SGLT-1, a cotransporter responsible for reabsorption of glucose from bile. SGLT-1 inhibition causes increased glucose saturation of bile, which can result in hepatocyte injury. It is pivotal to screen diabetics beforehand for NAFLD when considering hypoglycemic agents like dapagliflozin that may be hepatotoxic given the potential for acute liver failure as was seen in our patient.

Should Low Central Venous Pressure Be Maintained during Liver Transplantation?

Low central venous pressure, which indirectly reflects free hepatic venous pressure, is maintained during hepatic resection surgery to reduce intraoperative blood loss by facilitating hepatic venous outflow. However, whether the low central venous pressure protocol established for non-transplant hepatobiliary surgery should be generalized to liver transplantation is controversial because patients with cirrhosis have decreased portal and hepatic venous blood flow and vulnerability to renal failure. However, consistent with observations from hepatic resection surgeries, lowering central venous pressure during the preanhepatic phase significantly reduces blood loss and transfusion volume. Conversely, inherent study limitations and different study designs have yielded different results in terms of renal dysfunction. Although hepatic venous outflow promoted by lowering blood volume seems to facilitate a liver graft to accommodate portal blood flow increased by portal hypertension-induced splanchnic vasodilatation, the association between low central venous pressure and reduced incidence of portal hyperperfusion injury has not been demonstrated. Stroke volume variation predicts fluid responsiveness better than central venous pressure, but it has not been associated with a greater clinical benefit than central venous pressure to date. Therefore, the safety of maintaining low central venous pressure during liver transplantation has not been verified, and further randomized controlled studies are warranted to establish a fluid management protocol for each phase of liver transplantation to reduce intraoperative blood loss and transfusion rate, thereby maintaining liver graft viability. In conclusion, low central venous pressure reduces intraoperative blood loss but does not guarantee renoprotection or graft protection.

Correlation of HVPG level with ctp score, MELD Score, ascites, size of varices, and etiology in cirrhotic patients.

Background/Aim:This study intends to determine the correlation of a patient's hepatic venous pressure gradient (HVPG) measurement with six factors: Child–Turcotte–Pugh (CTP) score, model for end-stage liver disease (MELD) score, presence of ascites, size of varices, presence of variceal bleeding, and an etiology of cirrhosis. The study also aims to identify the predictors of higher HVPG measurements that can indirectly affect the prognosis of cirrhotic patients.Patients and Methods:Thirty patients diagnosed with cirrhosis were enrolled prospectively and each patient's HVPG level was measured by the transjugular catheterization of the right or middle hepatic vein. The wedged hepatic venous pressure (WHVP) and free hepatic venous pressure (FHVP) were measured using a 7F balloon catheter. The HVPG level was calculated as the difference between the WHVP and FHVP measurements.Results:The mean HVPG level was higher in alcoholic than in nonalcoholic cirrhosis (19.5 ± 7.3 vs 15.2 ± 4.5 mm Hg, P = 0.13). The mean HVPG was also higher in bleeders compared with nonbleeders (18.5 ± 5.3 vs 10.7 ± 3.1 mmHg, P = 0.001). Patients with varices had a higher mean HVPG level than those without varices (17.4 ± 5.8 vs 11.7 ± 3.9 mmHg, P = 0.04). The difference among the three categories of varices (small, large, and no varices) was statistically significant (P = 0.03). In addition, the mean HVPG level was higher in patients with ascites than in those without ascites (18.7 ± 4.7 vs 11 ± 5.3 mmHg, P = 0.002), and it was significantly higher in patients in CTP class C (21.8 ± 5.5 mmHg) as compared with those in CTP class B (16.9 ± 2.9 mmHg) and CTP class A (10.5 ± 4.1 mmHg; P ≤ 0.001).Conclusion:HVPG levels were significantly higher in patients in CTP class C as compared with those in CTP classes A and B, thereby indicating that an HVPG measurement correlates with severity of liver disease. A high HVPG level signifies more severe liver disease and can predict the major complications of cirrhosis.

Comparative randomized study on efficacy of losartan versus propranolol in lowering portal pressure in decompensated chronic liver disease

This study aimed to compare the efficacy of losartan, an angiotensin II receptor antagonist, with propranolol on portal hypertension in patients with decompensated chronic liver disease. In all, 30 patients with Child-Pugh B cirrhosis and large varices without any prior therapy for portal hypertension were randomized to either losartan (n = 15) or propranolol (n = 15). Clinical, biochemical and hemodynamic parameters including hepatic venous pressure gradient (HVPG), wedged hepatic venous pressure (WHVP), mean arterial blood pressure (MABP) and free hepatic venous pressure (FHVP) were measured at baseline and after 4-week therapy. Patients with HVPG < 12 mmHg were regarded as responders. An equal number of responders were seen in both groups (6/15, 40.0%). The reduction of WHVP and HVPG was greater in the losartan group than in the propranolol group, although no significant differences between them were found. Heart rate decreased more in the propranolol arm than in the losartan arm (P < 0.01); however, no correlation between the decrease of heart rate and the reduction of HVPG was observed. One patient in the losartan group, although a responder, had gastrointestinal bleeding 2 months after the drug administration, but the varices were small under endoscopy and did not require definitive therapy. The fall of MABP was greater with losartan, with no statistical difference between the two groups. The effect of losartan was comparable to propranolol in reducing portal pressure in decompensated Child-Pugh B chronic liver disease.

Hepato-systemic gradient of carbon monoxide in cirrhosis

Background and aims Experimental data suggest that in liver cirrhosis splanchnic and systemic vasculature exhibit marked endothelial Carbon monoxide (CO) overproduction, while recent data demonstrated heme oxygenase (HO) hyperactivity in the liver of rats with cirrhosis. No data are so far available on CO levels in the hepatic veins of cirrhotic patients. We aimed at evaluating whether plasma CO levels differ between systemic (peripheral vein) and hepatic (hepatic vein) circulation in patients with viral cirrhosis with and without ascites. Methods We enrolled 31 consecutive non-smoking in- or outpatients with liver cirrhosis. We measured wedge (occluded, WHVP) and free hepatic venous pressures (FHVP) and hepatic-vein pressure gradient (HVPG) was the calculated. Plasma level of NO and plasma CO concentration were determined both in peripheral vein and in the hepatic vein in cirrhotics. Results In cirrhotic patients plasma CO levels were significantly higher in the hepatic vein (16.66 ± 10.71 p.p.m.) than in the peripheral vein (11.71 ± 7.00 p.p.m). Plasma NO levels were significantly higher in peripheral vein (97.02 ± 21.11 μmol/ml) than in the hepatic vein (60.76 ± 22.93 μmol/ml). Conclusions In patients with liver cirrhosis we documented a hepato-systemic CO gradient as inferred by the higher CO values in the hepatic vein than in the peripheral vein. In cirrhotic patients, CO and NO exhibit opposite behavior in the liver, while both molecules show increased values in the systemic circulation. It can be speculated that increased intra-hepatic CO levels might represent a counterbalancing response to reduced NO intra-hepatic levels in human liver cirrhosis.

Should we routinely measure portal pressure in patients with cirrhosis, using hepatic venous pressure gradient (HVPG) as a guide for prophylaxis and therapy of bleeding and rebleeding? No

Portal hypertension (PH) is a severe complication of liver cirrhosis. Measurement of the degree of portal hypertension is usually performed by measuring the hepatic venous pressure gradient (HVPG) which is the difference between the free hepatic venous pressure (FHVP) and the wedged hepatic venous pressure (WHPG). The HVPG accurately reflects the degree of PH in the majority of liver diseases. PH is defined by an increase of HVPG values above the normal upper limit of 5 mm Hg, while clinically significant PH is defined by an HVPG to ≥ 10 mm Hg. Although measurement of HVPG potentially has several applications, in clinical practice its major use has been related to the assessment of hemodynamic response to pharmacological therapy, in order to evaluate the efficacy of treatment and to predict the risk of rebleeding from esophageal varices. When properly performed, HVPG is a reliable, safe and good predictive tool in the management of portal hypertension. However, the need for appropriate equipment, sufficient and reliable operators and costs, have discouraged its use outside Liver Units specifically devoted to the clinical management of portal hypertension. This has diminished its applicability. Combining its use with transjugular liver biopsy and using the prognostic value of HVPG may help encourage its use.

Comparison of balloon vs. straight catheter for the measurement of portal hypertension

The hepatic venous pressure gradient (HVPG) is used as an estimation of portal pressure (PP) in the management of patients with cirrhosis. Two methods are available using either a straight or a balloon catheter, but have never been compared head-to-head. To compare the two methods of determining HVPG, straight and balloon catheter, regarding reproducibility and reliability. In 47 patients with liver cirrhosis, HVPG was assessed using both catheters in sequence. In another 29 patients, the wedged hepatic venous pressure (WHVP) determined either with straight or balloon catheter was correlated with a direct measurement of PP. Variation coefficient and intraclass correlation coefficient were calculated. Variation coefficients for balloon catheter were 0.07 (HVPG), 0.02 (WHVP) and 0.06 [free hepatic venous pressure (FHVP)]. Variation coefficients for straight catheter were 0.17 (HVPG), 0.06 (WHVP) and 0.07 (FHVP), demonstrating a significantly wider variation of the HVPG and WHVP measurements (P < 0.001). Comparison of WHVP with PP revealed a correlation coefficient of 0.72 (P = 0.004) using balloon catheter and 0.58 (P = 0.011) using straight catheter. Measurements with the balloon catheter currently represent the most reliable and reproducible method to assess HVPG. The results are of particular clinical relevance if repeated measurements are required for therapeutic adjustments.

Right Atrial Pressure Is Not Adequate to Calculate Portal Pressure Gradient in Cirrhosis: A Clinical-Hemodynamic Correlation Study

Hepatic venous pressure gradient (HVPG), the difference between wedge and free hepatic venous pressure, is the preferred method for estimating portal pressure. However, it has been suggested that hepatic atrial pressure gradient (HAPG)--the gradient between wedge hepatic venous pressure and right atrial pressure (RAP)--might better reflect variceal hemodynamics. The aim of this study was to (1) investigate whether HAPG with nonselective beta-blockers correlates with prognosis in cirrhotic patients with portal hypertension at baseline and during treatment; (2) compare the prognostic value of HAPG with that of HVPG; and (3) investigate the agreement between portoatrial gradient (PAG) and portocaval gradient (PCG) in patients with transjugular intrahepatic portosystemic shunt (TIPS). We included 154 cirrhotic patients with varices with a complete hemodynamic study at baseline and on chronic treatment for primary (n = 71) or secondary (n = 83) prophylaxis for bleeding and 99 patients with TIPS. All patients were followed for up to 2 years; portal hypertensive-related bleeding and bleeding-free survival were analyzed. HVPG was equal or lower than HAPG in all patients (-3.2 mm Hg; P < 0.001). Agreement between HAPG and HVPG was modest, especially in patients with increased intra-abdominal pressure. One hundred two patients were HVPG nonresponders and 52 patients were HVPG responders to nonselective beta-blockers, whereas 101 patients were HAPG nonresponders and 53 patients were HAPG responders (k = 0.610). HVPG response revealed an excellent predictive value for bleeding risk and bleeding-free survival; HAPG did not. In our TIPS patients, 20% had a PCG < or =12 mm Hg and a PAG >12 mm Hg, which may have induced unnecessary overdilation of the TIPS. The excellent prognostic information provided by HVPG response to drug therapy is lost if HAPG response is considered. RAP should not be used for the calculation of portal pressure gradient in patients with cirrhosis.

Portal Hypertension Severity Does Not Predict Capsule Endoscopy Findings in the Small Bowel of Patients with Liver Cirrhosis and Chronic Anemia

Background: Capsule endoscopy (CE) is a non-invasive and safe tool for small bowel examination. Recent studies support its use to detect the source of bleeding in cirrhotics with portal hypertension (PH) and chronic gastrointestinal blood loss. Aim: To compare the findings of CE to portal-hepatic venous gradient (PHVG), indirect signs of PH (platelets <100,000/μL, oesophageal/gastric varices, gastropathy, spleen diameter >130 mm, portal vein diameter >12 mm), and intra-abdominal collaterals in cirrhotics with chronic anemia. Methods: From December 2006 to March 2008, 12 patients (8 males, mean age 56.3 years), with portal hypertensive liver cirrhosis (Child-Pugh score ranging 5 to 12) and chronic anemia (mean haemoglobin 9.2; range 7-10) were submitted to CE. CE findings were arbitrarily classified into 3 stages: stage 0 (no findings), stage 1 (mucosal hyperaemia and/or erosions), stage 2 (varices). Intra-abdominal collaterals were evaluated by angio-TC in 10 patients and PHVG was measured in 6 patients. Results: Small bowel CE findings were: absence of mucosal abnormalities (stage 0) in 1 patient; multiple mucosal erosions (stage 1) in 6 patients (in one active bleeding was present); multiple small bowel varices (stage 2) in 5 patients. Results of portal pressure measurement were: wedged hepatic venous pressure 24.8 ± 5.1 (mean ± SD; range 18-33); free hepatic venous pressure 11.2 ± 1.7 (mean ± SD; range 9-14); PHVG 13.7 ± 3.5 (mean ± SD; range 9-19). Platelets were 102,363 ± 94,610/μL (mean ± SD; range 30,000-335,000). Upper endoscopy showed: oesophageal varices F1 in 7 patients and F3 in 1 patient, portal hypertensive gastropathy in 8 patients. Angio-CT showed: portal vein diameter 16.9 ± 2.5 (mean ± SD; range 14-22); spleen diameter 160 ± 28 mm (mean ± SD; range 12-20; one patient with previous splenectomy); ascites (6 patients: 1 patient grade I, 2 patients grade II, 3 patients grade III); gastric (8 patients), paraesophageal (7 patients), retrogastric (2 patients), paraumbelical (4 patients), perisplenic (6 patients), omental (6 patients), and spleno-renal (2 patients) varices. No significant correlations were found between the presence and the stage of small bowel CE findings, and the PHVG, the number of indirect signs of PH or the type of intra-abdominal collaterals. Conclusions: In portal hypertensive cirrhotics with chronic anemia, the presence and the stage of small bowel mucosal abnormalities detected by CE can not be predicted by the PHVG, by the number of indirect signs of PH or by the type of intra-abdominal collaterals. In these subjects, only endoscopy can confirm or exclude the presence of small bowel mucosal alterations.

Nodular regenerative hyperplasia of liver as a consequence of ART

Nodular regenerative hyperplasia of liver as a consequence of ART

Efficacy of Antiviral Therapy on Hepatitis C Recurrence After Liver Transplantation: A Randomized Controlled Study

Recurrence of hepatitis C virus (HCV) infection is a relevant problem of liver transplantation programs. We evaluated the effect of antiviral therapy on disease progression in 81 HCV-infected liver transplantation recipients. Patients with mild hepatitis C recurrence (fibrosis stage F0 to F2, n = 54) were randomized to no treatment (group A, n = 27) or peginterferon alfa-2b/ribavirin for 48 weeks (group B, n = 27). Patients with severe recurrence (F3 to F4, cholestatic hepatitis) were treated (group C, n = 27). All patients (n = 81) underwent a liver biopsy at baseline and after follow-up; paired hepatic venous pressure gradient (HVPG) measurements were available in 51 patients. Thirteen (48%) patients of group B and 5 (18.5%) of group C achieved sustained virological response. Liver fibrosis progressed > or =1 stage in 40 (49%) of 81 patients: 19 (70%) of group A versus 7 (26%) of group B (P = .001) and in 14 (54%) of group C. HVPG increased (6.5 to 13 mm Hg, P < .01) in patients in whom fibrosis worsened, whereas it decreased (5 to 3.5 mm Hg, P = .017) or remained unchanged in those with fibrosis improvement or stabilization, respectively. The only variable independently associated with fibrosis improvement/stabilization was treatment (odds ratio [OR] =3.7, 95% confidence interval [CI] 1.3 to 10, P = .009). Among treated patients, alanine aminotransferase (ALT) normalization and viral clearance were independently associated with histological or hemodynamic improvement/stabilization (OR 5.3, 95% CI 1.5 to 18, P < .01; OR 7.4, 95% CI 1.4 to 38, P = .01; respectively). Our data demonstrate that in liver transplantation recipients, antiviral therapy slows disease progression (particularly in sustained virological responders), as shown by its effects on liver histology and on HVPG.

SIR 2005 Annual Meeting Film Panel Case: Inferior Mesenteric Artery–to–Inferior Mesenteric Vein Fistulous Connection

A 56-year-old man was admitted to the hospital because of lower gastrointestinal bleeding manifested by black, tarry stool. Medical history and physical examination were noncontributory; he had no history of alcohol or drug abuse. Laboratory findings included a hematocrit of 26.2% and a platelet count of 166,000/ L. International Normalized Ratio and aspartate aminotransferase, alanine aminotransferase, albumin, and bilirubin levels were normal. Serologic examinations were negative for hepatitis. Large esophageal varices were seen on upper endoscopy. A transvenous liver biopsy was performed, which demonstrated nodular regenerative hyperplasia. Arterial portography, hepatic venography, cavography, and venous pressures were normal. The corrected sinusoidal pressure (wedged minus free hepatic venous pressure) was 11 mm Hg. However, subsequent direct portography performed via a transjugular approach demonstrated a portal vein–to–hepatic vein gradient of 30 mm Hg. A surgical shunt was performed to manage the gastrointestinal bleeding. Intraoperatively, the inferior mesenteric vein was noted to be quite large and to interfere with mobilization of the left renal vein; the inferior mesenteric vein was divided and the limb in communication with the splenic vein was sewn to the left renal vein. Postoperative magnetic resonance (MR) angiography was performed (Fig 1) because the shunt could not be visualized on surveillance ultrasonography. Because of the findings, inferior mesenteric arteriography (Fig 2) was performed.