Therapeutic benefits of partial splenic embolization for thrombocytopenia in hepatocellular carcinoma patients treated with radiofrequency ablation

Aim: Partial splenic embolization (PSE) is a non‐surgical procedure developed to treat hypersplenism. The purpose of this study is to evaluate therapeutic benefits of PSE with follow‐up radiofrequency ablation (RFA) treatment in hepatocellular carcinoma (HCC) patients with thrombocytopenia. Methods: Between September 1999 and January 2007, a total of 20 patients with HCC who had a few lesions, each 3 cm or less in diameter, and liver function of Child‐Pugh class A or B were enrolled into our study. The patients were diagnosed with marked thrombocytopenia (<50 × 10³/mm³), or mild thrombocytopenia (<80 × 10³/mm³) with decreased prothrombin activity. They were treated once or twice with PSE. RFA was given as a follow‐up treatment 2 weeks after final PSE. The primary endpoint was a platelet‐count increase and improvement of prothrombin activity, and the secondary endpoint was the initiation of RFA. Results: PSE was performed successfully in 19 patients (95%). Two weeks after final PSE, platelet counts increased significantly (38 ± 14 × 10³/mm³ vs. 97 ± 43 × 10³/mm³; P < 0.0001), and prothrombin activity improved significantly (59.3 ± 19.8% vs. 65.2 ± 17.9%; P < 0.0001). No patients had major complications during the PSE procedure. The secondary endpoint was achieved in 18 of 19 patients (94.7%). The mean overall survival was 2257 days (95% confidence interval; range, 1659?2855 days). The Kaplan‐Meier cumulative survival rate was estimated to be 61.9% at 5 years. Conclusions: PSE is a safe and effective treatment for thrombocytopenia and has adjuvant therapeutic benefits for the therapy of HCC.     

Portal hemodynamic effects of sorafenib in patients with advanced hepatocellular carcinoma: a prospective cohort study

Background and aims

Sorafenib is currently in clinical use as an oral multikinase inhibitor that blocks tumor growth and cell proliferation in advanced hepatocellular carcinoma (HCC). It has been demonstrated in a translating study that sorafenib had a beneficial effect on portocollateral circulation in cirrhotic animals with portal hypertension. This study was prospectively performed to evaluate the portal hemodynamic effect of sorafenib in patients with advanced HCC using duplex Doppler ultrasonography (DDU).

Methods

Twenty-five Child-Pugh class-A patients with advanced HCC had received sorafenib at a dose of 400?mg twice daily. Primary outcomes were changes in portal venous area (PVA; cm²) as seen by using DDU before and after a 2-week administration of sorafenib. Secondary outcomes included the changes of laboratory data and other flow data revealed on DDU.

Results

PVA was significantly decreased after a 2-week administration (0.78?±?0.23 vs. 0.64?±?0.25, P?=?0.023), while the portal venous flow velocity (PVV; cm/s) was not significantly changed (0.22?±?0.06 vs. 0.24?±?0.07, P?=?0.17). Therefore, the congestion index (PVA/PVV), which reflects the pathophysiological hemodynamics of portal venous system, was significantly decreased (3.9?±?1.7 vs. 3.0?±?1.4, P?=?0.042).

Conclusions

We demonstrated the portal hemodynamic effect of sorafenib in patients with advanced HCC. Considering that this was a short-term study, because sorafenib could be a potential beneficial therapeutic agent for portal hypertension, it will be necessary to verify its clinical benefits for portal hypertension in future studies.     

Short-term Effects of Hepatic Arterial Buffer Responses Induced by Partial Splenic Embolization on the Hepatic Function of Patients with Cirrhosis According to the Child-Pugh Classification

Objective This study primarily aimed to investigate the short-term effects of partial splenic embolization (PSE) on the Child-Pugh score and identify predictive factors for changes in the score caused by PSE. The secondary aim was to analyze changes in various parameters at one month postoperatively using these identified factors. Methods Between September 2007 and December 2019, 118 patients with cirrhosis and hypersplenism underwent PSE at our hospital. Testing was conducted preoperatively and at one month after PSE. Results Overall, the Child-Pugh score was not significantly changed postoperatively. The Child-Pugh score before PSE was identified as the strongest independent predictor of ameliorated and deteriorated Child-Pugh scores after PSE. Higher pretreatment Child-Pugh scores were correlated with higher posttreatment amelioration rates of the score. A significant decrease in the portal vein diameter and a significant increase in the common hepatic artery diameter were evident at the same level postoperatively in 64 patients with Child-Pugh class A (group A) and in 54 patients with Child-Pugh class B or C (group B/C) preoperatively. According to Murray''s Law, PSE resulted in decreased portal venous flow and increased hepatic arterial flow, suggesting a hepatic arterial buffer response (HABR) induced by the procedure. Despite equivalent splenic infarction rates and similar posttreatment changes in hepatic hemodynamics, PSE significantly increased the Child-Pugh score of group A; however, the procedure significantly decreased the score of group B/C. Conclusion Considering original portal venous-hepatic arterial hemodynamics, PSE is expected to produce HABR-mediated hepatic functional improvements in cirrhosis patients with Child-Pugh class B/C.     

Different hemodynamic patterns of alcoholic and viral endstage cirrhosis: Analysis of explanted liver weight,degree of fibrosis and splanchnic Doppler parameters

Objective. In cirrhosis, portal hemodynamics is usually considered independently of the disease etiology. The objective of this study was to investigate the role of the etiology of liver disease on the relationship between liver blood flow and liver pathology in endstage cirrhosis. Material and methods. Portal blood velocity and volume, congestion index of the portal vein, and hepatic and splenic pulsatility indices were evaluated with echo-Doppler in cirrhotic patients immediately before liver transplantation. When a patent paraumbilical vein was present, its blood flow was measured and effective portal liver perfusion was calculated as portal blood flow minus paraumbilical blood flow. The hemodynamic parameters were correlated with liver weight and the pattern of the liver fibrosis morphometrically assessed in explanted livers. A total of 131 patients with alcoholic or viral cirrhosis were included in the study. Results. In alcoholic cirrhosis, liver weight was higher than that in viral disease (1246±295 g versus 1070±254 g, p=0.001), portal liver perfusion per gram of liver tissue was lower (0.49±0.36 ml g^?1 min^?1 versus 0.85±0.56 ml g^?1 min^?1, p=0.004) and hepatic pulsatility indices were higher (1.45±0.31 versus 1.26±0.30, p=0.018). The degree of liver fibrosis was similar in alcoholic and viral cirrhosis (11.7±5.5% versus 11.0±4.4%, p=NS). An inverse relationship between liver weight and Child-Pugh score was disclosed in viral (p<0.001) but not in alcoholic disease. Conclusions. A different hemodynamic pattern characterizes the advanced stage of cirrhosis of alcoholic and viral origin. A more severe alteration of intrahepatic portal perfusion, probably coexisting with a more severe hepatocyte dysfunction, and a higher liver weight can be detected in alcoholic cirrhosis.     

Wedged Hepatic Venous Pressure Does Not Reflect Portal Pressure in Patients with Cirrhosis and Hepatic Veno–Venous Communications

Some cirrhotic patients have hepatic veno–venous communications (HVVC) and large porto-systemic collaterals. However, the relationship between wedged hepatic vein pressure (WHVP) and portal vein pressure (PVP) in such patients is not clear. The aim of this study was to determine the relationships between simultaneously measured WHVP and PVP, and occluded hepatic and splenic portal venography in 100 cirrhotic patients (40 alcoholic and 60 hepatitis C virus (HCV)-related cirrhosis). PVP and WHVP were closely related in both groups (alcoholic-cirrhosis: 27.8 ± 4.7 and 27.5 ± 4.8 mmHg, HCV-cirrhosis: 27.3 ± 3.7 and 26.2 ± 4.4 mmHg, respectively). Occluded hepatic venography revealed that 13 of the 100 patients had HVVC (alcoholic-cirrhosis: 4, HCV-cirrhosis: 9). In patients with HVVC, PVP (27.9 ± 3.0 mmHg) was significantly higher than WHVP (21.9 ± 3.3 mmHg, P < 0.001). Large porto-systemic collaterals did not affect the relationship. We conclude that HVVC affects the relationship between PVP and WHVP. When WHVP is measured, occluded hepatic venography should be examined to detect HVVC.     

Acute administration of sildenafil enhances hepatic cyclic guanosine monophosphate production and reduces hepatic sinusoid resistance in cirrhotic patients

Aim: In liver cirrhosis, the increased production of nitric oxide (NO) contributes to increased systemic and splanchnic vasodilatation. The inhibition of phosphodiesterase-5 (PDE-5), an enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP), is widely used in the treatment of erectile dysfunction. The aim of our study is to evaluate the overall effects of PDE-5 inhibitor administration on splanchnic, pulmonary and systemic hemodynamics in cirrhotic patients. Methods: Sildenafil, a specific PDE-5 inhibitor, was administrated orally to cirrhotic patients (n = 7) to see the hemodynamic changes. A control group receiving a placebo was used as a point of comparison (n = 6). Results: Compared to the control group, the hepatic vein NO and cGMP levels were significantly increased after sildenafil administration in the sildenafil group (NO from 112.3 ± 43.5 to 325.3 ± 117.5 nM, P = 0.018; cGMP from 7.3 ± 0.4 to 19.2 ± 4.2 pmol, P = 0.018). The hepatic venous pressure gradient in the sildenafil group did not differ from that of the control group. However, a significantly decreased hepatic sinusoidal resistance in the sildenafil group (1999 ± 1243 vs. 1563 ± 1014 dyne/s/cm⁻⁵, P < 0.05) was noted. The study also found that the right arterial pressure, mean pulmonary arterial pressure and pulmonary capillary wedge pressure were reduced at 60 min after administration, compared with the basal parameters in cirrhotic patients receiving sildenafil (RAP1.3 ± 2.0 vs −0.6 ± 1.3 mmHg, MPAP 14.1 ± 11.3 vs 11.7 ± 9.5 mmHg, PCWP 4.6 ± 1.7 vs 2.9 ± 1.6 mmHg, P < 0.05 respectively). Conclusions: An oral administration of 50 mg of sildenafil significantly decreased the mean pulmonary arterial pressure and hepatic sinusoid resistance with a significant increase in hepatic NO and cGMP production, and did not worsen portal hypertension in cirrhotic patients.     

Systemic and pulmonary hemodynamics in patients with non-cirrhotic portal fibrosis (NCPF) is similar to compensated cirrhosis

Background Non-cirrhotic portal fibrosis (NCPF) is an important cause of portal hypertension (PHT) and variceal bleeding, especially in the developing countries. While the hepatic parenchyma and liver functions are normal, the patho-anatomic defect in these patients is pre- and peri-sinusoidal in nature. Aim To study the systemic and pulmonary hemodynamic alterations in patients with NCPF and compare them with compensated cirrhotic patients. Patients and Methods Patients with NCPF (n = 20, mean age 29.3 ± 9.8 year) and matched Child’s A cirrhotic patients (n = 17, age 34.1 ± 9.8 year) who had bled in the past, underwent hemodynamic measurements using a balloon tipped catheter. Results In NCPF patients, the hepatic venous pressure gradient (HVPG) was significantly lower than in the cirrhotic patients (4.9 ± 1.5 mmHg vs. 15.7 ± 4.5 mmHg; P < 0.01). NCPF patients had hyperdynamic circulation and peripheral vasodilatation comparable to cirrhotic patients; cardiac output (8.0 ± 1.2 l/min vs. 8.4 ± 1.9 l/min; P = 0.4), cardiac index (5.4 ± 0.8 l/min/m² vs. 5.5 ± 1.9 l/min/m²; P = 0.86), mean arterial pressure (88.2 ± 14.1 mmHg vs. 89.9 ± 17.3 mmHg; P = 0.73), systemic vascular resistance (852.8 ± 204.3 dynes · s/cm⁵ vs. 854.1 ± 189.9 dynes · s/cm⁵; P = 0.98) and pulmonary vascular resistance (41.6 ± 18.1 dynes · s/cm⁵ vs. 41.3 ± 17.9 dynes · s/cm⁵; P = 0.95) were comparable in the two groups. Conclusions NCPF associated portal hypertension leads to a hyperdynamic state with high cardiac index and low systemic and pulmonary vascular resistance comparable to compensated cirrhosis. These novel observations suggest a primary role of portal hypertension in the development of hyperdynamic state.     

Thrombosis of the Portal Venous System in Cirrhotic vs. Non-Cirrhotic Patients

Introduction and aim. Thrombosis is a vascular disorder of the liver often associated with significant morbidity and mortality. Cirrhosis is a predisposing factor for portal venous system thrombosis. The aim of this study is to determine differences between cirrhotics and non-cirrhotics that develop thrombosis in portal venous system and to evaluate if cirrhosis severity is related to the development of portal venous system thrombosis.Material and methods. We studied patients diagnosed with portal venous system thrombosis using contrast-enhanced computed tomography scan and doppler ultrasound at Medica Sur Hospital from 2012 to 2017. They were categorized into two groups; cirrhotics and non-cirrhotics. We assessed the hepatic function by Child-Pugh score and model for end-stage liver disease.Results. 67 patients with portal venous system thrombosis (25 with non-cirrhotic liver and 42 with cirrhosis) were included. The mean age (± SD) was 65 ± 9.5 years in cirrhotic group and 57 ± 13.2 years (p = 0.009) in noncirrhotic group. Comparing non-cirrhotics and cirrhotics, 8 non-cirrhotic patients showed evidence of extra-hepatic inflammatory conditions, while in the cirrhotic group no inflammatory conditions were found (p < 0.001). 27 (64.29%) cirrhotic patients had thrombosis in the portal vein, while only 9 cases (36%) were found in non-cirrhotics (p = 0.02).Conclusions. In cirrhotic patients, hepatocellular carcinoma and cirrhosis were the strongest risk factors to develop portal venous system thrombosis. In contrast, extrahepatic inflammatory conditions were main risk factors associated in non-cirrhotics. Moreover, the portal vein was the most frequent site of thrombosis in both groups.     

Value of diffusion-weighted magnetic resonance imaging in early diagnosis of ankylosing spondylitis

The objective of this study is to estimate the value of diffusion-weighted MRI (DWI) in the detection of abnormalities in sacroiliac joints in the patients with early ankylosing spondylitis (AS) and investigate the feasibility of whole-body DWI (WB-DWI) in systemic evaluation of AS. Sixteen patients with early AS, 18 patients with simple low back pain (LBP), and 18 healthy volunteers were involved in this study. All subjects underwent conventional MRI and DWI. Apparent diffusion coefficient (ADC) in subchondral bone marrows of sacroiliac joints was measured. Independent-sample t test was used to statistically analyze the difference of ADC values between groups. WB-DWI was performed in additional 12 patients with clinically confirmed AS. The image results were analyzed by multiple post-processing techniques, as compared to conventional MRI. In AS patients, mean ADC values were (0.494?±?0.170)?×?10^?3?mm²/s in sacrum and (0.513?±?0.129)?×?10^?3?mm²/s in ilium, which were significantly higher than those of LBP ((0.306?±?0.057)?×?10^?3?mm²/s in sacrum and (0.323?±?0.083)?×?10^?3?mm²/s in ilium) and healthy volunteers ((0.315?±?0.009)?×?10^?3?mm²/s in sacrum and (0.319?±?0.012)?×?10^?3?mm²/s in ilium). No statistical differences were found between simple LBP and healthy volunteers. Mean ADC value of multiple lesions in AS was (0.932?±?0.299)?×?10^?3?mm²/s. By WB-DWI, abnormal signals of sacroiliac joints and extra-sacroiliac joint lesions were demonstrated in the locations corresponding with clinical findings. Mean ADC values of multiple lesions were (1.298?±?0.323)?×?10^?3?mm²/s in sacrum and (1.216?±?0.311)?×?10^?3?mm²/s in ilium. DWI and WB-DWI were shown to be effective in differentiation and systemic evaluation of early AS. Both techniques are likely to play an importance role in the early diagnosis of AS and assessment of treatment response.     

Effect of changes in vascular tone on the haemodynamic characteristics of the portal vascular bed of the isolated perfused rat liver

The effect of altered vascular tone on the haemodynamic characteristics of the intrahepatic portal vascular bed was studied in the isolated perfused rat liver preparation. The relationship between portal venous inflow (Q) and portal perfusion pressure (P) was determined in the presence of a maximally effective concentration of a vasoconstrictor agent (noradrenaline, NA_max, 3 × 10^?5mol/L), an intermediate concentration (NA_med, 1 × 10^?6mol/L) or a vasodilator agent (papaverine, PAP, 6 × 10^?4mol/L). At flow rates greater than 20 mL/min, the pressure-flow relationship could be regarded as linear (P < 0.001), with mean values for the extrapolated intercept with the pressure axis (P_o) of 6.8 ± 0.9 mmHg for NA_max, 4.5 ± 0.5 mmHg for NA_med, and 1.65 ± 0.05 mmHg for PAP-treated preparations. Over the full flow range (0–70 mL/min), in both NA- and PAP-treated preparations, portal vascular conductance (G = Q/P) was related directly to perfusion pressure. Thus, G = C.P, where C is a constant (mean values for NA_max, NA_med, and PAP-treated preparations were 0.0090 ± 0.0020, 0.023 ± 0.005, and 0.26 ± 0.02 mL/min per g per mmHg², respectively). It is concluded that both C and P_o may be useful indices of tone in the isolated perfused rat liver, and that analysis of hepatic portal haemodynamics in this manner may have considerable practical value in studies of the action of vasoactive agents.     

A retrospective cohort study of partial splenic embolization for antiviral therapy in chronic hepatitis C with thrombocytopenia

Background

Although partial splenic embolization (PSE) is reportedly effective prior to interferon (IFN)-based therapy, the number of subjects in these studies is small, and the appropriate candidates and disease prognosis remain unknown.

Methods

PSE was performed in 30 patients with advanced hepatitis C who could not receive IFN-based therapy because of thrombocytopenia, platelet counts of ??100,000/mm³, and hypersplenism. Also, we compared 25 PSE-treated patients with 23 PSE-untreated patients with thrombocytopenia receiving pegylated IFN (PEG-IFN)-alpha 2b plus ribavirin over the same period.

Results

PSE significantly increased platelet and leukocyte counts. PSE was well tolerated with no severe complications. All the patients could receive IFN-based therapy. Discontinuation of therapy in the total cohort of PSE-treated patients was not due to thrombocytopenia. Although PSE did not significantly increase the sustained virological response (SVR) rate, it significantly maintained higher platelet counts throughout the observation period and increased the percentage of patients with 100% adherence to PEG-IFN in the total controlled study population and in subjects with genotype 2. In PSE-treated patients with genotype 2, a trend towards increased SVR was noted. Four patients developed hepatocellular carcinoma (HCC) at a median of 14.5?months after PSE, even though two of these patients had achieved an SVR.

Conclusions

IFN-based therapy following PSE had an advantage in the maintenance of higher platelet counts, and PSE possibly caused an increase in adherence to PEG-IFN. Although patients with genotype 2 might be better candidates for PSE, further evaluation is needed. Careful follow-up of PSE-treated patients, even though they may have achieved an SVR, is needed to detect HCC.     

Dose-dependent effects of a nitric oxide biosynthesis inhibitor on hyperdynamic circulation in two models of portal hypertension in conscious rats

The role of nitric oxide (NO) in the hyperkinetic circulation in portal hypertension has not been clearly elucidated. Different doses of NO inhibitors, haemodynamic values and experimental conditions might explain the discrepant results. The aim of the present study was to investigate the acute effects of a specific biosynthesis inhibitor of NO, Nω-nitro-L-arginine (L-NNA), on the systemic and splanchnic circulation in normal conscious rats and rats with portal hypertension due to either partial portal vein stenosis or secondary biliary cirrhosis. The administration of L-NNA (15 to 960 (μg.kg^-1.min^-1) induced a significant dose dependent increase in arterial pressure which was not different among the three groups of rats. Following an acute and maximal vasopressive dose of L-NNA (1 mg.kg^-1.min^-1) cardiac index decreased more in portal vein stenosed and cirrhotic rats (-45 ± 3% and -45 ± 2%, respectively) than in normal rats (-31 ± 2%), and systemic vascular resistance increased more in the two groups of portal hypertensive rats than in normals (+161 ± 13% and + 154 ± 10% vs + 85 ± 6%, respectively). L-NNA caused a greater decrease in portal tributary blood flow in portal vein stenosed and cirrhotic rats (-63 ± 4% and -55 ± 4%, respectively) than in normal rats (-45 ± 6%). Similarly, the increase in portal territory vascular resistance was significantly more marked in portal vein stenosed and cirrhotic rats (+ 337 ± 62% and +214 ± 24%, respectively) than in normal rats (+153 ± 23%). Portal pressure did not change. Following the acute administration of L-NNA, no significant difference in splanchnic and systemic haemodynamics were noted between portal vein stenosed and normal rats, except for portal pressure. In cirrhotic rats, splanchnic and systemic values remained different from normal rats. This study confirms that NO plays a role in the haemodynamic changes in portal hypertension, and shows that NO inhibitors have a dose-dependent effect in conscious portal hypertensive rats.     

Prolonged bleeding time in cirrhotic patients: Relationship to peripheral vasodilation and severity of cirrhosis

Abstract A prolonged bleeding time (>540 s), measured with a Simplate single template device, was found in 0% of 50 patients with chronic hepatitis and 38% of 154 cirrhotic patients. Cirrhotic patients with a prolonged bleeding time (n= 59) had lower platelet counts (P < 0.001) and a longer prothrombin time (P < 0.001) and activated partial thromboplastin time (P < 0.001) compared with cirrhotic patients with a normal bleeding time (n= 95). A weak but significant negative correlation existed between the bleeding time and platelet count in cirrhotic patients (n= 154, r= -0.3668, P < 0.001). Patients with decompensated cirrhosis had a longer bleeding time in comparison to patients with compensated cirrhosis (621±39 vs 478 ± 27 s, respectively, P < 0.01). The prolonged bleeding time was also discovered in 25% of 83 cirrhotic patients with a platelet count >80 × 10⁹/L and a prothrombin time < 17 s (usually taken as safe limits for invasive procedures). Twenty-seven of the 83 cirrhotic patients received a haemodynamic study by Swan-Ganz catheterization. A lower systemic vascular resistance was found in cirrhotic patients with an abnormal bleeding time than in cirrhotic patients with a normal bleeding time (844 ± 57 vs 1171 ± 60 dyne·s·cm^?5, respectively, P < 0.001), whereas both groups had similar hepatic venous pressure gradient (16.2 ± 1.2 vs 18.1 ± 1.4 mmHg, respectively, P > 0.05). There was a significant negative correlation observed between systemic vascular resistance and bleeding time in cirrhotic patients with a platelet count >80 × 10⁹/L and a prothrombin time < 17 s (n= 27, r= -0.63, P < 0.001). These results demonstrate that prolonged bleeding time is common in patients with cirrhosis. Peripheral vasodilation is probably an important factor in addition to platelet counts and the severity of liver disease in determining the bleeding time in cirrhosis.     

Immunotherapy of hepatocellular carcinoma with autologous lymphokine-activated killer cells and/or recombinant interleukin-2

Summary Five patients with hepatocellular carcinoma were subjected to immunotherapy: three patients were treated by adoptive immunotherapy with lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2), and two patients by systemic administration of rIL-2 alone. In one patient with diffuse-type hepatocellular carcinoma and portal vein thrombosis who was treated by infusion of LAK cells (a total number of 1.5x10¹⁰ cells/13 doses) and continuous rIL-2 administration (a total dose of 1.25x10⁸ units) via a percultaneously placed hepatic arterial catheter, the size of the tumor reduced dramatically and the portal vein thrombosis retracted. In two patients who had LAK cells infused (totals of 6.6x10⁹ cells/4 doses and 3.1x10⁹ cells/2 doses, respectively) during hepatic angiogram followed by systemic administration of rIL-2 twice a day, no clinical improvement was noticed. In two patients who received rIL-2 alone systemically (total doses of 8.9x10⁷ and 5.5x10⁷ units, respectively), neither clinical improvement nor severe side effects were observed. The results suggest that adoptive immunotherapy combined with continuous local administration of rIL-2 via a percutaneously placed hepatic arterial catheter may be an effective therapy without apparent side effects for patients with hepatocellular carcinoma who cannot be treated by conventional cancer therapy.     

Hemodynamic effects of combined treatment with somatostatin analogue (SMS 201-995) and low-dose isosorbide dinitrate on portal hypertension in conscious cirrhotic rats

The authors investigated whether combined treatment with the somatostatin analogue, SMS 201-995, and low-dose isosorbide dinitrate enhanced the hemodynamic effects of the individual agents on rats with thioacetamide-induced cirrhosis. Four groups of cirrhotic rats received SMS 201-995 (0.1 μg·min^?1·kg^?1), isosorbide dinitrate (10 μ·min^?1·kg^?1), both agents, or placebo, respectively. Hemodynamics were measured serially in conscious rats, using a radioactive microsphere method. SMS 201-995 reduced portal venous inflow 21±4% and portal pressure 17±3%. Isosorbide dinitrate decreased portal venous inflow 20±4%, by inducing splanchnic vasoconstriction mediated by low pressure baroreflexes, and this agent also decreased portal pressure, by 14±2%. Portal venous resistance rose 7.6±3% with isosorbide dinitrate alone, but decreased 18±4% with combination therapy. This effect may have been induced by the pronounced vasodilatory effect of isosorbide dinitrate on the venous vasculature, since the reflex splanchnic vasoconstriction that occurs with low-dose isosorbide dinitrate disappears when this agent is combined with SMS 201-995. The decrease in portal pressure was more marked (22±4%) and changes in systemic hemodynamics were milder with the combined treatment. It was concluded that combination therapy with SMS 201-995 and low-dose isosorbide dinitrate may be beneficial for portal hypertension in liver cirrhosis.     

Splenectomy prior to antiviral therapy in patients with hepatitis C virus related decompensated cirrhosis

Patients with hepatitis C virus-related decompensated cirrhosis can benefit from interferon-based antiviral therapy, but the common complication of cytopenia is a contraindication for this treatment. Splenectomy prior to interferon therapy may alleviate this problem. To investigate whether splenectomy improves the efficacy of antiviral therapy, 13 interferon-naïve hepatitis C virus decompensated cirrhotic patients underwent splenectomy between January 2008 and January 2011, followed 1–3 months later by an interferon-based therapeutic regimen (pegylated/standard interferon-α combined with ribavirin for 48 weeks). Ten (76.9%) of the patients developed postoperative complications, which included minor portal vein thrombosis (2/13, 15.4%) and transient ascites (8/13, 61.5%). At one-month post-splenectomy, the patients showed significantly increased platelet (pre-surgery: 48.2 ± 15.9 vs. 186.0 ± 70.6 × 10³ μL^?1, p < 0.001) and leukocyte (2.1 ± 0.5 vs. 5.7 ± 1.4 × 10³ μL^?1, p < 0.001) counts. Eight (61.5%) of the patients achieved sustained virological response, including all HCV genotype 2a-infected patients (4/4, 100%) and some of the genotype 1b-infected patients (4/9, 44.4%). Temporary interferon-α suspension was required for one patient to address severe intestinal infection. These results indicate that splenectomy prior to interferon-based therapy was safe and may facilitate adherence to subsequent antiviral therapy in selected HCV cirrhotic patients with portal hypertension and hypersplenism.     

Systemic and splanchnic hemodynamic changes in patients with hepatic schistosomiasis

Abstract: Although hepatic schistosomiasis is a common cause of portal hypertension, only a few hemodynamic studies, in humans, have been published on this subject. The aim of this study was to determine the systemic and splanchnic hemodynamic changes in hepatic schistosomiasis and to evaluate the influence of liver fibrosis on these changes. A retrospective analysis of a series of 13 patients with hepatic schistosomiasis who had undergone hemodynamic studies was performed. Portal or perisinusoidal fibrosis was present at liver biopsy in 8 patients. The control group included 22 patients with chronic hepatitis and normal hepatic venous pressure gradients. Patients with schistosomiasis exhibited high cardiac index (4.11±1.15 1 · min^-1 · m^-2 vs 2.99±0.85 1 · min^-1 · m^-2; p<0.05) and low systemic vascular resistance (1039±316 dyn · s · cm^-5 vs 1334±336 dyn · cm^-5; p<0.05). The hepatic venous pressure gradient and hepatic blood flow were normal. Azygos blood flow was markedly increased (0.90±0.66 1 · min^-1 vs 0.13±0.04 1 · min^-1; p<0.05). Hemodynamic values were not significantly different between patients with liver fibrosis and those without fibrosis at liver biopsy. In conclusion, patients with hepatic schistosomiasis had a hyperkinetic systemic and splanchnic circulation. In patients with esophageal varices, a normal hepatic venous pressure gradient confirmed presinusoidal portal hypertension. The presence of portal or perisinusoidal fibrosis did not influence hyperdynamic splanchnic state.     

Hepatic arterial blood flow in large hepatocellular carcinoma with or without portal vein thrombosis: assessment by transcutaneous duplex Doppler sonography

BACKGROUND: As liver cirrhosis progresses, the portal venous blood (PVBF) flow decreases, accompanied by an increase in hepatic arterial blood flow. Large hepatocellular carcinoma is a hypervascular tumour with a rapid growth, which seems to require an increase of the tumoral arterial blood flow. Furthermore, hepatocellular carcinoma is frequently associated with portal vein thrombosis, which subsequently impedes portal blood supply. METHODS: The purpose of our study was to estimate alterations in the hepatic arterial blood flow in large hepatocellular carcinomas occurring in liver cirrhosis, in comparison with liver cirrhosis and controls. Liver blood flow measurements were determined by duplex Doppler sonography in 47 patients with large hepatocellular carcinomas (13 with portal vein thrombosis and 34 without this thrombosis), 42 liver cirrhosis patients and 30 controls. The Doppler perfusion index was calculated as the ratio of hepatic arterial blood flow to total hepatic blood flow. RESULTS: The patients with liver cirrhosis had a significant increase of hepatic arterial blood flow as compared to controls (P < 0.001), accompanied by a significant reduction in PVBF (P < 0.005). As a result, the Doppler perfusion index was increased in patients with liver cirrhosis as compared to controls (P < 0.001). The hepatic arterial blood flow was increased in patients with hepatocellular carcinoma but without portal vein thrombosis as compared to the cirrhotic patients (P < 0.001), with a significant reduction of PVBF (P < 0.001). Hepatic arterial blood flow was also increased in patients with both hepatocellular carcinoma and portal vein thrombosis as compared to the patients without this thrombosis (P < 0.001). CONCLUSION: These results suggest that in large hepatocellular carcinomas there is a decreased PVBF, accompanied by an increased hepatic arterial blood flow. The hepatic arterial buffer response seems to be active in hepatocellular carcinomas and maintains liver perfusion to adequate levels.     

Diet Restriction Increases Ubiquinone Contents and Inhibits Progression of Hepatocellular Carcinoma in the Rat

Objective Arginine vasopressin (AVP) exerts a constrictive effect on the portal-systemic collaterals of non-cirrhotic portal hypertensive rats, but its effect on cirrhotic rats is unknown. The aim of this study was to investigate the response of AVP and the modulatory roles of nitric oxide and prostaglandin on collaterals of common bile duct-ligated (BDL) cirrhotic rats. Material and methods The collateral vascular responsiveness to graded concentrations of AVP (10^?10–3×10^?7 M) was tested by an in situ collateral perfusion system pretreated with N^ω-nitro-L-arginine (L-NNA, 100 μM), indomethacin (INDO, 10 μM), or both. The collateral responses to AVP with the pretreatment of a vasopressin V₁ receptor antagonist d(CH₂)₅Tyr(Me) arginine vasopressin or a V₂ receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP, 10^?10–3×10^?7 M) were also evaluated. Results The perfusion pressure of collaterals was significantly increased by AVP, and this effect was inhibited by the addition of the V₁ receptor antagonist. DDAVP had no effect on the collaterals. Incubation with L-NNA or L-NNA plus INDO, but not INDO alone, significantly potentiated the constrictive effects of AVP. The constrictive effect of AVP in the combination group was similar to that in the L-NNA alone group. Conclusions The results show that AVP produces a direct vasoconstrictive effect on the portal-systemic collaterals of BDL cirrhotic rats. The constrictive effect of AVP is mediated by the vasopressin V₁, instead of V₂, receptors. Nitric oxide may play a more important role than prostaglandin in modulating the collateral vascular response to AVP in BDL cirrhotic rats.     

肝硬化患者肝功能失代偿状况与门脉管径的关系

目的:探讨肝硬化患者肝功能失代偿状况、食管静脉曲张程度与门脉主干内径及脾静脉内径的关系。方法:对100例肝硬化失代偿期患者进行肝功能Child-pugh分级,内镜检查判断食管静脉曲张程度,彩色多谱勒B超检测门静脉主干内径及脾静脉内径。结果:肝功能分级越差,门静脉与脾静脉的内径越大(P<0.05),且随着门静脉及脾静脉内径增大,食管静脉曲张程度亦加重(P<0.05)。结论:门静脉及脾静脉内径能间接体现门静脉高压的程度,继而反映肝功能失代偿状况。