Surgical shunts for extrahepatic portal vein obstruction in pediatric patients: a systematic review

BackgroundExtrahepatic portal vein obstruction (EHPVO) causes portal hypertension in noncirrhotic children. Among surgical treatments, it is unclear whether the meso-Rex shunt (MRS) or portosystemic shunt (PSS) offers lower post-operative morbidity and superior patency over time. Our objective was to evaluate long-term outcomes comparing MRS and PSS for pediatric patients with EHPVO.MethodsA systematic review was conducted of articles reporting children undergoing surgical shunts for EHPVO from 1/2000–2/2020. Of 87 articles screened, 22 were eligible for inclusion. The primary outcome was shunt thrombosis and secondary outcomes included non-operative complications, stenosis, and re-operation.ResultsEighteen of 22 studies were of good quality and four had fair quality. Of 461 patients included, 340 underwent MRS and 121 underwent PSS. MRS were associated with a higher rate of post-operative thrombosis when compared to PSS (14.1% vs 5.8%, p = 0.021). There were 40/340 MRS patients (11.8%) that required at least one re-operation for either shunt thrombosis or stenosis, versus 5/121 PSS patients (4.1%), p = 0.019.ConclusionBoth MRS and PSS result in acceptable long-term patency rates, but the more technically demanding MRS is associated with higher post-shunt thrombosis, often requiring further operative intervention. This study suggests that PSS may offer advantages for pediatric patients with EHPVO.     

The relationship between intrahepatic portal systemic shunts and microsphere induced portal hypertension in the rat liver

Background—Portal hypertension is associated withgross haemodynamic disturbances characterised by high cardiac output,low peripheral vascular resistance, increased splanchnic blood flow, and portal systemic shunting.
Aims—To study the relationship betweenintrahepatic portal systemic shunts and microsphere induced portalhypertension in the rat liver.
Methods—Different sized microspheres weresequentially injected into the portal vein of male Wistar rats.
Results—Steady state portal venous pressure wasincreased by 102.2 (35.6)% (14.9 (3.6) mm Hg) and 272.3 (78.0)% (24.0 (2.2) mm Hg) above the basal pressure following sequential injections of 15 and 80 µm diameter microspheres, respectively. Sequential injection of 15, 40, and 80 µm diameter microspheres in either ascending or descending order of size did not generate further increases in portal venous pressure. A single injection of 1.8× 10⁵ 80 µm microspheres consistently produced a steadystate portal venous pressure of 19.0 (1.3) mm Hg but did not approachthe much higher value of 36.6 (43.2) mm Hg measured during clamping of the portal vein. These data indicate that the opening of patent intrahepatic shunts was responsible for the reduced pressures observedduring microsphere injections and further evidence for this wasprovided by the location of microspheres in the pulmonary vascular bed.The elevation in portal venous pressure achieved by microsphereinjections was not significantly different to that produced in ratssubjected to partial portal vein ligation (20.7(0.5) mm Hg, p>0.05).Wedged hepatic venous pressure decreased from 6.7 (0.7) to 3.0 (0.6) mmHg following injection of 80 µm microspheres, suggesting a decreasein total hepatic blood flow. Conversely, injection of 15 µmmicrospheres induced an increase in wedged hepatic venous pressure from7.0 (1.0) mm Hg to 12.4(1.8) mm Hg, indicating a localisedredistribution of blood flow at the presinusoidal level of the portalvenous vascular network and increased intrahepatic shunt flow.
Conclusion—It is suggested that there may be aprotective pathophysiological role for these shunts when the liver issubjected to changes which induce acute portal hypertension.

     

Differences in protein and energy metabolism following portal versus systemic administration of insulin in diabetic dogs

Aims/hypothesis In non-diabetic people, insulin levels in the liver are two-fold higher than those in the systemic circulation. In contrast, patients with type 1 diabetes have similar hepatic and systemic insulin levels because insulin is administered peripherally. The aim of this study was to compare the effects of systemic (SI) and pre-portal (PI) insulin administration on energy, glucose and protein metabolism in chronic insulin-dependent ketosis-prone diabetic dogs. Materials and methods We applied glucose-controlled insulin infusion, indirect calorimetry and stable isotope and radioisotope techniques to measure energy, protein and glucose metabolism. We maintained near-normoglycaemia at identical levels under both study conditions for 20 h. Results SI was associated with lower oxygen consumption (130±13 vs 161±8 ml/min), CO₂ production (99±10 vs 130±8 ml/min), respiratory quotient (0.76±0.02 vs 0.81±0.01) and energy expenditure (870±90 vs 1089±60 kcal/24 h) (p<0.05 for all differences). PI increased the respiratory quotient from the insulin-deprived state, whereas SI did not. Glucose kinetics were similar for SI and PI, whereas leucine oxidation (36±4 vs 54±5 μmol kg⁻¹ min⁻¹) and the fractional synthesis rates of liver tissue protein (0.68±0.6 vs 0.83±0.07%/h), albumin (0.55±0.06 vs 0.68±0.4%/h), and fibrinogen (1.73±0.23 vs 2.59±0.25%/h) were all lower during SI than PI (p<0.05). Conclusions/interpretation The route of insulin administration did not alter glucose metabolism but did affect protein synthesis in the liver. The potential impact of this altered liver protein metabolism on chronic complications needs careful evaluation. A similar decrease in energy expenditure resulting from systemic insulin administration during tight glycaemic control is a potential cause of weight gain.     

Obliteration of portal systemic shunts as therapy for hepatic encephalopathy in patients with non-cirrhotic portal hypertension.

The effects of obliteration of portal systemic shunts (PSS) in 5 patients with non-cirrhotic hepatic encephalopathy is reported. All patients had a history of disturbance of consciousness for several years, and examinations revealed large PSS, most of which connecting the left gastric vein to the left renal vein. After the obliteration of PSS, portal vein pressure elevated, the shunt ratio of the portal blood flow decreased, the indocyanine green disappearance rate increased, and serum albumin increased. Blood ammonia (NH3) decreased significantly accompanied by disappearance of hepatic encephalopathy. This treatment may open a way to improve the quality of life in patients with large PSS without severe hepatic injury.     

Clinical classification of congenital extrahepatic portosystemic shunts

Aim: Congenital extrahepatic portosystemic shunt (CEPS) is a rare anomaly in which the enteric blood bypasses the liver and drains into the systemic veins through various venous shunts. Patients with CEPS often have liver tumors and complications such as cardiac or other anomalies, but portosystemic encephalopathy and gastrointestinal bleeding occur only occasionally. The clinical problems differ for each individual with CEPS, and establishing a prognosis can be very difficult. Methods: We reviewed the clinical features of 136 reported cases of CEPS and classified these cases according to their portosystemic shunts. Results: We classified portal blood flow directly into the inferior vena cava (IVC) as type A (88 cases), portal blood flow into the renal vein as type B (36 cases), and portal blood flow into the iliac vein via an inferior mesenteric vein as type C (12 cases). Type A patients were complicated with cardiac anomalies at a higher rate than other types. Type C patients had lower prevalences of cardiac anomalies and portosystemic encephalopathy than the other types, but the prevalence of gastrointestinal bleeding was significantly higher (P < 0.0001). The prognosis of CEPS has improved, and only six deaths have been previously reported, all of which occurred in type A patients. Conclusions: We reviewed the previously reported cases of CEPS. Classification according to the portosystemic shunt system might be useful for investigating the clinical features of CEPS.     

Influence of portal delivery of insulin on intracellular glucose and lipid metabolism

We have investigated whether portal delivery of insulin as a result of intrahepatic islet cell autografts would prevent the development of metabolic alterations. Seven pancreatectomized dogs received islet autografts transplanted into the liver through the portal vein (PD). One year after transplantation, their intravenous glucose tolerance and insulin responses were similar to age-matched control (C) dogs (n = 5). Also, normal triglyceride content in arterial smooth muscle and striated muscle was observed in the dogs with portal insulin delivery in contrast to the substantial increases we observed in pancreatectomized dogs (n = 7) with pancreatic autografts that drained into the systemic circulation (SD). In these dogs, the tissue samples were taken at the age of 3 to 4 years. Triglyceride content (mean +/- SEM) in the aorta was 4.9 +/- 1.2 versus 2.6 +/- 0.6 versus 20.7 +/- 8.0 mumol/g (P less than .01) in C, PD, and SD models, respectively. The corresponding values for triglyceride content in striated muscles were 29.1 +/- 1.2, 25.9 +/- 1.5, and 171.4 +/- 46.6 mumol/g (P less than .01). Glucose-6-phosphate dehydrogenase (G-6-PDH) and malic enzyme, key enzymes for lipid synthesis, were also normal in the PD model, in contrast to the fivefold increased activity of these enzymes in the SD model (P less than .01). The glycolytic enzymes, hexokinase (HK) and phosphofructokinase (PFK), were normal compared with the decreased values in the SD. These data indicate that it is possible to normalize glucose and lipid metabolism in arterial walls by portal delivery of insulin, following intrahepatic islet cell transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spontaneous (natural) splenoadrenorenal shunts in extrahepatic portal venous obstruction: a series of 20 cases.

Large spontaneous (natural) splenoadrenorenal shunt on splenoportovenography was seen in 20 (9.4%) of the 213 patients with extrahepatic portal venous obstruction. Significantly less number of patients had a bleed and oesophageal varices in this group compared with patients having no spontaneous shunt. There was, however, no significant difference in the age, splenic size, splenic pulp pressure, anaemia, thrombocytopenia and leucopenia between the two groups.     

Comparison of portal and peripheral insulin delivery on carbohydrate metabolism in streptozotocin-diabetic rats

Summary Severely diabetic rats (150 mg streptozotocin/kg) were transplanted with fetal pancreatic islets: (a) under the kidney capsule to model peripheral insulin delivery, and (b) into the splenic pulp to model portal delivery. Long-term normoglycaemia, normal weight gain and normal peripheral insulin levels were achieved in both groups of transplanted animals. In both groups, 24-h fasted blood lactate, pyruvate and alanine were identical to those observed in sham-operated control animals. Blood glucose and plasma insulin responses to 300 mg oral glucose 8 weeks after transplantation were the same as in control animals. Hepatic glycogen concentration was, however, lower in fed rats with islets beneath the kidney capsule compared with control rats (p<0.01), suggesting inadequate hepatic insulinisation in the fed state with peripheral insulin delivery. Muscle glycogen was the same as in controls. Glucose turnover and glucose carbon recycling were not significantly different from results in normal control and splenic pulp islet-transplanted animals. The findings indicate that consistent normoglycaemia, normal glucose flux and normalisation of blood intermediary metabolites can be achieved in the rat with peripheral insulin delivery without associated hyperinsulinaemia.     

Effects of chronic systemic insulin delivery on insulin action in dogs

Summary The metabolic consequences of the prolonged systemic insulin delivery associated with human pancreas transplantation have not been precisely defined. To determine if systemic insulin delivery in the absence of immunosuppressive agents results in alterations in hepatic or extrahepatic insulin action, three groups of dogs were studied 2 months after either a sham operation or after their pancreatic venous drainage was severed and anastomosed to the inferior vena cava or portal vein (sham, peripheral and portal groups, respectively). The pattern of venous drainage was documented by measuring vena cava and portal insulin concentrations before and after glucose injection. Systemic insulin concentrations were higher (p<0.05) in the peripheral group than in the portal group both following a 14-h fast and after intravenous glucose. During a hyperinsulinaemic euglycaemic clamp (1 mU·kg^–1·min^–1), glucose utilization (measured using [6³H] glucose) was slightly lower (p=0.07) in the peripheral than in the portal group. Hepatic glucose release was equal in all groups. Carbon dioxide incorporation into glucose (an estimate of gluconeogenesis) was higher in the portal than peripheral group in the fasted state but not during insulin infusion. Plasma concentrations and flux rates of fatty acids and amino acids did not differ between groups. We conclude that chronic systemic insulin delivery results in a) systemic but not portal hyperinsulinaemia, b) a minimal impairment in insulin-stimulated glucose uptake, without altering insulin-induced suppression of hepatic glucose release, and c) no effect on fatty acid or amino acid turnover. Although chronic systemic insulin delivery appears to have a minimal effect on insulin action, it remains to be determined whether it has other deleterious effects such as enhancing atherogenesis.     

Pathomorphologic study on the extrahepatic portal vein in idiopathic portal hypertension

Patients with idiopathic portal hypertension (IPH) are known to have sclerotic changes of the intrahepatic portal vein radicles. In order to elucidate the pathological changes in the extrahepatic portal venous system in IPH, studies were carried out on the portal trunk in 12 patients with IPH, 59 patients with liver cirrhosis including some with associated hepatocellular carcinoma, and 12 normal matched control subjects. Histological examinations including histomorphometry were performed on the transverse sections of the portal trunk taken at autopsy. Most of the patients with IPH showed severe phlebosclerosis which was more pronounced than seen in liver cirrhosis. Thrombosis was also frequently observed in IPH. In IPH, the portal trunk was characterized by fibrous thickening of the intima and media with a prominent increase of elastic fibers. The mean area and thickness of the intima and media were significantly greater than in patients with liver cirrhosis. Sclerosis extensively involving both the extrahepatic and intrahepatic ramifications of the portal vein appeared to be characteristic of IPH.     

Occlusion of portosystemic shunts improves hyperinsulinemia due to insulin resistance in cirrhotic patients with portal hypertension

Background

Liver cirrhosis (LC) is often complicated by hyperinsulinemia due to insulin resistance (IR), which is considered to be closely related to shunt formation and impaired liver function. This study evaluates whether balloon-occluded retrograde transvenous obliteration (B-RTO) can affect glucose and insulin metabolism in patients with LC.

Methods

Twenty-five cirrhotic patients (mean age = 69.6 years; female/male = 12/13; hepatitis C virus/alcohol/nonalcoholic steatohepatitis = 14/6/5; Child-Pugh’s class A/B = 10/15) with gastric varices and/or hepatic encephalopathy caused by portosystemic shunts (PSS) due to portal hypertension (PH) underwent B-RTO at our hospital. Testing was performed before and at 1 month after the procedure.

Results

Shunt occlusion resulted in a decrease in extrahepatic collateral blood flow and an increase in portal venous flow, as well as a dramatic improvement in hepatic function markers. In addition, B-RTO significantly decreased homeostasis model assessment (HOMA) of IR without a statistical decline of HOMA of β-cell function. The 75-g oral glucose tolerance test (75-OGTT) revealed that occlusion of PSS reduced both fasting immunoreactive insulin (IRI) levels and the area under the curve for IRI. However, no significant change in preprandial or postprandial plasma glucose levels was observed. Furthermore, according to the criteria of the American Diabetes Association, B-RTO led to an improved 75-OGTT profile in 58.3 % of patients who had impaired glucose tolerance or diabetes mellitus before the procedure.

Conclusions

Shunt occlusion improves IR-related hyperinsulinemia through increased portal venous flow, ameliorated liver function, and consequent augmented hepatic insulin clearance in cirrhotic patients with PH.     

Transjugular intrahepatic portosystemic shunts and portal hypertension-related complications

Portal hypertension(PH)plays an important role in the natural history of cirrhosis,and is associated with several clinical consequences.The introduction of transjugular intrahepatic portosystemic shunts(TIPS)in the 1980s has been regarded as a major technical advance in the management of the PH-related complications.At present,polytetrafluoroethylene-covered stents are the preferred option over traditional bare metal stents.TIPS is currently indicated as a salvage therapy in patients with bleeding esophageal varices who fail standard treatment.Recently,applying TIPS early(within 72 h after admission)has been shown to be an effective and life-saving treatment in those with high-risk variceal bleeding.In addition,TIPS is recommended as the second-line treatment for secondary prophylaxis.For bleeding gastric varices,applying TIPS was able to achieve hemostasis in more than 90%of patients.More trials are needed to clarify the efficacy of TIPS compared with other treatment modalities,including cyanoacrylate injection and balloon retrograde transvenous obliteration of gastric varices.TIPS should also be considered in bleeding ectopic varices and refractory portal hypertensive gastropathy.In patients with refractory ascites,there is growing evidence that TIPS not only results in better control of ascites,but also improves long-term survivalin appropriately selected candidates.In addition,TIPS is a promising treatment for refractory hepatic hydrothorax.However,the role of TIPS in the treatment of hepatorenal and hepatopulmonary syndrome is not well defined.The advantage of TIPS is offset by a risk of developing hepatic encephalopathy,the most relevant postprocedural complication.Emerging data are addressing the determination the optimal time and patient selection for TIPS placement aiming at improving long-term treatment outcome.This review is aimed at summarizing the published data regarding the application of TIPS in the management of complications related to PH.     

Effects of insulin on glucose metabolism in sepsis

The study surveys potential effects of hyperglycemia on prognosis, complications and mortality of critical patients. Normalization of glycemia seems to be an effective therapeutic approach that influences morbidity and mortality of critical patients. Although insulin therapy has many positive effects, it is rather a way how to achieve normoglycemia. Authors present their own research of the impact of plasmatic insulin levels on glucose metabolism. It seems that the ability of critical patients to utilise and store glucose is significantly decreased due to their insulin resistance. Glucose oxidation is decreased only slightly. Glucose utilisation and oxidation in sepsis can be enhanced by administration of insulin.     

Mechanisms of extrahepatic vasodilation in portal hypertension

In liver cirrhosis, abnormal persistent extrahepatic vasodilation leads to hyperdynamic circulatory dysfunction which essentially contributes to portal hypertension. Since portal hypertension is a major factor in the development of complications in cirrhosis, the mechanisms underlying this vasodilation are of paramount interest. Extensive studies performed in cirrhotic patients and animals revealed that this vasodilation is associated on the one hand with enhanced formation of vasodilators, and on the other hand with vascular hyporesponsiveness to vasoconstrictors. The latter phenomenon has been termed "vascular hypocontractility". It is caused by a combination of different mechanisms and factors described in this review.     

Significance of intra- and extrahepatic portasystemic shunting in survival of cirrhotic patients

Survival and incidence of hemorrhage and encephalopathy were studied in 121 medically managed cirrhotic patients according to the type of naturally occurring portasystemic shunting. Three types of shunting were distinguishable using scintillation splenoportography, a method whereby morphological and hemodynamic data on portal and hepatic circulation were obtained by external detection. The three patterns were: (1) extrahepatic shunting with partial splenic blood flow diversion, (2) spontaneous total splenic blood flow diversion, and (3) intrahepatic shunting corresponding to portohepatic communications with a diameter larger than 10 m. The probability of 4-year survival was much lower in case of portasystemic shunting (18%) than in its absence (73%,P<0.01). Patients with intrahepatic shunting had a survival rate not significantly different from that of patients with extrahepatic shunting. However, they had the highest incidence of hemorrhage (71%), and hemorrhage was not due to rupture of esophageal varices. The highest incidence of encephalopathy was seen in patients with total splenic blood diversion (40%), but it was not significantly different from that of other cirrhotic patients. No group of patients can be significantly identified as a high-risk group.