Cerebral oedema in minimal hepatic encephalopathy due to extrahepatic portal venous obstruction

Background: Minimal hepatic encephalopathy (MHE) has recently been reported in patients with extrahepatic portal venous obstruction (EHPVO). Aims: To evaluate brain changes by magnetic resonance studies in EHPVO patients. Methods: Blood ammonia level, critical flicker frequency (CFF), brain metabolites on 1H‐magnetic resonance (MR) spectroscopy and brain water content on diffusion tensor imaging and magnetization transfer ratio (MTR) were studied in 31 EHPVO patients with and without MHE, as determined by neuropsychological tests. CFF and magnetic resonance imaging studies were also performed in 23 controls. Results: Fourteen patients (14/31, 45%) had MHE. Blood ammonia level was elevated in all, being significantly higher in the MHE than no MHE group. CFF was abnormal in 13% (4/31) with EHPVO and in 21% (3/14) with MHE. On 1H‐MR spectroscopy, increased Glx/Cr, decreased mIns/Cr, and no change in Cho/Cr were noted in patients with MHE compared with controls. Significantly increased mean diffusivity (MD) and decreased (MTR) were observed in the MHE group, suggesting presence of interstitial cerebral oedema (ICE). MD correlated positively with blood ammonia level (r=0.65, P=0.003) and Glx (r=0.60, P=0.003). Discussion: MHE was detected in 45% of patients with EHPVO while CFF was abnormal in only 13%. ICE was present in 7/10 brain regions examined, particularly in those with MHE. Hyperammonaemia elevated cerebral Glx levels correlated well with ICE. Conclusions: MHE was common in EHPVO; CFF could identify it only in a minority. ICE was present in EHPVO, particularly in those with MHE. It correlated with blood ammonia and Glx/Cr levels. Hyperammonaemia seems to contribute to ICE in EHPVO.     

Fifteen-year follow up of endoscopic injection sclerotherapy in children with extrahepatic portal venous obstruction

BACKGROUND AND AIM: Endoscopic sclerotherapy has emerged as an effective treatment for bleeding esophageal varices both in adults and children but the long-term outcome is poorly defined in children. The authors report a 15-year follow up of sclerotherapy in children with extrahepatic portal venous obstruction. METHODS: Between June 1982 and February 1992, 69 children with bleeding esophageal varices underwent sclerotherapy; variceal eradication was achieved in 63 (91.3%) patients, with procedure-related morbidity of 28.9% and mortality of 1.4%. Fifty-nine patients with variceal eradication were followed for between 10.4 and 20.1 years (mean, 15.1 +/- 3.1 years). RESULTS: After a median period of 3 years (range, 1.2-12.8 years), seven (11.9%) patients presented with recurrent bleeding (esophageal varices, four; gastric varices, two; and duodenal ulcer, one). Recurrent bleeding occurred in six of seven (85.7%) patients within the first 4 years of initial variceal eradication. Esophageal varices recurred in eight (13.6%) patients. Five of the seven patients with recurrent bleeding and all eight with recurrent varices were effectively treated with further sclerotherapy. Two patients with gastric variceal bleeding unresponsive to sclerotherapy underwent shunt surgery. Elective surgery was required in eight additional patients for reasons other than recurrent varices or bleeding. CONCLUSIONS: The authors conclude that (i) sclerotherapy is the ideal, safe and effective treatment for bleeding esophageal varices, that it prevented bleeding in 88.1% patients after variceal eradication and hence, should be included in primary management strategies; (ii) follow-up endoscopy should be performed on a yearly basis for the first 4 years after variceal eradication; and (iii) surgery is required as a complementary technique for patients with uncontrolled bleeding, painful splenomegaly, growth retardation and symptomatic portal biliopathy.     

Portographic changes with time in patients with extrahepatic portal venous obstruction

Portographic changes of successive splenoportovenograms in 27 patients with extrahepatic portal venous obstruction (EHPO) over a mean period of 27 months have been studied. No extension of the portal vein thrombus was observed either in 20 patients with EHPO who had variceal obliteration by endoscopic sclerotherapy or in the 12 patients who remained without treatment for a mean period of 33.4 months (five of them were later subjected to sclerotherapy). There was no evidence of spread of thrombosis in the portal veins with time.     

Splenic-intrahepatic left portal shunt in an adult patient with extrahepatic portal vein obstruction without recurrence after pancreaticoduodenectomy

In the last decade, a superior mesenteric-intrahepatic left portal shunt (Rex shunt) has been reported for successful management of extrahepatic portal vein obstruction in children. However, in adults, a mesocaval shunt has been generally performed for the surgical management of extrahepatic portal vein obstruction because of the complexity of the underlying disease and the difficulty of the superior mesenteric-intrahepatic left portal shunt. We herein report an adult patient who was successfully treated by splenic-intrahepatic left portal shunt with an artificial graft (6-mm polytetrafluoroethylene) for complete obstruction of the extrahepatic portal vein following pancreaticoduodenectomy. The shunt procedure not only relieved portal hypertension but also restored hepatic portal flow. In the near future, the Rex shunt should be considered for a beneficial management of extrahepatic portal vein obstruction, even in adults.     

Comparative efficacy of emergency endoscopic sclerotherapy for active variceal bleeding due to cirrhosis of the liver, non-cirrhotic portal fibrosis and extrahepatic portal venous obstruction

Patients with continued variceal bleeding due to portal hypertension (n = 202) were treated by endoscopic injection sclerotherapy after resuscitation. Portal hypertension was due to hepatic cirrhosis in 123, non-cirrhotic portal fibrosis (NCPF) in 49 and extrahepatic portal venous obstruction (EHO) in 30 patients. Polidocanol 1% was injected intravariceally. An adequate sclerotherapy was carried out in 97% of patients. Immediate haemostasis was achieved in 177 (88%) patients. Rebleeding occurred in 31 (17.5%) of 177 patients. By reinjection of varices, definitive control of bleeding occurred in 160 (79%) patients. There was no significant difference in terms of immediate control of bleeding in patients with different aetiologies of portal hypertension and hepatic functional status (Child's grade). Rebleeding episodes were lower in patients with EHO than cirrhosis of the liver and NCPF. Similarly, the Child's status significantly influenced the recurrence of bleeding which was lower in Child's A than B and B than C. The in-hospital mortality was 18.6%. This was also significantly related to Child's status and aetiology of portal hypertension. Minor complications occurred in 10.4% of patients. It is concluded that endoscopic sclerotherapy as the first line of treatment is an effective and technically feasible procedure for the control of active variceal bleeding, regardless of the cause of portal hypertension. Furthermore, the results were influenced by the aetiology of portal hypertension and hepatic functional status.     

轻微肝性脑病的MRI与^1H-MRS探讨

目的探讨轻微肝性脑病患者颅脑MRI及^1H-MRS的代谢变化。方法 22例经神经心理测试诊断为轻微肝性脑病患者和13例年龄、性别和受教育程度相匹配的健康志愿者,行MRI、^1H-MRS扫描,^1H-MRS兴趣区为双侧基底节。结果 22例患者中17例双侧基底节在T1WI上可见高信号,NAA/Cr值患者组与健康对照组之间差异无显著性（P〉0.05）,而mI/Cr和Cho/Cr值患者组与健康对照组比较显著降低（L：P〈0.01;R：P〈0.01）。结论 T1WI高信号是诊断轻微肝性脑病较为特征性征象,1HMRS能够无创性观察到轻微肝性脑病患者的脑代谢异常,有助于揭示肝性脑病的病理生理机制。     

Portal vein thrombosis： Etiology and clinical outcome of cirrhosis and malignancy-related non-cirrhotic, non-tumoral extrahepatic portal venous obstruction

The etiology and pathogenesis of portal vein thrombosis are unclear. Portal venous thrombosis presentation differs in cirrhotic and tumor-related versus non-cirrhotic and non-tumoral extrahepatic portal venous obstruction (EHPVO). Non-cirrhotic and non-tumoral EHPVO patients are young and present with well tolerated bleeding.Cirrhosis and tumor-related portal vein thrombosis patients are older and have a grim prognosis. Among the 118 patients with portal vein thrombosis, 15.3% had cirrhosis, 42.4% had liver malignancy (primary or metastatic), 6% had pancreatitis (acute or chronic), 5% had hypercoagulable state and 31.3% had idiopathy,12% had hypercoagulable state in the EHPVO group.     

Thromboelastographic evaluation of coagulation in patients with extrahepatic portal vein thrombosis and non‐cirrhotic portal fibrosis: A pilot study

Background and Aims: Non‐cirrhotic portal hypertension due to extrahepatic portal vein thrombosis (EHO) and non‐cirrhotic portal fibrosis (NCPF) is a major cause of upper gastrointestinal hemorrhage in India. Hypercoagulability has been proposed to explain the thrombosis in the portal vein in EHO and intrahepatic portal vein radicals in NCPF. However, some authors have reported hypocoagulability in these patients. Thromboelastography (TEG), which gives a dynamic assessment of coagulation, has potential for evaluating coagulation in these patients but has not been used so far. It was the aim of this study to evaluate the coagulation status in patients of EHO and NCPF using TEG. Methods: Thirty patients with EHO and 19 patients with NCPF were studied. TEG was done in all patients. R (reaction time), K (constant), α (angle), MA (maximal amplitude), A 60 (width of tracing after 60 min) were recorded and TEG index calculated and compared to controls. Results: Seven patients (23.3%) in the EHO group and eight (42.1%) in the NCPF group had severe thrombocytopenia (platlets, < 50 000 cells/dL). TEG showed significantly shorter R, higher MA and larger A in both EHO and NCPF compared to controls (P < 0.01). Thrombocytopenia normalized A but R continued to be significantly shorter in EHO and NCPF. Overt hypercoagulability (TEG index, > +2.5) was seen in two patients with EHO and one patient with NCPF. Conclusion: A latent hypercoagulable state exists in patients with EHO and NCPF which is partially masked by the thrombocytopenia secondary to splenomegaly and hypersplenism.     

Endoscopic treatment of extrahepatic bile duct strictures in patients with portal biliopathy carries a high risk of haemobilia: report of 3 cases

Extrahepatic portal venous obstruction can be associated with bile duct abnormalities, the entity being called portal biliopathy. Three cases are reported of extrahepatic bile duct strictures in patients with portal biliopathy who developed haemobilia during endotherapy. Although endoscopic therapy with stent placement can be successful in patients with portal biliopathy and could also lead to permanent stricture resolution, procedure-related haemobilia is not as uncommon as previously held. Shunt surgery could be a better option in fit patients, since it could provide definitive treatment in a young patient with an otherwise normal life expectancy.     

Efficacy of endoscopic sclerotherapy on long-term management of oesophageal varices: a comparative study of results in patients with cirrhosis of the liver, non-cirrhotic portal fibrosis (NCPF) and extrahepatic portal venous obstruction (EHO)

A prospective study was conducted to compare the results of long-term endoscopic variceal sclerotherapy in patients with different aetiologies of portal hypertension. A total of 404 consecutive patients were included. There were 234 patients with hepatic cirrhosis, 83 with non-cirrhotic portal fibrosis (NCPF) and 87 with extrahepatic portal venous obstruction (EHO). The mean follow-up for patients with cirrhosis, NCPF and EHO was 25, 37 and 28 months. A total of 73 (31%) patients with cirrhosis, 19 (23%) with NCPF and 10 (11.5%) with EHO rebled (P less than 0.05) on follow-up, prior to eradication of varices. Irrespective of the aetiology, 40 (17%) patients of Child's A class, 42 (33%) of Child's B and 20 (50%) of Child's C class rebled (P less than 0.01). The median bleeding free period (BFP) was longer (P less than 0.05) in patients with EHO than in cirrhotics. Patients in Child's A class had significantly longer BFP than those in Child's B, and the latter had a longer BFP than those in Child's C class (P less than 0.01). The probability of 7-year survival was also better with EHO (97.5%) and NCPF (73.6%) than cirrhotics (41%). Survivals in patients with EHO and NCPF were comparable (P less than 0.1). Similarly 7-year survival irrespective of aetiology in Child's A patients (90.7%) was longer than in Child's B (28.8%), and longer in Child's B than Child's C patients (0%). Success of eradication was greater (P less than 0.05) in EHO (92%) and NCPF (87%) than cirrhotic patients (75%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Coagulation profile and platelet function in patients with extrahepatic portal vein obstruction and non-cirrhotic portal fibrosis

BACKGROUND AND AIMS: Coagulation disorders commonly develop in patients with cirrhosis of the liver. They have also been reported in patients with non-cirrhotic portal fibrosis (NCPF) and extra-hepatic portal venous obstruction (EHPVO); the two conditions with portal hypertension and near-normal liver functions. The spectrum and prevalence of coagulation abnormalities and their association with the pathogenesis of these diseases and with hypersplenism was prospectively studied. METHODS: Eighteen EHPVO patients that included an equal number of NCPF patients and 20 healthy controls were prospectively studied. The coagulation parameters assessed included: international normalized ratio, partial thromboplastin time, and fibrinogen and fibrinogen degradation products. Platelet aggregation and malondialdehyde levels were measured. RESULTS: Both EHPVO (83%) and NCPF (78%) patients had a significantly prolonged international normalized ratio and a decrease in fibrinogen and platelet aggregation. The EHPVO patients had a significant prolongation in partial thromboplastin time (67% patients), with increased levels of fibrinogen degradation product levels occurring in all patients; these were normal in NCPF patients. Platelet malondialdehyde levels were normal in both groups. Hypersplenism was present in four EHPVO and seven NCPF patients. It did not significantly influence the coagulation profile in either NCPF or EHPVO patients. CONCLUSIONS: Coagulation anomalies are common and significant in both NCPF and EHPVO patients, suggestive of a mild disseminated intravascular coagulation disorder. These imbalances could be caused by chronic subclinical endotoxemia and cytokine activation after the initial portal thromboembolic event. The persistence of these abnormalities in adolescent patients indicates an ongoing coagulation derangement.     

Effect of shunt surgery on spleen size, portal pressure and oesophageal varices in patients with non-cirrhotic portal hypertension

Shunt surgery is considered to be the treatment of choice in patients with non-cirrhotic portal hypertension. There is little data on the effect of side-to-side lieno-renal (SSLR) shunt on oesophageal variceal size, splenic size and splenic pulp pressure (SPP) in patients with non-cirrhotic portal hypertension. We evaluated pre- and postoperatively endoscopic grading of varices, splenic size and SPP for predicting shunt patency in 86 patients with non-cirrhotic portal hypertension: 56 with extrahepatic portal venous obstruction (EHPVO) and 30 with non-cirrhotic portal fibrosis (NCPF). The EHPVO patients with patent shunts (n= 47) showed significant reduction in SPP (pre-operative 43.56±7.9 vs postoperative 29.96±7.7 cm of saline), splenic size (6.5±2.8 vs 4.00±2.6 cm below costal margin) and varices grades (2.96±0.5 vs 0.92±0.8). Patients with blocked shunt (n= 9) did not show significant reduction in SPP and varices grades. However, there was reduction in spleen size (8.6±3.0 vs 6.3±4.3). In the NCPF group, 28 had patent shunts and showed significant reduction in SPP (46.3±13.5 vs 33.8±7.6 cm of saline), splenic size (9.1±3.3 vs 6.8±4.6 cm below costal margin) and varices grades (2.8±0.7 vs 1.05±0.96). As only two patients with NCPF had blocked shunts, no statistical comparison between patients with patent and patients with blocked shunts could be done. In conclusion, following SSLR, there is a significant reduction in SPP and varices grades in patients with patent shunts. Endoscopic grading of varices can be used to predict shunt patency. However, spleen size is not a good criteria for predicting shunt patency.     

Cerebral diffusion tensor imaging and in vivo proton magnetic resonance spectroscopy in patients with fulminant hepatic failure

Background and Aim:  Cerebral edema is a major complication in patients with fulminant hepatic failure (FHF). The aim of this study was to evaluate the metabolite alterations and cerebral edema in patients with FHF using in vivo proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging, and to look for its reversibility in survivors.
Methods:  Ten FHF patients along with 10 controls were studied. Five of the 10 patients who recovered had a repeat imaging after three weeks. N-acetylaspartate, choline (Cho), glutamine (Gln), glutamine/glutamate (Glx), and myoinositol ratios were calculated with respect to creatine (Cr). Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in different brain regions.
Results:  Patients exhibited significantly increased Gln/Cr and Glx/Cr, and reduced Cho/Cr ratios, compared to controls. In the follow-up study, all metabolite ratios were normalized except Glx/Cr. Significantly decreased Cho/Cr were observed in deceased patients compared to controls. In patients, significantly decreased MD and FA values were observed in most topographical locations of the brain compared to controls. MD and FA values showed insignificant increase in the follow-up study compared to their first study.
Conclusions:  We conclude that the Cho/Cr ratio appears to be an in vivo marker of prognosis in FHF. Decreased MD values suggest predominant cytotoxic edema may be present. Persistence of imaging and MRS abnormalities at three weeks' clinical recovery suggests that metabolic recovery may take longer than clinical recovery in FHF patients.     

Effect of viral suppression on hepatic venous pressure gradient in hepatitis C with cirrhosis and portal hypertension

Portal hypertension is a predictor of liver‐related clinical events and mortality in patients with hepatitis C and cirrhosis. The effect of interferon‐free hepatitis C treatment on portal pressure is unknown. Fifty patients with Child‐Pugh‐Turcotte (CPT) A and B cirrhosis and portal hypertension (hepatic venous pressure gradient [HVPG] >6 mm Hg) were randomized to receive 48 weeks of open‐label sofosbuvir plus ribavirin at Day 1 or after a 24‐week observation period. The primary endpoint was sustained virologic response 12 weeks after therapy (SVR12) in patients who received ≥1 dose of treatment. Secondary endpoints included changes in HVPG, laboratory parameters, and MELD and CPT scores. A subset of patients was followed 48 weeks posttreatment to determine late changes in HVPG. SVR12 occurred in 72% of patients (33/46). In the 37 patients with paired HVPG measurements at baseline and the end of treatment, mean HVPG decreased by ‐1.0 (SD 3.97) mm Hg. Nine patients (24%) had ≥20% decreases in HVPG during treatment. Among 39 patients with pretreatment HVPG ≥12 mm Hg, 27 (69%) achieved SVR12. Four of the 33 (12%) patients with baseline HVPG ≥12 mm Hg had HVPG <12 mm Hg at the end of treatment. Of nine patients with pretreatment HVPG ≥12 mm Hg who achieved SVR12 and completed 48 weeks of follow‐up, eight (89%) had a ≥20% reduction in HVPG, and three reduced their pressure to <12 mm Hg. Patients with chronic HCV and compensated or decompensated cirrhosis who achieve SVR can have clinically meaningful reductions in HVPG at long‐term follow‐up. (EudraCT 2012‐002457‐29).