BACKGROUND/AIMS: Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial. METHODS: Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders. RESULTS: The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12-28 mmHg) to 13.5 mmHg (range, 6-20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12-27 mmHg) to 14 mmHg (range, 7-25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3-11 mmHg) vs. 3 mmHg (range, -8-10 mmHg), P=0.674]. The response rate (55.6% vs. 61.5%, P=0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups. CONCLUSIONS: The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended.
Adolescent ; Adult ; Aged ; Antihypertensive Agents/*therapeutic use ; Benzimidazoles/*therapeutic use ; Blood Pressure ; Drug Therapy, Combination ; Female ; Humans ; Hypertension, Portal/complications/*drug therapy ; Liver Cirrhosis/complications/diagnosis ; Male ; Middle Aged ; Propranolol/*therapeutic use ; Prospective Studies ; Tetrazoles/*therapeutic use ; Treatment Outcome ; Young Adult

Enbucrilate ; adverse effects ; therapeutic use ; Female ; Humans ; Hypertension, Portal ; diagnosis ; etiology ; Liver Cirrhosis, Biliary ; drug therapy ; Middle Aged ; Pulmonary Embolism ; chemically induced ; diagnosis ; Sepsis ; chemically induced ; etiology

Previous studies reported that oxaliplatin is associated with sinusoidal obstruction syndrome. However few reports on oxaliplatin induced liver fibrosis are found in the literature. Furthermore pathogenesis of liver fibrosis is not well known. We report a case of 45-yr-old Korean man in whom liver fibrosis with splenomegaly developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for colon cancer (T4N2M0). Thorough history taking and serological examination revealed no evidence of chronic liver disease. Restaging CT scans demonstrated a good response to chemotherapy. Five month after chemotherapy, he underwent right hepatectomy due to isolated metastatic lesion. The liver parenchyma showed diffuse sinusoidal dilatation and centrilobular vein fibrosis with necrosis without steatosis. We could conclude that splenomegaly was due to perisinusoidal liver fibrosis and liver cell necrosis induced portal hypertension by oxaliplatin. In addition, to investigate the pathogenesis of liver fibrosis, immunohistochemical stains such as CD31 and alpha-smooth muscle actin (alpha-SMA) were conducted with control group. The immunohistochemical stains for CD31 and alpha-SMA were positive along the sinusoidal space in the patient, while negative in the control group. Chemotherapy with oxaliplatin induces liver fibrosis which should be kept in mind as a serious complication.
Actins/metabolism ; Antigens, CD31/metabolism ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Camptothecin/*analogs & derivatives/therapeutic use ; Chemotherapy, Adjuvant ; Colonic Neoplasms/*drug therapy ; Fluorouracil/therapeutic use ; Humans ; Hypertension, Portal/etiology ; Immunohistochemistry ; Leucovorin/therapeutic use ; Liver Cirrhosis/*diagnosis/etiology/pathology ; Liver Neoplasms/secondary/surgery ; Male ; Middle Aged ; Organoplatinum Compounds/*administration & dosage/adverse effects/therapeutic use ; Splenomegaly/*diagnosis/etiology ; Thrombocytopenia/etiology ; Tomography, X-Ray Computed

While esophagogastric varices are common manifestations of portal hypertension, variceal bleeding from the jejunum is a rare complication of liver cirrhosis. In addition, ectopic variceal bleeding occurs in the duodenum and at sites of previous bowel surgery in most cases, including of stomas. We report a case of obscure overt gastrointestinal bleeding from jejunal varices in a 55-year-old woman who had not previously undergone abdominal surgery, who had liver cirrhosis induced by the hepatitis C virus. Emergency endoscopy revealed the presence of esophageal varices without stigmata of recent bleeding, and no bleeding focus was found at colonoscopy. She continued to produce recurrent melena with hematochezia and received up to 21 units of packed red blood cells. CT angiography revealed the presence of jejunal varices, but no active bleeding was found. Capsule endoscopy revealed fresh blood in the jejunum. The patient submitted to embolization of the jejunal varices via the portal vein, after which she had a stable hemoglobin level and no recurrence of the melena. This is a case of variceal bleeding from the jejunum in a liver cirrhosis patient without a prior history of abdominal surgery.
Angiography ; Capsule Endoscopy ; Embolization, Therapeutic ; Esophageal and Gastric Varices/complications/diagnosis ; Female ; *Gastrointestinal Hemorrhage ; Humans ; Hypertension, Portal ; Jejunal Diseases/*diagnosis/therapy ; Liver Cirrhosis/*diagnosis ; Melena/complications ; Middle Aged ; Tomography, X-Ray Computed

We report herein a case of 35-years-old woman in whom portal hypertension (esophageal varix and splenomegaly) developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for rectal cancer. She was transferred for the evaluation of etiology of new-onset portal hypertension. The esophageal varix and splenomegaly were absent before the oxaliplatin based adjuvant chemotherapy. Thorough history taking and serological exam revealed no evidence of chronic liver disease. Liver biopsy was done and there was no cirrhotic nodule formation. Instead, perivenular fibrosis was noted. Considering new development of esophageal varices and splenomegaly after 12 cycles of oxaliplatin-based adjuvant chemotherapy, we could conclude that portal hypertension in this patient were due to sinusoidal injury by oxaliplatin. Finally, we recommend regular follow-up with endoscopy and radiologic examination for checking the development of varices and for screening of varices and splenomegaly in patients with colo-rectal cancer who receive oxaliplatin-based chemotherapy.
Adult ; Antineoplastic Agents/*adverse effects/therapeutic use ; Chemotherapy, Adjuvant ; Esophageal and Gastric Varices/chemically induced ; Female ; Fibrosis ; Humans ; Hypertension, Portal/chemically induced/*diagnosis ; Liver/pathology ; Organoplatinum Compounds/*adverse effects/therapeutic use ; Positron-Emission Tomography ; Rectal Neoplasms/*drug therapy/surgery ; Splenomegaly/chemically induced ; Tomography, X-Ray Computed

We report herein a case of 35-years-old woman in whom portal hypertension (esophageal varix and splenomegaly) developed after 12 cycles of oxaliplatin based adjuvant chemotherapy for rectal cancer. She was transferred for the evaluation of etiology of new-onset portal hypertension. The esophageal varix and splenomegaly were absent before the oxaliplatin based adjuvant chemotherapy. Thorough history taking and serological exam revealed no evidence of chronic liver disease. Liver biopsy was done and there was no cirrhotic nodule formation. Instead, perivenular fibrosis was noted. Considering new development of esophageal varices and splenomegaly after 12 cycles of oxaliplatin-based adjuvant chemotherapy, we could conclude that portal hypertension in this patient were due to sinusoidal injury by oxaliplatin. Finally, we recommend regular follow-up with endoscopy and radiologic examination for checking the development of varices and for screening of varices and splenomegaly in patients with colo-rectal cancer who receive oxaliplatin-based chemotherapy.
Adult ; Antineoplastic Agents/*adverse effects/therapeutic use ; Chemotherapy, Adjuvant ; Esophageal and Gastric Varices/chemically induced ; Female ; Fibrosis ; Humans ; Hypertension, Portal/chemically induced/*diagnosis ; Liver/pathology ; Organoplatinum Compounds/*adverse effects/therapeutic use ; Positron-Emission Tomography ; Rectal Neoplasms/*drug therapy/surgery ; Splenomegaly/chemically induced ; Tomography, X-Ray Computed

Portal hypertensive gastropathy (PHG) is a term used to define the endoscopic findings of gastric mucosa with a characteristic mosaic-like pattern with or without red spots, and a common finding in patients with portal hypertension. These endoscopic findings correspond to dilated mucosal capillaries without inflammation. The pathogenesis of PHG in not well known, but portal hypertension and some humoral factors seem to be crucial factors for its development. Pharmacological (e.g. propranolol), or interventional radiological (such as transjugular intrahepatic portosystemic shunt) procedures may be useful in preventing re-bleeding from PHG. The classic features of gastric antral vascular ectasia (GAVE) syndrome include red, often haemorrhagic lesions predominantly located in the gastric antrum which can result in significant blood loss. Although the pathogenesis of GAVE is not clearly defined, it seems to be a separate disease entity from PHG, because GAVE generally does not respond to a reduction of portal pressures. Endoscopic ablation (such as argon plasma coagulation) is the first-line treatment of choice. This review will focus on the incidence, clinical importance, etiology, pathophysiology, and treatment of PHG and GAVE syndrome in the setting of portal hypertension.
Esophageal and Gastric Varices/*diagnosis/etiology/therapy ; Gastric Antral Vascular Ectasia/*diagnosis/etiology/therapy ; Gastric Mucosa/metabolism/pathology ; Humans ; Hypertension, Portal/*complications ; Portasystemic Shunt, Transjugular Intrahepatic ; Vasodilator Agents/therapeutic use

Ascites, hepatic encephalopathy and variceal hemorrhage are three major complications of portal hypertension. The diagnostic evaluation of ascites involves an assessment of its etiology by determining the serum-ascites albumin gradient and the exclusion of spontaneous bacterial peritonitis. Ascites is primarily related to an inability to excrete an adequate amount of sodium into urine, leading to a positive sodium balance. Sodium restriction and diuretic therapy are keys of ascites control. But, with the case of refractory ascites, large volume paracentesis and transjugular portosystemic shunts are required. In hepatorenal syndrome, splanchnic vasodilatation with reduction in effective arterial volume causes intense renal vasoconstriction. Splanchnic and/or peripheral vasoconstrictors with albumin infusion, and renal replacement therapy are only bridging therapy. Liver transplantation is the only definitive modality of improving the long term prognosis.
Anti-Bacterial Agents/therapeutic use ; Ascites/complications/*diagnosis/therapy ; Bacterial Infections/*diagnosis ; Hepatic Encephalopathy/complications ; Hepatorenal Syndrome/complications/*diagnosis/therapy ; Humans ; Hypertension, Portal/*complications ; Liver Transplantation ; Peritonitis/*diagnosis/drug therapy/etiology ; Serum Albumin/administration & dosage

Ascites ; diagnosis ; etiology ; therapy ; Diagnostic Imaging ; methods ; Humans ; Hydrothorax ; diagnosis ; etiology ; therapy ; Hypertension, Portal ; complications ; Liver Cirrhosis ; complications ; Liver Transplantation ; Pleural Effusion ; diagnosis ; etiology ; therapy ; Portasystemic Shunt, Transjugular Intrahepatic

Animals ; Diagnosis, Differential ; Disease Models, Animal ; Gastric Antral Vascular Ectasia ; diagnosis ; pathology ; Gastric Mucosa ; pathology ; Gastrointestinal Hemorrhage ; etiology ; pathology ; therapy ; Gastroscopy ; Humans ; Hypertension, Portal ; complications ; epidemiology ; pathology ; Intestinal Mucosa ; pathology ; Liver Cirrhosis ; complications ; pathology ; Liver Cirrhosis, Experimental ; complications ; pathology ; Rats ; Stomach Diseases ; epidemiology ; etiology ; pathology ; therapy