RESUMEN

AIM: To elucidate influencing factors of treatment response, then tolvaptan has been approved in Japan for liquid retention. METHODS: We herein conducted this study to clarify the influencing factors in 40 patients with decompensated liver cirrhosis complicated by liquid retention. Tolvaptan was administered at a dosage of 7.5 mg once a day for patients with conventional diuretic-resistant hepatic edema for 7 d. At the initiation of tolvaptan, the estimated hepatic venous pressure gradient (HVPG) value which was estimated portal vein pressure was measured using hepatic venous catheterization. We analyzed the effects of tolvaptan and influencing factors associated with treatment response. RESULTS: Subjects comprised patients with a median age of 65 (range, 40-82) years. According to the Child-Pugh classification, class A was 3 patients, class B was 19, and class C was 18. Changes from the baseline in body weight were -1.0 kg (P = 2.04 × 10(-6)) and -1.3 kg (P = 1.83 × 10(-5)), respectively. The median HVPG value was 240 (range, 105-580) mmH2O. HVPG was only significant influencing factor of the weight loss effect. When patients with body weight loss of 2 kg or greater from the baseline was defined as responders, receiver operating characteristic curve analysis showed that the optimal HVPG cutoff value was 190 mmH2O in predicting treatment response. The response rate was 87.5% (7/8) in patients with HVPG of 190 mmH2O or less, whereas it was only 12.5% (2/16) in those with HVPG of greater than 190 mmH2O (P = 7.46 × 10(-4)). We compared each characteristics factors between responders and non-responders. As a result, HVPG (P = 0.045) and serum hyaluronic acid (P = 0.017) were detected as useful factors. CONCLUSION: The present study suggests that tolvaptan in the treatment of liquid retention could be more effective for patients with lower portal vein pressure.

Asunto(s)

Antagonistas de los Receptores de Hormonas Antidiuréticas/uso terapéutico , Benzazepinas/uso terapéutico , Edema/tratamiento farmacológico , Cirrosis Hepática/complicaciones , Presión Portal , Equilibrio Hidroelectrolítico/efectos de los fármacos , Desequilibrio Hidroelectrolítico/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antagonistas de los Receptores de Hormonas Antidiuréticas/efectos adversos , Benzazepinas/efectos adversos , Edema/diagnóstico , Edema/etiología , Edema/fisiopatología , Femenino , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Selección de Paciente , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Tiempo , Tolvaptán , Resultado del Tratamiento , Desequilibrio Hidroelectrolítico/diagnóstico , Desequilibrio Hidroelectrolítico/etiología , Desequilibrio Hidroelectrolítico/fisiopatología

RESUMEN

OBJECTIVES: The addition of fluvastatin significantly improves sustained virological response (SVR) in pegylated interferon and ribavirin (peg-IFN/RBV) combination therapy for patients infected with the hepatitis C virus. However, the add-on effect on telaprevir-based triple combination therapy remains unknown. The aim of this study was to investigate the effect of fluvastatin on telaprevir-based combination therapy by conducting a prospective, open-label, randomized, controlled trial. PATIENTS AND METHODS: Among 124 genotype 1b-infected chronic hepatitis C patients recruited, 116 eligible patients were allocated randomly to two study arms; they received 12 weeks of telaprevir/peg-IFN/RBV, followed by 12 weeks of peg-IFN/RBV with or without 24 weeks of fluvastatin (fluvastatin group and control group, respectively). Treatment outcomes and adverse effects were compared between the two groups. RESULTS: There were 56 men and 60 women, median age 60 years (range, 28-71 years). Rapid virological response and end of treatment response rates were 87.9% (51/58) and 96.6% (56/58) in the control group and 75.9% (44/58) and 98.3% (57/58) in the fluvastatin group, respectively. SVR rates in the control group and the fluvastatin group were 84.5% (49/58) and 81.0% (47/58), respectively; there was no significant difference (P=0.806). Stratified analysis showed that no factors associated with the SVR rate were found between the two groups. No adverse events were associated with fluvastatin. CONCLUSION: In this trial, administration of fluvastatin with telaprevir/peg-IFN/RBV was a safe combination. However, fluvastatin had no add-on effect on 24-week telaprevir-based combination therapy for chronic hepatitis C genotype 1b-infected patients.

Asunto(s)

Ácidos Grasos Monoinsaturados/administración & dosificación , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Indoles/administración & dosificación , Oligopéptidos/administración & dosificación , Adulto , Anciano , Anticolesterolemiantes/administración & dosificación , Anticolesterolemiantes/efectos adversos , Antivirales/administración & dosificación , Antivirales/efectos adversos , Quimioterapia Combinada , Ácidos Grasos Monoinsaturados/efectos adversos , Femenino , Fluvastatina , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/virología , Humanos , Indoles/efectos adversos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Oligopéptidos/efectos adversos , Estudios Prospectivos , Resultado del Tratamiento

RESUMEN

AIM: Much is unknown about the effect of 25-hydroxyvitamin D3 levels on the outcome of pegylated interferon/ribavirin (PEG IFN/RBV) therapy for hepatitis C virus-related cirrhosis. The purpose of the present study was to analyze and elucidate factors, including 25-hydroxyvitamin D3 , that contribute to a sustained virological response (SVR) in patients with cirrhosis. METHODS: We analyzed whether 25-hydroxyvitamin D3 contributes to the response to PEG IFN/RBV therapy among 134 cirrhotic patients. RESULTS: SVR was achieved in 43 patients. The median 25-hydroxyvitamin D3 level was 20 ng/mL. Univariate analysis showed that the following factors contributed to SVR: low-density lipoprotein cholesterol, albumin, 25-hydroxyvitamin D3 , core a.a.70 (a.a.70) substitutions, the number of mutations at the interferon sensitivity-determining region and IL28B genotype. Multivariate analysis identified IL28B genotype and 25-hydroxyvitamin D3 as independent factors contributing to SVR. Subsequently, SVR rate was examined by using 25-hydroxyvitamin D3 and other important factors. The SVR rate was 51.8% in patients with core a.a.70 wild and ≥15 ng/mL of 25-hydroxyvitamin D3 , whereas the SVR rate was 7.1% in patients with core a.a.70 wild and <15 ng/mL of 25-hydroxyvitamin D3 . The SVR rate was 56.9% in patients with IL28B major genotype and ≥15 ng/mL of 25-hydroxyvitamin D3 . Surprisingly, the SVR rate was 0% in patients with IL28B minor genotype and <15 ng/mL of 25-hydroxyvitamin D3 . CONCLUSION: IL28B genotype and 25-hydroxyvitamin D3 were identified as independent factors contributing to SVR. Stratified analyses according to core a.a.70 substitution and IL28B genotype suggested that 25-hydroxyvitamin D3 influences the outcome of PEG IFN/RBV therapy for cirrhosis.

RESUMEN

BACKGROUND AND AIM: Fasudil, a Rho-kinase inhibitor, has been shown to reduce portal venous pressure in cirrhotic rats. However, its effects on portal and systemic hemodynamics have not been investigated in cirrhotic patients with portal hypertension. The aim of this study was to assess the effects of fasudil on the portal and systemic hemodynamics of cirrhotic patients with portal hypertension. METHODS: Twenty-three patients with cirrhosis and portal hypertension were studied. Systemic and portal hemodynamics were measured prior to and 50 min after the initiation of intravenous administration of 30 mg fasudil (n = 15) or placebo (n = 8). RESULTS: After fasudil, there were significant decreases in both mean arterial pressure (P < 0.05) and systemic vascular resistance (P < 0.05), whereas the heart rate increased significantly (P < 0.05). There was a significant decrease in the hepatic venous pressure gradient (P < 0.05). Portal vascular resistance also decreased significantly (P < 0.01). Placebo caused no significant effects. There were no symptomatic reactions caused by changes in the mean arterial pressure or heart rate after fasudil. CONCLUSIONS: In cirrhotic patients with portal hypertension, fasudil lowers portal vascular resistance, resulting in decreased portal venous pressure with reducing arterial pressure.

Asunto(s)

1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , Cirrosis Hepática/fisiopatología , Vena Porta/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Resistencia Vascular/efectos de los fármacos , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Adulto , Anciano , Animales , Presión Arterial/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Venas Hepáticas/efectos de los fármacos , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/fisiopatología , Infusiones Intravenosas , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Ratas , Presión Venosa/efectos de los fármacos , Adulto Joven

RESUMEN

AIM: The aim of this study was to investigate the predictive factors for the response of ascites to a transjugular intrahepatic portosystemic shunt (TIPS) and the impact of improvement of ascites on the overall prognosis of patients with cirrhosis and refractory ascites. METHODS: Forty-seven consecutive patients with liver cirrhosis who underwent TIPS for refractory ascites were studied retrospectively. The mean follow-up period was 615 ± 566 days. RESULTS: Thirty-six of the patients (77%) were responders at 4 weeks after TIPS (early responders) and 37 (79%) were responders at 8 weeks after TIPS. Of the 11 non-responders at 4 weeks, four showed an improvement of ascites at 8 weeks. Multivariate analysis showed that only the serum creatinine level before TIPS was an independent predictor of an early response. The cumulative survival rate of early responders was significantly higher than that of non-responders. The survival of patients grouped according to creatinine level was better in patients with serum creatinine of 1.9 mg/dL or less than in those with serum creatinine of more than 1.9 mg/dL. CONCLUSION: A low serum creatinine level in patients with refractory ascites is associated with an early response to TIPS. An early response of ascites to TIPS provides better survival. A serum creatinine level below 1.9 mg/dL is required for a good response to TIPS.

RESUMEN

Our aim was to evaluate the long-term efficacy and safety of percutaneous transhepatic obliteration (PTO) alone and combined with balloon-occluded retrograde transvenous obliteration (BRTO) for gastroesophageal varices refractory to BRTO alone. Between July 1999 and December 2010, 13 patients with gastroesophageal varices refractory to BRTO were treated with PTO (n = 6) or a combination of PTO and BRTO (n = 7). We retrospectively investigated the rates of survival, recurrence, or worsening of the varices; hepatic function before and after the procedure; and complications. The procedure achieved complete obliteration or significant reduction of the varices in all 13 patients without major complications. During follow-up, the varices had recurred in 2 patients, of which one had hepatocellular carcinoma, and the other died suddenly from variceal rebleeding 7 years after PTO. The remaining 11 patients did not experience worsening of the varices and showed significant improvements in the serum ammonia levels and prothrombin time. The mean follow-up period was 90 months, and the cumulative survival rate at 1, 3, and 5 years was 92.9%, 85.7%, and 85.7%, respectively. Both PTO and combined PTO and BRTO seem as safe and effective procedures for the treatment of gastroesophageal varices refractory to BRTO alone.

Asunto(s)

Oclusión con Balón/métodos , Várices Esofágicas y Gástricas/terapia , Adulto , Anciano , Várices Esofágicas y Gástricas/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del Tratamiento

RESUMEN

BACKGROUND: Serum vitamin D concentration is reported to show a decrease in older age. Patients with chronic hepatitis C (CHC) in Japan are older on average than those in Western countries. Moreover, the outcome of pegylated-interferon (PEG-IFN)/ ribavirin therapy combined with vitamin D in elderly patients is unclear. OBJECTIVES: This pilot study explored the efficacy and safety of alfacalcidol as vitamin D source in PEG-IFN/ ribavirin combination therapy for elderly CHC patients infected with hepatitis C virus genotype 1b. PATIENTS AND METHODS: Consecutive twenty CHC patients aged ≥ 65 years were enrolled in this pilot study. Fifteen patients met the inclusion criteria and received PEG-IFN/ ribavirin therapy combined with alfacalcidol. Four-week lead-in of oral alfacalcidol was conducted, and it was subsequently and concurrently administered in PEG-IFN/ ribavirin combination therapy (vitamin D group). Age, gender, and IL28B genotype-matched patients, who received PEG-IFN/ ribavirin alone, were saved as control group (n = 15) to compare the treatment outcome with the vitamin D group. RESULTS: Subjects consisted of 14 males and 16 females, with a median age of 70 years (65-78). The serum 25 (OH) D3 concentration in females (20 ng/ml, 11-37) was significantly lower than males (27 ng/mL, 13-49) (P = 0.004). Sustained virological response (SVR) rates were 33.3% (5/15) in the control group and 80.0% (12/15) in the vitamin D group, respectively (P = 0.025). While no significant difference was shown in the (SVR) rate between the two groups among males (P = 0.592), in females the SVR rate was significantly higher in the vitamin D group (87.5%, 7/8) than the control group (25.0%, 2/8) (P = 0.041). The relapse rates in the groups with and without alfacalcidol were 7.7% (1/13) and 61.5% (8/13), respectively (P = 0.011). Interestingly, in females, the relapse in the control group was shown in 5 of 7 (71.4%), whereas in the vitamin D group the relapse rate was decreased (1/8, 12.5%) (P = 0.041). No specific adverse events were observed in the vitamin D group. CONCLUSIONS: PEG-IFN/ ribavirin combined with alfacalcidol may be effective and safe in elderly CHC patients. In particular, concomitant administration of alfacalcidol may lead to a reduced relapse rate, and consequently improving the SVR rate in elderly females.

RESUMEN

BACKGROUND: The introduction of capsule endoscopy (CE) has facilitated the detection of mucosal changes in the small bowel, and such mucosal changes have been noted in cirrhotic patients with portal hypertension; these changes are described as portal hypertensive enteropathy. The aim of this study was to assess the effects of transjugular intrahepatic portosystemic shunt (TIPS) on the small bowel mucosal changes detected by CE in cirrhotic patients with portal hypertension. METHODS: TIPS was performed in fifteen cirrhotic patients with portal hypertension. All patients underwent CE before and 2 weeks after TIPS. The small bowel mucosal changes were defined as edema, angiodysplasia-like lesions, red spots, and small bowel varices. Changes in the portosystemic pressure gradient (PSG) and CE findings were evaluated. RESULTS: Before TIPS, small bowel edema was detected in all 15 patients, angiodysplasia-like lesions in 7, and red spots in 14 patients. The PSG decreased significantly, from 21.2 ± 2.6 before TIPS to 8.9 ± 3.3 mmHg (p < 0.001) after the procedure. After TIPS, the small bowel edema was attenuated in 8 of the 15 patients. In two patients with angiodysplasia-like lesions and 4 with red spots, these lesions were attenuated after TIPS. The average score for small bowel edema and the grade of red spots were reduced significantly after TIPS (2.3 ± 0.7-1.8 ± 0.6, p < 0.005 and 1.6 ± 0.9-1.3 ± 0.7, p < 0.05, respectively). Small bowel varices were seen in 4 patients before TIPS and all these varices disappeared after TIPS. CONCLUSIONS: In cirrhotic patients with portal hypertension, small bowel edema, red spots, and small bowel varices were attenuated after TIPS. Portal hypertension may be an important factor in the development of small bowel mucosal changes.

Asunto(s)

Hipertensión Portal/complicaciones , Mucosa Intestinal/patología , Intestino Delgado/patología , Cirrosis Hepática/complicaciones , Derivación Portosistémica Intrahepática Transyugular , Endoscopía Capsular , Femenino , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

BACKGROUND AND AIM: The most important factor influencing the effect of pegylated interferon (PEG-IFN)/ribavirin therapy (PEG) for chronic hepatitis C genotype 1b with high viral load is the interleukin 28B (IL28B) genotype. We investigated the usefulness of lead-in twice-daily interferon (IFN)-ß/ribavirin therapy (IFN-ß), and the early hepatitis C virus RNA (HCV-RNA) dynamics was compared between PEG and IFN-ß groups according to the IL28B genotype. METHODS: Forty-six patients were randomly allocated to PEG and IFN-ß groups, and HCV-RNA dynamics in an early phase of treatment were analyzed. RESULTS: The patients with minor IL28B genotype was 6/23 and 8/23 in IFN-ß and PEG groups, respectively. In the patients with IL28B major genotype, viral load reduction was marginally greater in IFN-ß group than in PEG group. In contrast, in the patients with the IL28B minor genotype, viral load reduction was significantly and numerically greater in IFN-ß group than in PEG group at 1 week (2.07 vs. 0.76 log IU/mL, P = 0.038), 2 weeks (2.73 vs. 1.01, P = 0.009), 4 weeks (2.72 vs. 1.55, P = 0.059), and 12 weeks (4.56 vs. 3.24, P = 0.104). The sustained virological response rates in the IL28B major genotype were similar between IFN-ß group (47.1%, 8/17) and PEG group (53.3%, 8/15). In contrast, the sustained virological response rates in the IL28B minor genotype were numerically higher in IFN-ß group (50.0%, 3/6) than in PEG group (12.5%, 1/8), although not statistically significant. CONCLUSION: It was suggested that lead-in twice-daily IFN-ß/ribavirin treatment followed by PEG-IFN/ribavirin combination therapy may modify the HCV-RNA dynamics compared with that by PEG-IFN/ribavirin therapy, and it is particularly useful for the IL28B minor genotype.

Asunto(s)

Antivirales/uso terapéutico , Genotipo , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Interferón beta/uso terapéutico , Interleucinas/genética , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Esquema de Medicación , Quimioterapia Combinada , Femenino , Marcadores Genéticos , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/genética , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferones , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , ARN Viral/sangre , Proteínas Recombinantes/uso terapéutico , Resultado del Tratamiento , Carga Viral

RESUMEN

BACKGROUND AND AIM: Although the anti-hepatitis C virus (HCV) effect of statins in vitro and clinical efficacy of fluvastatin combined with Pegylated interferon (PEG-IFN)/ribavirin therapy for chronic hepatitis C (CHC) have been reported, the details of clinical presentation are largely unknown. We focused on viral relapse that influences treatment outcome, and performed a post-hoc analysis by using data from a randomized controlled trial. METHODS: Thirty-four patients in the fluvastatin group and 33 patients in the non-fluvastatin group who achieved virological response (complete early virological response [cEVR] or late virological response [LVR]) with PEG-IFN/ribavirin therapy were subjected to this analysis. Factors contributing to viral relapse were identified by using multiple logistic regression analysis. RESULTS: Relapse rate in patients with cEVR was significantly lower in the fluvastatin group (2 of 23, 8.7%) than in the non-fluvastatin group (9 of 26, 34.6%; P = 0.042). The use of fluvastatin decreased relapse rate in patients with LVR (27.3% vs 57.1%), though not significantly. Overall, relapse rate was significantly lower in the fluvastatin group (14.7%; 5 of 34) than in the non-fluvastatin group (39.4%; 13 of 33; P = 0.027). Multivariate analysis identified absence of fluvastatin (P = 0.027, odds ratio [OR] = 3.98, 95% confidence interval [CI] = 1.05-15.11) and low total ribavirin dose (P = 0.002, OR = 2.41, 95% CI = 1.38-4.19) as independent factors contributing to relapse. CONCLUSION: The concomitant addition of fluvastatin significantly suppressed viral relapse, resulting in the improvement of sustained virological response rate, in PEG-IFN/ribavirin therapy for CHC patients with HCV genotype 1b and high viral load.

Asunto(s)

Antivirales/uso terapéutico , Ácidos Grasos Monoinsaturados/uso terapéutico , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Indoles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Intervalos de Confianza , Quimioterapia Combinada , Femenino , Fluvastatina , Hepatitis C Crónica/sangre , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Polietilenglicoles/uso terapéutico , ARN Viral/sangre , Proteínas Recombinantes/uso terapéutico , Recurrencia , Ribavirina/uso terapéutico

RESUMEN

BACKGROUND/AIM: Previous studies have reported small intestinal lesions in patients with portal hypertensive disease. However, the etiology of these lesions is not clear, as portal venous pressure was not measured in any of these studies. The aim of this study is to clarify the association between small intestinal lesions and hepatic venous pressure gradient (HVPG), which correlates well with portal venous pressure. METHODS: Thirty-five patients with liver cirrhosis were evaluated by capsule endoscopy for small intestinal lesions. HVPG was measured within 3 days of capsule endoscopy. Blood tests, clinical symptoms, Child-Pugh classification and HVPG were analyzed against small intestinal lesions such as edemas, red spots, angiodysplasia and varices. Lesions were categorized according to their location in the duodenum, jejunum or ileum. Edema was evaluated using a 4-grade capsule endoscopy scoring index. RESULTS: HVPG and edema scores increased with Child-Pugh scores. Red spots and angiodysplasia did not correlate with HVPG. Varices were detected in only 5 patients. The edema score was the factor which most strongly correlated with HVPG by multivariate analysis (p = 0.0008). There was also a strong linear relation between edema scores and HVPG (R = 0.75, p < 0.0001). CONCLUSION: Small intestinal edemas showed the strongest correlation with HVPG among all small intestinal lesions.

Asunto(s)

Endoscopía Capsular , Edema/patología , Hipertensión Portal/fisiopatología , Intestino Delgado/patología , Cirrosis Hepática/complicaciones , Presión Portal , Anciano , Enfermedades Duodenales/etiología , Enfermedades Duodenales/patología , Edema/etiología , Femenino , Humanos , Hipertensión Portal/etiología , Enfermedades del Íleon/etiología , Enfermedades del Íleon/patología , Intestino Delgado/fisiopatología , Enfermedades del Yeyuno/etiología , Enfermedades del Yeyuno/patología , Cirrosis Hepática/fisiopatología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante

RESUMEN

BACKGROUND: Treatment with terlipressin and albumin has been reported recently to be effective in improving renal function in the treatment of cirrhotic patients with hepatorenal syndrome (HRS). The aim of this prospective, multicenter study was to investigate the efficacy and safety of treatment with terlipressin and albumin in Japanese cirrhotic patients with type 1 HRS. METHODS: Eight cirrhotic patients with type 1 HRS were included in the study. Terlipressin (2.8 ± 0.4 mg/day) and albumin (25.7 ± 2.8 g/day) were given simultaneously for 6.3 ± 4.2 days. RESULTS: Urine volume was significantly increased (p < 0.05) at the end of treatment compared with baseline. Serum creatinine levels were significantly decreased from 2.84 ± 0.45 to 1.08 ± 0.33 mg/dl (-61.9 ± 9.9%, p < 0.05) after terlipressin and albumin administration. Creatinine clearance was significantly increased (p < 0.05) after treatment. Plasma renin activity and norepinephrine were significantly decreased (p < 0.05) after therapy. Six of the 8 patients (75%) showed a complete response (reduction of serum creatinine to 1.5 mg/dl or less). The cumulative probabilities of survival at 4 and 12 weeks were 63 and 13%, respectively. Complication of congestive heart failure possibly related to this regimen was seen in 1 patient, but ischemic adverse events were not observed during the treatment. CONCLUSIONS: Treatment with terlipressin and albumin improves renal function in cirrhotic patients with type 1 HRS. However, the survival of cirrhotic patients with type 1 HRS remains poor, although it may be improved by this specific therapy.

Asunto(s)

Albúminas/uso terapéutico , Antihipertensivos/uso terapéutico , Síndrome Hepatorrenal/tratamiento farmacológico , Lipresina/análogos & derivados , Anciano , Albúminas/administración & dosificación , Albúminas/efectos adversos , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Creatinina/sangre , Quimioterapia Combinada , Femenino , Síndrome Hepatorrenal/etiología , Humanos , Japón , Cirrosis Hepática/complicaciones , Lipresina/administración & dosificación , Lipresina/efectos adversos , Lipresina/uso terapéutico , Masculino , Persona de Mediana Edad , Norepinefrina/sangre , Estudios Prospectivos , Renina/sangre , Tasa de Supervivencia , Terlipresina , Resultado del Tratamiento

Asunto(s)

Endoscopía Capsular , Hipertensión Portal/patología , Intestino Delgado/patología , Anciano , Humanos , Cirrosis Hepática/complicaciones , Masculino

RESUMEN

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) has recently been reported to be effective in the treatment of cirrhotic patients with refractory ascites. However, the clinical utility of TIPS in the subset of refractory ascitic patients with good hepatic and renal function is uncertain. The aim of this study was to compare the efficacy of TIPS to that of large-volume paracentesis in cirrhotic patients with refractory ascites who have good hepatic and renal function. METHODS: Sixty cirrhotic patients with refractory ascites who presented with a Child-Pugh score of <11, serum bilirubin of <3 mg/dl and creatinine of <1.9 mg/dl were assigned randomly to TIPS (n = 30) or large-volume paracentesis plus albumin (n = 30). The primary endpoint was survival. The secondary endpoints were response to treatment and development of hepatic encephalopathy. RESULTS: The baseline characteristics were similar in the two groups. Seventeen patients treated with TIPS and 21 treated with paracentesis died during the study period. The cumulative probabilities of survival at 1 and 2 years were 80 and 64% in the TIPS group and 49 and 35% in the paracentesis group (p < 0.005). TIPS was significantly superior to paracentesis in the control of ascites (p < 0.005). Treatment failure was more frequent in the paracentesis group, whereas the frequency of hepatic encephalopathy was greater in the TIPS group. CONCLUSIONS: In cirrhotic patients with refractory ascites who have good hepatic and renal function, TIPS improves survival and provides better control of ascites than large-volume paracentesis.

Asunto(s)

Ascitis/cirugía , Cirrosis Hepática/cirugía , Paracentesis , Derivación Portosistémica Intrahepática Transyugular , Anciano , Albúminas/uso terapéutico , Ascitis/mortalidad , Ascitis/fisiopatología , Ascitis/prevención & control , Terapia Combinada , Diuréticos/uso terapéutico , Femenino , Encefalopatía Hepática/etiología , Encefalopatía Hepática/fisiopatología , Humanos , Cirrosis Hepática/mortalidad , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recurrencia , Resultado del Tratamiento , Ultrasonografía Doppler en Color

RESUMEN

A 72-year-old male with liver dysfunction and an increase in serum total protein/albumin (TP/Alb) ratio was referred to our hospital. There was a marked increase in serum immunoglobulin (Ig) G4 level (IgG/IgG4: 3,485/2,860 mg/dl). Diagnostic imaging did not reveal any enlargement of the pancreas or narrowing of the pancreatic duct. However, bilateral submaxillary gland swelling, sclerosing cholangitis, and retroperitoneal fibrosis were noted, suggesting multifocal fibrosclerosis. Histological examination of the submaxillary gland showed the infiltration of IgG4-positive plasma cells, although there was no narrowing of the pancreatic duct, leading to a diagnosis of IgG4-related disease with various extrapancreatic lesions. Systemic investigation before the introduction of steroid therapy revealed rectal cancer. After low-position anterior resection, steroid therapy was introduced, reducing the lesions. Recent studies have reported autoimmune pancreatitis/IgG4-related disease with malignant tumors. However, the association and pathogenesis remain to be clarified. Malignant tumors are detected before or after the treatment of autoimmune pancreatitis/IgG4-related disease; pretreatment diagnosis and post-treatment follow-up should be carefully performed, bearing in mind the concomitant development of malignant tumors.

RESUMEN

BACKGROUND AND AIM: Terlipressin has been shown to be effective in the management of hepatorenal syndrome. However, how terlipressin exerts its effect on the renal artery is unknown. The aim of the present study was to assess the effects of terlipressin on systemic, hepatic and renal hemodynamics in cirrhosis. METHODS: Twenty-eight patients with cirrhosis and portal hypertension were studied. Systemic and hepatic hemodynamics, hepatic and renal arterial resistive indices and neurohumoral factors were measured prior to and 30 min after intravenous administration of 1 mg terlipressin (n = 19) or placebo (n = 9). RESULTS: After terlipressin, there were significant increases in both mean arterial pressure (P < 0.001) and systemic vascular resistance (P < 0.001), whereas heart rate (P < 0.001) and cardiac output (P < 0.001) decreased significantly. There was a significant decrease in the hepatic venous pressure gradient (P < 0.001). Portal venous blood flow also decreased significantly (P < 0.001). The mean hepatic arterial velocity increased significantly (P < 0.001). Although there was a significant decrease in the hepatic arterial resistive index (0.72 +/- 0.08 to 0.69 +/- 0.08, P < 0.001) and renal arterial resistive index (0.74 +/- 0.07 to 0.68 +/- 0.07, P < 0.001), portal vascular resistance was unchanged (P = 0.231). Plasma renin activity decreased significantly (P < 0.005), and there was a significant correlation between this decline and the decrease in renal arterial resistive index (r = 0.764, P < 0.005). The effects of terlipressin on systemic, hepatic and renal hemodynamics were observed similarly in patients with and without ascites. Placebo caused no significant effects. CONCLUSION: Terlipressin decreases hepatic and renal arterial resistance in patients with cirrhosis.

Asunto(s)

Hemodinámica/efectos de los fármacos , Síndrome Hepatorrenal/tratamiento farmacológico , Hipertensión Portal/tratamiento farmacológico , Circulación Hepática/efectos de los fármacos , Cirrosis Hepática/tratamiento farmacológico , Lipresina/análogos & derivados , Circulación Renal/efectos de los fármacos , Vasoconstrictores/uso terapéutico , Anciano , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Síndrome Hepatorrenal/diagnóstico por imagen , Síndrome Hepatorrenal/etiología , Síndrome Hepatorrenal/fisiopatología , Humanos , Hipertensión Portal/diagnóstico por imagen , Hipertensión Portal/etiología , Hipertensión Portal/fisiopatología , Inyecciones Intravenosas , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/fisiopatología , Lipresina/administración & dosificación , Lipresina/efectos adversos , Lipresina/uso terapéutico , Masculino , Persona de Mediana Edad , Neurotransmisores/sangre , Efecto Placebo , Terlipresina , Resultado del Tratamiento , Ultrasonografía Doppler , Resistencia Vascular/efectos de los fármacos , Vasoconstrictores/administración & dosificación , Vasoconstrictores/efectos adversos

RESUMEN

In this prospective cohort study, we evaluated the use of transjugular intrahepatic portosystemic shunt (TIPS) in 50 patients with refractory ascites and a Child-Pugh score of 9.8. The mean duration of follow-up was 592 days. Ascites improved in 96% at 1 year and in 93% at 2 years. The cumulative survival rate was 71%, 52% and 18% at 1, 2 and 5 years. The Child-Pugh score and the performance status score improved significantly after TIPS. Thirty six patients required shunt revision during follow-up, due to shunt stenosis. Hepatic encephalopathy which was able to be controlled medically occurred in 26 patients. Our results suggest that although shunt revision may be needed, TIPS can control refractory ascites in most survival cases and improve QOL. However, the 5-year survival rate is still low in our TIPS-treated patients with refractory ascites.

Asunto(s)

Ascitis/cirugía , Derivación Portosistémica Intrahepática Transyugular , Ascitis/mortalidad , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Tasa de Supervivencia , Resultado del Tratamiento

RESUMEN

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.

Asunto(s)

Circulación Colateral/fisiología , Venas Hepáticas/fisiopatología , Circulación Hepática/fisiología , Cirrosis Hepática/fisiopatología , Presión Portal/fisiología , Femenino , Estudios de Seguimiento , Venas Hepáticas/diagnóstico por imagen , Humanos , Hipertensión Portal/diagnóstico , Hipertensión Portal/etiología , Hipertensión Portal/fisiopatología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Flebografía , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Ultrasonografía Doppler

RESUMEN

The aim of this prospective study was to investigate the incidence, clinical features and the short- and long-term clinical course of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) in Japanese patients. Eighty-seven consecutive patients with liver cirrhosis presenting with complications of portal hypertension underwent TIPS. The mean follow-up period after TIPS was 866 days. During the follow-up, HE occurred in 52% of patients throughout the follow-up period. The cumulative incidence of post-TIPS HE was 50.5+/-5.6% at 1 year (mean+/-S.D.). Most cases (89%) occurring within 7 days were easily controlled by the conventional therapy. Only two patients developed severe chronic HE, which was treated by reducing the shunt diameter. Older age, indication for TIPS (ascites) and higher retention rate of indocyanine green at 15min were identified as risk factors for post-TIPS HE. During long-term follow-up, the incident of post-TIPS HE decreased among survivals. The cumulative survival rate was similar in patients with or without post-TIPS HE. Our results indicate that post-TIPS HE are a frequent complication, particularly in the early months after TIPS. However, it can be easily managed in the majority of patients. The development of post-TIPS HE is not associated with poor prognosis in TIPS patients.

RESUMEN

The effect of octreotide on splanchnic hemodynamics was examined in cirrhotic patients both in the fasting and postprandial states using echo-Doppler flowmetry. The splanchnic parameters examined were portal venous blood flow (PVBF), superior mesenteric venous blood flow (SMVBF), and splenic venous blood flow (SPBF). In the fasting state, nine cirrhotic patients were examined at baseline and at 30 and 60min after octreotide administration. In the postprandial state, 16 cirrhotic patients were investigated in a prospective, placebo-controlled, crossover study. Data were collected at baseline, 30min after a standard liquid meal and at 30 and 60min after octreotide or placebo administration. In the fasting state, octreotide induced a mild reduction both in PVBF (-16%) and SMVBF (-12%). In contrast, in the postprandial state, octreotide induced a significantly larger decrease in PVBF (-32%) and SMVBF (-32%). SPBF showed no significant changes in either the fasting or postprandial state. Octreotide suppressed the release of glucagon, and in the postprandial state, changes in SMVBF significantly correlated with changes in glucagon after octreotide administration. We conclude that octreotide significantly reduces PVBF and SMVBF in the postprandial state, but has comparatively little effect in the fasting state, and may act via suppression of glucagon.