[Show abstract][Hide abstract] ABSTRACT: Critical illness-related corticosteroid insufficiency has been reported in acute variceal bleeding (AVB). In cirrhosis, free serum cortisol (FC) is considered optimal to assess adrenal function. Salivary cortisol (SC) is considered a surrogate for FC. We evaluated FC and its prognostic role in AVB.
European journal of gastroenterology & hepatology. 08/2014;
[Show abstract][Hide abstract] ABSTRACT: Early results of a randomised trial showed reduced fibrosis due to recurrent HCV hepatitis with tacrolimus triple therapy (TT) versus monotherapy (MT) following transplantation for HCV cirrhosis. We evaluated the clinical outcomes after a median 8 years of follow-up, including differences in fibrosis assessed by collagen proportionate area (CPA).
103 consecutive liver transplant recipients with HCV cirrhosis receiving cadaveric grafts were randomised to tacrolimus MT (n=54) or TT (n=49) with daily tacrolimus (0.1 mg/kg divided dose), azathioprine (1 mg/kg) and prednisolone (20 mg), the last tailing off to zero by 6 months. Both groups had serial transjugular biopsies with hepatic venous pressure gradient (HVPG) measurement. Time to reach Ishak stage 4 was the predetermined endpoint. CPA was measured in all biopsies. Factors associated with HCV recurrence were evaluated. Clinical decompensation was the first occurrence of ascites/hydrothorax, variceal bleeding or encephalopathy.
No significant preoperative, peri-operative or postoperative differences between groups were found. During 96 months median follow-up, stage 4 fibrosis was reached in 19 MT/11 TT with slower fibrosis progression in TT (p=0.009). CPA at last biopsy was 12% in MT and 8% in TT patients (p=0.004). 14 MT/ three TT patients reached HVPG≥10 mm Hg (p=0.002); 10 MT/three TT patients, decompensated. Multivariately, allocated MT (p=0.047, OR 3.23, 95% CI 1.01 to 10.3) was independently associated with decompensation: 14 MT/ seven TT died, and five MT/ four TT were retransplanted.
Long term immunosuppression with tacrolimus, azathioprine and short term prednisolone in HCV cirrhosis recipients resulted in slower progression to severe fibrosis assessed by Ishak stage and CPA, less portal hypertension and decompensation, compared with tacrolimus alone. ISRCTN94834276: Randomised study for immunosuppression regimen in liver transplantation.
[Show abstract][Hide abstract] ABSTRACT: Klippel-Trénaunay syndrome is a rare congenital syndrome characterized by capillary malformations, soft tissue and bone hypertrophy, and varicose veins. There is a well-established risk for thrombotic complications in these patients. A case of a young patient diagnosed post partum with the very rare liver involvement is presented. The complex clinical course, the multidisciplinary management and the long-term outcome are discussed.
Annals of Gastroenterology 01/2012; 25(4):365-367.
[Show abstract][Hide abstract] ABSTRACT: HCV related liver disease is the most common indication for liver transplantation. Recurrence of HCV infection is universal and has a substantial impact on patient and graft survival. Immunosuppression is a major factor responsible for the accelerated recurrence and compressed natural history of recurrent HCV infection. Accumulating experience has provided data to support certain strategies for immunosuppressive regimens. From the available evidence, more severe recurrence results from repeated bolus corticosteroid therapy and anti-lymphocyte antibodies used to treat rejection. Low dose and slow tapering of steroids are better than high dose maintenance and/or rapid tapering. Recent meta-analyses favour steroid-free regimens but these are complicated to interpret as the absence of steroids may simply represent less immunopotency. There is no difference in HCV recurrence between tacrolimus and cyclosporine regimens, but tacrolimus increases graft and patient survival in HCV transplanted patients. There may be a beneficial effect of maintenance azathioprine given for 6 months or longer. There is no conclusive evidence for benefit of mycophenolate and interleukin-2 receptor blockers. Few data are available for mTOR inhibitors. Better evidence is needed to establish the optimal immunosuppressive regimen for HCV recipients and more randomized trials should be performed.
Journal of Hepatology 09/2011; 56(4):973-83. · 9.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 35-year-old lady was admitted to our Department due to fever and symptoms from the respiratory and gastrointestinal system. She was recently diagnosed with eosinophilic gastroenteritis and had been on steroids until two months prior to admission. Legionella pneumophila pneumonia was diagnosed and targeted therapy was initiated. The combined approach to the two entities is discussed as well as the options for maintenance therapy.
Annals of Gastroenterology 01/2011; 24(4):325-327.
[Show abstract][Hide abstract] ABSTRACT: Less potent immunosuppression is considered to reduce the severity of hepatitis C virus (HCV) recurrence after liver transplantation. An optimal regimen is unknown. We evaluated tacrolimus monotherapy versus triple therapy in a randomized trial of 103 first transplants for HCV cirrhosis. One hundred three patients who underwent transplantation for HCV were randomized to tacrolimus monotherapy (n = 54) or triple therapy with tacrolimus, azathioprine, and steroids (n = 49), which were tapered to zero by 3 to 6 months. Both groups had serial transjugular biopsies with hepatic venous pressure gradient (HVPG) measurement. The time to reach Ishak stage 4 was the predetermined endpoint. All factors documented in the literature as being associated with HCV recurrence and the allocated treatment were evaluated for reaching stage 4 and HVPG >or= 10 mm Hg. No significant preoperative, perioperative, or postoperative differences, including the frequency of biopsies between groups, were found. During a mean follow-up of 53.5 months, 9 monotherapy patients and 6 triple therapy patients died, and 5 monotherapy patients and 4 triple therapy patients underwent retransplantation. Stage 4 fibrosis was reached in 17 monotherapy patients and 10 triple therapy patients (P = 0.04), with slower fibrosis progression in the triple therapy patients (P = 0.048). Allocated therapy and histological acute hepatitis were independently associated with stage 4 fibrosis. HVPG increased to >or=10 mm Hg more rapidly in monotherapy patients versus triple therapy patients (P = 0.038). In conclusion, long-term maintenance immunosuppression with azathioprine and shorter term prednisolone with tacrolimus in HCV cirrhosis recipients resulted in a slower onset of histologically proven severe fibrosis and portal hypertension in comparison with tacrolimus alone, and this was independent of known factors affecting fibrosis.
[Show abstract][Hide abstract] ABSTRACT: Renal failure is common in cirrhosis frequently due to hepatorenal syndrome (HRS). Terlipressin and albumin improve renal function with a trend to prolong survival in HRS, but prognostic factors with therapy have been poorly studied.
Forty-five cirrhotics seen consecutively in a single centre with renal failure defined as oliguria/anuria and/or rising creatinine and no response to volume loading, without intrinsic renal disease, sepsis, gastrointestinal bleeding [median Child-Pugh score 12(8-14)/Model for End-Stage Liver Disease 29(10-40)], had intravenous terlipressin and albumin and were audited retrospectively classified into three groups: group 1 HRS type 1 (15), group 2 HRS type 2 (11) and group 3(19): not fulfilling HRS 1 or 2 criteria. Baseline median creatinine was 1.7 (0.9-5.46) mg/dl and 30 (67%) had creatinine greater than 1.5 mg/dl. All 45 patients had initial colloid/albumin and 31 continued terlipressin (2-4 mg/day) for a median 8 (2-76) days.
Improvement in serum creatinine occurred in 23 (51%) [(1.3 mg/dl (0.6-3.9)] compared with baseline [1.7 mg/dl (0.92-3.75)] (P<0.001). In the multivariate analysis a greater reduction in creatinine between baseline and day 4 (95% confidence interval, odds ratio: 0.25) was associated with improved survival at 6 weeks.
Albumin and terlipressin improve renal failure in the absence of sepsis in cirrhosis independently of whether HRS criteria are fulfilled or not. Improvement at 4 days of therapy is associated with better survival. Randomized studies are needed for oliguria and rising creatinine in cirrhotics even if HRS criteria are not fulfilled.
European journal of gastroenterology & hepatology 11/2009; 22(4):481-6. · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transjugular intrahepatic portosystemic shunt (TIPS) has been reported superior to large-volume paracentesis for refractory ascites, but post-TIPS encephalopathy is a major complication. We intended to assess the outcome of limited diameter TIPS on ascites control, mortality, and encephalopathy in patients with refractory ascites at our centre.
TIPS was successfully performed on 56 patients. Initial stent dilatation was to 6 mm, if there was a reduction in portal pressure gradient (PPG) >25%, further dilatation was not proposed.
Either complete or partial response was obtained in 58%, 81%, 83%, and 93% of patients at 1, 3, 6, and 12 months, respectively. Mortality was 10%, 29%, 37%, and 50% at 1, 3, 6, and 12 months, respectively. In 27 patients (48%), a new episode of encephalopathy developed, but only 6 (22%) were grade III or IV and 23 (85%) responded quickly to treatment.
The results of our study confirm the efficacy of TIPS for refractory ascites. The use of narrow-diameter dilatation without aiming at lowering the PPG below a certain threshold might simplify the procedure and the follow-up for these patients.
Journal of Gastroenterology 08/2009; 44(10):1089-95. · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In patients with cirrhosis and bacterial infection there is impaired coagulation and a heparin effect on thromboelastography (TEG). Our aim was to assess the presence of a heparin effect on heparinase I-modified TEG in patients before and after transjugular intrahepatic portosystemic shunt (TIPS). Our hypothesis was that, given the presence of a portosystemic gradient of endotoxaemia, and the role of endotoxaemia on the release of heparinoids, the inflow of portal blood after TIPS might reveal heparinoids through a heparin effect on TEG.
Blood samples for heparinase I-modified TEG were taken before, 1 h after, 6 h after and the morning after TIPS, with further daily samples being taken until any TEG changes had reverted to baseline. A heparin effect was defined as an improvement of > or =20% in a TEG variable after addition of heparinase I.
We studied 10 patients (six males, mean age 48.8 years, mean Child score 8.8). The aetiology of liver disease was alcohol in six patients, Budd-Chiari syndrome in two, and hepatitis C virus and cryptogenic cirrhosis in one each. Indications for TIPS were recurrent variceal bleeding in four patients, refractory ascites or hydrothorax in four and Budd-Chiari syndrome in two. There was a statistically significant worsening in TEG parameters after TIPS placement. In eight patients a heparin effect appeared after TIPS and disappeared within 24-48 h.
We report the appearance of a transient heparin effect in systemic venous blood after TIPS in patients with cirrhosis or Budd-Chiari syndrome, suggesting the presence of heparinoid substances in the portal venous system in these patients.
Scandinavian Journal of Gastroenterology 01/2009; 44(12):1463-70. · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatitis C virus (HCV) allograft cirrhosis may progress rapidly requiring re-transplantation but its course is little studied. We evaluated serially biopsied patients who developed HCV-related allograft cirrhosis. We assessed outcome of graft cirrhosis in 55 out of 234 consecutive patients and predictors of decompensation and mortality, including hepatic venous pressure gradient (HVPG) in 38. Allograft cirrhosis (Ishak stage 6, 60%; stage 5, 40%) was diagnosed between 12 and 172 months (median, 52) from transplantation; subsequent follow up was 22 (1-78) months. Faster development (<or=48 months) was associated with tacrolimus and nonuse of azathioprine and prednisolone. Decompensation occurred in 22% with a probability of not developing decompensation reaching 60% at 5 years. Survival among compensated patients was 77% at 5 years, but fell rapidly after decompensation (12% at 1 year). Decompensation and mortality were independently associated with HVPG >or= 10 mmHg, Child-Pugh score >or= 7, and albumin levels <or= 32 g/dl but not with fibrosis stage 5 or 6, HCV genotype (1b, 34%) or immunosuppression used after diagnosis of cirrhosis. In conclusion, Ishak stage 5 and 6 HCV-related cirrhosis have similar prognosis after liver transplantation. An HVPG >or= 10 mmHg, in addition to liver dysfunction, gives independent prognostic information prior to decompensation, allowing early relisting before prognosis becomes extremely poor.
Transplant International 10/2008; 22(2):172-81. · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thromboelastography can be performed with native or citrated blood (a surrogate to native blood in healthy controls, surgical and cirrhotic patients). Activators such as kaolin are increasingly used to reduce the time to trace generation. To compare kaolin-activated thromboelastography with nonkaolin-activated thromboelastography of native and citrated blood in patients with liver disease, patients undergoing treatment with warfarin or low-molecular weight heparin and healthy volunteers. We studied thromboelastography parameters in 21 healthy volunteers (group 1) and 50 patients, including 20 patients with liver cirrhosis with a nonbiliary aetiology (group 2), 10 patients with primary biliary cirrhosis or primary sclerosing cholangitis (group 3), 10 patients on warfarin treatment (group 4) and 10 patients with enoxaparin prophylaxis (group 5). Thromboelastography was performed using four methods: native blood (kaolin-activated and nonkaolin-activated) and citrated blood (kaolin-activated and nonkaolin-activated). For all thromboelastography parameters, correlation was poor (Spearman correlation coefficient < 0.70) between nonkaolin-activated and kaolin-activated thromboelastography, for both citrated and native blood. In healthy volunteers, in patients with liver disease and in those receiving anticoagulant treatment, there was a poor correlation between nonkaolin-activated and kaolin-activated thromboelastography. Kaolin-activated thromboelastography needs further validation before routine clinical use in these settings, and the specific methodology must be considered in comparing published studies.
Blood Coagulation and Fibrinolysis 09/2008; 19(6):495-501. · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Somatostatin (SST) acts as an inhibitory peptide of various secretory and proliferative processes. Apart from neuroendocrine tumors, where SST analogues have an established role, they have been tested in other tumors such as hepatocellular carcinoma (HCC) in the view of the fact that chemotherapy is not working. Several positive reports have been published. Approximately 40% of patients respond with improved survival and an impressive quality of life. A usual misunderstanding in trial designs is that, although SST is not a rescue drug, selection of patients is inappropriate, with mostly moribund patients being recruited. SST analogues do not seem to work in 60% of HCCs and this has been linked to the presence of SST receptors (SSTR) in the tumor, while several resistance mechanisms might be involved. Future management should engage more specific SST analogues targeted to a tumor with a known SSTR map. The use of somatostatin analogues as an adjunct therapy in combination with other treatment modalities should also be investigated.
Digestive Diseases and Sciences 03/2008; 53(9):2359-65. · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Progression of fibrosis following recurrent hepatitis C virus (HCV) infection is frequent after liver transplantation (LT). Histology remains the gold standard to assess fibrosis, but the value of hepatic venous pressure gradient (HVPG) is being explored. We evaluated patients with recurrent HCV infection after LT to assess whether HVPG correlates with liver histology, particularly fibrosis. A total of 90 consecutive patients underwent 170 HVPG measurements concomitant with transjugular liver biopsy (TJB), with 31.5 (range, 6-156) months of follow up. Median biopsy length was 22 mm and total portal tract count was 12 (complete 6, partial 6). Median HVPG was 4 mmHg: 38% of patients > or =6 mmHg (portal hypertension, PHT), 13% > or =10 mmHg. HVPG correlated with Ishak stage (r = 0.73, P < 0.001) for mild (0-3) and severe fibrosis (4-6), and grade score (r = 0.47, P < 0.001), but neither correlated with interval from LT nor biopsy length. HVPG was > or =10 mmHg in 15 patients: 12 had stage 5 or 6, and 3 severe portal expansion. HVPG was repeated in 49, between 7 and 60 months with weak correlation to fibrosis score (r = 0.30, P = 0.045). A total of 12 patients with HVPG > or =6 mmHg had fibrosis score < or =3, while 8 patients had normal HVPG but fibrosis stage > or =4. These discrepancies were mostly associated with specific histological features such as perisinusoidal fibrosis rather than errors in measuring HVPG. In 29 with HVPG <6 mmHg at 1 yr, none decompensated compared to 4 of 13 (31%) with PHT. In conclusion, HVPG correlates with fibrosis and its progression, due to recurrent HCV infection, assessed in TJB.