C. Barrios

Hepatitis C Recurrence After Liver Transplantation: Viral and Histologic Response to Full‐Dose Peg‐Interferon and Ribavirin

Hepatitis C recurrence after liver transplantation (LT) is universal, and frequently leads to cirrhosis and death. The aim of our study was to assess the efficacy and safety of 48‐weeks of full‐dose peg‐interferon‐α‐2a (n = 4) or α‐2b (n = 51) plus ribavirin (>11 mg/kg/day) in a multicentric cohort of 55 patients ≥12 months after LT. All subjects had histologically proven HCV recurrence, excluding severe cholestatic recurrence. Mean age was 54.3 ± 9.7, 77% male, 90.9% genotype 1, 32.7% cirrhotics. All but 5 patients received monotherapy with tacrolimus (54.5%), cyclosporine (30.7%) or mycophenolate mofetil (5.5%). The rates of end‐of‐treatment response and sustained virological response (SVR) were 66.7% and 43.6%, respectively. Low baseline HCV‐RNA (p = 0.005) and a length from LT to therapy between 2–4 years (p = 0.011) were predictors of SVR. The lack of achieving a viral load decrease ≥1‐log10 at week 4 and/or 2‐log10 at week 12 was 100% predictive of failure. The most frequent side effects were neutropenia (76,4%), anemia (60%) and infectious complications (30.9%). Toxicity led to peg‐interferon withdrawal in 16 (29%) subjects. In 15 patients with post‐treatment biopsy, the histological activity index was significantly improved (p = 0.006), whereas fibrosis did not change (p = 0.14). Three patients died (cholangitis, hepatic artery thrombosis and lung cancer). In conclusion, HCV therapy after LT was very effective, although it led to a significant rate of toxicity.

Octreotide prevents postprandial splanchnic hyperemia in patients with portal hypertension

An increase in splanchnic blood flow is a physiological response to food intake. In patients with cirrhosis whose hepatic vascular resistance is already high, this increase in flow leads to marked increases in portal pressure. This study investigates whether octreotide prevents the increases in hepatic flow and portal pressure that follow the ingestion of a meal in patients with cirrhosis. Twenty-two patients with cirrhosis and portal hypertension were randomized to receive a mixed liquid meal (520 kcal) plus a single subcutaneous injection of either placebo or octreotide (200 micrograms). In the placebo group the ingestion of a meal was followed by an increase in the hepatic venous pressure gradient (+ 19.4 +/- 4.3%, p < 0.01) and hepatic blood flow (+ 38.2 +/- 14.6%, p < 0.05) at 30 min. In contrast, in the octreotide group eating caused no significant change in the hepatic venous pressure gradient (-2.8 +/- 3.6%, NS), while hepatic flow was decreased (-6.08 +/- 5.4%, p < 0.05). Octreotide blunted the postprandial increase in serum insulin and glucagon levels observed in the placebo group. In conclusion, in patients with cirrhosis and portal hypertension, octreotide prevents the postprandial increase in hepatic blood flow, and consequently also in portal pressure. These findings suggest that this drug could play a role in the long-term management of portal hypertension.

Pamidronate in the prevention of bone loss after liver transplantation: a randomized controlled trial

Rapid bone loss and high rates of fractures occur following liver transplantation. To analyze the effect of intravenous pamidronate on bone loss after liver transplantation. A randomized, double‐blind, placebo‐controlled study was performed. Seventy‐nine patients were randomized to two groups of treatment: the pamidronate group (n = 38) was treated with 90 mg/IV of pamidronate within the first 2 weeks and at 3 months after transplantation; the placebo group (n = 41) received glucose infusions at the same time points. All patients received calcium and vitamin D. Bone mineral density (BMD) at the lumbar spine (L2–L4) and proximal femur using dual energy X‐ray absorptiometry and also spinal X‐rays were performed before, and at 6 and 12 months after liver transplantation. Biochemical and hormonal determinations were performed previous to transplantation, at 24 h before and after treatment, as well as at 6 and 12 months after liver transplantation. At 12 months after transplantation, there were significant differences in lumbar BMD changes (6 months: pamidronate 1.6% vs. placebo 0.8%, P = NS; 12 months: pamidronate 2.9% vs. placebo 1%, P < 0.05). Femoral neck BMD decreased in the pamidronate‐ and placebo groups during the first 6 months (6 months: pamidronate −3.1% vs. placebo −2.9%, P = NS; 12 months: pamidronate −3.2% vs. placebo −3.1%, P = NS). BMD at the trochanter remained stable in the pamidronate group, whilst a reduction was observed in the placebo group at 6 months (6 months: pamidronate −0.7% vs. placebo −3.7%, P < 0.05; 12 months: pamidronate −0.5% vs. placebo −1.2%, P = NS). Moreover, no significant differences in the incidence of fractures, serum parathyroid hormone and serum 25‐hydroxyvitamin D values between both groups were found. Pamidronate did not increase the risk of serious adverse events. The results of this study show that 90 mg of intravenous pamidronate within the first 2 weeks and at 3 months following liver transplantation preserve lumbar bone mass during the first year, without significant adverse events. However, pamidronate does not reduce bone loss at the femoral neck and furthermore it does not reduce skeletal fractures.

Oral administration of clonidine in patients with alcoholic cirrhosis

The effects of long-term oral clonidine treatment on hepatic and systemic hemodynamics and on quantitative liver function tests were investigated in 15 patients with alcoholic cirrhosis. Clonidine was administered at a mean dose of 0.33 +/- 0.1 mg/day (mean +/- SD) for a mean period of 64 +/- 10 days. Oral clonidine induced a significant reduction in the hepatic venous pressure gradient from 18.8 +/- 3.0 mm Hg to 15.9 +/- 3.4 mm Hg (P less than 0.001), which was the result of an increase in the free hepatic venous pressure from 5.1 +/- 4.2 mm Hg to 8.7 +/- 3.8 mm Hg (P less than 0.05). In 10 of the 15 patients (67%), the reduction in the hepatic venous pressure gradient was greater than 10% of baseline values. Hepatic blood flow did not change significantly after clonidine treatment. Additionally, treatment with clonidine decreased mean arterial pressure by 15.5% +/- 6% (P less than 0.001), heart rate by 17.7% +/- 7% (P less than 0.001), and cardiac output by 14.6% +/- 7% (P less than 0.001). However, systemic vascular resistance did not change significantly. There were no adverse effects on liver function, as shown by the nonsignificant changes in galactose-elimination capacity (149 +/- 59 vs. 170 +/- 58 mg/min), hepatic clearance of indocyanine green (0.19 +/- 0.10 vs. 0.17 +/- 0.07 L/min), and hepatic intrinsic clearance of indocyanine green (0.23 +/- 0.14 vs. 0.21 +/- 0.1 L/min) before and after clonidine treatment, respectively. In none of the patients was the drug withdrawn because of side effects, although 12 subjects complained of dry mouths. This study suggests that in patients with alcoholic cirrhosis, long-term oral clonidine administration achieves a reduction in the hepatic venous pressure gradient without adverse effects on hepatic blood flow and liver function.

Arterioportal fistula, a rare cause of presinusoidal portal hypertension

The arterio-portal fistula (APF) is a rare, treatable and reversible cause of pre-sinusoidal portal hypertension (PPH). We describe a case of a patient with APF following an ultrasound-guided percutaneous liver biopsy (PLB) in which endovascular treatment was given by Surgical Radiology, together with a literature review. We present the case of 35-year-old woman who received a liver transplant in 2007 due to acute fulminant autoimmune hepatitis under immunosuppressive treatment with Sirolimus (1 mg/24 h orally). She presented with 2 weeks of development of asthenia and abdominal distension. Upon physical exploration, clinical signs of ascites were found. Analysis showed increasing transaminases and cholestasis enzymes (ALT 65 U/L, AST 57 U/L, GGT 356 U/L) and 56% prothrombin activity, with remaining parameters within normality. She was admitted with the diagnosis of hydropic decompensation in probable relation to pre-existing hepatopathy at cirrhosis stage of the transplanted liver.