Liver Transplantation for Familial Amyloid Polyneuropathy (Val30Met): Long-Term Follow-up Prospective Study in a Nontransplant Center.

BACKGROUND: Familial amyloidosis polyneuropathy (FAP) is a rare, progressive, and life-threatening disease inherited in the autosomal dominant pattern. Liver transplantation is the only proven disease-modifying treatment to date. AIM: To study the long-term outcomes of patients transplanted for FAP under a multidisciplinary team care. METHODS: We included adult patients who were transplanted for FAP indication and were followed up in a relevant clinic or admitted in our department. RESULTS: Twelve patients (6 male) with a mean age of 43 years and mean follow-up post-transplant of 100 months were included. Three patients died in this period, 1 due to a disease-related cause. All patients had peripheral neuropathy (25% severe). Eighty-three percent had autonomic nervous system dysfunction; all men, except one, erectile dysfunction; and half of the patients several genitourinary manifestations. Gastrointestinal involvement was present in 75% of the patients. The severity of several complications related to FAP was found to be associated with waiting on the transplant list for more than 12 months. CONCLUSIONS: Patients transplanted for FAP have a long survival. Prolonged stay on the transplant waiting list is associated with frequency and severity of disease complications. These patients are best managed in the context of multidisciplinary team care.

Transjugular liver biopsy in patients with diffuse liver disease: comparison of three cores with one or two cores for accurate histological interpretation.

BACKGROUND: Transjugular liver biopsy (TJLB) can be performed to obtain more than two cores safely. This advantage has not been evaluated in terms of diagnostic accuracy or grading/staging evaluation. AIM: To evaluate whether three separate cores of TJLB provide more histological information compared with two or one cores. METHODS: Twenty-three patients, who had three separate passes, with each core >/=7mm in length using a 19G Tru-cut needle, were evaluated. Each TJLB was blindly coded; the pathologist randomly assessed: (a) each core separately covering the other two, (b) two cores simultaneously covering the third and (c) the three cores together for diagnostic yield, inflammation and fibrosis. RESULTS: The mean TJLB length was 32+/-5.5mm. In 12 one-core (52%) and 18 2-core (78%) assessments, diagnosis (mainly cirrhosis) was made correctly in each core. The within-patient standard deviations for one-core vs two-core assessment were similar for grading (0.42 and 0.47, respectively), but higher for staging (0.39 and 0.15, respectively). Staging was underestimated in assessing one-core and less for two cores compared to three cores. CONCLUSION: Three non-fragmented cores (each core >/=7mm in length) of TJLB can be considered a minimum requirement for histological assessment, giving better reproducibility in diagnosis as well as for inflammation and fibrosis.

An evaluation of emergency sclerotherapy of varices in randomized trials: looking the needle in the eye.

BACKGROUND: The role of sclerotherapy for acute variceal bleeding is challenged by vasoactive drugs and by ligation. AIM: A meta-analysis was performed to evaluate whether sclerotherapy remains a gold standard in acute variceal bleeding. METHODS: Sclerotherapy was evaluated across four randomized trial groups: (a) combined with vasoconstrictors vs. vasoconstrictors alone (five trials, with 400 patients); (b) vs. vasoconstrictors alone (15 trials, with 1296 patients); (c) vs. combination of vasoconstrictors and sclerotherapy (eight trials, with 1026 patients); (d) vs. ligation (12 trials, with 1309 patients). We used the risk difference (absolute risk reduction) as our main effect measure. RESULTS: The efficacy of acute sclerotherapy was highest vs. ligation at 95 %, with a small advantage for ligation (an overtube was used in eight trials) of 2.5 % (95 % CI 0.4 % to 4.6 %) ( P = 0.018), but no survival difference. Efficacy of sclerotherapy combined with vasoconstrictors vs. vasoconstrictors alone was 86 %, whereas it was 83 % for sclerotherapy vs. vasoconstrictors alone. In both these groups sclerotherapy was superior for control of bleeding at, respectively, 16.3 % (95 % CI 8.7 % to 23.9 % ( P = 0.0001) and 5.9 % (95 % CI, 1.5 % to 10.3 %) ( P = 0.008), with increased survival in the latter. In the combination group of sclerotherapy with vasoconstrictors, the efficacy of sclerotherapy alone was 69 %, with the combination superior in controlling bleeding, at 13.2 % (95 % CI, 8.4 % to 18.1 %) ( P < 0.0001) but with no survival difference. CONCLUSION: This comparison of sclerotherapy across trials demonstrates a problem in defining its real efficacy. The conclusive evidence for substituting banding ligation or the combination of vasoconstrictors with sclerotherapy as better therapeutic approaches has not been provided in randomized trials. Sclerotherapy can remain a gold standard in variceal bleeding but there is scope for further studies of ligation and vasoactive drugs.

Rejection rates in a randomised trial of tacrolimus monotherapy versus triple therapy in liver transplant recipients with hepatitis C virus cirrhosis.

BACKGROUND: Reducing immunosuppression not only reduces complications but also may lessen recurrent hepatitis C virus (HCV) infection after liver transplantation. PATIENTS/METHODS: HCV-infected cirrhotic patients randomised to tacrolimus monotherapy (MT) or triple therapy (TT) using tacrolimus 0.1 mg/kg/day, azathioprine 1 mg/kg/day, and prednisolone 20 mg/day, tapering over 3 months. RESULTS: Twenty-seven patients (MT) and 29 (TT)--median follow up 661 days (range, 1-1603). Rejection episodes (protocol/further biopsies) within first 3 months and use of empirical treatment were evaluated. New rejection was diagnosed if repeat biopsy (5-day interval) did not show improvement. Treated rejection episodes: 20 MT (15 biopsy-proven) vs. 24 TT (21 biopsy-proven), with 19 (MT) vs. 24 (TT) methylprednisolone boluses. Overall: 35 episodes (MT) and 46 (TT). Fewer MT patients had histological rejection (70%) than TT patients (86%), with fewer episodes of rejection (18.5% vs. 10%), and more moderate rejection (22% vs. 41%). The MT group had higher early tacrolimus levels. Rates of renal dysfunction, retransplantation, and death were not significantly different. CONCLUSION: Tacrolimus monotherapy is a viable immunosuppressive strategy in HCV-infected liver transplant recipients.

Transjugular liver biopsy: how good is it for accurate histological interpretation?

BACKGROUND: A transjugular liver biopsy (TJLB) specimen is often smaller or more fragmented than a percutaneous liver biopsy (PLB) specimen. Recently, for PLB, the minimum requirements to evaluate chronic hepatitis have been set at 20-25 mm length and > or =11 complete portal tracts. AIM: To evaluate and compare length of TJLB and PLB specimens, portal tract number, fragmentation and adequacy for histopathological diagnosis and staging. PATIENTS AND METHODS: 326 consecutive TJLB specimens in 274 patients (109 who had undergone a transplantation), always using three passes (19-G Tru-cut) and 40 consecutive PLB specimens (15-G Menghini). RESULTS: No technical failures occurred with the TJLB, and histological diagnosis was possible in 98.5%. The median (range) number of fragments was 5 (1-13) and the median total length was 22 (3-46) mm, with 65% of specimens > or =20 mm and 36% > or =25 mm; 60% of TJLB specimens were > or =28 mm long had > or =11 complete portal tracts. No difference in complete portal tract number or biopsy length was found between PLB and TJLB specimens. CONCLUSION: A TJLB specimen with three passes is adequate for histological diagnosis, with 89% of specimens being either > or =15 mm or having > or =6 complete portal tracts. Although adequate sampling remains a limitation for staging and grading of chronic hepatitis, TJLB is comparable to PLB in this respect.

Obstructive jaundice secondary to neuroendocrine tumour in a patient with von Recklinghausen's disease.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder, with variable clinical manifestations and unpredictable course, associated with an increased incidence of various tumours. Plexiform neurofibromas are hallmark lesions of NF1; they are slow-growing tumours, which account for substantial morbidity, including disfigurement and functional impairment, and may even be life-threatening. Neuroendocrine tumours (NETs), a rare diverse group of neoplasms, are occasionally associated with neurofibromatosis. Pancreatic NETs are tumours with an incidence of less than 1/100 000 population/year and complex patterns of behaviour, which often need complicated strategies for optimal management. We present the case of a young adult with NF1, having a unique concurrence of plexiform neurofibroma involving the liver with an ampullary NET, and we discuss step by step the management in a specialist centre.

Assessment of the agreement between wedge hepatic vein pressure and portal vein pressure in cirrhotic patients.

BACKGROUND: Measuring wedged hepatic venous pressure and hepatic venous pressure gradient as indices of portal pressure is being increasingly used in assessing the prognosis and response to pharmacological treatment for portal hypertension in cirrhotic patients. AIM: To re-evaluate the agreement and correlation between wedged hepatic pressures and directly measured portal pressures. METHODS: Medline search for studies comparing direct portal with wedged hepatic pressure measurement and assessment of correlation and agreement of the pooled data. RESULTS: Eleven suitable studies included 320 patients. Coefficient of determination (r2) was 0.87 in all patients, 0.87 in 102 patients with alcoholic liver disease, 0.83 in 88 patients with non-alcoholic liver disease and 0.75 in 53 patients with hepatitis C-related liver disease. Coefficient of determination was 0.85 in the 194 patients in whom a wedge catheter and 0.90 in the 113 patients in whom a balloon catheter was used. Agreement according to the method of Bland and Altman was also found to be good, with only 4-8% of the measurements outside 2 standard deviations. CONCLUSIONS: Wedged hepatic pressure measurement correlates well with direct portal pressure measurement and the agreement is sufficiently good to use this as a surrogate measurement.

Management of portal hypertension.

Treatment of portal hypertension is evolving based on randomised controlled trials. In acute variceal bleeding, prophylactic antibiotics are mandatory, reducing mortality as well as preventing infections. Terlipressin or somatostatin combined with endoscopic ligation or sclerotherapy is the best strategy for control of bleeding but there is no added effect of vasoactive drugs on mortality. Non-selective beta-blockers are the first choice therapy for both secondary and primary prevention; if contraindications or intolerance to beta-blockers are present then band ligation should be used. Novel therapies target the increased intrahepatic resistance caused by microcirculatory intrahepatic deficiency of nitric oxide and contraction of activated intrahepatic stellate cells.