Massive spontaneous portosystemic shunt is a solid, easily identifiable prognostic factor in patients with cirrhosis.

OBJECTIVES: Spontaneous portosystemic shunts (SPSSs) are associated with complications and death in cirrhosis. We evaluated chronic portosystemic encephalopathy (CPSE) and survival in cirrhotic patients with massive (>10 mm diameter) SPSS (MSPSS). METHODS: We have retrospectively compared 77 cirrhotic patients with MSPSS and 77 paired-matched patients without SPSS. RESULTS: More patients with MSPSS presented with CPSE (40.3% vs. 20.8%, P = 0.010) or died (33.8% vs. 18.2%, P = 0.039). Model for Endstage Liver Disease (MELD) score [hazard ratio (HR) 1.146, 95% confidence interval (CI) 1.099-1.195], follow-up (FU) ascites (HR 5.128, 95% CI 2.396-10.973) and age (HR 1.048, 95% CI 1.017-1.080) were associated with CPSE; and MELD score (HR 1.082, 95% CI 1.035-1.131), FU renal failure (HR 9.319, 95% CI 3.595-24.158), and FU ascites (HR 4.320, 95% CI 1.615-11.555) were associated with death. Liver function worsened faster in the MSPSS group. Among patients with better liver function (MELD < 11.5), MSPSS patients presented worse survival (P = 0.048, Breslow test). Comparing patients by the Child-Pugh group, we did not find differences in survival; in patients from Child-Pugh group B + C, the MSPSS group presented less time free of CPSE (P < 0.05, log-rank test). Patients with splenorenal MSPSS presented better survival (P = 0.04, log-rank test), and patients with umbilical MSPSS had shorter time free of CPSE (P < 0.016, log-rank test). CONCLUSION: MSPSS increased CPSE and death risks during long FU. Even with better liver function (MELD < 11.5), MSPSS was associated with lower survival. Splenorenal MSPSS presented better survival and the umbilical type was associated with shorter time free of CPSE.

Wilson disease: revision of diagnostic criteria in a clinical series with great genetic homogeneity.

BACKGROUND: Wilson disease is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene. An early diagnosis is crucial to prevent evolution of the disease, as implantation of early therapeutic measures fully prevents its symptoms. As population genetics data predict a higher than initially expected prevalence, it was important to define the basic diagnostic tools to approach population screening. METHODS: A highly genetically homogeneous cohort of 70 patients, belonging to 50 unrelated families, has been selected as a framework to analyze all their clinical, biochemical and genetic characteristics, to define the disease in our population, with an estimated prevalence of 1 in 12,369, and determine the most useful features that reach diagnostic value. RESULTS: Serum ceruloplasmin below 11.5 mg/dL and cupremia below 60 µg/mL, were the best analytical predictors of the disease in asymptomatic individuals, while cupruria or hepatic copper determination were less powerful. Genetic analysis reached a conclusive diagnosis in all 65 patients available for complete testing. Of them, 48 were carriers of at least one p.Leu708Pro mutant allele, with 24 homozygotes. Nine patients carried a promoter deletion mutation, revealing that extended sequencing beyond the ATP7B gene-coding region is essential. All mutations caused hepatic damage since early ages, increasing its severity as diagnosis was delayed, and neurological symptoms appear. CONCLUSION: Serum ceruloplasmin determination followed by genetic screening would reduce costs and favor the prioritization of non-invasive procedures to reach a definitive diagnosis, even for asymptomatic cases.