Cirrhosis in an infant heterozygous for classical citrullinaemia

Classical citrullinaemia is caused by the inherited deficiency of argininosuccinate synthetase. Although varying degrees of liver involvement have been observed in urea cycle defects, including classical citrullinaemia, the co-existence of liver failure in a patient heterozygous for the disease has not been reported before. A female infant was investigated to find out the aetiology of early infantile liver failure. She was later found to be a heterozygote for the G390R mutation found in severe citrullinaemia patients. CONCLUSION: Classical citrullinaemia is a phenotypically heterogeneous disease, and observations for signs of its presence should be made even in heterozygotes.     

Timing of lamivudine administration according to Child class in patients with decompensated cirrhosis

BACKGROUND: Few clinical trials have investigated the use of lamivudine (LAM) in patients with decompensated cirrhosis related to chronic hepatitis B. The aim of the present study was to evaluate the efficacy of extended LAM treatment and to determine the timing of LAM administration in patients with decompensated cirrhosis. METHODS: A total of 17 patients were treated with LAM 100 mg/day. The mean duration of follow up was 28 +/- 8.4 months (range: 14-42 months). All patients were evaluated for evidence of clinical, biochemical and serologic replication of hepatitis B virus (HBV) infection. There were 12 patients with Child class B and five with Child class C. RESULTS: Ten of 17 patients (58.2%) responded to LAM treatment. Of the breakthrough patients, six (86%) had YMDD motif variants. Clinical improvement was observed in nine out of 10 responders (90%), six of the seven breakthrough patients (86%) and five of six patients with YMDD variant DNA. Mean time to achieve a 2-point reduction in Child-Pugh-Turcotte score was 14 months in patients with Child class C, compared with 5.9 months in those with Child class B (P < 0.001). Mean time required to gain a 0.5 g/dL increment in albumin was 14 months in Child class C and 5.8 months in Child class B. Hepatitis B e antigen (HBeAg) seroconversion was achieved in five of 13 HBeAg-positive patients at the last follow up and during the follow-up period. CONCLUSION: Long-term administration of LAM for patients with decompensated cirrhosis is effective. Earlier LAM administration in Child class B patients led to improved clinical outcomes.     

Single photon emission computed tomography and statistical parametric mapping analysis in cirrhotic patients with and without minimal hepatic encephalopathy

OBJECTIVE: The early diagnosis and treatment of cognitive impairment in cirrhotic patients is needed to improve the patients' daily living. In this study, alterations of regional cerebral blood flow (rCBF) were evaluated in cirrhotic patients using statistical parametric mapping (SPM). The relationships between rCBF and neuropsychological test, severity of disease and biochemical data were also assessed. METHODS: 99mTc-ethyl cysteinate dimer single photon emission computed tomography was performed in 20 patients with non-alcoholic liver cirrhosis without overt hepatic encephalopathy (HE) and in 20 age-matched healthy subjects. Neuropsychological tests were performed in 16 patients; of these 7 had minimal HE. Regional CBF images were also analyzed in these groups using SPM. RESULTS: On SPM analysis, cirrhotic patients showed regions of significant hypoperfusion in the superior and middle frontal gyri, and inferior parietal lobules compared with the control group. These areas included parts of the premotor and parietal associated areas of the cortex. Among the cirrhotic patients, those with minimal HE had regions of significant hypoperfusion in the cingulate gyri bilaterally as compared with those without minimal HE. CONCLUSIONS: Abnormal function in the above regions may account for the relatively selective neuropsychological deficits in the cognitive status of patients with cirrhosis. These findings may be important in the identification and management of cirrhotic patients with minimal HE.     

Fatal and life threatening rupture of splenic artery aneurysms in children with portal hypertension

Aneurysms of the splenic artery (SAAs) are a rare complication of portal hypertension in adults. Although the risk of rupture is small, associated mortality is high. Furthermore, circulatory changes that occur following liver transplantation (OLT) may increase the risk of SAA rupture. The incidence in children with portal hypertension is unknown and thus we present our experience with two children who had ruptured SAA, one of whom died. Although there are no accepted methods for routine screening, hepatic angiography should be considered in children with long-standing portal hypertension (more than 10 yr), in order to detect and consider resection of the aneurysms, either before or at the time of liver transplantation.     

New support for branched-chain amino acid supplementation in advanced hepatic failure

Nutritional supplementation with branched-chain amino acids (BCAA) has been a topic of considerable debate for more than two decades. Several studies have demonstrated that supplementation with BCAA is associated with improvement of the catabolic state commonly seen in people with cirrhosis, whereas other studies have showed an improvement in portosystemic encephalopathy in patients with liver disease. Some studies have also shown there to be no benefit in BCAA supplementation in advanced cirrhosis. A recent large clinical trial showed that long-term BCAA supplementation may be useful in preventing progressive hepatic failure and improving liver function in some patients.     

补中益气汤合西药治疗肝硬化低蛋白血症62例

探讨中西医结合对肝硬化低蛋白血症的治疗效果。设治疗组 6 2例 ,以中药补中益气汤合西药治疗肝硬化低蛋白血症 ,西药对照组 (38例 )常规西药对症治疗。疗程 6周。结果 :治疗组总有效率 87 2 5 % ,明显优于对照组 6 3 16 % (P <0 0 5 ) ,复发率明显低于对照组 (P <0 0 5 ) ,治疗组治疗前后白蛋白显著升高 (P <0 0 5 ) ,球蛋白显著降低 (P <0 0 5 ) ,白蛋白与球蛋白之比显著升高 (P <0 0 5 ) ,而对照组治疗前后血清蛋白无显著差异 (P >0 0 5 )。提示中西医结合治疗肝硬化低蛋白血症疗效明显优于西药对照组。     

Risk factors for early death due to recurrence after liver resection for hepatocellular carcinoma: results of a multicenter study

BACKGROUND AND OBJECTIVES: Recurrence after partial liver resection for hepatocellular carcinoma (HCC) is a major cause of death from this disease. To identify risk factors for early death from recurrence after liver resection for HCC. METHODS: All 547 patients in this study had greater than 1 year of follow-up after complete resection of HCC (1980-1999) at one of the four hepatobiliary centers in Japan, France, and the United States. Patients who died of recurrence < or =1 year post-resection and all of those alive at least 1 year were compared. Survival and clinicopathological factors associated with death from recurrence within 1 year of resection were analyzed. RESULTS: Overall postoperative mortality rate was 5%. In the first postoperative year, 123 (22%) patients died. Of these, 53 (43%) died of recurrence, 30 (24%) of postoperative complications, and 40 (33%) of liver failure/hemorrhage. On multivariate analysis, tumor size greater than 5 cm (P < 0.02; odds ratio, 3.0), multiple tumors (P < 0.01; odds ratio, 3.3), and greater than 5 mitoses per 10 high-power fields (P < 0.03; odds ratio, 3) were associated with increased risk of early death due to recurrence. CONCLUSIONS: These findings enable identification of patients with HCC who are at high risk for early death due to recurrence following potentially curative resection who might be candidates for adjuvant therapy trials.     

Hepatic insufficiency and liver transplantation in a patient with COACH syndrome

An 8-yr-old-patient was diagnosed with COACH syndrome at the moment of her first bleeding episode from esophageal varices. Investigations revealed biliary cirrhosis as the cause of portal hypertension, no visible kidney cyst or impairment of renal function, cerebellar dysplasia with non-disabling ataxia, and minimal mental retardation. By the age of 12 yr she had developed liver insufficiency and, after a challenging discussion, underwent a liver transplantation. She subsequently developed an abdominal aspergillosis, which required several abdominal explorations and splenectomy as well as 6 months of therapy with liposomal amphotericin B, but survived and in long-term follow-up is in good health, with completed puberty, and has finished school.     

Clinical and laboratory differentiation of cirrhosis and extrahepatic portal venous obstruction in children

BACKGROUND AND AIM: Differentiation between cirrhosis and extrahepatic portal venous obstruction (EHPVO) in children presenting with features of portal hypertension is important for cost-effective management and proper resource utilization. We undertook this study to differentiate clinical and laboratory features between these two groups of patients. METHODS: Clinical features and laboratory parameters at presentation of children with portal hypertension and cirrhosis of the liver were analyzed. The variables analyzed were age at presentation, duration of symptoms, incidence and frequency of upper gastrointestinal (GI) bleeding, encephalopathy, jaundice, ascites, splenomegaly, and presence of dilated abdominal veins. The laboratory parameters studied were hemoglobin, prothrombin time, serum bilirubin, albumin, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase. Two groups were compared using appropriate statistical methods; and the differentiating features were analyzed using logistic regression analysis. RESULTS: Of the total of 120 cases, cirrhosis was diagnosed in 28.3% and EHPVO in 71.6%. Children with EHPVO, in comparison to cirrhosis, had significantly higher frequency of upper GI bleeding (61.6%vs 14.7%), increased number of previous bleeding episodes (2.7 +/- 0.5 vs 1.2 +/- 0.4), longer duration of symptoms (25.7 +/- 4.6 vs 12.3 +/- 3 months) and a lower frequency of jaundice (2%vs 76.4%). Low hemoglobin (6.4 +/- 2.7 g/dL) and preserved liver functions characterized by normal bilirubin, albumin levels and prothrombin time were observed in EHPVO cases. Cirrhosis patients had higher hemoglobin (8.8 +/- 2.8 g/dL) and abnormal liver function tests. CONCLUSION: Presence of UGI bleeding and the absence of jaundice are 97.5% accurate in predicting diagnosis of EHPVO.     

Prevalence of diabetes mellitus in Japanese patients infected chronically with hepatitis C virus

Background: To examine the relationship between hepatitis C virus (HCV) infection and diabetes mellitus (DM) in Japanese populations, a retrospective study was done in 866 patients with chronic viral disease. Methods: The present study included 707 HCV-infected and 159 hepatitis B virus (HBV)-infected patients. The prevalences of HBV- and HCV-related cirrhosis were 32% and 33%, respectively. A case-control study was also conducted to determine the seroprevalence of HCV infection in a cohort of 459 diabetics. Results: The prevalence of DM was higher in HCV-infected patients (20.9%; P < 0.02) than in HBV-infected subjects (11.9%). In the cirrhotic patients, DM was observed in 30.8% of the subjects with HCV compared with 11.8% of those with HBV (P < 0.01). Multivariate analysis revealed that the major independent variables associated with type II DM were male sex (odds ratio, 1.54; p = 0.020) and cirrhosis (odds ratio, 1.97; P = 0.0007). The relative odds of the development of DM were calculated to be 3.2 times higher in HCV-infected cirrhotic patients than in HBV-infected ones. In the case-control study of the diabetic cohort, 10.5% of patients were infected with HCV compared with 1.1% with HBV (P < 0.0001). The results indicate that HCV infection is closely associated with DM, compared with HBV infection. Cirrhosis was an independent risk factor for DM. Conclusions: Taken together, the findings indicate that cirrhosis appears to be a more important predictor of glucose intolerance than HCV infection, and the combination of both factors increases the risk of DM in our populations. Received: April 18, 2002 / Accepted: October 25, 2002 Reprint requests to: S. Kakumu