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Management of chronic liver disease.

Childhood liver disorders have, in general, mode of presentations which are distinct from that in adult population. It is due to varying etiology and natural history of the liver diseases in childhood. Chronic hepatitis B and C can be managed with alpha interferon. Remission rates in children have been reported to be between 20-58%. Recently available lamuvidine has also been used in combination with interferon therapy. Oral chelation therapy and liver transplantation have radically affected the outcome of patients with Wilson's disease. Corticosteroids and immunosuppressive therapy are effective in reducing both morbidity and mortality due to auto-immune hepatitis. Offending carbohydrates are eliminated from the diet of patients with galactosemia and hereditary fructose intolerance. The most important and often neglected component of management of chronic liver diseases in childhood are nutritional management and prompt interventions for ascites, spontaneous bacterial peritonitis, portal hypertension and hepatic encephalopathy. With definitive etiological and histological assessment and institution of specific as well as supportive therapy, children with chronic liver disease can have a prolonged survival with improved quality of life. Several of them can potentially receive the liver transplant as and when it becomes available.

Adolescent↗

[Predictive factors for progression to cirrhosis in chronic liver diseases].

Chronic liver diseases complications generally occur when fibrosis progresses to cirrhosis. It is recognised that some patients do not progress while others develop significant fibrosis. Factors influencing the fibrosis progression rate are especially studied in chronic hepatitis C. Among many identified factors, the most important are those warranted a medical action such as alcohol consumption, obesity, other metabolic disorders and immunosuppression in case of HIV-HCV coinfection. Especially, in case of chronic liver disease, regular alcohol consumption should be avoided; overweight and metabolic disorders should be controlled. The control of liver damage aetiologies could decrease or even stop fibrosis progression.

Adolescent↗

Differences in intrahepatic portal-systemic shunting in alcoholic and nonalcoholic liver disease as assessed by liver scan, portal pressure, and E. coli antibodies.

The interrelationship among portal vein pressure, 99mTc sulfur colloid liver/spleen scan abnormality, and serum E. coli antibody titers has been examined in 33 patients with alcoholic liver disease (ALD) and compared with 24 patients with liver disease not related to alcohol (non-ALD). A correlation between portal vein pressure and liver scan abnormality is seen in both groups, but for a given degree of portal hypertension there is a much greater redistribution of sulfur colloid in the ALD group (P less than 0.01). E. coli antibody titers are significantly higher in the ALD patients compared with the non-ALD patients (P less than 0.02), and they show a positive correlation with scan abnormality but not with portal vein pressure. It is suggested that the differences in scan appearance and E. coli antibody titers in these two groups of liver disease patients may be related to differences in intrahepatic shunting.

Alcoholism↗

Role of therapeutic drug monitoring in a patient with human immunodeficiency virus infection and end-stage liver disease undergoing orthotopic liver transplantation.

Pharmacological interactions between protease inhibitors and tacrolimus require careful monitoring to prevent toxicity in the posttransplantation period. A 42-year-old man with human immunodeficiency virus (HIV) infection and end-stage liver disease due to hepatitis C virus (HCV) received an orthotopic liver transplant. At the time of surgery the patient was on triple antiretroviral therapy (tenofovir, lamivudine, and lopinavir/ritonavir) with a stable CD4(+) count (>500 cells/mm(3)) and HIV-1 RNA (<50 copies/mL). Immunosuppression was maintained with tacrolimus (0.5 mg at a single dose once per week). One month after surgery HCV recurrence was documented. Pharmacokinetic evaluation of lopinavir/ritonavir showed a rapid increase in the area under the curve. Drug concentrations returned to normal levels, with reduction in liver enzymes. At the same time, tacrolimus dosages were reduced to a maintenance dose of 0.5 mg every 2 weeks. The patient, at 17 months postoperatively, is alive in good health with normal liver function and HCV RNA load levels. This is the first case in which a profound change in the pharmacokinetics of a protease inhibitor caused by a drug-drug interaction was observed during transient liver damage. Because this clinical event is particularly common in HIV-infected patients, our findings suggest that therapeutic drug monitoring should be performed to determine the impact of potential drug interactions in the early posttransplantation period, at the time of resumption of therapy or introduction of new anti-retroviral therapy and during HCV recurrence in order to optimize both tacrolimus and protease inhibitor treatment.

Adult↗

Chronic liver disease prevention strategies and liver transplantation.

Chronic liver disease is a considerable burden on society, being one of the three main causes of death in certain regions of Africa and Asia. Liver transplant is the only treatment option for cirrhosis, which is the end stage of many chronic liver diseases. This article reviews the preventable causes of cirrhosis and the preventive strategies which could be implemented in order to avoid the catastrophic consequences of cirrhosis. With small variations around the world, 70 to 80% of the end stage liver diseases are caused by excessive alcohol consumption and by viral hepatitis, both of which are potentially preventable. Excessive alcohol consumption has important public health consequences because of its involvement not only with cirrhosis, but also with motor vehicle accidents, unemployment, domestic violence etc. Among the viral causes, Hepatitis Virus B and C have the greatest impact on public health. Effective vaccine is available for Hepatitis Virus B and must be put in use. While a vaccine for Hepatitis Virus C is awaited, effective preventive strategies should be undertaken to avoid the preventable cases of end stage liver disease.

Adolescent↗

Detection of metastatic liver disease. Use of liver scans and biochemical liver tests.

The records of 94 patients with a known diagnosis of extrahepatic cancer having liver scan, biochemical liver tests (alkaline phosphatase, SGOT, lactic dehydrogenase, and bilirubin levels, and subsequent liver biopsy within a six-week period were reviewed. The sensitivity, specificity, and accuracy of the scan and biochemical tests in the detection of metastatic liver disease were calculated. The most sensitive single examination was the group of biochemical liver tests. Liver scans performed in the presence of normal biochemical test results were insensitive when compared with the liver scan alone or the liver scan in the presence of abnormal biochemical test results. The specificity and accuracy of all tests and test combinations were statistically equivalent. Screening for hepatic metastases in patients with cancer is best accomplished with the more sensitive and less expensive group of biochemical liver tests, reserving the liver scan for those patients with abnormal biochemical test results.

Alkaline Phosphatase↗

Endoscopic stenting of gallbladder for symptomatic cholelithiasis in patients with end-stage liver disease awaiting orthotopic liver transplantation.

Cholecystectomy in patients with advanced cirrhosis is associated with excessive morbidity and mortality. Symptomatic cholelithiasis in patients awaiting orthotopic liver transplantation poses unique management issues. Three patients with end-stage liver disease, severe enough to warrant hepatic transplantation, developed symptoms and complications of cholelithiasis requiring intervention. Each underwent placement of a biliary stent from gallbladder to duodenum at endoscopic retrograde cholangiopancreatogram. In each case, biliary symptoms and complications ceased after stent placement. Two patients remained symptom-free until they underwent successful liver transplantation, and the third awaits transplant and is currently free of symptoms of cholelithiasis. Endoscopic placement of gallbladder stents represents a temporizing alternative for the management of patients with symptomatic cholelithiasis awaiting hepatic transplantation.

Adult↗

[Gastrointestinal surgery and gastroenterology. XV. Polycystic liver disease].

Polycystic liver disease is a congenital disorder with an autosomal dominant pattern of inheritance. There are two variants. In one, liver cysts occur as an extra-renal phenomenon in autosomal dominant polycystic kidney disease. In the other, the disease is not associated with renal pathology. The cysts have to reach a certain diameter before becoming clinically manifest and therefore are generally only detected many years after birth. Polycystic liver disease causes symptoms in 20% of the patients. These symptoms are the consequence of the weight and size of the liver or of complications such as abscess formation, obstructive jaundice or the Budd-Chiari syndrome. Most symptoms can be treated at least temporarily by fenestration of the larger cysts and resection of parts of the liver, which are affected by large groups of small cysts. A permanent cure of the disease is only obtained by liver transplantation.

Digestive System Surgical Procedures↗

Hepatic estrogen receptor in human liver disease.

Human liver contains estrogen receptors which render it sensitive to estrogen. Specific hormone binding to cytosol and nuclei from normal liver containing such receptors is of high affinity, low capacity, saturable, and specific for steroidal and nonsteroidal estrogens. Although estrogens alter metabolism and may produce disease, little data is available concerning estrogen receptor levels found in diseased liver. Herein we report estrogen receptor levels in human female liver containing diseases associated with oral contraceptives. Binding studies demonstrated cytosolic and nuclear estrogen receptors in human hepatic adenoma and focal nodular hyperplasia. Nuclear estrogen receptor levels in neoplastic tissue were greater than those in normal tissue. In addition, one hepatic adenoma resected from a patient taking tamoxifen contained no cytosolic estrogen receptor, and nuclear estrogen receptor levels were significantly lower than those found in normal tissue. These differences in binding capacity suggest a potential for greater hormone responsiveness in neoplastic liver tissue.

Carcinoma, Hepatocellular↗

[The prognostic value of end-stage liver disease model in liver cirrhosis].

OBJECTIVES: The prognostic ability of the model for end-stage liver disease (MELD) has been validated in many countries, but its abilities remain uncertain in China. Our aim is to evaluate the abilities of MELD in prognosis of liver cirrhosis. METHODS: A cohort of 315 patients with liver cirrhosis were retrospectively studied and followed up at least for one year. MELD score was obtained for each patient according to the modified formula by Kamath P.S.. The area under the receiver operating characteristic (ROC) curve (AUC) was used to compare MELD and Child-Turcotte-Pugh (CTP) score and classification in predicting accuracy. Kaplan-Meier survival analysis was used to compare the mortality in subgroups ranked by the MELD score. RESULTS: The AUC values generated by the ROC curves for the MELD were 0.95, 0.85 and 0.83 respectively in predicting 3, 6 month and 1 year survival, and were all more than 0.80 in predicting longer time survival, whereas the AUC was 0.82, 0.78, 0.74 for CTP score and 0.70, 0.66, 0.61 for CTP classification respectively in predicting 3, 6 month and 1 year survival. The differences of AUCs between the MELD and CTP classification were significant in predicting 6 month and 1, 3 and 4 year survival, but were not significant in predicting other time point survival. The differences of AUCs between the MELD and CTP score were not significant in predicting survival. In the subgroups of patients ranked by MELD score lower than 10, 10 to 20, 20 to 30, and more than 30, the survival rate was significant different (P = 0.000). CONCLUSIONS: MELD is a useful prognosis indicator for the liver cirrhosis. The ability of prognosis by MELD is similar to Child-Turcotte-Pugh classification and score.

Area Under Curve↗

Liver transplantation for polycystic liver disease.

Polycystic liver disease (PLD) may provoke massive hepatomegaly and severe physical and social handicaps. Data on orthotopic liver transplantation (OLT) for PLD are rare and conflicting. Conservative surgery (resection or fenestration) is indicated for large single cysts, but its value for small diffuse cysts is questionable. In addition, conservative surgery is not devoid of morbidity and mortality. OLT offers the prospect of a fully curative treatment, but controversy remains because those patients usually have preserved liver function. Thus, we reviewed our experience with OLT for PLD. Sixteen adult women underwent OLT for small diffuse PLD between 1990 and 1999. Mean age was 45 years (range, 34 to 56 years). Fourteen patients had combined liver and kidney cystic disease, but only 1 patient required combined liver and kidney transplantation, whereas 13 patients underwent OLT alone. Two patients had isolated PLD. Indications for transplantation were massive hepatomegaly causing physical handicaps (n = 16), social handicaps (n = 16), malnutrition (n = 4), and cholestasis and/or portal hypertension (n = 5). OLT caused no technical difficulty in 15 of 16 patients (surgery duration, 6.8 hours; range, 5 to 8 hours), with blood transfusions of 7.9 units (range, 0 to 22 units). One patient who underwent attempted liver-mass reduction pre-OLT died of bleeding and pulmonary emboli. Native liver weight was 10 to 20 kg. Posttransplantation immunosuppression consisted of cyclosporine or FK506, azathioprine, and steroids (discontinued at 3 months). Morbidity included biliary stricture (2 patients), revision for bleeding and hepatitis (1 patient), pneumothorax and subphrenic collection (1 patient), and tracheostomy (1 patient). One patient died of lung cancer 6 years posttransplantation. Both patient and graft survival rates are 87.5% (follow-up, 3 months to 9 years). Of 15 patients who underwent OLT alone, only 1 patient needed a kidney transplant 4 years after OLT. Kidney function has remained satisfactory in the other patients despite the use of cyclosporine or FK506 (last follow-up creatinine level, 1.55 mg/dL; range, 0.80 to 2.85 mg/dL). OLT had a dramatic impact on daily quality of life, enabling these patients to go back to a fully active life style. OLT offers the chance of a definitive treatment in patients with extensive, small, diffuse PLD that has evolved into severely handicapping hepatomegaly. In contrast to previous studies, combined liver and kidney transplantation is rarely needed. Patient symptoms and chances of definitive palliation offered by OLT must be balanced against the risks of transplantation and lifelong commitment to immunosuppression.

Adult↗

[Orthotopic liver transplantation in therapy of advanced polycystic liver disease].

Polycystic liver disease (PLD) is an autosomal-dominant hereditary disease which usually presents together with polycystic kidney degeneration (ADPKD). The renal problems determine the course of this disease. Due to the development of dialysis an increasing number of patients present with symptoms from their liver cysts: These range from compression caused by hepatomegaly, which can severely limit the quality of life, to chronic liver failure. Ten patients with advanced symptoms of PLD underwent orthotopic liver transplantation, five of them with combined renal transplantation. Postoperative complications occurred in three patients. One patient died postoperatively from multiorgan failure after experiencing coagulopathy of unknown origin. After follow-up of 6-60 months, all patients had better quality of life after transplantation. There was a complete relief of symptoms; liver or renal failure did not occur. Liver transplantation should be considered in patients with highly symptomatic PLD. In the case of severe hepatomegaly or liver and renal failure the combined liver and renal transplantation are able to cure the PLD and ADPKD without rising the disadvantage of immunosuppression incurred with single organ transplantation.

Adult↗

Anaesthesia and liver disease.

Severe liver disease is not a common problem in patients presenting for anaesthesia and surgery. However, because many vital functions are performed by the liver, impairment of these has important implications for the anaesthetist. In addition, since the metabolism and elimination of drugs may be altered, the response of the patient to anaesthetic agents may be unpredictable.

Anesthesia↗

Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Liver biopsy is considered as the gold standard for assessing non-alcoholic fatty liver disease (NAFLD) histologic lesions. The aim of this study was to determine the diagnostic utility of non-invasive markers of fibrosis, validated in chronic viral hepatitis and alcoholic liver disease (FibroTest, FT), in patients with NAFLD. METHODS: 170 patients with suspected NAFLD were prospectively included in a reference center (Group 1), 97 in a multicenter study (Group 2) and 954 blood donors as controls. Fibrosis was assessed on a 5 stage histological scale validated by Kleiner et al from F0 = none, F1 = perisinusoidal or periportal, F2 = perisinusoidal and portal/periportal, F3 = bridging and F4 = cirrhosis. Histology and the biochemical measurements were blinded to any other characteristics. The area under the ROC curves (AUROC), sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV, NPV) were assessed. RESULTS: In both groups FT has elevated and not different AUROCs for the diagnosis of advanced fibrosis (F2F3F4): 0.86 (95%CI 0.77-0.91) versus 0.75 (95%CI 0.61-0.83; P = 0.10), and for F3F4: 0.92 (95%CI 0.83-0.96) versus 0.81 (95%CI 0.64-0.91; P = 0.12) in Group 1 and Group 2 respectively. When the 2 groups were pooled together a FT cutoff of 0.30 had a 90% NPV for advanced fibrosis (Se 77%); a FT cutoff of 0.70 had a 73% PPV for advanced fibrosis (Sp 98%). CONCLUSION: In patients with NAFLD, FibroTest, a simple and non-invasive quantitative estimate of liver fibrosis reliably predicts advanced fibrosis.

Age Factors↗