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Biomedical subjects

Andrew Burroughs

Publications and source records attributed to Andrew Burroughs.

At least 19 recordsLinked to original sources

Severe venoocclusive disease after liver transplantation treated with transjugular intrahepatic portosystemic shunt.

Venoocclusive disease (VOD) is due to hepatic sinusoidal lining injury leading to portal hypertension; its incidence after liver transplantation is about 2%. When severe, it does not respond to medical therapy and has a high mortality; retransplantation is the only therapeutic option. However, there are no detailed data regarding the use of transjugular intrahepatic portosystemic shunt for VOD after liver transplantation. We describe two patients who developed severe VOD after liver transplantation, failed defibrotide therapy, and were treated by transjugular intrahepatic portosystemic shunt (TIPS). The portal hypertension resolved completely and one had full histological recovery. We believe that TIPS should be attempted as it may resolve progressive portal hypertension and the hepatic congestion, while allowing the clinician time for listing for further liver transplantation if the patient fails to respond.

Female↗

Transjugular intrahepatic portosystemic shunt in the management of ascites and hepatorenal syndrome.

Ascites is the most common complication of liver cirrhosis and when it develops mortality is 50% at 5 years, apart from liver transplantation. Large volume paracentesis has been the only option for ascites refractory to medical treatment. The role of transjugular intrahepatic portosystemic shunt in the management of diuretic-resistant ascites has been evaluated in many cohort studies and five randomized trials up to now, clearly showing improvement in natriuresis and clinical efficacy. It, however, remains unclear how transjugular intrahepatic portosystemic shunt affects survival and quality of life, because hospital admissions owing to worsening encephalopathy may counterbalance the reduced need of paracentesis. What is clear is that the patient selection is critical. About 30% of patients with ascites develop hepatorenal syndrome at 5 years, leading to high mortality in its severe and progressive form. As its main pathogenetic factor is derangement of circulatory function owing to portal hypertension, these patients may benefit from transjugular intrahepatic portosystemic shunt, but this has been shown only in small series, in which mortality remains very high, owing to the underlying poor liver function.

Ascites↗

Liver transplantation and hepatitis C virus: systematic review of antiviral therapy.

Antiviral therapy for recurrent hepatitis C after liver transplantation is increasingly used. This systematic review presents both viral and histological response in three areas: pretransplant (5 studies/180 patients), preemptive therapy soon after transplant (10 studies/417 patients), and therapy for established disease (75 studies/2027 patients). There were only 16 randomized studies (543 patients). Significant dose reductions and drug stoppage rates occurred. The data on histological improvement and risk of rejection are conflicting. Even the best antiviral therapy (pegylated interferon/ribavirin) is neither easily used nor reasonably effective. The best strategy will be pretransplant treatment, most likely with newer agents.

Antiviral Agents↗

Survival of cirrhotic patients with early hepatocellular carcinoma treated by percutaneous ethanol injection or liver transplantation.

For "early" hepatocellular carcinoma (HCC), surgery, orthotopic liver transplantation (OLT) and percutaneous ethanol injection (PEI) improve the natural history of the disease. We performed a retrospective study to evaluate the outcome of patients with cirrhosis and early HCC treated by PEI (n = 417) or OLT (n = 172). Overall, 589 patients with cirrhosis were studied. The proportion of patients in Child-Turcotte-Pugh (CTP) classes A, B, and C was 52.5%, 33.6%, and 13.9%, respectively. Most patients (78.9%) had solitary HCC. Overall 5-year and 10-year cumulative survival rates were 36.1% and 15.5% after PEI, and 66.3% and 49.1% after OLT, respectively (P < .0001). Overall 5-year and 10-year cumulative tumor-free survival rates were 25.3% and 18.0% after PEI, and 84.6% and 82.2% after OLT, respectively (P < .0001). When patients were sorted according to the severity of cirrhosis, mean survival times in PEI and OLT patients were 67 and 80 months in CTP class A (P = .05), 38 and 90 months in class B (P < .0001), and 31 and 95 months in class C (P = .0004). Similarly, mean tumor-free survival times in the 2 series of patients were 49 and 98 months in CTP class A (P < .0001), 39 and 121 months in class B (P < .0001), and 35 and 139 months in class C (P < .0001). In conclusion, this study challenges the therapeutic efficacy of PEI for patients with cirrhosis and early HCC, when compared to OLT: the proportion of both long-term survivors and tumor-free survivors was increased by OLT over PEI. The benefit of OLT extends to all patients, regardless of the degree of liver impairment.

Aged↗

Systemic treatment and liver transplantation for hepatocellular carcinoma: two ends of the therapeutic spectrum.

Hepatocellular carcinoma is the fifth most common malignant disorder and causes nearly 1 million deaths a year worldwide. A background of cirrhosis is the major risk factor, and in Asia and subSaharan Africa, cirrhosis is attributable mainly to endemic hepatitis B infection. In Europe and the USA the incidence of hepatocellular carcinoma is increasing as a result of the high prevalence of hepatitis C. The only curative treatments are surgical resection or liver transplantation, but only a few patients are eligible for these procedures. Local ablative treatments such as ethanol injection can lengthen survival in selected patients, and radiofrequency ablation also shows promise. Unfortunately, most patients are suitable only for palliative treatment because of the extent of their tumour or background liver disease or both. For these patients, a wide range of therapeutic interventions have been assessed, including transarterial embolisation (with or without chemotherapy), hormone therapy with antioestrogens and androgens, octreotide, interferon, and both arterial and systemic chemotherapy, of which only chemoembolisation improves survival over symptomatic care. Tamoxifen is ineffective, and there are insufficient randomised data to show the benefit of any other intervention. In this review, we focus on two ends of the therapeutic spectrum--transplantation, which is highly effective but applicable to only a few patients, and systemic chemotherapy, which is of uncertain benefit but widely applicable.

Antineoplastic Agents↗

Hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cause of cancer, and its incidence is increasing worldwide because of the dissemination of hepatitis B and C virus infection. Patients with cirrhosis are at the highest risk and should be monitored every 6 months. Surveillance can lead to diagnosis at early stages, when the tumour might be curable by resection, liver transplantation, or percutaneous treatment. In the West and Japan, these treatments can be applied to 30% of patients, and result in 5-year survival rates higher than 50%. Resection is indicated among patients who have one tumour and well-preserved liver function. Liver transplantation benefits patients who have decompensated cirrhosis and one tumour smaller than 5 cm or three nodules smaller than 3 cm, but donor shortage greatly limits its applicability. This difficulty might be overcome by living donation. Most HCC patients are diagnosed at advanced stages and receive palliative treatments, which have been assessed in the setting of 63 randomised controlled trials during the past 25 years. Meta-analysis shows that only chemoembolisation improves survival in well-selected patients with unresectable HCC.

Carcinoma, Hepatocellular↗

Piperacillin-tazobactam versus ciprofloxacin plus amoxicillin in the treatment of infective episodes after liver transplantation.

An optimum antimicrobial regimen for bacterial infection after orthotopic liver transplantation has not been identified. In this prospective 4 year study of patients undergoing liver transplantation, patients were randomized to receive either piperacillin-tazobactam (112 patient episodes) or ciprofloxacin plus amoxicillin (105 patient episodes) for empirical treatment of infective episodes in the first 3 months after transplant. Metronidazole was added to the ciprofloxacin-amoxicillin regimen where anaerobic infection was suspected. Patient groups were comparable with respect to clinical, biochemical and haematological parameters. At the 72 h primary efficacy end-point, the overall response rate for the intention-to-treat group was 74/112 (66.1%) for piperacillin-tazobactam and 63/105 (60.0%) for ciprofloxacin plus amoxicillin (P=0.399); the corresponding figures for the per-protocol (PP) group were 73/82 (89.0%) (piperacillin-tazobactam) and 61/80 (76.3%) (ciprofloxacin plus amoxicillin) (P=0.038). At the end-of-study assessment, 58.9% of episodes in the piperacillin-tazobactam group had a successful clinical outcome, compared with 50.5% in the ciprofloxacin plus amoxicillin group (P=0.222); the corresponding figures for the PP group were 83.5% (piperacillin-tazobactam) and 68.8% (ciprofloxacin plus amoxicillin) (P=0.038). Staphylococci and aerobic Gram-negative bacilli were the predominant pathogens in both groups. Bacteria resistant to the study drugs were encountered, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and multiply-resistant Klebsiella spp. Empirical monotherapy with piperacillin-tazobactam is an effective treatment for infective episodes in liver transplant patients.

Adolescent↗

Midterm cost-effectiveness of the liver transplantation program of England and Wales for three disease groups.

Liver transplantation has never been the subject of a randomized controlled trial, and there remains uncertainty about the magnitude of benefit and cost-effectiveness for specific patient groups. This article reports the results of an economic evaluation of adult liver transplantation in England and Wales. Patients placed on the waiting list for a liver transplant were observed over 27 months. The costs and health benefits of a comparison group, representing experience in the absence of liver transplantation, were estimated using a combination of observed data from patients waiting for a transplant and published prognostic models. The analysis focuses on three disease groups, for each of which prognostic models were available: primary biliary cirrhosis (PBC), alcoholic liver disease (ALD), and primary sclerosing cholangitis (PSC). A higher proportion of patients with ALD were assessed for a transplant but not placed on the waiting list. The estimated gain in quality-adjusted life-years from transplantation was positive for each of the disease groups. The mean incremental cost per quality-adjusted life-year (95% bootstrap confidence intervals) from time of listing to 27 months for patients with PBC, ALD, and PSC are pound 29,000 (pounds 1,000 to pounds 59,000), pounds 48,000 (pounds 12,000 to pounds 83,000) and pounds 21,000 (-pounds 23,000 to pounds 60,000), respectively. In conclusion, liver transplantation increases the survival and health-related quality of life of patients with each of three end-stage liver diseases. However, the extent of this increase differs between different disease groups. Cost-effectiveness estimates were poorer for patients with ALD over the 27-month period than for patients with PBC or PSC. This in part reflects the costs of the higher number of ALD patients assessed for each transplant.

Adolescent↗

Applications and limitations of blood eosinophilia for the diagnosis of acute cellular rejection in liver transplantation.

This study evaluates the predictive value of the blood eosinophil count in the diagnosis of acute cellular rejection, its value as a marker of response to treatment, the diagnostic use in a subgroup of patients with normal transaminases and compares blood eosinophilia in patients with and without hepatitis C virus infection. A consecutive cohort of 101 liver transplant patients, 275 liver biopsies, and blood eosinophils recorded on the day or one day before biopsy were analyzed. An elevated eosinophil count has a positive predictive value for acute cellular rejection of 82%. A normal eosinophil count excludes moderate/severe rejection with a predictive value of 86%. The eosinophil count decreases in 69% of patients following treatment of acute cellular rejection with corticosteroids irrespective of treatment outcome. Acute cellular rejection in the presence of an elevated eosinophil count occurs significantly less often (p = 0.007) in patients with hepatitis C virus. An elevated eosinophil count is a valuable marker of acute cellular rejection. However, blood eosinophil levels should not be used to predict acute cellular rejection following treatment with corticosteroids. Blood eosinophilia, seen less often in patients with hepatitis C virus, may reflect an over-diagnosis of acute cellular rejection in these patients.

Adult↗