Evaluation of the aspartate aminotransferase/platelet ratio index and enhanced liver fibrosis tests to detect significant fibrosis due to chronic hepatitis C.

BACKGROUND: The assessment of liver fibrosis in chronic hepatitis C patients is important for prognosis and making decisions regarding antiviral treatment. Although liver biopsy is considered the reference standard for assessing hepatic fibrosis in patients with chronic hepatitis C, it is invasive and associated with sampling and interobserver variability. Serum fibrosis markers have been utilized as surrogates for a liver biopsy. METHODS: We completed a prospective study of 191 patients in which blood draws and liver biopsies were performed on the same visit. Using liver biopsies the sensitivity, specificity, and negative and positive predictive values for both aspartate aminotransferase/platelet ratio index (APRI) and enhanced liver fibrosis (ELF) were determined. The patients were divided into training and validation patient sets to develop and validate a clinically useful algorithm for differentiating mild and significant fibrosis. RESULTS: The area under the ROC curve for the APRI and ELF tests for the training set was 0.865 and 0.880, respectively. The clinical sensitivity in separating mild (F0-F1) from significant fibrosis (F2-F4) was 80% and 86.0% with a clinical specificity of 86.7% and 77.8%, respectively. For the validation sets the area under the ROC curve for the APRI and ELF tests was, 0.855 and 0.780, respectively. The clinical sensitivity of the APRI and ELF tests in separating mild (F0-F1) from significant (F2-F4) fibrosis for the validation set was 90.0% and 70.0% with a clinical specificity of 73.3% and 86.7%, respectively. There were no differences between the APRI and ELF tests in distinguishing mild from significant fibrosis for either the training or validation sets (P=0.61 and 0.20, respectively). Using APRI as the primary test followed by ELF for patients in the intermediate zone, would have decreased the number of liver biopsies needed by 40% for the validation set. Overall, use of our algorithm would have decreased the number of patients who needed a liver biopsy from 95 to 24-a 74.7% reduction. CONCLUSIONS: This study has shown that the APRI and ELF tests are equally accurate in distinguishing mild from significant liver fibrosis, and combining them into a validated algorithm improves their performance in distinguishing mild from significant fibrosis.

Terlipressin therapy for reversal of type 1 hepatorenal syndrome: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Hepatorenal syndrome (HRS) is a serious complication of advanced liver disease and carries a poor prognosis. Recent trials have indicated that terlipressin may be effective in reversing HRS. Our aim was to evaluate the efficacy of terlipressin therapy in reversing type 1 HRS defined as a serum creatinine <1.5 mg/dL during treatment. METHODS: Randomized controlled trials in which patients with type 1 HRS received at least 3 days of terlipressin therapy and albumin in the intervention arm were included after a systematic search of the published English reports. Studies with other vasoconstrictor therapies in the control group were excluded. RESULTS: A total of 223 patients with HRS type 1 in four different trials, were included in the final analysis. Alcohol-related cirrhosis was the most common underlying etiology. The risk ratio for reversal in type 1 HRS with terlipressin therapy was 3.66 (95% confidence interval 2.15-6.23). Recurrence of HRS was low (8%). Serious side-effects requiring discontinuation of therapy were seen only in 6.8% of patients on terlipressin therapy. There was a trend towards improved transplant-free survival at 90 days in the terlipressin group (relative risk 1.86 95% confidence interval 1.0-3.4, P = 0.05). CONCLUSIONS: Terlipressin is effective in reversing HRS type 1. Recurrence of HRS is rare with at least 14 days of therapy. Serious side-effects requiring discontinuation of therapy are less common. There appears to be a survival benefit in patients with HRS treated with terlipressin.

Effect of bisphosphonates on bone mineral density in liver transplant patients: a meta-analysis and systematic review of randomized controlled trials.

SUMMARY: Bone mineral density (BMD) loss after liver transplantation (LT) results in considerable morbidity with the increased risk of fractures. Data on the efficacy of bisphosphonate use in post LT patients is scarce. This meta-analysis aims to summarize the results from published randomized controlled trials (RCTs) on the topic of interest. Electronic databases were searched to identify relevant publications. A total of 157 articles were identified and reviewed. Individual authors were contacted from relevant RCTs to obtain individual patient data where necessary to uniformly quantify BMD values post LT pre- and post LT. A total of six RCTs were used for final data extraction. (i) Lumbar Spine: In 364 patients (six studies, 182 in intervention and control groups each), bisphosphonate therapy improved BMD by 0.03 g/cm(2) (95% C.I. 0.01-0.05 g/cm(2); P = 0.02) at 12 months post LT. (ii) Femoral neck: In 268 patients (four studies, 130 bisphosphonate, 138 control), bisphosphonate use did not result in a statistically significant change in BMD at the end of 1 year. None of the studies noted serious adverse effects related to bisphosphonate administration. Data on incident fractures could not be pooled because of heterogeneity. Bisphosphonate therapy during the first year in LT recipients appears to reduce accelerated bone loss and improve bone mineral density at the lumbar spine.

Effect of bariatric surgery on nonalcoholic fatty liver disease: systematic review and meta-analysis.

BACKGROUND & AIMS: Weight loss in overweight or obese individuals results in marked improvement or resolution of hypertension, diabetes mellitus, and hyperlipidemia. However, the overall effect of weight loss on nonalcoholic fatty liver disease (NAFLD) remains unclear. This systematic review and meta-analysis is an effort to explore the effect of weight loss after bariatric surgical procedures on NAFLD. METHODS: We performed an electronic literature search of published articles on bariatric surgery and liver histology since inception to September of 2007. Primary outcome measures were improvement and/or resolution in the 3 components of NAFLD (steatosis, steatohepatitis, and fibrosis) after bariatric surgery-induced weight loss. A pooled proportion of patients with improvement or resolution was calculated for steatosis, steatohepatitis, and fibrosis using a random effects model. Heterogeneity among the studies was assessed using the I(2) (inconsistency) statistic and subgroup analyses. RESULTS: A total of 15 studies (766 paired liver biopsies) were selected for final data extraction. The percentage reduction in mean body mass index after bariatric surgeries ranged from 19.11 to 41.76. The pooled proportion of patients with improvement or resolution in steatosis was 91.6% (95% confidence interval [CI], 82.4%-97.6%), in steatohepatitis was 81.3% (95% CI, 61.9%-94.9%), in fibrosis was 65.5% (95% CI, 38.2%-88.1%), and for complete resolution of nonalcoholic steatohepatitis was 69.5 (95% CI, 42.4%-90.8%). CONCLUSIONS: Steatosis, steatohepatitis, and fibrosis appear to improve or completely resolve in the majority of patients after bariatric surgery-induced weight loss.

Neutropenic enterocolitis: An unusual complication of HCV combination therapy with PEG-IFN and ribavirin.

Drug induced neutropenia as a consequence of intensive chemotherapy for hematological malignancies and solid tumors is known to be associated with severe, life-threatening infections such as neutropenic enterocolitis. However, the neutropenia associated with HCV combination therapy with Pegylated Interferon [PEG-IFN] and ribavirin is considered to be well tolerated in patients without other co-morbidities. We present a case of a severe gastrointestinal complication in a patient receiving HCV combination therapy and advocate caution in continuing therapy in patients with neutropenia, especially in the presence of underlying co-morbidities such as cirrhosis.