Arvind R. Murali

Hepatocellular carcinoma: From diagnosis to treatment.

Hepatocellular carcinoma (HCC) is the sixth most prevalent malignancy worldwide and is a rising cause of cancer related mortality. Risk factors for HCC are well documented and effective surveillance and early diagnosis allow for curative therapies. The majority of HCC appears to be caused by cirrhosis from chronic hepatitis B and hepatitis C virus. Preventive strategies include vaccination programs and anti-viral treatments. Surveillance with ultrasonography detects early stage disease and improves survival rates. Many treatment options exist for individuals with HCC and are determined by stage of presentation. Liver transplantation is offered to patients who are within the Milan criteria and are not candidates for hepatic resection. In patients with advanced stage disease, sorafenib shows some survival benefit.

Topical steroids in eosinophilic esophagitis: Systematic review and meta‐analysis of placebo‐controlled randomized clinical trials

Eosinophilic esophagitis (EoE) is a clinicopathologic condition characterized by symptoms of esophageal dysfunction in the presence of eosinophil‐predominant inflammation of esophageal mucosa. Topical steroids are recommended as first line pharmacologic therapy in EoE. We aimed to determine the efficacy of topical steroids in inducing histologic and clinical remission in children and adults with EoE.

Chronic hepatitis E: A brief review

Hepatitis E viral infection has traditionally been considered an acute, self-limited, water borne disease similar to hepatitis A, endemic to developing countries. However, over the past decade, zoonotic transmission and progression to chronicity in human patients has been identified, resulting in persistently elevated transaminase levels, progressive liver injury and cirrhosis. In addition to liver injury, neurological, renal and rheumatological manifestations have also been reported. Chronic hepatitis E occurs mainly in immunosuppressed individuals such as transplant recipients, human immunodeficiency virus patients with low CD4 counts and in patients with hematological malignancies receiving chemotherapy. Diagnosis is established by persistent elevation of hepatitis E virus RNA in the stool or serum. This population often requires treatment with antiviral agents, particularly ribavirin, as spontaneous clearance with reduction in immunosuppression occurs only in about a third of the patients. The purpose of this review, is to further discuss the clinical presentation, and recent advances in diagnosis, treatment and prophylaxis of chronic hepatitis E.

Utility of confocal laser endomicroscopy in identifying high-grade dysplasia and adenocarcinoma in Barrett's esophagus: a systematic review and meta-analysis.

Confocal laser endomicroscopy (CLE) is a novel endoscopic technique that has emerged as an important tool in the in-vivo visualization and detailed assessment of the mucosal layer and subcellular structures in Barrett’s esophagus. Current guidelines recommend four-quadrant random biopsies for identification of high-grade dysplasia (HGD) in Barrett’s esophagus. However, random biopsies are associated with sampling error and inconsistent histopathologic interpretation. CLE, by providing targeted biopsies, could decrease the sampling error and increase the yield of detection of HGD/adenocarcinoma [esophageal adenocarcinoma (EAC)]. We carried out a meta-analysis to evaluate the diagnostic accuracy of the CLE-based targeted biopsies in detecting HGD/adenocarcinoma compared with four-quadrant random biopsies. A search using medical subject headings (MeSH) terms and keywords was performed in the MEDLINE and Cochrane review databases and relevant studies were identified. All the studies that compared the diagnostic yield from CLE-based targeted biopsies to detect HGD/adenocarcinoma with a gold standard of histopathology were included and a meta-analysis was carried out to estimate the pooled sensitivity, specificity, and positive and negative likelihood ratios using Meta-Disc software. There were a total of seven studies with 345 patients and 3080 lesions that were finally included in the meta-analysis. All the studies had reported per-lesion analyses; however, only four of the seven studies had data reported on per-patient analyses. ‘Per-lesion’ analysis for the diagnosis of HGD/adenocarcinoma yielded a pooled sensitivity and specificity of 68% [95% confidence interval (CI) of 64–73%] and 88% (95% CI of 87–89%), respectively. The pooled positive and negative likelihood ratios were 6.56 (95% CI of 3.61–11.90) and 0.24 (95% CI of 0.09–0.63), respectively. Similar numbers were calculated on the basis of ‘per-patient’ basis, which showed a pooled sensitivity and specificity of 86% (95% CI of 74–96%) and 83% (95% CI of 77–88%), respectively. The pooled positive and negative likelihood ratios were 5.61 (95% CI of 2.00–15.69) and 0.21 (95% CI of 0.08–0.59), respectively. CLE, by providing targeted biopsies, has a good diagnostic accuracy in identifying HGD/EAC; however, the overall prevalence of HGD/EAC in the studies included was much higher than what would be seen in clinical practice and these results should be interpreted with caution. Because of its relatively low sensitivity and negative predictive value, CLE may currently not replace standard biopsy techniques for the diagnosis of HGD/EAC in Barrett’s esophagus.

Graft Versus Host Disease after Liver Transplantation in Adults: A Case series, Review of Literature, and an Approach to Management

Background Graft-versus-host-disease (GVHD) after liver transplantation (LT) is a deadly complication with very limited data on risk factors, diagnosis and management. We report a case series and a comprehensive review of the literature. Methods Data were systematically extracted from reports of GVHD after LT, and from the United Network for Organ Sharing database. Group comparisons were performed. Results One hundred fifty-six adult patients with GVHD after LT have been reported. Median time to GVHD onset was 28 days. Clinical features were skin rash (92%), pancytopenia (78%), and diarrhea (65%). Six-month mortality with GVHD after LT was 73%. Sepsis was the most common cause of death (60%). Enterobacter bacteremia, invasive aspergillosis, and disseminated Candida infections were frequently reported. Recipient age over 50 years is a risk factor for GVHD after LT. Hepatocellular carcinoma was overrepresented, whereas chronic hepatitis C was underrepresented, in reported United States GVHD cases relative to all United Network for Organ Sharing database LT cases. Mortality rate with treatment of GVHD after LT was 84% with high-dose steroids alone, 75% to 100% with regimens using dose increases of calcineurin inhibitors, and 55% with IL-2 antagonists. Mortality was 25% in small case series using the CD2-blocker alefacept or TNF-&agr; antagonists. Conclusions Age older than 50 years and hepatocellular carcinoma appear to be risk factors for GVHD. Hepatitis C may be protective. High-dose steroids and calcineurin inhibitors are ineffective in the treatment of GVHD after LT. CD2-blockers and TNF-&agr; antagonists appear promising. We propose a diagnostic algorithm to assist clinicians in managing adults with GVHD after LT.

Locoregional Therapy with Curative Intent versus Primary Liver Transplant for Hepatocellular Carcinoma: Systematic Review and Meta-analysis

Background Locoregional therapy with curative intent (CLRT) followed by salvage liver transplantation (SLT) in case of hepatocellular carcinoma (HCC) recurrence is an alternative to primary liver transplantation (LT) in selected patients with HCC. Methods We performed a systematic review and meta-analysis of studies comparing the survival of patients treated with CLRT versus LT, stratified by the stage of liver disease, extent of cancer, and whether SLT was offered or not. Results We included 48 studies involving 9835 patients (5736 patients with CLRT and 4119 patients with primary LT). Five-year overall survival (OS) and disease-free survival (DFS) was worse for all categories of CLRT combined, than for primary LT (odds ratio [OR] for OS, 0.59; 95% confidence interval [CI], 0.48-0.71; P < 0.01). However, 5-year OS for CLRT and primary LT was not significantly different among patients with (i) Child-A cirrhosis and (ii) single HCC lesion, although DFS was worse. When SLT was offered after CLRT, intention-to-treat analysis showed no significant difference in 5-year OS (OR, 1.0; 95% CI, 0.6-1.7) between CLRT-SLT and primary LT, though noninferiority could not be shown. Only 32.5% patients with HCC recurrence after CLRT actually received SLT, as the rest were not medically eligible. Thus, the DFS was worse with CLRT-SLT (OR, 0.31; 95% CI, 0.2-0.6) compared with LT. Conclusions CLRT-SLT may be offered as first-line therapy to patients with HCC and well-compensated cirrhosis instead of primary LT because it may lead to better utilization of donor liver. However, a large proportion of patients with HCC recurrence after CLRT may not be candidates for SLT.

The Bedside Index for Severity in Acute Pancreatitis: a systematic review of prospective studies to determine predictive performance

ABSTRACT Background: predicting the development of severe disease has remained a major challenge in management of acute pancreatitis. The Bedside Index for Severity in Acute Pancreatitis (BISAP) is easy to calculate from the data available in the first 24 hours. Here, we performed a systematic review to determine the prognostic accuracy of the BISAP for severe acute pancreatitis (SAP). Methods: major databases of biomedical publications were searched during the first week of October 2015. Two independent reviewers searched records in two phases. Studies that reported prognostic accuracy of the BISAP for SAP from prospective cohorts were included. The pooled area under the receiver operating curve (AUC) was calculated. Results: Twelve studies were included for data-synthesis and methodology quality assessment was performed for 10. All the studies had enrolled consecutive patients, had a broad spectrum of the disease severity, reported explicit interpretation of the predictor, outcome of interest was well defined and had adequate follow-up. Blinded outcome assessment was reported in only one study. The pooled AUC was 0.85 (95% CI 0.80–0.90). There was significant heterogeneity, I2 86.6%. Studies using revised Atlanta classification in defining SAP had a pooled AUC of 0.92 (95% CI, 0.90–0.95), but heterogeneity persisted, I2 67%. Subgroup analysis based on rate of SAP (>20% vs <20%) did not eliminate the heterogeneity. Conclusion: the BISAP has very good predictive performance for SAP across different patient population and etiologies. Studies to evaluate the impact of incorporating the BISAP into clinical practice to improve outcome in acute pancreatitis are needed before adoption could be advocated with confidence.