Sujan Ravi

Unusually High Rates of Hepatocellular Carcinoma After Treatment With Direct-Acting Antiviral Therapy for Hepatitis C Related Cirrhosis

Dear Editors: Direct-acting antiviral (DAA) therapy has revolutionized the treatment of hepatitis C virus (HCV) infection, with very high rates of sustained virologic response (SVR) and an excellent safety profile. Interferon-based therapies in the past have shown improved outcomes, including reduced risk for occurrence and recurrence of hepatocellular carcinoma (HCC) with the achievement of SVR. However, data on the impact of DAA therapy on the natural history and development of HCC are limited. Recently, studies have shown unexpected high HCC recurrence rate of 27%-29% among patients treated with resection or ablation, who received DAA therapy. However, similar results were not reproduced in analyses of three prospective cohorts from France. Among patients with HCV-related cirrhosis without prior history of HCC, DAA treatment was not associated with reduction in the occurrence of HCC. In one of these studies, de novo occurrence of HCCwas reported at rate of 3.17%within 6months of completing DAA therapy for HCV infection. With scanty and conflicting data on the association of HCC with DAA therapy, we performed this retrospective study to examine occurrence of de novo HCC among HCV-infected patients with cirrhosis during or after treatment with DAA.

Regorafenib: an evidence-based review of its potential in patients with advanced liver cancer

Hepatocellular carcinoma (HCC) is the second-most common cause of cancer-related death in the world. In spite of HCC surveillance with repeated imaging, about 50% of patients are diagnosed at an advanced stage and are not amenable to curative treatment options. Sorafenib, a multikinase inhibitor, remains the standard of care for advanced HCC. Over the last 5 years, several other medications have been tested in Phase III trials. However, they have not shown any added benefit over sorafenib. Regorafenib, another multikinase inhibitor, has demonstrated inhibition of a broader range of kinases, along with higher inhibition potential in preclinical models. After its safety and pharmacological properties was studied in Phase I trials, a Phase II study evaluating the role of Regorafenib in patients with advanced HCC who progressed on sorafenib therapy demonstrated efficacy and a manageable safety profile. A Phase III trial is ongoing, and its result will help us better evaluate the role of Regorafenib in patients with advanced HCC.

Use of automated irrigation pumps improves quality of bowel preparation for colonoscopy.

AIM To evaluate the effectiveness of automated irrigation pumps (AIPs) in improving the quality of the bowel preparation and the yield of colonoscopy. METHODS A retrospective observational study was conducted at a single medical center. Outpatient colonoscopies performed during a 4-mo time period when AIPs were not in use, were compared to colonoscopies performed during control period. The main outcomes measured were quality of bowel preparation, procedures aborted due to poor preparation, recommendations to repeat at short interval due to sub-optimal bowel preparation and adenoma detection rates. RESULTS One thousand and thirty-seven colonoscopies were included. A higher proportion of cases did not achieve a satisfactory bowel preparation when AIPs were not used (24.4% vs 10.3%, P < 0.01). The number of procedures aborted due to inadequate preparation was not significantly different, however a repeat procedure at a short interval was recommended in a higher proportion of cases when AIPs were not used (21.3% vs 6.9%, P < 0.01). Good or excellent preparation was 2.91 (95%CI: 2.04-4.15) times more likely when AIPs were used. Detection of polyps and adenomas was not significantly different. CONCLUSION AIP use during colonoscopy results in a higher proportion of colonic preparation rated as satisfactory, although polyp detection rate is not significantly affected. Recommendations for repeat colonoscopy at shorter interval significantly decrease with the use of AIPs. This study supports the use of the irrigation pumps in endoscopy units to improve the quality of colonoscopy.

Ammonia level at admission predicts in-hospital mortality for patients with alcoholic hepatitis

Abstract Objective. Alcoholic hepatitis (AH), a unique clinical syndrome among patients with chronic and active alcohol use, is associated with high short-term mortality. An elevated ammonia level is associated with mortality in patients with acute liver failure; however, its impact in AH has not been well-studied. Methods. A retrospective study was performed on patients admitted to a tertiary-care hospital with the discharge diagnosis of AH. Patients meeting criteria for AH were included in the final data analysis. Multivariate logistic regression models were built to examine the impact of serum ammonia in predicting in-hospital mortality (IHM) and 30-day mortality (TDM). Subgroup analysis was also performed, which was limited to patients who had hepatic encephalopathy. Results. Of the 105 AH patients included, 26 (25%) died during the initial hospitalization. Among the 79 patients who survived initial hospitalization, 30 (39%) died within 30 days. Information about ammonia levels at admission was available for 82 patients. Of these, 25 patients had IHM and significantly higher ammonia level (97 vs. 69 μmol/L, P < 0.01). Among the 57 who survived hospitalization, ammonia levels were not significantly different (71 vs. 67 μmol/L, P = 0.69) in patients with and without TDM. The addition of ammonia to the multivariate regression models including age, sex, cirrhosis, treatment and model for end-stage liver disease (MELD) score improved the C statistics for IHM from 0.708 to 0.801 and for TDM from 0.756 to 0.766, respectively. These results were identical, even when limited to patients with hepatic encephalopathy. Conclusion. AH patients with elevated ammonia levels at admission have higher IHM; however, they do not seem to play a significant role in 30-day mortality for patients who survived hospitalization.

Biomarkers of Renal Injury in Cirrhosis: Association with Acute Kidney Injury and Recovery after Liver Transplantation.

Background: To define urine or serum biomarkers in predicting renal function recovery after liver transplantation (LT). Methods: Adults listed for LT (February 2011-July 2014) and with modified diet for renal disease-6 (MDRD-6) <60 mL/min provided urine/blood samples at baseline and serially until LT for biomarkers in serum (pg/mL) and urine (pg/mg creatinine). Results: Of 271 LT listed patients (mean age 57 years, 63% males, median listing MELD 17.5), 1 year acute kidney injury (AKI) probability was 49%, with odds of 1.3-, 3.0-, 4.6-, and 8.5-fold times for listing MELD 16-20, 21-25, 26-30, and >30, compared to MELD <16. Thirty-seven people died over 1 year from the time of listing, with twofold increased odds with AKI. Among 67 patients with MDRD <60, only urinary epidermal growth factor was different comparing AKI (increase in serum creatinine ≥0.3 mg/dL from baseline within past 3 months) vs. no AKI (2,254 vs. 4,253, p = 0.003). Differences between acute tubular necrosis (ATN) and hepatorenal syndrome could not be ascertained for a small sample of 3 patients with ATN. Analyzing 15 of 43 receiving LT and MDRD-6 <30 prior to LT, biomarkers were not different comparing 5 patients recovering renal function (MDRD-6 >50 mL/min) at 6 months vs. 10 without recovery. Conclusions: AKI is common among LT listed patients, with a negative impact on transplant-free survival. Serum and urine biomarkers are not associated with the recovery of renal function after LT. Multicenter studies are suggested to (a) develop strategies to reduce the development of AKI and (b) derive novel biomarkers for use in accurately predicting renal recovery after LT.

Text Messaging Approach Improves Weight Loss in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Study

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease. The only effective treatment is 7%‐10% weight loss. Mobile technology is increasingly used in weight management. This study was performed to evaluate the effects of text messaging intervention on weight loss in patients with NAFLD.

Sa1103 The use of Irrigation Pumps During Colonoscopy Improves the Quality of the Exam and Decreases the Likelihood of Repeating the Procedure at a Short Interval

Background/Aims: Pyridoxine or vitamin B6 deficiency is an established cause of sideroblastic anemia through the inhibition of heme synthesis. Reduced levels of this micronutrient has also been implicated in sickle cell anemia and anemia of pregnancy. In 1984, Diehl et al demonstrated an association between low serum alanine transaminase (ALT) and pyridoxine deficiency. The correlation between decreased pyridoxine and serum ALT level can therefore serve as a tool to identify patients with microcytic anemia associated with pyridoxine deficiency. Malabsorption is a prominent cause of pyridoxine deficiency, which is frequent in patients with IBD. Similarly, patients with cirrhosis suffer from defects in vitamin metabolism and thus are also susceptible to pyridoxine deficiency. We conducted a prospective study to identify pyridoxine deficiency in these patients using low ALT values as a marker of B6 deficiency. We theorize that supplementation with pyridoxine will correct the anemia. Methods: Patients with anemia who had either cirrhosis or Crohns disease at Albany Medical Center and some from Johns Hopkins Hospital were identified. Of the 203 patients with Crohns disease and 202 patients with cirrhosis, 29 and 33 patients, respectively, met the inclusion criteria and were incorporated into this study. Inclusion criteria were hematocrit < 36 g/dL, mean corpuscular volume (MCV) < 80, total iron < 30 ug/dL, and ALT < 25 IU/ L. Patients with folate deficiency or vitamin B12 deficiency were excluded from the study. Results: All eligible patients were contacted by letters or telephone calls. Preliminary results from the first 8 patients with microcytic anemia refractory to iron supplementation revealed low serum ALT and lower than normal plasma pyridoxine levels. These patients were prescribed 50 mg of oral pyridoxine to be taken daily. A repeat pyridoxine level, complete blood count, and iron studies were redrawn at the end of 2 months of treatment to evaluate for improvement in anemia. Of those 8 patients, six patients have completed treatment with improvement in hematocrit, ALT and pyridoxine levels. The remainig patients from both groups continue to be investigated. Conclusions: Persistent anemia unresponsive to iron supplementation associated with low ALT level may be due to pyridoxine deficiency in malnourished patients with chronic gastrointestinal or liver disease.