K. Gautham Reddy

Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy

Glycerol phenylbutyrate (GPB) lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion in the form of phenylacetyl glutamine, which is excreted in urine. This randomized, double‐blind, placebo‐controlled phase II trial enrolled 178 patients with cirrhosis, including 59 already taking rifaximin, who had experienced two or more hepatic encephalopathy (HE) events in the previous 6 months. The primary endpoint was the proportion of patients with HE events. Other endpoints included the time to first event, total number of events, HE hospitalizations, symptomatic days, and safety. GPB, at 6 mL orally twice‐daily, significantly reduced the proportion of patients who experienced an HE event (21% versus 36%; P = 0.02), time to first event (hazard ratio [HR] = 0.56; P < 0.05), as well as total events (35 versus 57; P = 0.04), and was associated with fewer HE hospitalizations (13 versus 25; P = 0.06). Among patients not on rifaximin at enrollment, GPB reduced the proportion of patients with an HE event (10% versus 32%; P < 0.01), time to first event (HR = 0.29; P < 0.01), and total events (7 versus 31; P < 0.01). Plasma ammonia was significantly lower in patients on GPB and correlated with HE events when measured either at baseline or during the study. A similar proportion of patients in the GPB (79%) and placebo groups (76%) experienced adverse events. Conclusion: GPB reduced HE events as well as ammonia in patients with cirrhosis and HE and its safety profile was similar to placebo. The findings implicate ammonia in the pathogenesis of HE and suggest that GPB has therapeutic potential in this population. (Clinicaltrials.gov, NCT00999167). (Hepatology 2014;59:1073‐1083)

Multiphasic analysis of the temporal development of the distal gut microbiota in patients following ileal pouch anal anastomosis.

BackgroundThe indigenous gut microbiota are thought to play a crucial role in the development and maintenance of the abnormal inflammatory responses that are the hallmark of inflammatory bowel disease. Direct tests of the role of the gut microbiome in these disorders are typically limited by the fact that sampling of the microbiota generally occurs once disease has become manifest. This limitation could potentially be circumvented by studying patients who undergo total proctocolectomy with ileal pouch anal anastomosis (IPAA) for the definitive treatment of ulcerative colitis. A subset of patients who undergo IPAA develops an inflammatory condition known as pouchitis, which is thought to mirror the pathogenesis of ulcerative colitis. Following the development of the microbiome of the pouch would allow characterization of the microbial community that predates the development of overt disease.ResultsWe monitored the development of the pouch microbiota in four patients who underwent IPAA. Mucosal and luminal samples were obtained prior to takedown of the diverting ileostomy and compared to samples obtained 2, 4 and 8 weeks after intestinal continuity had been restored. Through the combined analysis of 16S rRNA-encoding gene amplicons, targeted 16S amplification and microbial cultivation, we observed major changes in structure and function of the pouch microbiota following ileostomy. There is a relative increase in anaerobic microorganisms with the capacity for fermentation of complex carbohydrates, which corresponds to the physical stasis of intestinal contents in the ileal pouch. Compared to the microbiome structure encountered in the colonic mucosa of healthy individuals, the pouch microbial community in three of the four individuals was quite distinct. In the fourth patient, a community that was much like that seen in a healthy colon was established, and this patient also had the most benign clinical course of the four patients, without the development of pouchitis 2 years after IPAA.ConclusionsThe microbiota that inhabit the ileal-anal pouch of patients who undergo IPAA for treatment of ulcerative colitis demonstrate significant structural and functional changes related to the restoration of fecal flow. Our preliminary results suggest once the pouch has assumed the physiologic role previously played by the intact colon, the precise structure and function of the pouch microbiome, relative to a normal colonic microbiota, will determine if there is establishment of a stable, healthy mucosal environment or the reinitiation of the pathogenic cascade that results in intestinal inflammation.

Co-management Between Hospitalist and Hepatologist Improves the Quality of Care of Inpatients With Chronic Liver Disease

Background and Goals: Our institution shifted the care of patients with chronic liver disease (CLD) from Internal Medicine faculty, house staff, and consulting hepatology service to a co-managed unit staffed by academic hospitalists and hepatologists. The effect of co-management between hospitalists and hepatologists on the care of patients hospitalized with complications of CLD such as spontaneous bacterial peritonitis (SBP) is unknown. Study: A retrospective chart review of 56 adult patients admitted with CLD and SBP from July 1, 2004 to June 30, 2010 was performed. Adherence rates to current management guidelines were measured along with costs and outcomes of care. Results: Patients admitted under the 2 models of care were similar; however, they consistently underwent paracentesis within 24 hours (100% vs. 79%, P=0.013), had appropriate avoidance of fresh-frozen plasma use (75% vs. 43%, P=0.05), received albumin (97% vs. 65%, P=0.002), and were discharged on SBP prophylaxis (91% vs. 37%, P<0.001) under the co-managed model compared with the conventional model. Costs of care were similar between the 2 groups. We note a trend toward improved outcomes of care under the co-management model as measured by transfer rates to the intensive care unit, inpatient mortality, 30-day readmission, and mortality rates. Conclusions: These results support co-management between hospitalists and hepatologists as a superior model of care for hospitalized patients with SBP. Furthermore, this study adds to the growing literature indicating that efforts are needed to improve the quality of care delivered to CLD patients.

Persistent spontaneous bacterial peritonitis: a common complication in patients with spontaneous bacterial peritonitis and a high score in the model for end-stage liver disease

Objectives: Spontaneous bacterial peritonitis (SBP) is associated with a high mortality rate. After antibiotic therapy, improvement in fluid polymorphonuclear (PMN) cell count is expected within 2 days. However, our institution recognized cases unresponsive to standard treatment. Methods: To study these recalcitrant cases, we completed a retrospective chart review of patients admitted for SBP to the University of Chicago from 2002 to 2007. SBP was defined by an ascitic PMN cell count ≥250/ml. Results: Of 55 patients with SBP, 15 did not show improvement in fluid PMN cell count to below 250/ml with standard treatment, leading to a prevalence of 27%. The patients with persistent SBP were younger than those with nonpersistent SBP [mean (SD) 51.80 (9.84) compared with 58.13 (8.79); p = 0.0253]. Persistent SBP had a higher serum ascites albumin gradient (SAAG) [median (Q1, Q3) 1.85 (1.50, 2.41) compared with 1.10 (0.60, 1.60)] and a higher score in the model for end-stage liver disease (MELD) [mean (SD) 27.98 (8.09) compared with 22.22 (8.10)] than nonpersistent SBP patients; p = 0.027 and p = 0.023, respectively. In addition, persistent SBP patients were more likely to have a positive ascitic fluid culture than nonpersistent SBP patients [odds ratio (OR) (95% CI) 4.33 (1.21, 15.47); p = 0.024]. Importantly, in-hospital mortality in the persistent SBP group was 40%, compared with 22.5% in the nonpersistent SBP group [OR = 2.30 (0.64, 8.19); p = 0.20]. Conclusions: The risk of persistent SBP is nearly 40% in patients with MELD score >25, SAAG >1.5 or positive ascitic fluid culture. Furthermore, patients who develop persistent SBP tend to experience a higher mortality rate. This study underscores the importance of further examination of this vulnerable population.

Risk Factors for Inadequate Colonoscopy Bowel Preparations in African Americans and Whites at an Urban Medical Center

Objectives Poor bowel preparation leads to inadequate examinations and shorter surveillance intervals for colorectal cancer screening. Previous studies regarding risk factors for inadequate preparation have not included large numbers of African Americans. Our aim was to determine the prevalence of inadequate bowel preparation on initial and follow-up colonoscopy in a large, racially diverse patient population. Methods Colonoscopies performed during a 1-year period were analyzed retrospectively. Factors including age, sex, race, and start time were recorded. Patient ZIP codes were linked to census data to estimate education and income. For examinations with inadequate bowel preparations, we collected data on recommendations and the preparation quality of follow-up procedures. Results We included 3741 patients (40.2% African American). Of these, 66.9% had adequate bowel preparation and 33.1% had inadequate bowel preparation. African Americans had the highest prevalence of inadequate preparations at 43.0%. African American race was a predictor of inadequate bowel preparation, despite controlling for education and income. Age, male sex, and procedure taking place after 12 PM also were risk factors for inadequate preparation. Receipt of specific preparation instructions on the endoscopy report did not affect preparation quality on follow-up examination. Our study found a high rate (33.1%) of inadequate bowel preparations, and African American race was found to be an independent risk factor for inadequate preparation. We validated previously reported risk factors including age, male sex, and later procedure time. Finally, we noted high rates of inadequate preparation on follow-up examinations. Conclusions Improving the quality of colonoscopy bowel preparation is important for colorectal cancer prevention, especially in high-risk populations such as African Americans.

Workforce in hepatology: Update and a critical need for more information

The field of hepatology has experienced dramatic changes since the last workforce study in hepatology over 15 years ago. Hepatology practice has been dominated by hepatitis C but is now being overtaken by patients with nonalcoholic fatty liver disease. Expertise once attainable only through informal training, hepatology now has an accredited fellowship pathway and is recognized as a distinct discipline from gastroenterology with its own board certification. These changes that have occurred since the last workforce study in the prevalence and therapy of liver diseases and training may impact workforce needs. The time has come to conduct an updated analysis of the state of the hepatology workforce. The purpose of this article is to discuss the current issues facing training and workforce in hepatology and propose the next steps in conducting a workforce study. (Hepatology 2017;65:336‐340).

When Should Patients with Bleeding Esophageal Varices Undergo TIPS Versus Endoscopic Therapy

Acute variceal bleeding is a serious sequela of cirrhosis and portal hypertension, which carries significant morbidity and mortality. Advances in therapeutic techniques as well as accessibility and overall safety of esophagogastroduodenoscopy (EGD) allowed for endoscopic management to emerge as first line therapy two decades ago, and remain first-line therapy today. Transjugular intrahepatic portosystemic shunt (TIPS) is a critical rescue therapy for those that fail endoscopic management, while rescue TIPS carries significant morbidity and mortality, efforts to identify patients that are likely to fail endoscopy and benefit from early TIPS are ongoing. Surgical portosystemic shunts, particularly distal splenorenal shunt, can be considered for refractory bleeding in ideal patients with minimal comorbidities, where surgeon experience is adequate and TIPS cannot be performed.

Early and Severe Radiation Esophagitis Associated With Concurrent Sirolimus.

Case Report A 30-year-old man presented with a history of progressive shortness of breath for 3 months and fevers and right-sided chest pain for 2 weeks. The patient’s oncologic history was significant for a neuroblastoma at age 6 years that was treated with right nephrectomy, high-dose chemotherapy, 12 Gy total-body irradiation, and autologous stem-cell transplantation. Five years later, he was diagnosed with hepatitis C that was attributed to blood transfusions. Despite treatment with several interferon-based therapies, the hepatitis C persisted and progressed to cirrhosis. This was later complicated by hepatocellular carcinoma (HCC) and end-stage liver disease, for which the patient underwent an orthotopic liver transplantation. He began receiving tacrolimus, a calcineurin inhibitor, for immunosuppression, and surveillance abdominal imaging for the next 5 years was negative for HCC recurrence. The patient subsequently presented with shortness of breath, fevers, and right-sided chest pain. Computed tomography demonstrated a new mediastinal mass and large right-sided pleural effusion. Bronchoscopy with transbronchial fine-needle aspiration of a right paratracheal lymph node showed necrotic cells that were consistent with carcinoma. Sternotomy revealed a retrocaval mass adherent to the superior vena cava, precluding curative resection. Biopsy yielded cytokeratin CAM 5.2–positive necrotic cells. Given the history of HCC and elevated -fetoprotein, these findings were consistent with metastatic HCC. Sorafenib was started, but development of a total-body rash required discontinuation. Because of neutropenia, the patient was not considered a candidate for chemotherapy. The immunosuppression was then changed to the mTOR inhibitor sirolimus at a dose of 1 mg orally once per day and 2 mg orally once every other day to take advantage of its antineoplastic benefits. However, repeat imaging demonstrated progressive mediastinal disease with mass effect on the left brachiocephalic vein. Given the concern with respect to superior vena cava syndrome, the patient elected to proceed with a course of aggressive palliative RT. Sixty Gy in 2-Gy fractions using three-dimensional conformal RT with 6 megavoltage (MV) photon beams was prescribed. Segments and wedges were used to spare critical structures. To adequately cover the target volume, the esophagus (shown in medium blue in Fig 1A) was included in the planning target volume (red color wash) and the 100% isodose line (red). The esophageal mean dose was 19.2 Gy, maximum dose was 62.8 Gy, and volume receiving 60 Gy (V60) was 4.7% (1.1 cm). After receiving 6 Gy, the patient reported symptoms of heartburn. Famotidine 20 mg orally was increased to twice per day. At 16 Gy, the patient reported mild odynophagia, which was consistent with acute grade 1 esophageal toxicity. He was prescribed 10 mL of sucralfate suspension (100 mg/mL) 1 hour before meals and before bedtime, 10 mL of 1:1:1 viscous lidocaine 2%/liquid Maalox (Novartis, Summit, NJ)/diphenhydramine elixir every 6 hours as needed, and pantoprazole 40 mg orally once per day. After receiving 22 Gy, the patient developed severe retrosternal chest pain when swallowing that was consistent with acute grade 3 esophagitis. He was prescribed oxycodone 5 mg orally as needed every 4 to 6 hours and 10 mL of nystatin swish and swallow (100,000 U/mL) four times per day. His symptoms