Accuracy of Noninvasive Fibrosis Scores in Predicting the Presence of Fibrosis in Patients after Liver Transplantation.

OBJECTIVES: Several scoring systems have been developed to noninvasively predict the presence of advanced fibrosis in patients with chronic liver disease. Hepatitis C virus and nonalcoholic fatty liver disease are the 2 most common indications for orthotopic liver transplant and are associated with disease recurrence that can lead to fibrosis progression. Here, we evaluated the performance of commonly used fibrosis scores in assessing the presence of advanced fibrosis in patients after orthotopic liver transplant. MATERIALS AND METHODS: Our study consisted of consecutive patients with hepatitis C virus or nonalcoholic fatty liver disease who underwent a liver biopsy after transplant and had laboratory measurements within 1 week of biopsy. Graft fibrosis was determined by an experienced pathologist (stage F0-F4). Advanced fibrosis was defined as stage F3-F4. The following fibrosis scores were calculated for each patient: aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase/platelet ratio index, and fibrosis-4 index. RESULTS: We analyzed 93 patients with median age of 59 years (25th and 75th percentile of 53 and 64 y) and median body mass index of 31.8 kg/m² (25th and 75th percentile of 27 and 37.6 kg/m²). Of total patients, 41 (44%) were diabetic. Median time to liver biopsy posttransplant was 27.7 months (25th and 75 percentile of 10.8 and 59.9 mo). We found that 54 patients (58%) had no fibrosis, 15 (16.1%) had F1, 8 (8.6%) had F2, 7 (7.5%) had F3, and 9 (9.7%) had F4. Overall, advanced fibrosis (F3-F4) was present in 16 patients. Aspartate aminotransferase/alanine amino-transferase ratio, aspartate aminotransferase/platelet ratio index, and fibrosis-4 index were not significantly different between patients with and without advanced fibrosis (all P > .05). The calculated fibrosis scores had poor diagnostic accuracy for presence of advanced fibrosis posttransplant. CONCLUSIONS: Commonly used liver fibrosis scores are not accurate in predicting the presence of advanced fibrosis in patients after liver transplant.

Histology and Glutamine Synthetase Immunoreactivity in Liver Biopsies From Patients With Congestive Heart Failure.

BACKGROUND: Long-standing congestive heart failure can induce a constellation of histopathology changes in the liver that can range from mild sinusoidal dilation to advanced fibrosis and loss of normal perivenular expression of glutamine synthetase (GS). Liver biopsies might be performed to assess the perioperative risk of these patients or to determine the need of synchronous liver transplant. We aimed to assess interobserver agreement in recognizing these liver histologic features in patients undergoing evaluation for heart transplantation and to examine whether immunohistochemistry of GS will aid the diagnosis of cardiac hepatopathy (CH). METHODS: Hematoxylin-eosin and trichrome-stained slides from 36 liver biopsies from patients undergoing evaluation for heart transplantation were reviewed by four liver pathologists. Histologic features of CH were reviewed and an overall fibrosis (stage) was assessed according to a recently proposed congestive hepatic fibrosis score (CHFS). In addition, 24 liver biopsies with a consensus diagnosis of CH and eight liver biopsies with no significant pathological changes were subjected to immunohistochemistry for GS. The Fleiss' kappa coefficient (K) analysis was performed to determine the interobserver agreement. Further, histologic features of CH were correlated with the staining pattern of GS. RESULTS: Sinusoidal dilation, centrilobular hepatocyte atrophy, centrilobular fibrosis and hemorrhage were the most common findings in this cohort with a substantial-to-fair level of interobserver agreement among four reviewers. The overall agreement on the diagnosis of CH and CHFS was moderate (K = 0.55, 95% confidence interval (CI): 0.32 - 0.73) and fair (K = 0.35, 95% CI: 0.24 - 0.49), respectively. Twelve (of 24, 50%) cases of CH showed loss of the normal perivenular GS staining, while the remaining 12 cases of CH and all eight controls showed retained GS expression. Histologic features of CH (presence of sinusoidal dilation, centrilobular hepatocyte atrophy, hemorrhage, and centrilobular fibrosis) and the stage of fibrosis (CHFS) were not correlated with the loss of GS staining. CONCLUSION: Most common features of CH can be interpreted with fair-to-substantial level of agreement by liver pathologists, with an overall moderate level agreement for the diagnosis and fair agreement for CHFS. Loss of normal perivenular expression of GS only occurs in 50% CH and thus is not a sensitive marker for CH.

Update on the management of intestinal failure.

Intestinal failure is a serious complication of conditions such as inflammatory bowel disease, mesenteric ischemia, and radiation enteritis--and of extensive bowel resection performed because of these diseases. Imbalances of fluids and electrolytes and poor nutritional status manifest as chronic diarrhea or increased ostomy output. Prompt referral to a center specializing in intestinal rehabilitation is key to achieving nutritional homeostasis and, in some cases, can help the patient return to oral food intake. We review the intestinal sequelae of bowel resection and provide an update on intestinal rehabilitation with dietary modification, drug therapy, and parenteral nutrition. We also review current experience with intestinal transplant, a potentially lifesaving option in select patients when intestinal rehabilitation fails or parenteral nutrition causes severe complications.

Management of gastroparesis-associated malnutrition.

Gastroparesis (GP) is a chronic debilitating dysmotility characterized by unrelenting nausea, vomiting, bloating, early satiety, postprandial fullness and abdominal pain. Patients with GP experience other associated conditions, including gastroesophageal reflux disease, gastric bezoars and small bowel bacterial overgrowth. Furthermore, GP is associated with poor quality of life, increased emergency room visits, hospitalizations and subsequent increased healthcare costs. Currently, the managements of GP consist of glycemic control, antiemetics, prokinetics and the use of gastric electrical stimulation. However, most GP patients are at risk for significant nutritional abnormalities. As such, it is essential to screen and diagnose malnutrition in these patients. Poor oral intake in such patients could be supplemented by enteral tube feeding. Parenteral nutrition, although a last resort, is associated with a number of complications and should be used only for the short term. In summary, a systematic approach including initial nutritional screening, diet recommendations, medical therapy, nutritional re-evaluation and enteral and parental nutrition should be considered in complex GP patients.

Intestinal Failure: Adaptation, Rehabilitation, and Transplantation.

Intestinal failure (IF) is a state in which the nutritional demands are not met by the gastrointestinal absorptive surface. A majority of IF cases are associated with short-bowel syndrome, which is a result of malabsorption after significant intestinal resection for numerous reasons, some of which include Crohn's disease, vascular thrombosis, and radiation enteritis. IF can also be caused by obstruction, dysmotility, and congenital defects. Recognition and management of IF can be challenging, given the complex nature of this condition. This review discusses the management of IF with a focus on intestinal rehabilitation, parenteral nutrition, and transplantation.

Sofosbuvir-based treatment is safe and effective in patients with chronic hepatitis C infection and end stage renal disease: a case series.

BACKGROUND & AIMS: Interferon and ribavirin-free regimens to treat chronic hepatitis C virus (HCV) infection in patients with end stage renal disease are not approved and represent an area of unmet clinical need. We report our experience on the safety and efficacy of sofosbuvir/simeprevir and sofosbuvir/ledipasvir therapy in patients on haemodialysis. METHODS: Patients with chronic HCV infection on haemodialysis were included in this study. Patients were started on either sofosbuvir/simeprevir or sofosbuvir/ledipasvir. Routine clinical and laboratory data were collected at baseline and during treatment. The primary outcome was sustained virological response at week 12 (SVR12). RESULTS: Eight patients with mean age 56.8 ± 20 years were included in this study. Seven were treatment naïve and one was a priori null responder to interferon-based therapy. Four patients were started on sofosbuvir/simeprevir and four on sofosbuvir/ledipasvir for 12 weeks. Therapy was well tolerated overall with nausea/vomiting, pruritus, headache and a 2 g/dl drop in haemoglobin developing in one patient each. No patient discontinued therapy because of side effects. Comparison of labs at baseline and nadir levels during treatment revealed no significant change in haemoglobin (10.8 ± 2.4 g/dl vs 10.3 ± 1.6 g/dl), platelet count (198 ± 164 k/µl vs 184.5 ± 162/µl) and bilirubin (0.3 ± 0.4 mg/dl vs 0.25 ± 0.15 mg/dl). Eight of eight patients had undetectable HCV RNA at the end of treatment. One patient was lost to follow up and the remaining seven achieved SVR12. CONCLUSION: Full dose sofosbuvir/simeprevir or sofosbuvir/ledipasvir therapy for HCV-infected patients with end stage renal disease was well tolerated with no discontinuation owing to side effects and no significant adverse events.

The role of endoscopy in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a group of chronic immune-mediated disorders of the gastrointestinal tract. It is often the result of the interaction of genetic and environmental factors. The role of endoscopy in disease surveillance is unprecedented. However, there is considerable debate in therapeutic goals in IBD patients, ranging from the resolution of clinical symptoms to mucosal healing. Furthermore, deep remission has recently been advocated for altering disease course in these patients. Additionally, neoplasia continues to be a significant cause of morbidity and mortality in IBD patients. This review discussed the role of several endoscopic techniques in assessing mucosal healing and neoplasia with emphasis on novel non-invasive endoscopic techniques.

Clinical impact of alcohol-related cirrhosis in the next decade: estimates based on current epidemiological trends in the United States.

BACKGROUND: Identifying changes in the epidemiology of liver disease is critical for establishing healthcare priorities and allocating resources to develop therapies. The projected contribution of different etiologies toward development of cirrhosis in the United States was estimated based on current publications on epidemiological data and advances in therapy. Given the heterogeneity of published reports and the different perceptions that are not always reconcilable, a critical overview rather than a formal meta-analysis of the existing data and projections for the next decade was performed. METHODS: Data from the World Health Organization Global Status Report on Alcohol and Health of 2014, Scientific Registry of Transplant Recipients from 1999 to 2012, National Institute on Alcohol Abuse and Alcoholism, and the Centers for Disease Control and Prevention were inquired to determine future changes in the epidemiology of liver disease. RESULTS: Alcohol consumption has increased over the past 60 years. In 2010, transplant-related costs for liver recipients were the highest for hepatitis C (~$124 million) followed by alcohol-related cirrhosis (~$86 million). We anticipate a significant reduction in incidence cirrhosis due to causes other than alcohol because of the availability of high efficiency antiviral agents for hepatitis C, universal and effective vaccination for hepatitis B, relative stabilization of the obesity trends in the United States, and novel, potentially effective therapies for nonalcoholic steatohepatitis. The proportion of alcohol-related liver disease is therefore likely to increase in both the population as a whole and the liver transplant wait list. CONCLUSIONS: Alcohol-related cirrhosis and alcohol-related liver disorders will be the major cause of liver disease in the coming decades. There is an urgent need to allocate resources aimed toward understanding the pathogenesis of the disease and its complications so that effective therapies can be developed.

Efficacy of morning-only 4 liter sulfa free polyethylene glycol vs 2 liter polyethylene glycol with ascorbic acid for afternoon colonoscopy.

AIM: To compare the bowel cleansing efficacy of same day ingestion of 4-L sulfa-free polyethylene glycol (4-L SF-PEG) vs 2-L polyethylene glycol solution with ascorbic acid (2-L PEG + Asc) in patients undergoing afternoon colonoscopy. METHODS: 206 patients (mean age 56.7 years, 61% male) undergoing outpatient screening or surveillance colonoscopies were prospectively randomized to receive either 4-L SF-PEG (n = 104) or 2-L PEG + Asc solution (n = 102). Colonoscopies were performed by two blinded endoscopists. Bowel preparation was graded using the Ottawa scale. Each participant completed a satisfaction and side effect survey. RESULTS: There was no difference in patient demographics amongst groups. 4-L SF-PEG resulted in better Ottawa scores compared to 2-L PEG + Asc, 4.2 vs 4.9 (P = 0.0186); left colon: 1.33 vs 1.57 respectively (P = 0.0224), right colon: 1.38 vs 1.63 respectively (P = 0.0097). No difference in Ottawa scores was found for the mid colon or amount of fluid. Patient satisfaction was similar for both arms but those assigned to 4-L SF-PEG reported less bloating: 23.1% vs 11.5% (P = 0.0235). Overall polyp detection, adenomatous polyp and advanced adenoma detection rates were similar between the two groups. CONCLUSION: Morning only 4-L SF-PEG provided superior cleansing with less bloating as compared to 2-L PEG + Asc bowel preparation for afternoon colonoscopy. Thus, future studies evaluating efficacy of morning only preparation for afternoon colonoscopy should use 4-L SF-PEG as the standard comparator.

An Update on Treatment of Drug-Induced Liver Injury.

Drug-induced liver injury (DILI) has been linked to more than 1,000 medications and remains the most common cause of acute liver failure in the United States. Here, we review the most current literature regarding treatment and make recommendations for the management of this relatively common disease. Since treatment of DILI remains largely elusive, recent studies have attempted to define new management strategies for these difficult patients. Early diagnosis and withdrawal of the suspected medication is the mainstay of treatment of DILI. For acetaminophen and Amanita mushroom poisoning, there are specific therapies in use. Finally, there are other possible management modalities for DILI, including corticosteroids and ursodeoxycholic acid.

Role of high definition colonoscopy in colorectal adenomatous polyp detection.

AIM: To investigate the rates of polyp detection in a mixed risk population using standard definition (SDC) vs high definition colonoscopes (HDC). METHODS: This was a retrospective cohort comparative study of 3 colonoscopists who each consecutively performed 150 SDC (307, 200 pixel) and 150 HDC (792, 576 pixels) in a community teaching hospital. RESULTS: A total of 900 colonoscopies were evaluated (mean age 56, 46.8% men), 450 with each resolution. Polyps of any type were detected in 46.0% of patients using SDC and 43.3% with HDC (P = 0.42). There was no significant difference between the overall number of polyps, HDC (397) and SDC (410), detected among all patients examined, (P = 0.73). One or more adenomatous polyps were detected in 24.2% of patients with HDC and 24.9% of patients with SDC colonoscopy (P = 0.82). There was no significant difference between HDC (M = 0.41) and SDC (M = 0.42) regarding adenomatous polyp (P = 0.88) or advanced adenoma (P = 0.56) detection rate among all patients examined. CONCLUSION: HDC did not improve yield of adenomatous polyp, advanced adenoma or overall polyp detection in a population of individuals with mixed risk for colorectal cancer.