Do Patients With NASH-related Cirrhosis Have Better Overall Survival Compared With Other Etiologies of Cirrhosis? A Population-based Study.

GOALS AND BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. We aim to explore the clinical outcomes of NASH cirrhosis compared with other etiologies of cirrhosis. METHODS: We utilized an EHR-based database (TriNetX) to study the outcomes of NASH cirrhosis. Patients diagnosed with NAFLD or NASH and cirrhosis between January 2016 and December 2019 were identified utilizing appropriate ICD-10-CM codes. The primary outcome was 3-year overall survival. Secondary outcomes were decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation. The Control group was patients with other etiologies of cirrhosis than NASH. Study and control groups were matched for demographic characters and comorbidities using propensity score matching. RESULTS: We identified 45,063 patients with NASH cirrhosis. The NASH cirrhosis cohort comprised older (61 vs. 59 y) White (78% vs. 64%) women (58% vs. 38%) with more comorbidities (diabetes mellitus, obesity, ischemic heart disease, history of cancer, chronic kidney disease). After propensity score matching, patients with NASH cirrhosis had a better 3-year survival (78% vs. 74%, HR 0.79, 95% CI 0.77-0.82) compared with patients with non-NASH cirrhosis. Hepatocellular carcinoma was diagnosed less commonly in patients with NASH cirrhosis (6.7% vs. 10.6%, P<0.001), and liver transplantation was performed more often for NASH cirrhosis compared with non-NASH cirrhosis [Risk ratio 1.13 (1.08-1.18)]. CONCLUSIONS: Patients with NASH cirrhosis probably have better 3-year overall survival than other etiologies of cirrhosis. This is an interesting finding, as patients with NASH are older and have more comorbidities. Improved survival can be partly explained by a higher probability of liver transplantation and improvements in cardiovascular outcomes.

Cytomegalovirus Proctitis in a Patient with Chronic Lymphocytic Leukemia on Ibrutinib Therapy: A Case Report.

Ibrutinib is a Bruton tyrosine kinase (BTK) inhibitor that has shown significant efficacy in patients with lymphoid carcinomas, mostly chronic lymphocytic leukemia (CLL). Cytomegalovirus (CMV) infection is not a common infectious complication associated with ibrutinib. To increase the clinical awareness about this rare entity, we present the first case of CMV proctitis in an immunocompromised host who was being treated with ibrutinib. An 88-year old female with a history of CLL treated with ibrutinib presented with two days of painless hematochezia. Physical examination revealed cachexia and temporal wasting; bright red blood was observed on the digital rectal examination. A complete blood count demonstrated a significant decrease in hemoglobin from her baseline. Subsequent colonoscopy revealed a circumferential rectal ulcer; biopsy of the rectal ulcer was positive for CMV immunostain. The patient was treated with intravenous ganciclovir and later transitioned to valganciclovir for a total of 21 days of treatment. Her condition resolved, and she was found doing well at the follow-up visit.

Universal Index for Cirrhosis (UIC index): The development and validation of a novel index to predict advanced liver disease.

AIM: The purpose of this study was to create and validate a novel serological diagnostic index to predict cirrhosis of all etiologies. METHODS: This was a retrospective observational study of 771 patients, age >18 years, who underwent a liver biopsy. The stage of fibrosis and routine laboratory values were recorded. The data were randomly separated into 2 datasets (training 50% and testing 50%). A stepwise logistic regression model was used to develop the novel index. The area under the curve of receiver operating characteristic (AUROC) was applied to compare the new index to existing ones (Fibro-Q, FIB4, APRI, AAR), which was also validated in the testing dataset. RESULTS: Variables associated with the presence of cirrhosis were first assessed by univariate analysis then by multivariable analysis, which indicated serum glutamic-oxaloacetic acid transaminase, serum glutamic-pyruvic transaminase, international normalized ratio, albumin, blood urea nitrogen, glucose, platelet count, total protein, age, and race were the independent predictors of cirrhosis (P<0.05). Regression formula for prediction of cirrhosis was generated and a novel index was subsequently created. The diagnostic performance of the novel index for predicting cirrhosis was assessed using the receiver operating characteristic curve. The new index had significantly higher AUROC (0.83, 95% CI: 0.79-0.87) than Fibro-Q (0.80, 95% CI: 0.76-0.85), FIB4 (0.79, 95% CI: 0.74-0.83), APRI (0.74, 95% CI: 0.69-0.78), and AAR (0.72, 95% CI: 0.67-0.78). CONCLUSION: The novel index had the highest AUROC curve when compared with current indices and can be applied to all etiologies of chronic liver disease.

Liver function tests in identifying patients with liver disease.

BACKGROUND AND AIMS: Many patients with liver disease come to medical attention once they have advanced cirrhosis or acute decompensation. Most often, patients are screened for liver disease via liver function tests (LFTs). There is very limited published data evaluating laboratory values with biopsy-proven stages of hepatic fibrosis. We set out to evaluate whether any correlation exists between routine LFTs and stages of hepatic fibrosis. METHODS: A large retrospective observational study on 771 liver biopsies was conducted for evaluating the stage of fibrosis with AST, ALT, INR, BUN, creatinine, platelets, alkaline phosphatase, bilirubin, and albumin. Mean and 95% confidence intervals were used to describe the distributions of serum markers in different fibrosis stages. Multivariable generalized linear models were used and a two-tailed P-value was calculated. RESULTS: ALT was not statistically significant for any stage, and AST was statistically significant for stage 3 and 4 fibrosis. INR was statistically significant only in stage 4 disease but remained near the upper limit of normal range. Albumin failed to show a clinically relevant association. Platelets remained within normal laboratory range for all stages. The remaining laboratory values failed to show statistical and clinical significance. CONCLUSION: The health care burden from chronic liver disease (CLD) will likely continue to rise, unless clinicians are made aware that normal or near normal laboratory findings may be seen in asymptomatic patients. Earlier identification of asymptomatic patients will allow for treatment with new promising modalities and decrease morbidity and mortality from CLD. Our study shows that laboratory values correlate poorly with liver disease.

Seroconverting nonresponder of high-dose intramuscular HBV vaccine with intradermal HBV vaccine: A case report.

INTRODUCTION: Liver disease is a leading cause of death among human immunodeficiency virus (HIV)-infected patients in the United States. Patients with HIV and hepatitis B virus (HBV) coinfection have accelerated liver disease, higher rates of cirrhosis, and liver cancer, and markedly increased liver-related mortality. The CDC and US Advisory Committee on Immunization Practices recommend hepatitis B vaccination for all HIV-infected individuals. Unfortunately, HIV-infected patients have a worse response rate after standard HBV vaccination. Intradermal (ID) vaccination continues to emerge as an important modality in such difficult to vaccinate individuals and should be considered whenever permissible. Herein, we report a case of a 46-year-old male with HIV who failed to mount an immune response to standard intramuscular vaccine, standard booster dose, and repeat high-dose booster vaccine but subsequently mounted an immune response to the ID vaccine which was sustained at 3 months postvaccination. CONCLUSION: ID vaccination continues to emerge as an important modality in difficult to vaccinate individuals and should be considered in all applicable cases.

Treatment of orofacial granulomatosis: a case report.

BACKGROUND: Orofacial granulomatosis is a relatively recent term coined by Wiesenfield et al. in 1985 to define granulomatous lesions of oral mucosa without intestinal involvement. When it presents in a triad encompassing facial nerve palsy, lip swelling, and fissured or furrowed tongue it is called Melkersson-Rosenthal syndrome while monosymptomatic or oligosymptomatic forms are referred to as granulomatous cheilitis. It is an uncommon clinicopathologic entity which is distinct from classic Crohn's disease. The NOD2 variant which is commonly associated with Crohn's has not been shown to have any association with orofacial granulomatosis. CASE PRESENTATION: We present a case of a 31-year-old white man who had painful swelling of the lip with oral ulcers and difficulty eating for 2 to 3 years. He was diagnosed as having granulomatous cheilitis based on characteristic biopsy findings. There was serologic evidence of Crohn's disease with anti-Saccharomyces cerevisiae antibodies. However, he was not found to have any gastrointestinal involvement based on computed tomography enterography, and upper and lower endoscopies. He failed to respond to nonsteroidal anti-inflammatory drugs, steroids, and dapsone therapy but responded well to high doses of infliximab. CONCLUSIONS: Our case questions whether granulomatous cheilitis really exists or is it simply a variant of Crohn's disease with only oral presentation. Our patient did not have symptoms of Crohn's disease; moreover, endoscopic studies and computed tomography enterography were unremarkable for evidence of intestinal involvement. Our case is also the first reported case where high-dose infliximab alone has been used with sustained response for approximately 8 months. In conclusion, more research is needed to assess the underlying pathology as well as ideal treatment options for patients with orofacial granulomatosis. We propose that high-dose infliximab should be considered in patients who do not respond to traditional therapies.

Drug-induced dyspnea versus cystic fibrosis exacerbation: a diagnostic dilemma.

Cystic fibrosis (CF) is a disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator protein in the epithelial membrane, and affects at least 30,000 people in the USA. There are between 900 and 1000 new cases diagnosed every year. Traditionally, CF has been treated symptomatically with pancreatic enzymes, bronchodilators, hypertonic saline, and pulmozyme. In July 2015, the US Food and Drug Administration approved Orkambi (lumacaftor/ivacaftor), a combination drug that works on reversing the effects of the defective cystic fibrosis transmembrane conductance regulator protein. Orkambi and mucolytics decrease the viscosity of mucous secretions, leading to an accumulation of hypoviscous fluid in the alveoli, resulting in dyspnea. This presentation can be mistaken for an infective exacerbation. We present a case in which a young female with CF recently started on Orkambi therapy presented to her primary care physician with dyspnea and increased respiratory secretions and was admitted to the hospital for 2 weeks of intravenous and inhaled antibiotic therapy for a presumed CF exacerbation. We highlight this case to bring awareness and educate patients and clinicians of the side-effect profile of Orkambi therapy with an intent to avoid unnecessary hospitalizations, inpatient antibiotics, and other costly medical services.

Are self-expandable metal stents superior to plastic stents in palliating malignant distal biliary strictures? A meta-analysis and systematic review.

BACKGROUND: Palliation for inoperable malignant distal biliary strictures can be achieved with self-expandable metal stents (SEMS) and plastic stents (PS). This is a meta-analysis to compare PS and SEMS. The aim of the study is to compare clinical outcomes in patients with SEMS and PS. METHODS: Study selection criteria were studied using SEMS and PS for palliation in patients with malignant distal biliary stricture. For data collection and extraction, articles were searched in Ovid journals, Medline, Cochrane database, and Pubmed. Pooled proportions were calculated using both Mantel-Haenszel method and DerSimonian Laird method for statistical analysis. RESULTS: Initial search identified 1376 reference articles, of which 112 were selected and11 studies (N = 947) were included in this analysis. Pooled analysis showed SEMS patency to be 167.7days (95% CI = 159.2-176.3) compared to 73.3days (95% CI = 69.8-76.9) in PS. SEMS have lower odds of occlusion when compared to PS with an odds ratio of 0.48 (95% CI = 0.34-0.67). SEMS has a lower odds of cholangitis compared to SP, with an odds ratio of 0.46 (95% CI = 0.30-0.69). CONCLUSION: SEMS seem to be superior to PS with better patency periods and survival duration. SEMS have lower occlusion rates, re-intervention rates, and cholangitis.

An Unusual Cause of Acute Upper Gastrointestinal Bleeding: Acute Esophageal Necrosis.

Acute esophageal necrosis (AEN), also called "black esophagus," is a condition characterized by circumferential necrosis of the esophagus with universal distal involvement and variable proximal extension with clear demarcation at the gastroesophageal junction. It is an unusual cause of upper gastrointestinal bleeding and is recognized with distinct and striking mucosal findings on endoscopy. The patients are usually older and are critically ill with shared comorbidities, which include atherosclerotic cardiovascular disease, diabetes mellitus, hypertension, chronic renal insufficiency, and malnutrition. Alcoholism and substance abuse could be seen in younger patients. Patients usually have systemic hypotension along with upper abdominal pain in the background of clinical presentation of hematemesis and melena. The endoscopic findings confirm the diagnosis and biopsy is not always necessary unless clinically indicated in atypical presentations. Herein we present two cases with distinct clinical presentation and discuss the endoscopic findings along with a review of the published literature on the management of AEN.

Covered versus uncovered self-expandable metal stents for malignant biliary strictures: A meta-analysis and systematic review.

Self-expandable metal stents (SEMS) are used for palliating inoperable malignant biliary strictures. It is unclear if covered metal stents are superior to uncovered metal stents in these patients. We compared clinical outcomes in patients with covered and uncovered stents. Studies using covered and uncovered metallic stents for palliation in patients with malignant biliary stricture were reviewed. Articles were searched in MEDLINE, PubMed, and Ovid journals. Fixed and random effects models were used to calculate the pooled proportions. Initial search identified 1436 reference articles, of which 132 were selected and reviewed. Thirteen studies (n = 2239) for covered and uncovered metallic stents which met the inclusion criteria were included in this analysis. Odds ratio for stent occlusion rates in covered vs. uncovered stents was 0.79 (95 % CI = 0.65 to 0.96). Survival benefit in patients with covered vs. uncovered stents showed the odds ratio to be 1.29 (95 % CI = 0.95 to 1.74). Pooled odds ratio for migration of covered vs. uncovered stents was 9.9 (95 % CI = 4.5 to 22.3). Covered stents seemed to have significantly lesser occlusion rates, increased odds of migration, and increased odds of pancreatitis compared to uncovered stents. There was no statistically significant difference in the survival benefit, overall adverse event rate, and patency period of covered vs. uncovered metal stents in patients with malignant biliary strictures.

Bile cast nephropathy: A case report and review of the literature.

Bile cast nephropathy is a condition of renal dysfunction in the setting of hyperbilirubinemia. There are very few cases of this condition reported in the last decade and a lack of established treatment guidelines. While the exact etiology remains unknown, bile cast nephropathy is presumed to be secondary to multiple concurrent insults to the kidney including direct toxicity from bile acids, obstructive physiology from bile casts, and systemic hypoperfusion from vasodilation. Therapy directed at bilirubin reduction may improve renal function, but will likely need dialysis or plasmapheresis as well. We report our case of bile cast nephropathy and the therapeutic measures undertaken in a middle-aged male with chronic renal insufficiency that developed hyperbilirubinemia and drug-induced liver injury secondary to antibiotic use. He developed acute renal injury in the setting of rising bilirubin. He subsequently had a progressive decline in renal and hepatic function, requiring dialysis and plasmapheresis with some improvement, ultimately requiring transplantation.

Impact of bowel preparation type on the quality of colonoscopy: a multicenter community-based study.

BACKGROUND: High-quality bowel preparation is crucial for achieving the goals of colonoscopy. However, choosing a bowel preparation in clinical practice can be challenging because of the many formulations. This study aims to assess the impact the type of bowel preparation on the quality of colonoscopy in a community hospital setting. METHODS: A retrospective, observational study was conducted utilizing a colonoscopy screening/surveillance database in central Illinois during the period of January 1, 2010, to March 31, 2014. Patients without bowel preparation assessment were excluded from this study. Controlling for the confounders, generalized linear models were used to estimate the adjusted impact [odds ratio (OR)] of bowel preparation type on the quality of preparation (excellent, good, fair, and poor), and on the detection of advanced adenoma. The association between the time of withdrawal after insertion and the quality of preparation was also examined using a linear model. RESULTS: A total of 28,368 colonoscopies; half the patients were male, and the average age was 61±9 years. Polyethylene glycol (PEG) was used in the majority (70.2%) of bowel preparations, followed by sodium sulfate (21.4%), sodium phosphate (2.5%), magnesium sulfate (0.4%), and others. Compared with PEG, magnesium sulfate had a poorer quality of bowel preparations (OR=0.6, 95% CI 0.4-0.9; p<0.05), whereas the quality of bowel preparation was significantly improved by using sodium sulfate (OR=5.7, 95% CI 5.4-6.1; p<0.001) and sodium phosphate (OR=2.1, 95% CI 1.8-2.5; p<0.001). For those who had adequate bowel preparation, the better quality of preparation significantly increased the detection rate of advanced adenoma (5.0, 3.6, and 2.9% for excellent, good, and fair, respectively). CONCLUSION: When possible, sodium sulfate-based preparations should be recommended in the community setting for colonoscopy because of their high quality of bowel preparation.

Irritable Bowel Syndrome: A Clinical Review.

Symptoms of irritable bowel syndrome (IBS) are common in population studies including chronic abdominal pain associated with altered bowel habits. Patients often have associated gastrointestinal and somatic symptoms suggesting a possible common contributing mechanism, but the heterogeneous symptom patterns of individual patients make generalizations difficult. The pathophysiology of IBS is incompletely understood but includes disturbances of the brain-gut axis. Central mechanisms are: the psychosocial history and environment, dysfunctional brain processing of peripheral signals attributed to the intestine including the enteric nervous system, the microbiome and the innate and adaptive immune system. As a result there is visceral hypersensitivity and disturbed intestinal secretory and motor activity. Some mechanisms of visceral pain hypersensitivity may overlap with other pain syndromes including fibromyalgia (FMS). Central Sensitization (CS) would offer a way to conceptualize an integration of life experience and psychologic response into a biopsychosocial framework of pathophysiology, diagnosis and treatment of IBS. Corticotropin-releasing factor, a principle regulator in the stress and pain response may contribute to a neuroendocrine mechanism for the brain-gut interaction. The positive diagnostic approach to IBS symptoms to avoid excess testing and enhance the patient-provider therapeutic relationship requires the recognition of the "cluster" of IBS symptoms while identifying "alarm" symptoms requiring specific attention. The severity of the symptoms and other individual psychosocial factors characterize patients who seek medical care. The presence of significant psychosocial comorbidities adds to the complexity of management which often requires a multidisciplinary approach. Several treatment options exist but no single method is effective for all the symptoms of IBS. The therapeutic benefit of the well-executed physician-patient relationship is considered essential to success in managing IBS symptoms over the long term.

Recent advances in vaccination of non-responders to standard dose hepatitis B virus vaccine.

Hepatitis B virus (HBV) infection is a global health problem. It is estimated there are more than 2 billion individuals exposed to the virus and 250 million are chronically infected. Hepatitis B is the cause of more than 600000 annual deaths due to cirrhosis and hepatocellular carcinoma. An effective vaccine exists and preventative initiatives center around universal vaccination especially in those at highest risk. Effective vaccination algorithms have led to a significant decline in the development of new infections and its devastating consequences. The vaccine is administered intramuscularly in three doses, with 95% showing long lasting serologic immunity. An additional fourth dose or a repeated higher dose three course regimen is given to those that fail to show immunity. Despite these additional regimens, some remain vulnerable to hepatitis B and are deemed non-responders. Individuals with chronic disease states such as kidney disease, liver disease, diabetes mellitus, as well as those with a genetic predisposition, and those on immunomodulation therapy, have the highest likelihood of non-response. Various strategies have been developed to elicit an immune response in these individuals. These include increased vaccination dose, intradermal administration, alternative adjuvants, alternative routes of administration, co-administration with other vaccines, and other novel therapies. These alternative strategies can show improved response and lasting immunity. In summary, HBV vaccination is a major advance of modern medicine and all individuals at risk should be sought and vaccinated with subsequent adequate titers demonstrated.

Bilateral and unilateral stenting for malignant hilar obstruction: a systematic review and meta-analysis.

BACKGROUND: Stents are used for palliating inoperable malignant bile duct hilar obstruction. It is not clear if bilateral stenting provides any advantage over unilateral stenting in these patients. Compare bilateral and unilateral stenting in malignant hilar obstruction. STUDY SELECTION CRITERIA: Studies using stents for palliation in patients with malignant hilar obstruction were selected. DATA COLLECTION AND EXTRACTION: Articles were searched in MEDLINE, PubMed, Ovid journals, CINAH, International Pharmaceutical Abstracts, OLDMEDLINE, MEDLINE nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Two reviewers independently searched and extracted data. Any differences were resolved by mutual agreement. STATISTICAL METHODS: Pooled proportions were calculated using both the Mantel-Haenszel method (fixed effects model) and DerSimonian-Laird method (random effects model). The heterogeneity among studies was tested using Cochran's Q test based upon inverse variance weights. The initial search identified 1,640 reference articles, of which 169 were selected and reviewed. Thirteen studies (n = 340) for bilateral metallic stents, eight studies (n = 575) for unilateral metallic stents, eight studies (n = 367) for bilateral plastic stenting, and seven studies (n = 850) for unilateral plastic stenting which met the inclusion criteria were included in this analysis. Pooled data are shown in Tables 1 and 2. The pooled estimates by the fixed and random effect models were similar. The p for chi-squared heterogeneity for all the pooled accuracy estimates was >0.10. Bilateral metal stenting seems to have lower odds of overall complications when compared to unilateral metallic stenting. Bilateral metal stents seem to have higher odds of lowering bilirubin than unilateral metal stents, but the 30-day mortality was no different. For metal stents, bilateral metal stents are superior in palliating symptoms due to hyperbilirubinemia. Unilateral plastic stenting seems to have similar odds of overall complications, cholangitis, and 30-day mortality when compared to bilateral plastic stenting for malignant hilar strictures. In patients with malignant hilar stricture, unilateral plastic stenting is comparable to bilateral plastic stenting for adverse events.

Irreversible pulmonary hypertension associated with the use of interferon alpha for chronic hepatitis C.

The interferons are a complex group of virally induced proteins produced by activated macrophages and lymphocytes, which have become the mainstay of therapy for hepatitis C infection. Sustained viral response (SVR) rates in noncirrhotic patients vary from 40-80% with interferon-based therapy. This, along with transplantation, has drastically changed the course of hepatitis C virus (HCV) infection over the last two decades. Numerous side effects associated with interferon therapy have been reported. These range from transient flu-like symptoms to serious effects such as cardiac arrhythmias, cardiomyopathy, renal and liver failure, polyneuropathy, and myelosuppression. Pulmonary side effects including pneumonitis, pulmonary fibrosis, and reversible pulmonary hypertension have been reported. Herein, we present four cases in which irreversible pulmonary hypertension was diagnosed after prolonged treatment with interferon alpha. In each case, other causes of pulmonary hypertension were systematically eliminated. Pulmonary artery hypertension, which may be irreversible, should be considered in patients being treated with interferon alpha who present with exertional dyspnea and do not have a readily identifiable inflammatory or thromboembolic cause.