Drug-Induced Acute-on-Chronic Liver Failure in Asian Patients
American Journal of Gastroenterology. 114(6):929-937, June 2019.
Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF.
METHODS:
We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation.
RESULTS:
Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non–drug-induced ACLF (38.8%) ( P = 0.007). The Cox regression model identified arterial lactate ( P < 0.001) and total bilirubin ( P = 0.008) as predictors of mortality.
DISCUSSION:
Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.
- SDC
Home Biofeedback for the Treatment of Dyssynergic Defecation: Does It Improve Quality of Life and Is It Cost-Effective?
American Journal of Gastroenterology. 114(6):938-944, June 2019.
Biofeedback therapy, whether administered at home or in office settings, is effective for dyssynergic defecation (DD). Whether home biofeedback improves quality of life (QOL) and is cost-effective when compared with office biofeedback is unknown.
METHODS:
QOL was assessed in 8 domains (SF-36) at baseline and after treatment (3 months), alongside economic evaluation during a randomized controlled trial (RCT) comparing home and office biofeedback in patients with DD (Rome III). Costs related to both biofeedback programs were estimated from the hospital financial records, study questionnaires, and electronic medical records. A conversion algorithm (Brazier) was used to calculate the patient's quality-adjusted life years (QALYs) from SF-36 responses. Cost-effectiveness was expressed as incremental costs per QALY between the treatment arms.
RESULTS:
One hundred patients (96 female patients, 50 in each treatment arm) with DD participated. Six of the 8 QOL domains improved ( P < 0.05) in office biofeedback, whereas 4 of the 8 domains improved ( P < 0.05) in home biofeedback; home biofeedback was noninferior to office biofeedback. The median cost per patient was significantly lower ( P < 0.01) for home biofeedback ($1,112.39; interquartile range (IQR), $826–$1,430) than for office biofeedback ($1,943; IQR, $1,622–$2,369), resulting in a cost difference of $830.11 The median QALY gained during the trial was 0.03 for office biofeedback and 0.07 for home biofeedback ( P = NS). The incremental cost-effectiveness ratio was $20,752.75 in favor of home biofeedback.
Discussion:
Biofeedback therapy significantly improves QOL in patients with DD regardless of home or office setting. Home biofeedback is a cost-effective treatment option for DD compared with office biofeedback, and it offers the potential of treating many more patients in the community.
Cannabinoid Use in Patients With Gastroparesis and Related Disorders: Prevalence and Benefit
American Journal of Gastroenterology. 114(6):945-953, June 2019.
Gastroparesis (Gp) can be a challenging disorder to manage due to the paucity of treatment options. We do not know how frequently patients with Gp symptoms resort to cannabinoids to address their symptoms. This study (i) determines the prevalence of cannabinoid use in patients with Gp symptoms, (ii) describes the patients with Gp symptoms using cannabinoids, and (iii) assesses the patients' perceived benefit of cannabinoids for Gp symptoms.
METHODS:
Consecutive outpatients with symptoms suggestive of Gp seen on follow-up at our academic center from June 2018 to September 2018 filled out questionnaires on their symptoms and the current treatments.
RESULTS:
Of 197 patients, nearly half (n = 92, 46.7%) reported current (35.5%) or past (11.2%) use of cannabinoids, including tetrahydrocannabinol (n = 63), dronabinol (n = 36), and/or cannabidiol (n = 16). Of these, most perceived improvement in Gp symptoms from cannabinoids (93.5% with tetrahydrocannabinol, 81.3% with cannabidiol, and 47.2% with dronabinol). Cannabinoids were used most commonly via smoking (n = 46). Patients taking cannabinoids were younger (41.0 ± 15.4 vs 48.0 ± 15.9 years; P < 0.01) and had a higher Gastroparesis Cardinal Symptom Index total score (3.4 ± 1.0 vs 2.8 ± 1.3; P < 0.01) compared with patients with no history of cannabinoid use.
CONCLUSIONS:
A third of patients with Gp symptoms actively use cannabinoids for their chronic symptoms. Most of these patients perceive improvement in their symptoms with cannabinoids. Patients taking cannabinoids were younger and more symptomatic than those not taking cannabinoids. Further studies on the efficacy and safety of cannabinoids in Gp will be useful.
A Randomized, Multicenter, Prospective, Crossover, Open-Label Study of Factors Associated With Patient Preferences for Naloxegol or PEG 3350 for Opioid-Induced Constipation
American Journal of Gastroenterology. 114(6):954-963, June 2019.
To determine patient preference for treating opioid-induced constipation (OIC) using naloxegol or polyethylene glycol (PEG) 3350 in patients receiving opioids for noncancer pain.
Methods:
This crossover study included two 2-week active treatment periods, each preceded by a 1-week washout period (NCT03060512). Individuals with baseline Bowel Function Index scores ≥30 were randomized to 1 of 2 treatment sequences (naloxegol/PEG 3350 or PEG 3350/naloxegol). Patient preference (primary end point) was measured at the end of the second treatment period.
Results:
Of 276 patients randomized, 246 completed both treatment periods and reported preference (per protocol). Similar proportions of patients reported overall preference for naloxegol (50.4%) or PEG 3350 (48.0%; P = 0.92); 1.6% reported no preference. Medication characteristics influencing preference were similar for both treatments, except convenience and working quickly, which were strong influences of preference for higher proportions of patients preferring naloxegol (69.9% and 39.0%, respectively) vs those preferring PEG 3350 (29.9% and 27.4%, respectively). Patients aged <50 years or receiving laxatives within the previous 2 weeks generally preferred naloxegol. Changes from baseline in overall Bowel Function Index and Patient Global Impression of Change scores were similar between treatments, but analyses according to treatment preference revealed clinical improvement aligned with reported preference. Safety profiles were generally consistent with known medication profiles.
Conclusions:
Almost equal proportions of patients with OIC reported similar preference for daily naloxegol or PEG 3350 treatment, and their preference was generally supported by clinically relevant and measurable improvements in OIC symptoms.
Incidence of Advanced Colorectal Neoplasia in Individuals With Untreated Diminutive Colorectal Adenomas Diagnosed by Magnifying Image-Enhanced Endoscopy
American Journal of Gastroenterology. 114(6):964-973, June 2019.
Because of the increasing number of detected diminutive colorectal adenomas, the “diagnose-and-do-not-resect” approach has recently attracted attention as an alternative to resection. We evaluated the cumulative incidence of advanced colorectal neoplasia (ACN) in individuals with untreated diminutive adenomas and compared this incidence in individuals without adenomas.
METHODS:
Data from 1,378 individuals who underwent first screening colonoscopy (CS) and at least one follow-up CS without polypectomy were analyzed. Patients with no adenomas or with only nonadvanced diminutive adenomas (<5 mm) diagnosed by magnifying image-enhanced endoscopy were scheduled to undergo a follow-up CS within 5 years after the initial CS without treatment. The participants were divided into 2 groups: those with untreated diminutive adenomas (group A) and those with no adenomas (group B). The cumulative incidence of ACN and the hazard ratio were assessed using Gray's test and the Fine and Gray model.
RESULTS:
During the median follow-up period of 60.9 months, 21 ACNs were detected. The 5-year cumulative incidences of ACN in group A (n = 361) and group B (n = 1,017) were 1.4% (95% confidence interval [CI]: 0.5–3.4) and 0.8% (95% CI: 0.3–1.7), respectively, without a statistically significant difference ( P = 0.23). No ACNs developed from unresected adenomas. The smoking status was significantly associated with the incidence of ACN, and the hazard ratio for ACN in group A vs group B adjusted for smoking status was 1.43 (95% CI: 0.52–3.90; P = 0.48).
DISCUSSION:
The low 5-year cumulative incidence of ACN suggests the potential to adopt the “diagnose-and-do-not-resect” strategy as an alternative option for diminutive adenomas not requiring excessive surveillance.
Protease-Sensitive Pancreatic Lipase Variants Are Associated With Early Onset Chronic Pancreatitis
American Journal of Gastroenterology. 114(6):974-983, June 2019.
Premature activation of the digestive protease trypsin within the pancreatic parenchyma is a critical factor in the pathogenesis of pancreatitis. Alterations in genes that affect intrapancreatic trypsin activity are associated with chronic pancreatitis (CP). Recently, carboxyl ester lipase emerged as a trypsin-independent risk gene. Here, we evaluated pancreatic lipase ( PNLIP ) as a potential novel susceptibility gene for CP.
METHODS:
We analyzed all 13 PNLIP exons in 429 nonalcoholic patients with CP and 600 control subjects from Germany, in 632 patients and 957 controls from France, and in 223 patients and 1,070 controls from Japan by DNA sequencing. Additionally, we analyzed selected exons in further 545 patients with CP and 1,849 controls originating from Germany, United States, and India. We assessed the cellular secretion, lipase activity, and proteolytic stability of recombinant PNLIP variants.
RESULTS:
In the German discovery cohort, 8/429 (1.9%) patients and 2/600 (0.3%) controls carried a PNLIPmissense variant ( P = 0.02, odds ratio [OR] = 5.7, 95% confidence interval [CI] = 1.1–38.9). Variants detected in patients were prone to proteolytic degradation by trypsin and chymotrypsin. In the French replication cohort, protease-sensitive variants were also enriched in patients with early-onset CP (5/632 [0.8%]) vs controls (1/957 [0.1%]) ( P = 0.04, OR = 7.6, 95% CI = 0.9–172.9). In contrast, we detected no protease-sensitive variants in the non-European populations. In the combined European data, protease-sensitive variants were found in 13/1,163 cases (1.1%) and in 3/3,000 controls (0.1%) (OR = 11.3, 95% CI = 3.0–49.9, P < 0.0001).
CONCLUSIONS:
Our data indicate that protease-sensitive PNLIP variants are novel genetic risk factors for the development of CP.
- SDC
Increasing Rates of Diagnosis, Substantial Co-Occurrence, and Variable Treatment Patterns of Eosinophilic Gastritis, Gastroenteritis, and Colitis Based on 10-Year Data Across a Multicenter Consortium
American Journal of Gastroenterology. 114(6):984-994, June 2019.
The literature related to eosinophilic gastritis (EG), gastroenteritis (EGE), and colitis (EC) is limited. We aimed to characterize rates of diagnosis, clinical features, and initial treatments for patients with EG, EGE, and EC.
METHODS:
In this retrospective study, data were collected from 6 centers in the Consortium of Eosinophilic Gastrointestinal Researchers from 2005 to 2016. We analyzed demographics, time trends in diagnosis, medical history, presenting symptoms, disease overlap, and initial treatment patterns/responses.
RESULTS:
Of 373 subjects (317 children and 56 adults), 38% had EG, 33% EGE, and 29% EC. Rates of diagnosis of all diseases increased over time. There was no male predominance, and the majority of subjects had atopy. Presenting symptoms were similar between diseases with nausea/vomiting and abdominal pain, the most common. One hundred fifty-four subjects (41%) had eosinophilic inflammation outside of their primary disease location with the esophagus the second most common gastrointestinal (GI) segment involved. Multisite inflammation was more common in children than in adults (68% vs 37%; P < 0.001). Initial treatment patterns varied highly between centers. One hundred-nine subjects (29%) had follow-up within 6 months, and the majority had clinical, endoscopic, and histologic improvements.
CONCLUSIONS:
In this cohort, EG, EGE, and EC were diagnosed more frequently over time, and inflammation of GI segments outside the primary disease site co-occurrence of atopy was common with a lack of male predominance. Symptoms were similar between diseases, and initial treatment strategies were highly variable. Future investigation should assess the cause of the increased prevalence of eosinophilic GI disorders and prospectively assess outcomes to establish treatment algorithms.
- SDC
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