Yen-Po Wang

Statins decrease the risk of decompensation in hepatitis B virus– and hepatitis C virus–related cirrhosis: A population-based study

Statin use decreases the risk of decompensation and mortality in patients with cirrhosis due to hepatitis C virus (HCV). Whether this beneficial effect can be extended to cirrhosis in the general population or cirrhosis due to other causes, such as hepatitis B virus (HBV) infection or alcohol, remains unknown. Statin use also decreases the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV and HCV infection. It is unclear whether the effect can be observed in patients with pre‐existing cirrhosis. The goal of this study was to determine the effect of statin use on rates of decompensation, mortality, and HCC in HBV‐, HCV‐, and alcohol‐related cirrhosis. Patients with cirrhosis were identified from a representative cohort of Taiwan National Health Insurance beneficiaries from 2000 to 2013. Statin users, defined as having a cumulative defined daily dose (cDDD) ≥28, were selected and served as the case cohort. Statin nonusers (<28 cDDD) were matched through propensity scores. The association between statin use and risk of decompensation, mortality, and HCC were estimated. A total of 1350 patients with cirrhosis were enrolled. Among patients with cirrhosis, statin use decreased the risk of decompensation, mortality, and HCC in a dose‐dependent manner (P for trend <0.0001, <0.0001, and 0.009, respectively). Regression analysis revealed a lower risk of decompensation among statin users with cirrhosis due to chronic HBV (adjusted hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.25‐0.62) or HCV infection (HR, 0.51; 95% CI, 0.29‐0.93). The lowered risk of decompensation was of borderline significance among statin users with alcohol‐related cirrhosis (HR, 0.69; 95% CI, 0.45‐1.07). Conclusion: Statin use decreases the decompensation rate in both HBV‐ and HCV‐related cirrhosis. Of borderline significance is a decreased decompensation rate in alcohol‐related cirrhosis. (Hepatology 2017;66:896–907).

Gastroesophageal reflux disease and risk for bipolar disorder: a nationwide population-based study.

Background Studies have shown that chronic inflammation may play a vital role in the pathophysiology of both gastroesophageal reflux disease (GERD) and bipolar disorder. Among patients with GERD, the risk of bipolar disorder has not been well characterized. Objective We explored the relationship between GERD and the subsequent development of bipolar disorder, and examined the risk factors for bipolar disorder in patients with GERD. Methods We identified patients who were diagnosed with GERD in the Taiwan National Health Insurance Research Database. A comparison cohort without GERD was matched according to age, sex, and comorbidities. The occurrence of bipolar disorder was evaluated in both cohorts based on diagnosis and the prescription of medications. Results The GERD cohort consisted of 21,674 patients, and the comparison cohort consisted of 21,674 matched control patients without GERD. The incidence of bipolar disorder (incidence rate ratio [IRR] 2.29, 95% confidence interval [CI] 1.58–3.36, P<.001) was higher among GERD patients than among comparison cohort. Multivariate, matched regression models showed that the female sex (hazard ratio [HR] 1.78, 95% CI 1.76–2.74, P = .008), being younger than 60 years old (HR 2.35, 95% CI 1.33–4.16, P = .003), and alcohol use disorder (HR 4.89, 95% CI 3.06–7.84, P = .004) were independent risk factors for the development of bipolar disorder among GERD patients. Conclusions GERD may increase the risk of developing bipolar disorder. Based on our data, we suggest that attention should be focused on female patients younger than 60 years, and patients with alcohol use disorder, following a GERD diagnosis.

A Rare Cause of Gastrointestinal Bleeding

62 Question: A 60-year-old woman presented to our emergency room with epigastric fullness and passage of tarry stool for 1 week. She also had progressive shortness of breath, dizziness, and generalized weakness. On physical examination, slight tachycardia (heart rate, 104 bpm) with anemic conjunctiva was noted. Blood tests showed low hemoglobin (6.9 g/dL). Esophagogastroduodenoscopy revealed a polypoid tumor with superficial ulcerations and hematin coatings, suggesting recent bleeding, near superior duodenal angle of duodenum (Figure A). A barium study showed a filling defect over mesenteric side of second portion of duodenum, resulting in luminal narrowing (Figure B, black arrow). Biopsy at the overlying mucosa showed inflammatory changes without neoplastic cells. Abdominal computed tomography disclosed an enhancing soft tissue mass in the second portion of the duodenum (Figure C, D, white arrow). Tumor markers (carcinoembryonic antigen and carbohydrate antigen 19-9) were within normal limits. The patient underwent pancreaticoduodenotomy with limited antrectomy to remove the tumor. What is your diagnosis of this duodenal tumor? Look on page 261 for the answer and see the GASTROENTEROLOGY web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Detecting Minimal Hepatic Encephalopathy in an Endemic Country for Hepatitis B: The Role of Psychometrics and Serum IL-6

Background & Aims It remains unknown what the prevalence of minimal hepatic encephalopathy is in Taiwan, a highly endemic country for chronic viral hepatitis infection. It is also unclear whether abnormal serum cytokine levels can be indicative of the presence of minimal hepatic encephalopathy. We aimed to standardize the tests of psychometric hepatic encephalopathy score and predictive value of proinflammatory cytokines in minimal hepatic encephalopathy in Taiwan. Methods 180 healthy subjects and 94 cirrhotic patients without a history of overt hepatic encephalopathy from a tertiary center were invited to participate in this cross-sectional study. Blood sampling for determination of serum levels of interleukin 6 and 18 and tumor necrosis factor-α was performed. Based on the normogram of psychometric hepatic encephalopathy score from healthy volunteers, patients with minimal hepatic encephalopathy were identified from the cirrhotic patients using the criterion of a psychometric hepatic encephalopathy score less than −4. Results In the healthy subjects, age and education were predictors of subtests of psychometric hepatic encephalopathy score. Minimal hepatic encephalopathy was identified in 27 (29%) cirrhotic patients. Serum interleukin 6 level (OR = 6.50, 95% CI = 1.64–25.76, P = 0.008) was predictive of the presence of minimal hepatic encephalopathy after multivariate analysis. Conclusions The psychometric hepatic encephalopathy score can be a useful tool for detecting patients with minimal hepatic encephalopathy in Taiwan and around one third of cirrhotic outpatients fulfill this diagnosis. A high serum interleukin 6 level is predictive of the presence of minimal hepatic encephalopathy.

Increased serum interleukin-6, not minimal hepatic encephalopathy, predicts poor sleep quality in nonalcoholic cirrhotic patients.

Sleep–wake disturbances are common in patients with cirrhosis and have a considerable effect on health‐related quality of life; however, the underlying mechanism behind the phenomenon is unclear. Cytokines are involved in the mediation of signalling pathways regulating fibrogenesis, leading to cirrhosis. In addition, increased cytokines could contribute to sleep disturbances.

P2X7 Receptor Mediates Spinal Microglia Activation of Visceral Hyperalgesia in a Rat Model of Chronic Pancreatitis

Background & Aims Molecular mechanisms underlying the activated spinal microglia in association with the pain in chronic pancreatitis (CP) remain unknown. We tested whether P2X7R on spinal microglia mediates the pathogenesis of visceral pain using a CP rat model. Methods The CP model was induced via intraductal injection of 2% trinitrobenzene sulfonic acid into male Sprague-Dawley rats. Hyperalgesia was assessed based on the mechanical sensitivity to Von-Frey filaments (VFFs), and nocifensive behaviors were measured in response to electrical stimulation of the pancreas. Three weeks after CP induction, spinal cord samples were harvested for immunostaining, immunoblot, and real-time polymerase chain reaction analyses of the P2X7R. Changes in nocifensive behaviors and associated molecular effectors were assessed by blocking spinal cord P2X7R pharmacologically using the selective P2X7R antagonist brilliant blue G (BBG) or genetically using short interfering RNA (siRNA). Results CP induced a significant up-regulation of spinal P2X7R expression, which colocalized with a microglial marker (OX-42). Intrathecal administration of BBG significantly attenuated CP-related visceral hyperalgesia in response to VFF-mediated or electrical stimulation of the pancreas, which was associated with suppressed spinal expression of P2X7R and inhibited activation of spinal microglia. Intrathecal injection of siRNA to knock down P2X7R expression in the spinal cord would suppress the nociceptive behaviors in CP rats. Conclusions Spinal microglia P2X7R mediates central sensitization of chronic visceral pain in CP. BBG may represent an effective drug for the treatment of chronic pain in CP patients.

Sexual Abuse Is Associated With an Abnormal Psychological Profile and Sleep Difficulty in Patients With Irritable Bowel Syndrome in Taiwan

Background/Aims Both sexual and physical abuse history have been reported to be associated with irritable bowel syndrome (IBS) in Western countries. The impact of abuse history in IBS patients in Asia remains unclear. We aim to determine the prevalence of abuse history, its associated psychological profiles, and sleep problems among IBS patients in Taiwan. Methods In total, 194 Rome III-defined IBS patients were invited to participate. Age- and sex-matched healthy carriers of chronic hepatitis B or hepatitis C without chronic abdominal symptoms were identified as disease-controls. We administered a validated questionnaire to evaluate bowel symptoms, physical/sexual abuse history, anxiety/depression (Hospital Anxiety and Depression Scale [HADS]), and sleep quality. Results IBS patients had a significantly higher prevalence of sexual abuse history than the disease-control group both before (16.5% vs 6.7%, P < 0.05) and after (16.0% vs 6.6%, P < 0.05) adolescence. These significant differences were mainly observed in women (13.4% vs 3.4%, P < 0.05). No difference was noted in history of physical abuse between the 2 groups. IBS patients with a history of sexual abuse had significantly higher HADS scores and higher frequencies of sleep difficulty than those without. Conclusions In Taiwan, sexual abuse history was more prevalent in female IBS patients than controls. Sexual abuse history may contribute to higher anxiety/depression levels and sleep difficulties, which are commonly experienced in IBS patients. In Asia, abuse history should be obtained when approaching IBS patients to facilitate better management.

An Octogenarian With Dysphagia and Weight Loss

n 82-year-old woman with a history of congestive Aheart failure (CHF)/hypertension was referred to us with a preliminary diagnosis of achalasia. She suffered from dysphagia from both solid and liquid foods with weight loss (from 38 to 33 kg) for weeks before her admission to a regional hospital. An esophagogastroduodenoscopy showed much food retention. Acute respiratory failure from aspiration pneumonia and CHF happened thereafter, which resolved after antibiotics, diuretics, and mechanical ventilation. At examination, the patient had severe kyphosis with a nasogastric tube in place. Pansystolic murmurs with bilateral lower pulmonary crackles were noted. Chest radiographs showed a tortuous aorta with signs of CHF. A barium study disclosed an indentation at the mid-tolower esophagus and a beak-like appearance at the esophagogastric junction (Figure A). A repeat esophagogastroduodenoscopy showed intact esophageal mucosa with a narrowed lumen in the lower esophagus, which seemingly was a result of compression of an extramural pulsating mass. High-resolution manometry (HRM) showed 2 high-pressure zones with synchronous and rhythmic pressure changes at approximately 32 and 42 cm from the nostril, with heightened corresponding pressures to 67 and 78 mm Hg, respectively (Figure B). The peristaltic wave upon wet swallowing was interrupted by the proximal high-pressure zone (Figure B, arrow). The distal high-pressure zone overlapped with the lower esophageal sphincter (LES), resulting in a high, 4-second, integrated relaxation pressure (24 mm Hg) and mimicking nonrelaxation of the LES. A computed topography with 3-dimensional reconstruction of blood vessels showed cardiomegaly with marked tortuosity of the thoracic aorta (Figure C, posterior view). Multiple compression fractures in the thoracic spine also were noted. The tortuous, deviated, and reverse S-shaped aorta, which may be related to an advanced age and severe kyphosis, together with the dilated left atrium and left ventricle, caused the compressions at the mid-tolower esophagus and esophagogastric junction. These results led us to the diagnosis of dysphagia aortica, instead of achalasia. The patient’s dysphagia improved after adequate control of CHF/hypertension and has been free from dysphagia since then. Dysphagia aortica was used to describe difficult swallowing caused by external compression of the esophagus from an ecstatic, tortuous, atherosclerotic, or aneurysmal aorta. It is an uncommon condition and often observed in elderly hypertensive women with short stature and kyphosis. Besides the mechanical factor, disturbed peristalsis from ischemia of the enteric nervous system resulting from disturbed venous return in the high-pressure zone also may contribute to dysphagia. Because there is no gold standard for diagnosing dysphagia aortica, the diagnosis of dysphagia aortica depends on multiple diagnostic modalities including symptom assessment, structural abnormalities, and motility

Dysphagia in a young woman.

A 31-year-old woman presented to our clinic with a history of intermittent dysphagia to both solid and liquid food for several years. Her dysphagia increased in severity, and in recent months, was accompanied by frequent postprandial chest tightness, and vomiting. Physical examination and routine laboratory workup showed no obvious abnormalities. Oesophagogastroduodenoscopy (fi gure A, B, and video) showed an elongated pouch with a blind end originating from the mid-oesophagus. A demarcation was clearly seen between the epithelium in the pouch and the normal oesophageal mucosa. Upper gastrointestinal series (fi gure C) showed an 8·4 × 2·8 cm pouch stemming from the thoracic oesophagus. The tubular structure’s blind end did not connect with the distal oesophagus, suggesting an incomplete duplication of the oesophagus. Lancet 2013; 382: 426