Evidence-based approach to management of hepatic encephalopathy in adults.

Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function and represents one of the many complications of portal hypertension and decompensated liver disease. Although ammonia is clearly implicated in the pathogenesis of HE, the pathogenesis of HE is multifactorial with numerous mechanisms that results in functional impairment of neuronal cells. The initial management of HE focuses on supportive care and stabilization which includes providing appropriate nutritional support. Thereafter, focus should be on identifying and treating the precipitating factors. There are many therapeutic agents available for the management of HE, most of which are directed towards lowering the gut nitrogen load and thus the serum ammonia level. This review aims to provide an update on the conventional and emerging treatment options for HE.

Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The standard of care for treatment of celiac disease (CD) is a stringent lifetime gluten-free diet (GFD). Larazotide acetate (AT-1001) is an anti-zonulin which functions as a gut permeability regulator for treatment of CD. We endeavored to conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) which studied the efficacy and safety of AT-1001 in patients with CD. METHODS: We examined four databases from inception to 20-August-2020. We pooled continuous outcomes as mean difference and dichotomous outcomes as risk ratio with 95% confidence interval under the fixed-effects meta-analysis model. RESULTS: Four RCTs met our eligibility criteria, comprising 626 patients (AT-1001, n=465, placebo, n=161). Three and two RCTs reported outcomes of patients undergoing gluten challenge (intake of 2.4-2.7 grams of gluten/day) and GFD, respectively. For change in lactulose-to-mannitol ratio, the endpoint did not significantly differ between AT-1001 and placebo groups, irrespective of the gluten status. Subgroup analysis of patients undergoing gluten challenge showed AT-1001 treatment (compared with placebo) significantly correlated with better symptomatic improvement in the two endpoints of change in total gastrointestinal symptom rating scale (total GSRS) and CD-specific GSRS (CD-GSRS). However, no significant difference was noted among patients undergoing GFD for the abovementioned two efficacy endpoints. Compared with placebo, AT-1001 favorably reduced the adverse event (AE) of gluten-related diarrhea in patients who underwent gluten challenge. Other AEs were comparable between both AT-1001 and placebo groups. CONCLUSIONS: AT-1001 is largely well-endured and seems somehow superior to placebo in alleviating gastrointestinal symptoms among CD patients undergoing gluten challenge. Nevertheless, additional RCTs are warranted to validate these findings.

Syphilitic hepatitis as a manifestation of secondary syphilis.

Syphilis is a multisystem disease caused by the spirochete Treponema pallidum. Among various organs affected, liver involvement is seen infrequently and can be missed. Here we present a case of hepatitis due to secondary syphilis that completely resolved with penicillin G therapy.

The Effect of Raloxifene Treatment on Lipid Profile in Elderly Individuals: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

PURPOSE: To perform a systematic review and meta-analysis of randomized clinical trials (RCTs) to elucidate the effects of raloxifene on the lipid profile in elderly individuals. METHODS: A systematic review and meta-analysis of RCTs was performed following the PRISMA statement. Data on triglycerides (TGs), total cholesterol (TC), HDL-C, and LDL-C were extracted. Relevant publications up to October 2020 were detected through searches in the PubMed/MEDLINE, Web of Science, Scopus, and Embase databases. Changes were reported as weighted mean differences (WMDs) and 95% CIs using random-effects models. FINDINGS: Nine studies were selected, with a duration of intervention ranging from 2 and 12 months and a raloxifene dose of 60 to 120 mg/d. Studies were performed in healthy individuals and in those with disorders, such as osteoporosis, type 2 diabetes, and kidney disease required long-term hemodialysis. Overall, TG (WMD, -6.50 mg/dL; 95% CI, -34.18 to 21.20 mg/eL; P = 0.646), LDL-C (WMD, -17.86 mg/dL; 95% CI, -42.44 to 6.72 mg/dL; P = 0.154), and HDL-C (WMD, 2.35 mg/dL; 95% CI, -1.14 to 5.84 mg/dL; P = 0.187) levels did not change significantly after the administration of raloxifene. In contrast, TC levels decreased after raloxifene therapy (WMD, -6.59 mg/dL; 95% CI, -13.13 to -0.05 mg/dL; P = 0.048). IMPLICATIONS: Raloxifene therapy decreased TC levels but did not alter TG, HDL-C, and LDL-C concentrations in elderly individuals. Regarding the LDL-C levels, although the finding lacked statistical significance, we believe that there was a mean reduction that deserves further clinical attention as much as TC.

Impact of early cholecystectomy on the readmission rate in patients with acute gallstone cholangitis: a retrospective single-centre study.

BACKGROUND AND AIMS: The pathogenesis of acute cholangitis (AC) occurs with biliary obstruction followed by bacterial growth in the bile duct. The leading cause of AC is obstructing gallstones. There have been conflicting theories about the optimal timing for cholecystectomy following AC. The aim of this study is to assess the impact of early cholecystectomy on the 30-day readmission rate, 30-day mortality, 90-day readmission rate and the length of hospital stay. METHODS: This retrospective study was performed between January 2015 and January 2021 in a high-volume tertiary referral teaching hospital. Included patients were 18 years or older with a definitive diagnosis of acute gallstone cholangitis who underwent endoscopic retrograde cholangiopancreatography (ERCP) with complete clearance of the bile duct as an index procedure. We divided the patients into two groups: patients who underwent ERCP alone and those who underwent ERCP with laparoscopic cholecystectomy (LC) on the same admission (ERCP+LC). Data were extracted from electronic medical records. The primary endpoint of the study was the 30-day readmission rate. RESULTS: A total of 114 patients with AC met the inclusion criteria of the study. The ERCP+LC group had significantly lower rates of 30-day readmission (2.2% vs 42.6%, p<0.001), 90-day readmission (2.2% vs 30.9%, p<0.001) and 30-day mortality (2.2% vs 16.2%, p=0.017) when compared with the ERCP group. In a multivariate logistic regression analysis, patients in the ERCP+LC group had 90% lower odds of 30-day readmission compared with patients who did not undergo LC during admission (OR=0.1, 95% CI (0.032 to 0.313), p<0.001). CONCLUSION: Performing LC on same day admission was associated with a decrease in 30-day and 90-day readmission rate as well as 30-day mortality.

Persistent lactic acidosis in the Mauriac syndrome in type 1 diabetes mellitus.

Mauriac syndrome is an uncommon clinical condition arising in the setting of poorly controlled type 1 diabetes mellitus. Clinical features include hepatomegaly and liver abnormalities indistinguishable from nonalcoholic fatty liver disease. Early diagnosis and management are essential, as Mauriac syndrome is reversible.

Polyethylene glycol versus lactulose in the treatment of hepatic encephalopathy: a systematic review and meta-analysis.

BACKGROUND: Hepatic encephalopathy (HE) is defined as brain dysfunction that occurs because of acute liver failure or liver cirrhosis and is associated with significant morbidity and mortality. Lactulose is the standard of care till this date; however, polyethylene glycol (PEG) has gained the attention of multiple investigators. METHODS: We screened five databases namely PubMed, Scopus, Web of Science, Cochrane Library and Embase from inception to 10 February 2021. Dichotomous and continuous data were analysed using the Mantel-Haenszel and inverse variance methods, respectively, which yielded a meta-analysis comparing PEG versus lactulose in the treatment of HE. RESULTS: Four trials with 229 patients were included. Compared with lactulose, the pooled effect size demonstrated a significantly lower average HE Scoring Algorithm (HESA) Score at 24 hours (Mean difference (MD)=-0.68, 95% CI (-1.05 to -0.31), p<0.001), a higher proportion of patients with reduction of HESA Score by ≥1 grade at 24 hours (risk ratio (RR)=1.40, 95% CI (1.17 to 1.67), p<0.001), a higher proportion of patients with a HESA Score of grade 0 at 24 hours (RR=4.33, 95% CI (2.27 to 8.28), p<0.0010) and a shorter time to resolution of HE group (MD=-1.45, 95% CI (-1.72 to -1.18), p<0.001) in favour of patients treated with PEG. CONCLUSION: PEG leads to a higher drop in the HESA Score and thus leads to a faster resolution of HE compared with lactulose.

Liver Cirrhosis Secondary to Autoimmune Hepatitis in a Patient with Alpha-1 Antitrypsin ZZ Phenotype: A "Double Hit" Phenomenon.

Alpha-1 antitrypsin deficiency has been known to cause pulmonary and hepatic diseases. Cirrhosis in patients with alpha-1 antitrypsin deficiency, especially in a homozygotes ZZ phenotype, has been described to occur exclusively as a congenital disease. We present the case of a young 28-year-old female who was initially followed for thrombocytopenia and was found to have cirrhosis of the liver with autoimmune histological features suggesting the possibility that another "second hit" can contribute to a more rapid progression of liver disease.

Keep an Eye Out for Crohn's Disease: Orbital Myositis as the Initial Sign before Gastrointestinal Manifestations.

Extraintestinal manifestations of Crohn's disease sometimes occur and can present prior to intestinal symptoms. Ocular manifestations of Crohn's disease are considered rare, with orbital myositis an even rarer manifestation with only a handful of cases reported in the literature. We present the case of a young woman who was diagnosed with orbital myositis, which was initially attributed to pseudotumor cerebri after an extensive negative work-up. Months later, the patient presented with haematochezia, and was subsequently diagnosed with Crohn's disease. LEARNING POINTS: Orbital myositis is a rare manifestation of inflammatory bowel disease (IBD), and even more rarely is the initial presentation before the development of intestinal luminal disease.Orbital myositis is a rare extraintestinal manifestation of Crohn's disease and mimics thyroid ophthalmopathy. When a thyroid function test is negative, it is important to keep IBD in mind.

An Early Presentation of Buried Bumper Syndrome.

Percutaneous endoscopic gastrostomy (PEG) is a well-established and successful method of nutritional delivery. Complications, although rare, are divided into early or late. Buried bumper syndrome (BBS) is usually a late complication of PEG tube insertion and can cause many issues such as pressure necrosis, peritonitis, and septic shock. Endoscopic evaluation is the definitive diagnosis, and treatment depends on each patient and the degree of depth of disc migration. We present to you a case of buried bumper syndrome in a 66-year-old female that was initially thought to be complicated with peritonitis, and surprisingly occurring only one week after initial PEG tube placement.

Duodenal bulb obstruction caused by a gallstone (Bouveret syndrome) successfully treated with endoscopic measures.

Bouveret syndrome is the rarest variant of gallstone ileus, with a high morbidity and mortality rate as well as life-threatening complications. We present a case of an 86-year-old woman who presented with abdominal pain and was diagnosed with acute cholecystitis. After laparoscopic cholecystectomy, her symptoms did not improve. She then underwent endoscopic retrograde cholangiopancreatography and was found to have a stone causing duodenal bulb obstruction. The stone was removed using a snare, and her symptoms improved greatly. This rare case of Bouveret syndrome with no apparent fistula was successfully treated using endoscopic measures.

Percutaneous Mechanical Pulmonary Thrombectomy in a Patient With Pulmonary Embolism as a First Presentation of COVID-19.

There has been a high incidence of thromboembolic diseases in patients with coronavirus disease 2019 (COVID-19) pneumonia. We present a case of a healthy 32-year-old male with no past medical history who presented with shortness of breath, tested positive for COVID-19, and was found to have a large acute saddle pulmonary embolism.

A Rare Case of Pancreatic Tuberculosis Diagnosed via Endoscopic Ultrasound-Guided Fine Needle Aspiration and Polymerase Chain Reaction.

Pancreatic tuberculosis (TB) is a very rare condition even in endemic areas of the world where the disease is considered to be highly prevalent. The presenting features are usually vague and its radiological features mimic pancreatitis and pancreatic malignancy. We present a case of a 26-year-old active military male, originally from Virginia with no past medical history who presented to the ED with a two-week history of abdominal pain, increased nausea and vomiting, decreased appetite, increased darkening of his urine, and pale-colored stools. His physical examination was remarkable for conjunctival icterus as well as generalized abdominal tenderness. His laboratory results were remarkable for a total bilirubin of 4.7 mg/dL, direct bilirubin of 3.9 mg/dL, and alkaline phosphatase of 583 U/L. A CT scan was performed showing an intrahepatic dilatation and abrupt obstruction of the common bile duct at the level of a mass. Subsequent MRI of the abdomen was performed which showed a pancreatic mass at the uncinate process obstructing the common bile duct and causing intrahepatic bile dilation. The patient was deemed a surgical candidate and endoscopic retrograde cholangiopancreatography (ERCP)/endoscopic ultrasound (EUS) was performed for the sake of staging and showed a biliary compression in the middle of the common bile duct for which a stent was placed, and fine-needle aspiration (FNA) of the pancreatic mass was performed which was consistent with necrotizing granulomatous lymphadenitis. After further diagnostic studies, the patient was diagnosed with pancreatic TB. This case highlights the unusual presentation of extrapulmonary TB as well as the importance of EUS-guided FNA in diagnosing pancreatic TB which was presumed to be a malignant mass and candidate for unnecessary surgical resection.

A Case of A Mesenteric Cyst Mimicking a Biloma.

Mesenteric cysts are a rare entity, with approximately 1,000 cases reported in the literature. Its etiology is unknown but was theorized to be a benign ectopic lymphatic proliferation in the mesentery. Imaging with surgical excision and pathologic microscopic evaluation is needed for diagnosis, but no specific guidelines for its management have been documented. Per most cases in the literature, drainage of mesenteric cysts is suboptimal and associated with increased risk of recurrence and infection, making surgical resection the treatment of choice. With its varying locations and presentations, diagnosis can be tricky especially given the rarity of its occurrence. Differential diagnosis includes pancreatic pseudocyst, hemangioma, choledochal cyst, hydatid cyst, cystic teratoma, etc. We present a 35-year-old woman who came in with worsening right upper quadrant (RUQ) pain due to chronic cholelithiasis and was found to have a large RUQ cystic mass adherent to the gallbladder, suggesting possible biloma or pancreatic pseudocyst; however, tissue analysis was positive for a mesenteric cyst.

Endoscopic Management of Giant Walled-Off Pancreatic Necrosis With a High Risk of Bleeding.

Walled-off pancreatic necrosis (WOPN) is one of the late complications of acute pancreatitis. We present a 37-year-old man who developed a large WOPN 6 weeks after treatment of severe complicated pancreatitis. Imaging studies revealed a necrotic retroperitoneal fluid collection measuring 27 × 12 × 27 cm with large crossing blood vessels. Cystogastrostomy was performed using a lumen-apposing metal stent. He underwent multiple necrosectomies with significant improvement in the cyst size. Bleeding is a major complication of direct endoscopic necrosectomy; hence, specific imaging and a careful approach should be taken into consideration, especially in WOPN with a high risk of bleeding.

Atypical Presentation of a Rare Disease: Eosinophilic Cholangitis Posing as a Cancer.

BACKGROUND A variety of benign etiologies of biliary stricture may initially be mistaken for hilar cholangiocarcinoma. Consequently, many patients undergo surgery for a benign disease that could have been treated medically. Eosinophilic cholangitis (EC) is an uncommon, benign, self-limiting disease that should be considered when approaching a case of obstructive jaundice since it causes biliary stricture formation. Transmural eosinophilic infiltration of the biliary tree is characteristic of EC. It may initially be indistinguishable from hilar cholangiocarcinoma. CASE REPORT We present a rare case of an 84-year-old male who was referred to our hospital for abdominal mass investigation with the provisional diagnosis of cholangiocarcinoma. During the workup, the index of suspicion for malignancy remained high as the typical laboratory and radiological findings for benign causes of biliary stricture were not present. Hence, the patient underwent left hepatectomy with caudate lobe resection and received a retrograde diagnosis of EC. CONCLUSIONS This case demonstrates that EC could present in the elderly with cardinal signs of cancer and absence of the typical findings of EC which was not previously reported. Since only 70% of patients present with peripheral eosinophilia, we stress on the importance of implementing diagnostic criteria for EC in the setting where peripheral eosinophilia is absent. Furthermore, this disorder has been reported to respond well to steroid therapy, hence, diagnostic criteria for EC would provide another treatment option for elderly and/or those who are not fit for surgery.