Increasing Alkaline Phosphatase as the Primary Manifestation of Disseminated Histoplasmosis in an AIDS Patient Without Pulmonary Disease.

Histoplasmosis is an infection caused by the dimorphic fungi Histoplasma. Hepatic involvement in the setting of disseminated histoplasmosis from a pulmonary source is well documented. Hepatic involvement as the primary manifestation in the absence of pulmonary disease is rare. We present a patient with acquired immune deficiency syndrome found to have disseminated histoplasmosis with worsening alkaline phosphatase as the primary manifestation of disease, which has not been reported in a review of the literature. After diagnosis, the patient was started on appropriate therapy with alkaline phosphatase return to baseline.

Combination strategies for pharmacologic treatment of non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is defined as hepatic steatosis, inflammation, and hepatocyte injury with or without fibrosis. It has emerged as the second leading indication for liver transplantation with a rising death rate in the non-transplantable population. While there are many drugs in evaluation, currently no approved therapies are on the market for this condition. Given this importance, the Food and Drug Administration has provided formal guidance regarding drug development for stopping or reversing NASH or NASH associated fibrosis. The complex pathogenesis of NASH and its bidirectional relationship with metabolic syndrome has highlighted multiple drugs of interest that address metabolic, inflammatory, and fibrotic factors. A few promising liver specific targets include farnesoid X receptor agonists and peroxisome proliferator-activated receptor agonists. Previously studied drug classes such as glucagon-like peptide-1 analogs or sodium/glucose transport protein 2 inhibitors have also demonstrated ability to improve hepatic steatosis. Here we discuss current rationale, scientific work, and preliminary data in combining multiple drugs for the purposes of a multimodal attack on the pathogenesis of NASH. We highlight multiple Phase 2 and Phase 3 studies that demonstrate the potential to achieve a response rate higher than previously assessed monotherapies for this condition. Ultimately, one of these combination strategies may rise above in its safety and efficacy to become a part of a standardized approach to NASH.

The presence of diabetes impacts liver fibrosis and steatosis by transient elastography in a primary care population.

INTRODUCTION AND OBJECTIVES: Noninvasive liver assessment in type 2 diabetes (T2DM) in a primary care population identifies higher risk non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate the association of T2DM with liver fibrosis and steatosis by transient elastography (TE). MATERIALS AND METHODS: This is a retrospective study of a TE referral program where primary care physicians were able to order TE. Patients with alcohol abuse were excluded. TE and Controlled Attenuation Parameter (CAP) scores were obtained. Multivariable linear and logistic regression models were used to adjust for confounders. RESULTS: 28% had T2DM. The mean TE score in T2DM patients was 8.3 (±6) kilopascal (kPa) and 6.4 (±3.7) kPa in those without T2DM (p = 0.0001). Those with T2DM had a higher CAP (322 ± 51 dB/m vs. 296 ± 57 dB/m, p < 0.0001). In multivariable analysis, T2DM was associated with TE score (ß: 1.9, 95% confidence interval [CI]: 0.74-3.1, p = 0.001) and CAP (ß: 2.8, 95% CI: 9.3-36.2, p = 0.001). Patients with T2DM had higher-risk TE scores and more steatosis by CAP. CONCLUSION: T2DM is associated with liver fibrosis and steatosis by TE within a primary care population. A TE referral pathway may be utilized for T2DM patients who are at higher risk of NAFLD and its complications.

Mortality on the UNOS Waitlist for Patients with Autoimmune Liver Disease.

BACKGROUND: Outcomes on the liver transplant waitlist can vary by etiology. Our aim is to investigate differences in waitlist mortality of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) using the United Network for Organ Sharing (UNOS) database. METHODS: We identified patients who were listed for liver transplantation from 1987 to 2016 with a primary diagnosis of AIH, PBC, or PSC. We excluded patients with overlap syndromes, acute hepatic necrosis, missing data, and those who were children. The primary outcome was death or removal from the waitlist due to clinical deterioration. We compared waitlist survival using competing risk analysis. RESULTS: Between 1987 and 2016, there were 7412 patients listed for liver transplant due to AIH, 8119 for PBC, and 10,901 for PSC. Patients with AIH were younger, more likely to be diabetic, and had higher listing model for end-stage liver disease (MELD) scores compared to PBC and PSC patients. Patients with PBC and AIH were more likely to be removed from the waitlist due to death or clinical deterioration. On competing risk analysis, AIH patients had a similar risk of being removed from the waitlist compared to those with PBC (subdistribution hazard ratio (SHR) 0.94, 95% CI 0.85-1.03) and higher risk of removal compared to those with PSC (SHR 0.8, 95% CI 0.72 to 0.89). CONCLUSION: Autoimmune hepatitis carries a similar risk of waitlist removal to PBC and a higher risk than PSC. The etiology of this disparity is not entirely clear and deserves further investigation.

Incidence and risk factors of dysphagia after variceal band ligation.

BACKGROUND AND AIM: There is a lack of data on long-term morbidity, particularly dysphagia, following endoscopic variceal band ligation (EVL). The aim of this study are to assess the incidence of dysphagia and variables associated with this complication after EVL. METHODS: We identified individuals who completed at least one session of EVL as their sole treatment for varices from August 2012 to December 2017. Included patients achieved "complete eradication" of varices not requiring further therapy. Patients ≥90 days from their last EVL session completed a modified version of the Mayo Clinic Dysphagia Questionnaire. Individuals with dysphagia were invited to undergo a barium esophagram. Patients with pre-EVL dysphagia were excluded. RESULTS: Of the patients, 68 possessed inclusion criteria, nine (13.2%) died and 20 (29.4%) were lost to follow up. For the remaining 39 (57.4%) patients, 23 were males, mean age of 61.7±8.6 years. The most common etiology of liver disease was hepatitis C virus (n=18; 46.2%). The median number of banding sessions was 2.0 (interquartile range [IQR], 1.0-4.0) with a median of 9.0 bands placed (IQR, 3.0-14.0). Twelve patients (30.8%) developed new-onset dysphagia post-EVL. In univariate analysis, pre-EVL MELD score and non-emergent initial banding were associated with long-term dysphagia. In a regression model adjusted for age, sex, number of bands, and use of acid suppression after EVL, no factor was independently associated with dysphagia (all P>0.05). No strictures were identified on subsequent esophageal evaluation. CONCLUSION: Approximately 30% of patients developed new-onset, chronic dysphagia post-EVL. Incident dysphagia was associated with a non-emergent initial banding session. The mechanism for dysphagia remains unknown.

Pharmacologic management of primary sclerosing cholangitis: what's in the pipeline?

Introduction: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by biliary inflammation, fibrosis, and stricturing. Although considered progressive, its course is difficult to predict, and there is currently no definitive therapy shown to alter disease course and prevent death or the need for liver transplantation. Areas covered: There are multiple agents in the pipeline targeting various pathways hypothesized to lead to and drive this disease. Some are already used for other treatment indications, including antibiotics such as oral vancomycin, metronidazole, and minocycline. Other agents including obeticholic acid, nor-ursodeoxycholic acid, and monoclonal antibodies are also under investigation. This narrative review focuses on the most recent published clinical trials available for discussion. We attempt to summarize the data on current and future treatment options. Expert opinion: The rarity of this condition and poor understanding of its pathophysiology have created a void for safe and effective treatment options to alter mortality or transplant free survival. Nevertheless, some agents currently being tested have demonstrated therapeutic potential. We await validation and prospective data on these agents in hopes of modifying the disease course for patients in the future.

Elevated methane levels in small intestinal bacterial overgrowth suggests delayed small bowel and colonic transit.

Limited research exists regarding the relationship between small intestinal bacterial overgrowth (SIBO), small bowel transit (SBT), and colonic transit (CT). Furthermore, symptom analysis is limited between the subtypes of SIBO: hydrogen producing (H-SIBO) and methane producing (M-SIBO). The primary aims of this study are to: compare the SBT and CT in patients with a positive lactulose breath test (LBT) to those with a normal study; compare the SBT and CT among patients with H-SIBO or M-SIBO; compare the severity of symptoms in patients with a positive LBT to those with a normal study; compare the severity of symptoms among patients with H-SIBO or M-SIBO.A retrospective review was performed for 89 patients who underwent a LBT and whole gut transit scintigraphy (WGTS) between 2014 and 2016. Seventy-eight patients were included. WGTS evaluated gastric emptying, SBT (normal ≥40% radiotracer bolus accumulated at the ileocecal valve at 6 hours), and CT (normal geometric center of colonic activity = 1.6-7.0 at 24 hours, 4.0-7.0 at 48 hours, 6.2-7.0 at 72 hours; elevated geometric center indicates increased transit). We also had patients complete a pretest symptom survey to evaluate nausea, bloating, constipation, diarrhea, belching, and flatulence.A total of 78 patients (69 females, 9 males, mean age of 48 years, mean BMI of 25.9) were evaluated. Forty-seven patients had a positive LBT (H-SIBO 66%, M-SIBO 34%). Comparison of SBT among patients with a positive LBT to normal LBT revealed no significant difference (62.1% vs 58.6%, P = .63). The mean accumulated radiotracer was higher for H-SIBO compared to M-SIBO (71.5% vs 44.1%; P < .05). For CT, all SIBO patients had no significant difference in geometric centers of colonic activity at 24, 48, and 72 hours when compared to the normal group. When subtyping, H-SIBO had significantly higher geometric centers compared to the M-SIBO group at 24 hours (4.4 vs 3.1, P < .001), 48 hours (5.2 vs 3.8, P = .002), and at 72 hours (5.6 vs 4.3, P = .006). The symptom severity scores did not differ between the positive and normal LBT groups. A higher level of nausea was present in the H-SIBO group when compared to the M-SIBO group.Overall, the presence of SIBO does not affect SBT or CT at 24, 48, and 72 hours. However, when analyzing the subtypes, M-SIBO has significantly more delayed SBT and CT when compared to H-SIBO. These results suggest the presence of delayed motility in patients with high methane levels on LBT.