Hepatitis E in immunocompromised individuals.

Hepatitis E virus (HEV) originally identified as a cause of acute icteric hepatitis in developing countries has grown to be a cause of zoonotic viral hepatitis in developed countries such as the United States. While there are eight identified genotypes to date, genotype 1 (HEV1), HEV2, HEV3, HEV4 are the most common to infect humans. HEV1 and HEV2 are most common in developing countries including Latina America, Africa and Asia, and are commonly transmitted through contaminated water supplies leading to regional outbreaks. In contrast HEV3 and HEV4 circulate freely in many mammalian animals and can lead to occasional transmission to humans through fecal contamination or consumption of undercooked meat. The incidence and prevalence of HEV in the United States is undetermined given the absence of FDA approved serological assays and the lack of commercially available testing. In majority of cases, HEV infection is a self-limiting hepatitis requiring only symptomatic treatment. However, this is not the case in immunocompromised individuals, including those that have undergone solid organ or stem cell transplantation. In this subset of patients, chronic infection can be life threatening as hepatic insult can lead to inflammation and fibrosis with subsequent cirrhosis and death. The need for re-transplantation as a result of post-transplant hepatitis is of great concern. In addition, there have been many reported incidents of extrahepatic manifestations, for which the exact mechanisms remain to be elucidated. The cornerstone of treatment in immunocompromised solid organ transplant recipients is reduction of immunosuppressive therapies, while attempting to minimize the risk of organ rejection. Subsequent treatment options include ribavirin, and pegylated interferon alpha in those who have demonstrated ribavirin resistance. Further investigation assessing safety and efficacy of anti-viral therapy is imperative given the rising global health burden. Given this concern, vaccination has been approved in China with other investigations underway throughout the world. In this review we introduce the epidemiology, diagnosis, clinical manifestations, and treatment of HEV, with emphasis on immunocompromised individuals in the United States.

Nonalcoholic fatty liver disease is associated with worse intestinal complications in patients hospitalized for Clostridioides difficile infection.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease with increasing prevalence worldwide. Clostridioides difficile infection (CDI) remains the most common cause of nosocomial diarrhea in developed countries. AIM: To assess the impact of NAFLD on the outcomes of hospitalized patients with CDI. METHODS: This study was a retrospective cohort study. The Nationwide Inpatient Sample database was used to identify a total of 7239 adults admitted as inpatients with a primary diagnosis of CDI and coexisting NAFLD diagnosis from 2010 to 2014 using ICD-9 codes. Patients with CDI and coexisting NAFLD were compared to those with CDI and coexisting alcoholic liver disease (ALD) and viral liver disease (VLD), individually. Primary outcomes included mortality, length of stay, and total hospitalization charges. Secondary outcomes were in-hospital complications. Multivariate regression was used for outcome analysis after adjusting for possible confounders. RESULTS: CDI with NAFLD was independently associated with lower rates of acute respiratory failure (2.7% vs 4.2%, P < 0.01; 2.7% vs 4.2%, P < 0.05), shorter length of stay (days) (5.75 ± 0.16 vs 6.77 ± 0.15, P < 0.001; 5.75 ± 0.16 vs 6.84 ± 0.23, P <0.001), and lower hospitalization charges (dollars) (38150.34 ± 1757.01 vs 46326.72 ± 1809.82, P < 0.001; 38150.34 ± 1757.01 vs 44641.74 ± 1660.66, P < 0.001) when compared to CDI with VLD and CDI with ALD, respectively. CDI with NAFLD was associated with a lower rate of acute kidney injury (13.0% vs 17.2%, P < 0.01), but a higher rate of intestinal perforation (P < 0.01) when compared to VLD. A lower rate of mortality (0.8% vs 2.7%, P < 0.05) but a higher rate of intestinal obstruction (4.6% vs 2.2%, P = 0.001) was also observed when comparing CDI with NAFLD to ALD. CONCLUSION: Hospitalized CDI patients with NAFLD had more intestinal complications compared to CDI patients with VLD and ALD. Gut microbiota dysbiosis may contribute to the pathogenesis of intestinal complications.

Obstructive jaundice, a rare presentation of lung cancer: A case report.

Lung cancer metastases to the pancreas are rare but potentially life-threatening. Oftentimes, the presence of symptoms is indicative of extensive disease burden. This report describes a case of primary lung adenocarcinoma metastasizing to the head of the pancreas presenting as obstructive jaundice. The patient was a 61-year-old female veteran who presented with a chronic dyspnea, weight loss, and 3-weeks of nausea and vomiting found to have jaundice, elevated alkaline phosphatase levels, hyperbilirubinemia, and transaminitis. Imaging of her chest revealed large pulmonary parenchymal nodules throughout both lungs with a large left lower lobe mass and consolidation. Abdominal imaging showed a large heterogeneous mass in the pancreatic head, a grossly dilated common bile duct, and enlarged retroperitoneal lymph nodes contiguous with the mass. Pancreatic head biopsies revealed metastatic cancer cells from her lung adenocarcinoma which was confirmed via cytology and the presence of thyroid transcription factor - 1 and cytokeritin-7 expression and the absence of tumor protein 63 staining. Lung adenocarcinomas commonly metastasize to the bones, liver, and central nervous system but very rarely to the pancreas. There have been only a few reported cases of pancreatic tumors that manifested clinically as a result of primary lung cancer metastases however, even though uncommon, hematogenous spread of cancerous tissue should be considered on the differential as a cause for obstructive jaundice in the setting of lung adenocarcinoma.

Cellular based treatment modalities for unresectable hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is unfortunately associated with an overall poor prognosis and high mortality. Early and intermediate stages of HCC allow for treatment with surgical resection, ablation and even liver transplantation, however disease progression warrants conventional systemic therapy. For years treatment options were limited to molecular-targeting medications, of which sorafenib remains the standard of care. The recent development and success of immune checkpoint inhibitors has proven to be a breakthrough in the treatment of HCC, but there is an urgent need for the development of further novel therapeutic treatments that prolong overall survival and minimize recurrence. Current investigation is focused on adoptive cell therapy including chimeric antigen receptor-T cells (CAR-T cells), T cell receptor (TCR) engineered T cells, dendritic cells, natural killer cells, and tumor infiltrating lymphocyte cells, which have shown remarkable success in the treatment of hematological and solid tumor malignancies. In this review we briefly introduce readers to the currently approved systemic treatment options and present clinical and experimental evidence of HCC immunotherapeutic treatments that will hopefully one day allow for revolutionary change in the treatment modalities used for unresectable HCC. We also provide an up-to-date compilation of ongoing clinical trials investigating CAR-T cells, TCR engineered T cells, cancer vaccines and oncolytic viruses, while discussing strategies that can help overcome commonly faced challenges when utilizing cellular based treatments.

Reflux esophagitis is associated with higher risks of acute stroke and transient ischemic attacks in patients hospitalized with atrial fibrillation: A nationwide inpatient sample analysis.

ABSTRACT: Reflux esophagitis (RE) is a subset of gastroesophageal reflux disease (GERD) with endoscopic evidence of esophageal inflammation, which has been linked to an increased incidence of atrial fibrillation (AF). However, data on the effect of RE on patient outcomes is limited. We sought to examine the potential association of RE with outcomes of patients with AF in a nationwide study.The National Inpatient Sample (NIS) database was queried to identify hospitalized adult patients with AF and RE between 2010 and 2014. Primary outcomes included inpatient mortality, length of stay (LOS), and total hospital charges. AF related complications such as acute stroke, transient ischemic attack (TIA) and acute heart failure were assessed as secondary outcomes. Propensity score matching and multivariate regression analysis were used.Six lakh sixty seven thousands five hundred twenty patients were admitted for primary diagnosis of AF out of which 5396 had a secondary diagnosis of RE. In the AF with RE cohort, the average age was 73.6 years, 41.5% were male, and 79.9% were Caucasian. There was a greater prevalence of concomitant dyslipidemia, chronic liver disease and chronic pulmonary disease (P < .01) when compared to the AF without RE cohort. Patients with AF and RE also had higher incidence of acute strokes and TIAs (P < .05), longer LOS (P < .001), and higher hospital charges (P < .05) with no difference in acute heart failure (P = .08), hospital mortality (P = .12), or CHA2DS2-VASc score (P = .67).In hospitalized patients with AF, RE was associated with a higher rate of acute stroke and TIAs, longer LOS, and greater hospital charges.

The effects of diabetes mellitus on clinical outcomes of hospitalized patients with acute diverticulitis.

OBJECTIVES: Acute diverticulitis is a common gastrointestinal illness due to diverticular inflammation and focal necrosis. Diabetes mellitus has been reported to influence the outcomes of patients with diverticular disease. Our study aimed to examine the inpatient outcomes and complications of patients with acute diverticulitis and coexisting diabetes mellitus. METHODS: The Nationwide Inpatient Sample was used to identify adult patients in 2014 admitted for acute diverticulitis. Primary outcomes were mortality, length of stay (LOS), and total hospitalization charges. Secondary outcomes were complications of acute diverticulitis and interventions. RESULTS: In total, 44 330 of patients with acute diverticulitis and diabetes mellitus were included in the analysis. Acute diverticulitis patients with diabetes mellitus had a higher rate of diverticular bleeding (P < 0.0001), but lower rates of abscess (P < 0.0001), obstruction (P < 0.0001) and colectomy (P < 0.0001) when compared to acute diverticulitis patients without diabetes mellitus. Complicated diabetes mellitus was associated with a longer LOS (P = 0.00003) and greater total hospitalization charges (P = 0.0021) compared to uncomplicated diabetes mellitus when coexisting with acute diverticulitis. CONCLUSIONS: Acute diverticulitis with diabetes mellitus is associated with a higher rate of diverticular bleeding, lower rates of abscess, obstruction, and colectomy compared to acute diverticulitis without diabetes mellitus. When coexisting with acute diverticulitis, complicated diabetes mellitus is not associated with higher rates of mortality or diverticulitis-related complications compared to uncomplicated diabetes mellitus.

Efficacy and safety of anti-hepatic fibrosis drugs.

Recent progress in our understanding of the pathways linked to progression from hepatic insult to cirrhosis has led to numerous novel therapies being investigated as potential cures and inhibitors of hepatic fibrogenesis. Liver cirrhosis is the final result of prolonged fibrosis, which is an intimate balance between fibrogenesis and fibrinolysis. A number of these complex mechanisms are shared across the various etiologies of liver disease. Thankfully, investigation has yielded some promising results in regard to reversal of fibrosis, particularly the indirect benefits associated with antiviral therapy for the treatment of hepatitis B and C and the farnesoid receptor agonist for the treatment of primary biliary cholangitis and metabolic associated fatty liver disease. A majority of current clinical research is focused on targeting metabolic associated fatty liver disease and its progression to metabolic steatohepatitis and ultimately cirrhosis, with some hope of potential standardized therapeutics in the near future. With our ever-evolving understanding of the underlying pathophysiology, these therapeutics focus on either controlling the primary disease (the initial trigger of fibrogenesis), interrupting receptor ligand interactions and other intracellular communications, inhibiting fibrogenesis, or even promoting resolution of fibrosis. It is imperative to thoroughly test these potential therapies with the rigorous standards of clinical therapeutic trials in order to ensure the highest standards of patient safety. In this article we will briefly review the key pathophysiological pathways that lead to liver fibrosis and present current clinical and experimental evidence that has shown reversibility of liver fibrosis and cirrhosis, while commenting on therapeutic safety.