Epidemiology of hepatitis D virus infection in Europe: Is it vanishing?

Co-infection with hepatitis delta virus (HDV) is a challenging health care problem worldwide, estimated to occur in approximately 5%-10% of patients with chronic hepatitis B virus (HBV) infection. While HBV prevalence is decreasing globally, the prevalence of HDV infection is rising in some parts mainly due to injection drug use, sexual transmission and immigration from high endemicity areas. Eastern Europe and the Mediterranean are among the regions with high rates of endemicity for HDV and the immigration from high endemicity areas to Central and Western Europe has changed the HDV epidemiology. We aimed to review the prevalence of HDV infection in Europe. A paucity of publication appears in many European countries. Prevalence studies from some countries are old dated and some other countries did not report any prevalence studies. The studies are accumulated in few countries. Anti-HDV prevalence is high in Greenland, Norway, Romania, Sweden and Italy. Belgium, France, Germany, Spain, Switzerland, Turkey and United Kingdom reported decreasing prevalences. Among cirrhotic HBV patients, Germany, Italy and Turkey reported higher rates of HDV. The studies including centres across the Europe reported that HIV-HBV coinfected individuals have higher prevalence of HDV infection. The immigrants contribute the HDV infection burden in Greece, Italy, and Spain in an increasing rate. Previous studies revealed extremely high rates of HDV infection in Germany, Greece, Italy and Sweden. The studies report a remarkably high prevalence of hepatitis delta among HIV/HBV-coinfected individuals, individuals who inject drugs, immigrants and severe HBV infected patients across Europe. The HDV infection burden still appears to be significant. In the lack of an effective HDV therapy, prevention strategies and active screening of HBV/HDV appear as the most critical interventions for reducing the burden of liver disease related to HDV infection in Europe.

Gastric Glomus Tumors: The Roles of Endoscopic Ultrasound and Shared Decision-Making.

Gastric glomus tumors (GGTs) are mesenchymal neoplasms with indolent behavior that originate from the subepithelial layers of the stomach and represent up to 1% of all gastric tumors. GGT is detected incidentally during esophagogastroduodenoscopy (EGD) in a proportion of patients. Endoscopic ultrasound (EUS) evaluation of GGT is essential to establish the diagnosis and to differentiate it from gastrointestinal stromal tumors or gastric neuroendocrine tumors. An 80-year-old man who presented for abdominal discomfort was incidentally found to have a gastric antral nodule on EGD. Endoscopic biopsy demonstrated moderately erythematous gastric antral mucosa and a 1.5 cm subepithelial lesion along the greater curvature. An EUS revealed a subepithelial 1.6 cm × 1.3 cm isoechoic, homogenous lesion with small calcifications. Immunohistochemical staining of the fine needle biopsy specimen of the nodule was positive for neoplastic cells, smooth muscle actin, vimentin, patchy muscle-specific actin, and synaptophysin. There were no atypical cytologic features. These findings were consistent with GGT. The patient was not deemed to be a candidate for surgical resection due to advanced age and resolution of his symptoms. A shared decision was made to pursue regular surveillance. EUS is essential for evaluation of GGT. Currently, there are no guideline recommendations for surveillance of GGT detected on routine EGD in asymptomatic individuals. A definitive surgical treatment with partial gastrectomy was favored in previously published literature. For asymptomatic patients with GGT or those with resolution of symptoms, careful surveillance with serial abdominal imaging and EUS may be a reasonable option, especially in older patients with poor surgical candidacy.

Overlapping Hepatotoxicity and Colitis Associated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that are widely used for the management of many solid-organ and hematologic cancers. These agents work by inhibition of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death-1 (PD-1), and PD ligand 1 (PD-L1). Hyperactivation of immune system results in ICI-associated adverse events. Simultaneous hepatotoxicity and colitis associated with ICIs is rare and potentially overlooked, as clinical symptoms are often nonspecific. A 73-year-old man with metastatic squamous cell carcinoma presented six weeks after starting pembrolizumab with abdominal discomfort and diarrhea. Pembrolizumab therapy was held, and supportive therapy with antidiarrheals provided partial relief. After initial workup, ICI-associated hepatitis (ICIH) and ICI-related colitis (ICIC) were diagnosed. Colitis resolution required corticosteroids. This case illustrates the importance of high index of clinical suspensions for gastrointestinal and hepatic adverse events associated with ICIs, which may be overlooked and result in severe complications. While isolated ICIH and ICIC are well known adverse events, overlapping ICIH and ICIC is rare. Prompt recognition, cessation of the inciting agent, and initiation of early supportive therapy are essential. Treatment may require corticosteroids or mycophenolate mofetil.

The number of hepatocellular carcinoma foci as predictor of poor response to tumor-directed therapies in patients awaiting liver transplantation: a prospective cohort study.

BACKGROUND AND AIMS: Tumor-directed therapies (TDTs) are a constitutive part of hepatocellular carcinoma (HCC) treatment in patients awaiting liver transplantation (LT). While most patients benefit from TDTs as a bridge to LT, some patients drop out from the waiting list due to tumor progression. The study aimed to determine the risk factors for poor treatment outcome following TDTs among patients with HCC awaiting LT. METHODS: A total of 123 patients with HCC were evaluated with 92 patients meeting Milan Criteria enrolled in the prospective cohort study. Tumor response was evaluated using the modified Response Evaluation Criteria for Solid Tumors for HCC 1 month after the procedure. The risk factors for progressive disease (PD) and dropout were evaluated. RESULTS: After TDT, 55 patients (59.8%) achieved complete or partial response (44.6% and 15.2% respectively), 17 patients (18.5%) had stable disease, and 20 patients (21.7%) were assessed as PD. Multivariate analysis revealed a significant and independent association between the number of HCC foci and PD ( P  = 0.03, OR = 2.68). There was no statistically significant association between treatment response and demographics, MELDNa score, pre-and post-treatment alpha-fetoprotein (AFP), cumulative tumor burden the largest tumor size, or TDT modality. PD was the major cause of dropout in our cohort. Pre-treatment AFP levels ≥200 ng/ml had a strong association with dropout after TDTs ( P  = 0.0005). CONCLUSION: This study demonstrated the presence of multifocal HCC is the sole prognostic factor for PD following TDTs in HCC patients awaiting LT. We recommend prioritizing patients with multifocal HCC within Milan criteria by exception points for LT to improve the dropout rate.

Effect of acute kidney injury on hospital-based outcomes in patients admitted for variceal hemorrhage. Analysis of national inpatient sample database.

Introduction: Acute kidney injury (AKI) is known to be a marker of mortality in patients with cirrhosis and variceal hemorrhage. Aim: To study the effect of AKI on hospital-based outcomes in patients with variceal hemorrhage. Material and methods: We obtained data from the National Inpatient Sample for the years 2016-2018. Study inclusion criteria comprised adult variceal hemorrhage patients who also had AKI. The primary outcome of interest was in-hospital mortality. Secondary outcomes were length of stay, hospital charge, shock, blood transfusion, and ICU admission. We also determined the independent predictors of mortality in variceal hemorrhage patients using multivariate regression analysis. We used 2 different methods: multivariate logistic regression and propensity matching to adjust for confounders. Results: The number of people included in this study was 124,430, of whom 32,315 (26%) had AKI. Mortality in variceal hemorrhage patients with AKI was 30.4% in comparison to 4.8% without AKI. The presence of AKI was associated with increased odds of mortality (AOR = 8.28, 95% CI: 7.45-9.20, p < 0.01), ICU admissions (AOR = 4.76, 95% CI: 4.42-5.13, p < 0.01), blood transfusion (AOR = 1.24, 95% CI: 1.15-1.32, p < 0.01), and shock (AOR = 3.41, 95% CI 3.07-3.79, p < 0.01). The patients with AKI also had increased length of stay and hospital charges. Higher Charlson co-morbidity index, African American race, and being admitted to large sized hospital were independently associated with increased mortality. Conclusions: After analyzing the combined NIS dataset of 2016-2018, we concluded that patients admitted with variceal hemorrhage who has AKI are prone to adverse hospital outcomes.

The changing epidemiology of delta hepatitis in Türkiye over three decades: A systematic review.

Hepatitis D virus (HDV) infection represents the most serious form of chronic hepatitis. Turkey is among the countries with high HDV and intermediate hepatitis B virus prevalence. In Turkey, hepatitis B virus (HBV) vaccine series was included in the routine vaccination program in 1998. There have been regional differences in prevalence of HBV and HDV. Although a decline in HDV prevalence is estimated, there are uncertainties about the epidemic patterns of it. HDV prevalence was studied in varying groups and geographic regions. In this study, we aimed to analyse hepatitis D epidemiology in all groups and geographic regions in recent 35 years. During the study period of 35 years, 111 publications were noted. The analysis was done on the basis of three periods: 1999 and before (Period 1), 2000-2009 (Period 2), and 2010 and after (Period 3). The groups studied included inactive carrier state, chronic hepatitis B, all HBsAg-positive individuals and special groups. Among inactive HBV carriers, HDV prevalence did not change significantly over three decades. Among patients with chronic hepatitis, studies reported decreasing (from Period 1 to Period 2) and then increasing (from Period 2 to period 3) HDV prevalence. The studies including all HBsAg-positive patients reported decreasing (from Period 1 to Period 2) and then increasing (from Period 2 to period 3) HDV prevalence. Cumulative data of these 3 groups were taken to reveal HDV prevalence in HBV-infected patients, and it showed decreasing (from Period 1 to Period 2) and then increasing (from Period 2 to period 3) HDV prevalence. Cumulative data of these 3 groups analysed according to the geographic regions of the country showed that Eastern and Southeastern Anatolia regions still have a high burden of HDV. The study showed that although HDV prevalence decreased from 8.3% in Period 1 to 4.8% in Period 2, it tended to increase 5.5% in Period 3. HDV infection is still a healthcare problem in Turkey.

A Case of Light Chain Deposition Disease Leading to Acute Liver Failure and Review of Literature.

Light chain deposition disease (LCDD) is a monoclonal immunoglobulin deposition disease characterized by light chain deposition in soft tissues and viscera, causing systemic organ dysfunction with an underlying lymphoproliferative disorder. While the kidney is the most affected organ, cardiac and hepatic involvement is also seen with LCDD. Hepatic manifestation can range from mild hepatic injury to fulminant liver failure. Herein, we are presenting a case of an 83-year-old woman with a monoclonal gammopathy of undetermined significance (MGUS), who presented to our institution with acute liver failure progressing to circulatory shock and multiorgan failure. After an extensive workup, a diagnosis of hepatic LCDD was determined. In conjunction with the hematology and oncology department, chemotherapy options were discussed, but given her poor prognosis, the family decided to pursue a palliative route. Though establishing a prompt diagnosis is important for any acute condition, the rarity of this condition, along with paucity of data, makes timely diagnosis and treatment challenging. The available literature shows variable rates of success with chemotherapy for systemic LCDD. Despite chemotherapeutic advances, liver failure in LCDD indicates a dismal prognosis, where further clinical trials are difficult owing to the low prevalence of the condition. In our article, we will also be reviewing previous case reports on this disease.

Liver injury on admission linked to worse outcomes in COVID-19: an analysis of 14,138 patients.

Background: Infection with the SARS-CoV-2 virus, which can result in hepatic inflammation and injury that varies from mild to severe and potentially acute fulminant liver injury, may be associated with poor outcomes. Our aims were to: (I) assess baseline clinical and demographic characteristics in patients with coronavirus disease 2019 (COVID-19) who did and did not have abnormalities in liver chemistries [alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (Tbili)] and (II) evaluate associations between abnormalities in liver chemistries and the primary outcomes of in-hospital death, intubation, and hospital length of stay (LOS). Methods: In this nationwide retrospective cohort study of 14,138 patients, we analyzed associations between abnormalities in liver chemistries (ALT, AST, ALP, and Tbili) and mortality, intubation, and prolonged hospital LOS in patients with laboratory-confirmed COVID-19. We used Pearson's chi-squared tests to detect significant differences in categorical variables for patients with and without abnormal liver chemistries. Welch's two-sample t-tests were used to make comparisons of liver chemistry (ALT, AST, ALP, Tbili) and serum albumin results. All other continuous variables were analyzed using independent samples t-tests. A P value of <0.05 was considered significant. Results: Propensity score matching demonstrated that abnormalities in liver chemistries at admission are significantly associated with increased risk for mortality (RR 1.70) and intubation (RR 1.44) in patients with COVID-19. Elevated AST is the liver chemistry abnormality associated with the highest risk for mortality (RR 2.27), intubation (RR 2.12), and prolonged hospitalization (RR 1.19). Male gender, pre-existing liver disease, and decreased serum albumin are also significantly associated with severe outcomes and death in COVID-19. Conclusions: Routine liver chemistry testing should be implemented and used for risk stratification at the time of COVID-19 diagnosis.

Lymphocytic Esophagitis: A Case Series of Esophageal Disease with Increasing Frequency.

BACKGROUND: Lymphocytic esophagitis (LE) is a poorly understood clinical finding that has been increasingly identified in the last decade. Previous studies proposed increased frequency of LE in elderly females, as well as associations with smoking and pediatric Crohn's disease. OBJECTIVE: We aimed to determine the patient characteristics and clinical features of our adult LE patients. As inflammation in the esophagus has been linked to cancer, this review also describes this association. However, there are no reported cases of malignant transformation in those with underlying lymphocytic esophagitis. METHODS: We retrospectively reviewed records for patients at the University of Missouri Hospital- Columbia (located in the USA) who had a histopathological diagnosis of LE. Cases of LE were identified using the pathology reporting system at the University of Missouri Hospital for esophageal biopsy specimens for the above-mentioned period. RESULTS: The data of a total of 20 adult cases with esophageal biopsy specimens consistent with LE were included. CONCLUSION: LE seems to be a benign but disturbing clinical problem and should be remembered in elderly females complaining of dysphagia or refractory reflux symptoms. It has similar endoscopic findings of eosinophilic esophagitis with rings and esophagitis. Smoking and hiatal hernia are common risk factors. The majority of LE patients can respond to proton pump inhibitor (PPI) therapy. Endoscopic dilations and steroid therapy should be considered for PPI nonresponder LE patients.

Non-Alcoholic Fatty Pancreas Disease: The Unsung Disease.

Non-alcoholic fatty pancreas disease (NAFPD) is a relatively new and emerging disease that is increasingly diagnosed yearly, like non-alcoholic fatty liver disease (NAFLD). It is associated especially with metabolic syndrome and obesity. As awareness of pancreatic steatosis and its clinical implications increase, it is diagnosed more frequently. The researchers have explained the clinical importance of NAFPD and the diseases it causes, such as pancreatitis, pancreatic insufficiency, and pancreatic cancer. Although the definitive treatment is not yet established, the primary treatment approach is weight loss since NAFPD is associated with metabolic syndrome as well as obesity. Although pharmacological agents, such as oral hypoglycemic agents, have been investigated in animal experiments, studies on humans have not been conducted. Since the research on NAFPD is still insufficient, it is a subject that needs to be investigated, and further studies are needed to explore its pathophysiology, clinical impact, and its management.

Respiratory Syncytial Virus Associated Hepatitis in Pregnancy.

Respiratory syncytial virus (RSV) predominantly affects children and typically manifests as an upper respiratory tract infection. Primary RSV infection in immunosuppressed adults may increase risks of disseminated infection manifesting as RSV hepatitis. A 29-year-old pregnant woman of 10 weeks gestation presented with mild right upper quadrant abdominal pain, intractable nausea, and vomiting, requiring hospitalization. Due to initial lab work showing significantly elevated liver transaminases, she underwent a thorough workup to evaluate for causes of hepatitis. Common viral and autoimmune etiologies of hepatitis were excluded with appropriate serologies. A respiratory viral molecular panel (RVP) was obtained to evaluate for SARS-CoV-2/coronavirus disease 2019 (COVID-19) infection, despite lack of typical respiratory symptoms. No structural pathologies were detected on abdominal imaging with ultrasound and magnetic resonance imaging. No other etiologies for the patient's hepatitis were detected other than RSV infection detected on RVP. The patient's care required close coordination between multiple different subspecialties. Her condition improved due to the early detection of RSV infection and prompt initiation of supportive care. This case highlights the need for providers to consider obtaining an RVP early in workup of hepatitis to evaluate for RSV infection, even when patients have minimal respiratory symptoms. A high index of suspicion is required for early identification of RSV hepatitis as timely supportive care may prevent progression to acute liver failure.

Human Papillomavirus Infection and Oropharyngeal and Gastrointestinal Cancers: A Causal Relationship?

The human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The risk of being infected at least once in a lifetime among both men and women is estimated to be 50%. Although the majority of HPV infections are asymptomatic and improve within 2 years, approximately 10% of individuals develop a persistent infection and have an increased risk of developing carcinomas. The association of HPV and genital cancer is well established. However, there is evidence that HPV may also be associated with other cancers, including those of the gastrointestinal system. The aim of this review is to organize the current evidence of associations between HPV infections and oropharyngeal and gastrointestinal cancers, including the following: oropharyngeal, esophageal, gastric, colorectal, and anal cancers. A comprehensive review of the most up-to-date medical literature concluded that an HPV infection might have a role in the oncogenesis of gastrointestinal tract cancers. HPV may have a causal relationship with oropharyngeal and esophageal squamous cell cancers. However, the association between HPV and gastric and colorectal cancers is weaker. The development of cancer in the oropharyngeal and gastrointestinal tract is usually multifactorial, with HPV having a role in at least a subset of these cancers. HPV infections pose a big challenge due to their burden of infection and their oncogenic potential.

The 8th Wonder of the Cancer World: Esophageal Cancer and Inflammation.

Esophageal cancer is a devastating malignancy which can be detected at an early stage but is more often diagnosed as an advanced process. It affects both men and women and inflicts the young and the elderly. There are multiple underlying factors involved in the pathogenesis of this cancer including inflammation. The interplay of these factors promotes inflammation through various mechanisms including the recruitment of pro-inflammatory cells, mediators such as cytokines, reactive oxygen species, and interleukins, among others. The presentation can vary widely with one of the most notable symptoms being dysphagia. Diagnosis is based on clinical symptomatology, imaging and endoscopy with biopsy. Once the diagnosis has been established, treatment and prognosis are based on the stage of the disease. This review outlines esophageal cancer and its link to inflammation in relation to pathogenesis, along with clinical features, diagnosis and treatment.

Immunological and Metabolic Alterations in Esophageal Cancer.

Esophageal cancer is one of the most common types of gastrointestinal malignancies that is encountered. It has a global distribution and affects males and females, and is linked to significant morbidity and mortality. The mechanisms underlying pathophysiology are multifactorial and involve the interaction of genetic and environmental factors. This review article describes the immunological and metabolic changes that occur in malignancy of the esophagus.

Safety of anticoagulation use for treatment of portal vein thrombosis in liver cirrhosis and its effect on hospital-based outcomes: an insight from a US nationwide database.

BACKGROUND AND AIM: Anticoagulation use for portal vein thrombosis (PVT) in patients with advanced liver disease is controversial. We investigated the effect of anticoagulation on outcomes in patients with PVT with cirrhosis. METHODS: We reviewed National Inpatient Sample data from 2016 to 2018 to identify patients with PVT. Our outcomes were in-hospital mortality, variceal bleeding, hepatic encephalopathy, acute kidney injury (AKI), hepatorenal syndrome (HRS), spontaneous bacterial peritonitis (SBP), sepsis and hospital resource utilisation. RESULTS: We included 60 505 patients with PVT, out of whom 6.63% (4015) were on anticoagulation. The overall mortality in the anticoagulation group was 2.12% compared with 9.72% in the no anticoagulation group. The adjusted odds of mortality were low in the anticoagulation group (adjusted OR (AOR) 0.27, 95% CI 0.15 to 0.46, p<0.001). Patients on anticoagulation had 29% lower odds of variceal bleeding (AOR 0.71, 95% CI 0.53 to 0.96, p=0.03). Lower odds of HRS (AOR 0.56, 95% CI 0.37 to 0.85, p=0.01) and AKI (AOR 0.57, 95% CI 0.48 to 0.69, p<0.001) were also seen in the anticoagulation group. Patients in the anticoagulation group also showed lower odds of SBP (AOR 0.62, 95% CI 0.43 to 0.89, p=0.01) and sepsis (AOR 0.57, 95% CI 0.35 to 0.93, p=0.03). Anticoagulation use resulted in shorter hospital stay by 1.15 days (adjusted length of stay -1.15, 95% CI -1.51 to -0.79, p<0.001). The mean difference in total hospital charges between the anticoagulation and the no anticoagulation group was -$20 034 (95% CI -$27 077 to -$12 991, p<0.001). CONCLUSION: Our analysis found that anticoagulation use is safe and associated with better outcomes in patients with PVT with advanced liver disease.

Are Drugs Associated with Microscopic Colitis? A Systematic Review and Meta-Analysis.

There is growing evidence of the association of Microscopic Colitis (MC) with the use of specific medications such as proton pump inhibitors (PPIs), Selective serotonin reuptake inhibitors (SSRIs), Non-Steroidal anti-inflammatory drugs (NSAIDs), Statins and H2-receptor antagonists (H2RA). In our study, we calculated the pooled odds of MC in patients using these drugs. We performed a detailed search of major databases, including PubMed/Medline, Scopus, web of science, and Embase, to include the studies in which odds of MC were reported after using above mentioned drugs. A random-effects model was used to pool the estimates. Thirteen studies were included in our analysis consisting of 304,482 patients (34,194 cases and 270,018 controls). In eight studies, the control group consisted of a random population selected based on age, gender and same birth year, whereas 3 studies recruited patients who presented with diarrhea and underwent colonoscopy and biopsy to rule out MC. Two studies reported odds of MC for both diarrhea and random control groups. Patients taking PPIs were more likely to develop MC, AOR 2.65 (95% CI 1.81-3.50, I2 98.13%). Similarly, higher odds of association were found in patients taking SSRIs (OR 2.12, 95% CI 1.27-2.96, I2 96.46%), NSAIDs (OR 2.02, 95% CI 1.33-2.70, I2 92.70%) and Statins (OR 1.74, 95% CI 1.19-2.30, I2 96.36%). No difference in odds of developing MC was seen in patients using H2RA compared to the control group (OR 2.70, 95% CI 0.32-5.08, I2 98.67%). We performed a subgroup analysis based on the control group and found higher odds of MC in patients on PPIs compared to the random control group (OR 4.55, 95% CI 2.90-6.19, I2 98.13%). Similarly, higher odds of MC were noted for SSRI (OR 3.23, 95% CI 1.54-4.92, I2 98.31%), NSAIDs (OR 3.27, 95% CI 2.06-4.48, I2 95.38%), and Statins (OR 2.23, 95% CI 1.41-3.06, I2 98.11%) compared to the random control group. Contrary lower odds of MC were seen in the PPI and H2RA group compared to the diarrhea control group (OR 0.68, 95% CI 0.48-0.88, I2 7.26%), (OR 0.46, 95% CI 0.14-0.78, I2 0%) respectively. We found no difference in odds of MC in patients on SSRIs (OR 0.96, 95% CI 0.49-1.42, I2 37.89%), NSAIDs (OR 1.13, 95% CI 0.49-1.76, I2 59.37%) Statins (OR 0.91, 95% 0.66-1.17, I2 0%) and H2RA (OR 3.48, 95% CI -0.41-7.36, I2 98.89%) compared to the diarrhea control group. We also analyzed the association use of PPIs and NSAIDs with the development of collagenous colitis (CC) and lymphocytic colitis. Only the use of NSAIDs was associated with increased odds of developing collagenous colitis (OR 1.61, 95% CI 1.50-1.72, I2 0%). No increased odds of CC and LC were seen in PPI users. PPIs, NSAIDs, SSRIs, and Statins are associated with an increased risk of MC compared to the random control group. On the contrary, the use of PPIs, NSAIDs, SSRIs, and Statins is not associated with an increased risk of MC when compared to the diarrhea control group.