Recent Advances in Protective Vaccines against Hepatitis Viruses: A Narrative Review.

Vaccination has been confirmed to be the safest and, sometimes, the only tool of defense against threats from infectious diseases. The successful history of vaccination is evident in the control of serious viral infections, such as smallpox and polio. Viruses that infect human livers are known as hepatitis viruses and are classified into five major types from A to E, alphabetically. Although infection with hepatitis A virus (HAV) is known to be self-resolving after rest and symptomatic treatment, there were 7134 deaths from HAV worldwide in 2016. In 2019, hepatitis B virus (HBV) and hepatitis C virus (HCV) resulted in an estimated 820,000 and 290,000 deaths, respectively. Hepatitis delta virus (HDV) is a satellite virus that depends on HBV for producing its infectious particles in order to spread. The combination of HDV and HBV infection is considered the most severe form of chronic viral hepatitis. Hepatitis E virus (HEV) is another orally transmitted virus, common in low- and middle-income countries. In 2015, it caused 44,000 deaths worldwide. Safe and effective vaccines are already available to prevent hepatitis A and B. Here, we review the recent advances in protective vaccines against the five major hepatitis viruses.

Aspartate transferase-to-platelet ratio index-plus: A new simplified model for predicting the risk of mortality among patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a spectrum of clinical syndromes with serious involvement of the lung and frequent effection of the liver and hemostatic system. Blood biomarkers are affordable, rapid, objective, and useful in the evaluation and prognostication of COVID-19 patients. AIM: To investigate the association between aspartate transferase-to-platelet ratio index (APRI) and in-hospital mortality to develop a COVID-19 mortality prediction model. METHODS: A multicenter cohort study with a retrospective design was conducted. Medical records of all consecutive adult patients admitted to Al-Azhar University Hospital (Assiut, Egypt) and Chest Hospital (Assiut, Egypt) with confirmed COVID-19 from July 1, 2020 to October 1, 2020, were retrieved and analyzed. The patient cohort was classified into the following two categories based on the APRI: (1) COVID-19 presenting with APRI ≤ 0.5; and (2) COVID-19 presenting with APRI (> 0.5 and ≤ 1.5). The association between APRI and all-cause in-hospital mortality was analyzed, and the new model was developed through logistic regression analyses. RESULTS: Of the 353 patients who satisfied the inclusion criteria, 10% were admitted to the intensive care unit (n = 36) and 7% died during the hospital stay (n = 25). The median age was 40 years and 50.7% were male. On admission, 49% had aspartate transferase-dominant liver injury. On admission, APRI (> 0.5 and ≤ 1.5) was independently associated with all-cause in-hospital mortality in unadjusted regression analysis and after adjustment for age and sex; after stepwise adjustment for several clinically relevant confounders, APRI was still significantly associated with all-cause in-hospital mortality. On admission, APRI (> 0.5 and ≤ 1.5) increased the odds of mortality by five-times (P < 0.006). From these results, we developed a new predictive model, the APRI-plus, which includes the four predictors of age, aspartate transferase, platelets, and serum ferritin. Performance for mortality was very good, with an area under the receiver operating curve of 0.90. CONCLUSION: APRI-plus is an accurate and simplified prediction model for mortality among patients with COVID-19 and is associated with in-hospital mortality, independent of other relevant predictors.

Hepatocellular injury and the mortality risk among patients with COVID-19: A retrospective cohort study.

BACKGROUND: Clearly, infection with severe acute respiratory syndrome coronavirus 2 is not limited to the lung but also affects other organs. We need predictive models to determine patients' prognoses and to improve health care resource allocation during the coronavirus disease 2019 (COVID-19) pandemic. While treating COVID-19, we observed differential outcome prediction weights for markers of hepatocellular injury among hospitalized patients. AIM: To investigate the association between hepatocellular injury and all-cause in-hospital mortality among patients with COVID-19. METHODS: This multicentre study employed a retrospective cohort design. All adult patients admitted to Al-Azhar University Hospital, Assiut, Egypt and Abo Teeg General Hospital, Assiut, Egypt with confirmed COVID-19 from June 1, 2020, to July 30, 2020 were eligible. We categorized our cohort into three groups of (1) patients with COVID-19 presenting normal aminotransferase levels; (2) patients with COVID-19 presenting one-fold higher aminotransferase levels; and (3) patients with COVID-19 presenting two-fold higher aminotransferase levels. We analysed the association between elevated aminotransferase levels and all-cause in-hospital mortality. The survival analysis was performed using the Kaplan-Meier method and tested by log-rank analysis. RESULTS: In total, 376 of 419 patients met the inclusion criteria, while 29 (8%) patients in our cohort died during the hospital stay. The median age was 40 years (range: 28-56 years), and 51% were males (n = 194). At admission, 54% of the study cohort had liver injury. The pattern of liver injury was hepatocellular injury with an aspartate aminotransferase (AST) predominance. Admission AST levels were independently associated with all-cause in-hospital mortality in the logistic regression analysis. A one-fold increase in serum AST levels among patients with COVID-19 led to an eleven-fold increase in in-hospital mortality (P < 0.001). Admission AST levels correlated with C-reactive protein (r = 0.2; P < 0.003) and serum ferritin (r = 0.2; P < 0.0002) levels. Admission alanine aminotransferase levels correlated with serum ferritin levels (r = 0.1; P < 0.04). Serum total bilirubin levels were independently associated with in-hospital mortality in the binary logistic regression analysis after adjusting for age and sex but lost its statistical significance in the fully adjusted model. Serum ferritin levels were significantly associated with in-hospital mortality (P < 0.01). The probability of survival was significantly different between the AST groups and showed the following order: a two-fold increase in AST levels > a one-fold increase in in AST levels > normal AST levels (P < 0.0001). CONCLUSION: Liver injury with an AST-dominant pattern predicts the severity of COVID-19. Elevated serum ferritin levels are associated with fatal outcomes.

Current situation of viral hepatitis in Egypt.

An estimated 8-10 million people suffer from viral hepatitis in Egypt. Hepatitis A virus (HAV) and hepatitis E virus (HEV) are the major causes of viral hepatitis in Egypt as 50% or more of the Egyptian population are already exposed to HAV infection by the age of 15. In addition, over 60% of the Egyptian population test seropositive for anti-HEV in the first decade of life. HEV mainly causes self-limiting hepatitis; however, cases of fulminant hepatitis and liver failure were reported in Egypt. Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) are the main causes of chronic hepatitis, liver cirrhosis, and liver cancer (hepatocellular carcinoma [HCC]) in Egypt. Globally, Egypt had the highest age-standardized death rate due to cirrhosis from 1990 to 2017. The prevalence rate of HBV (1.3%-1.5%) has declined after national infantile immunization. Coinfection of HBV patients with HDV is common in Egypt because HDV antibodies (IgG) vary in range from 8.3% to 43% among total HBV patients. After the conduction of multiple national programs to control HCV infection, a lower rate of HCV prevalence (4.6%) was recently reported. Data about the incidence of HCV after treatment with direct antiviral agents (DAAs) are lacking. An HCC incidence of 29/1000/year in cirrhotic patients after DAA treatment is reported. A higher rate of infiltrative pattern among HCC patients after DAA treatment is also recognized. Viral hepatitis is one of the major public health concerns in Egypt that needs more attention and funding from health policymakers.

Tacrolimus or infliximab for severe ulcerative colitis: short-term and long-term data from a retrospective observational study.

OBJECTIVE: Treatment of severe ulcerative colitis (UC) is challenging. Although the efficacy of tacrolimus (TAC) and infliximab (IFX) have been evaluated in patients with severe UC, the safety and efficacy levels of sequential therapies (TAC→IFX/IFX→TAC) in these patients remain unclear. The aim of this study was to assess short-term and long-term outcomes in patients with severe UC treated with TAC and IFX. METHODS: From October 2001 to February 2014, 29 patients with consecutive severe UC treated with TAC or IFX were retrospectively evaluated. Median follow-up duration was 27 months (range 0.5-118 months). The primary end point was short-term outcomes at 8 weeks after induction of TAC (TAC group, n=22) or IFX (IFX group, n=7). The secondary end point included long-term outcomes and colectomy-free survival. The clinical response was evaluated based on a partial Mayo score. RESULTS: The clinical remission (CR) rate at 8 weeks in the TAC and IFX groups was 63.6% and 71.4%, respectively. In 13 of the 29 patients (10 in the TAC group, 3 in the IFX group), sequential therapies were used in their clinical courses. In 9 of these 13 patients (6 in the TAC group, 3 in the IFX group), CR was achieved and maintained by sequential therapies. Overall cumulative colectomy-free survival was 79.3% at 118 months. CONCLUSIONS: TAC and IFX had similar effects on remission induction in patients with severely active UC. Sequential therapies could rescue patients with UC who failed initial treatment with TAC or IFX. In clinical practice, sequential therapies might be deliberately performed.

Efficacy of Thiopurines in Biologic-Naive Japanese Patients With Crohn's Disease: A Single-Center Experience.

BACKGROUND/AIMS: Early use of biologics in patients with Crohn's disease (CD) improves quality of life. However, the effects of the early use of immunomodulators on long-term outcomes remain unclear. This study aimed to evaluate the effects of immunomodulators in patients with CD. METHODS: Between January 2004 and December 2011, 47 biologic-naive CD patients treated with thiopurines alone for remission maintenance were analyzed. The patients were classified into 2 groups depending on the presence or absence of digestive complications. We evaluated the efficacy of and predictive factors for thiopurine use for remission maintenance. RESULTS: The cumulative relapse rates at 24 and 60 months were 13.7% and 35.4%, respectively. Regarding patient characteristics, there was a significant difference in patient history of surgery between the non-relapse and relapse groups (P=0.021). The cumulative relapse rate was lower in patients without a history of surgery than in those with such a history (27.2% and 52.9% at 60.0 months, respectively). Multivariate analysis suggested that the prevalence of stricturing and penetrating complications is an independent factor for relapse. The cumulative relapse rate in patients without a history of surgery was significantly lower in the non-stricturing and non-penetrating group than in the stricturing and penetrating group (11.8% at 85.0 months vs. 58.5% at 69.0 months; P=0.036). CONCLUSIONS: Thiopurine use might be beneficial for the long-term maintenance of remission in biologic-naive Crohn's disease patients without digestive complications and a history of surgery.

Usefulness of Adalimumab for Treating a Case of Intestinal Behçet's Disease With Trisomy 8 Myelodysplastic Syndrome.

Behçet's disease (BD) is a systemic vasculitis, while myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematologic disorders characterized by ineffective hematopoiesis. Some studies suggest a relationship between MDS and BD, especially intestinal BD, and trisomy 8 seems to play an important role in both diseases. There are several reports on patients with BD comorbid with MDS involving trisomy 8 that frequently have intestinal lesions refractory to conventional medical therapies. Tumor necrosis factor (TNF)-α is strongly involved in the pathophysiology of several autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, and BD. In addition, TNF-α plays an important role in the pathophysiology of MDS by inhibiting normal hematopoiesis and inducing the programmed cell death of normal total bone marrow cells and normal CD34+ cells. Recent clinical reports demonstrate the favorable effect of TNF-α antagonists in patients with refractory intestinal BD and in those with MDS. We present the case of a patient with intestinal BD and MDS involving trisomy 8 who was successfully treated with adalimumab.