Drug induced liver injury (DILI) is a relatively rare hepatic condition in response to the use of medications, illegal drugs, herbal products or dietary supplements. It occurs in susceptible individuals through a combination of genetic and environmental risk factors believed to modify drug metabolism and/or excretion leading to a cascade of cellular events, including oxidative stress formation, apoptosis/necrosis, haptenization, immune response activation and a failure to adapt. The resultant liver damage can present with an array of phenotypes, which mimic almost every other liver disorder, and varies in severity from asymptomatic elevation of liver tests to fulminant hepatic failure. Despite recent research efforts specific biomarkers are not still available for routine use in clinical practice, which makes the diagnosis of DILI uncertain and relying on a high degree of awareness of this condition and the exclusion of other causes of liver disease. Diagnostic scales such as the CIOMS/RUCAM can support the causality assessment of a DILI suspicion, but need refinement as some criteria are not evidence-based. Prospective collection of well-vetted DILI cases in established DILI registries has allowed the identification and validation of a number of clinical variables, and to predict a more severe DILI outcome. DILI is also in need of properly designed clinical trials to evaluate the efficacy of new DILI treatments as well as older drugs such as ursodeoxycholic acid traditionally used to ameliorate cholestasis or corticosteroids now widely tried in the oncology field to manage the emergent type of hepatotoxicity related to immune checkpoint inhibitors.

Drug induced liver injury: an update

Millions of children are exposed to tuberculosis (TB) each year, many of which become infected with Mycobacterium tuberculosis. Most children can immunologically contain or eradicate the organism without pathology developing. However, in a minority, the organism overcomes the immunological constraints, proliferates and causes TB disease. Each year a million children develop TB disease, with a quarter dying. While it is known that young children and those with immunodeficiencies are at increased risk of progression from TB infection to TB disease, our understanding of risk factors for this transition is limited. The most immunologically disruptive process that can happen during childhood is infection with another pathogen and yet the impact of co-infections on TB risk is poorly investigated. Many diseases have overlapping geographical distributions to TB and affect similar patient populations. It is therefore likely that infection with viruses, bacteria, fungi and protozoa may impact on the risk of developing TB disease following exposure and infection, although disentangling correlation and causation is challenging. As vaccinations also disrupt immunological pathways, these may also impact on TB risk. In this article we describe the pediatric immune response to M. tuberculosis and then review the existing evidence of the impact of co-infection with other pathogens, as well as vaccination, on the host response to M. tuberculosis. We focus on the impact of other organisms on the risk of TB disease in children, in particularly evaluating if co-infections drive host immune responses in an age-dependent way. We finally propose priorities for future research in this field. An improved understanding of the impact of co-infections on TB could assist in TB control strategies, vaccine development (for TB vaccines or vaccines for other organisms), TB treatment approaches and TB diagnostics.

Examining the Complex Relationship Between Tuberculosis and Other Infectious Diseases in Children.

Background Infection with Hepatitis C Virus (HCV) increases the hepatotoxicity of anti-tuberculosis drugs. The purpose of this systematic review and meta-analysis is to determine the prevalence of HCV infection in patients with tuberculosis (TB). Methods PubMed/MEDLINE, ISI/Web of Sciences, CINAHL, EMBASE, the Cochrane Library and Scopus were searched from January 2000 to March 2018. The overall prevalence of HCV in patients with TB was calculated using the random-effect model with 95% confidence interval (CI). To evaluate heterogeneity, I2 test was used. Egger's regression test was utilized to check publication bias. Results Twenty-one articles were selected for the final analysis based on the inclusion/exclusion criteria. A total of 15,542 patients with TB participated in the studies. The overall prevalence of HCV infection in patients with TB was 7% [95%CI: 6-9]. Subgroup analysis revealed that diagnostic test (P=0.0039), geographical background (P=0.0076) and gender distribution (P=0.0672) were statistically significant moderators. Men had a higher risk for HCV than women (Odds Ratio, OR=2.02; 95%CI: 1.28-3.18). Conclusion The results of this study highlighted the importance of screening HCV in TB patients. Knowing whether HCV is present or not in these patients can be helpful in effectively treating them.

/pdf/prevalence-of-hepatitis-c-virus-in-tuberculosis-patients-a-42f89r05rr.pdf

Prevalence of Hepatitis C Virus in Tuberculosis Patients: A Systematic Review and Meta-Analysis.

BACKGROUND/AIMS Patients with inflammatory bowel disease (IBD) often require immunosuppressive therapy and blood transfusions and therefore are at a high risk of contracting infections due to hepatitis B (HBV) and hepatitis C (HCV) and human immunodeficiency virus (HIV). In the present study, we assessed the prevalence of these infections in patients with IBD. METHODS This retrospective study included 908 consecutive patients with IBD (ulcerative colitis [UC], n=581; Crohn's disease [CD], n=327) who were receiving care at a tertiary care center. Ninety-five patients with intestinal tuberculosis (ITB) were recruited as disease controls. Prospectively maintained patient databases were reviewed for the prevalence of HBV surface antigen, anti-HCV antibodies, and HIV (enzyme-linked immunosorbent assay method). HCV RNA was examined in patients who tested positive for anti-HCV antibodies. Prevalence data of the study were compared with that of the general Indian population (HBV, 3.7%; HCV, 1%; HIV, 0.3%). RESULTS The prevalence of HBV, HCV, and HIV was 2.4%, 1.4%, and 0.1%, respectively, in the 908 patients with IBD. Among the 581 patients with UC, 2.2% (12/541) had HBV, 1.7% (9/517) had HCV, and 0.2% (1/499) had HIV. Among the 327 patients with CD, 2.8% (8/288) had HBV, 0.7% (2/273) had HCV, and 0% (0/277) had HIV. One patient with CD had HBV and HCV coinfection. The prevalence of HBV, HCV, and HIV in patients with ITB was 5.9% (4/67), 1.8% (1/57), and 1.2% (1/84), respectively. CONCLUSIONS The prevalence of HBV, HCV, and HIV in north Indian patients with IBD is similar to the prevalence of these viruses in the general community. Nonetheless, the high risk of flare after immunosuppressive therapy mandates routine screening of patients with IBD for viral markers.

/pdf/prevalence-of-hepatitis-b-hepatitis-c-and-human-3ydkxqhyn7.pdf

Prevalence of hepatitis B, hepatitis C and human immunodeficiency viral infections in patients with inflammatory bowel disease in north India.

Background: Hepatitis and HIV are the most common co-infections in tuberculosis (TB) patients and
may have an effect on the liver enzymes in these co-infected TB patients.

/pdf/sero-prevalence-of-hepatitis-b-and-c-virus-and-high-risk-of-31y7ye6n6i.pdf

Sero-prevalence of Hepatitis B and C virus and High Risk of Hepatotoxicity among TB/HIV Positive and HIV Negative Population in Western Cameroon

AIM: To assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and association with drug induced liver injury (DILI) in patients undergoing anti-tuberculosis (TB) therapy.

METHODS: Four hundred and twenty nine patients with newly diagnosed TB - either active disease or latent infection - who were due to commence anti-TB therapy between September 2008 and May 2011 were included. These patients were prospectively tested for serological markers of HBV, HCV and human immunodeficiency virus (HIV) infections - hepatitis B core antigen (HBcAg), hepatitis B surface antigen (HBsAg), hepatitis B e antigen, IgG and IgM antibody to HBcAg (anti-HBc), HCV IgG antibody and HIV antibody using a combination of enzyme-linked immunosorbent assay, Western blot assay and polymerase chain reaction techniques. Patients were reviewed at least monthly during the TB treatment initiation phase. Liver function tests were measured prior to commencement of anti-TB therapy and 2-4 wk later. Liver function tests were also performed at any time the patient had significant nausea, vomiting, rash, or felt non-specifically unwell. Fisher’s exact test was used to measure significance in comparisons of proportions between groups. A P value of less than 0.05 was considered statistically significant.

RESULTS: Of the 429 patients, 270 (62.9%) had active TB disease and 159 (37.1%) had latent TB infection. 61 (14.2%) patients had isolated anti-HBc positivity, 11 (2.6%) were also HBsAg positive and 7 (1.6%) were HCV-antibody positive. 16/270 patients with active TB disease compared to 2/159 patients with latent TB infection had markers of chronic viral hepatitis (HBsAg or HCV antibody positive; P = 0.023). Similarly the proportion of HBsAg positive patients were significantly greater in the active vs latent TB infection group (10/43 vs 1/29, P = 0.04). The prevalence of chronic HBV or HCV was significantly higher than the estimated United Kingdom prevalence of 0.3% for each. We found no association between DILI and presence of serological markers of HBV or HCV. Three (5.3%) patients with serological markers of HBV or HCV infection had DILI compared to 25 (9.5%) patients without; P = 0.04.

CONCLUSION: Viral hepatitis screening should be considered in TB patients. DILI risk was not increased in patients with HBV/HCV.

pdf/viral-hepatitis-prevalence-in-patients-with-active-and-wyry9wp69m.pdf

Viral hepatitis prevalence in patients with active and latent tuberculosis.

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Viral hepatitis prevalence in patients with active and latent tuberculosis.