Risk Of Severe Hepatitis Research Articles

Association between 9-month isoniazid prophylaxis of latent tuberculosis and severe hepatitis in patients treated with TNF inhibitors

To investigate associations between isoniazid for latent tuberculosis and risk of severe hepatitis, affecting patients with rheumatoid arthritis or ankylosing spondylitis whose treatment includes tumor necrosis factor inhibitors. Our self-controlled case series study analyzed Taiwan’s National Health Insurance Database from 2003 to 2015 to identify RA or AS patients, aged ≥ 20 years, receiving TNF inhibitors and a 9-month single isoniazid treatment. The outcome of interest was hospitalization due to severe hepatitis. We defined risk periods by isoniazid exposure (days): 1–28, 29–56, 57–84, 85–168, 169–252, and 253–280. To compare risk of severe hepatitis in exposed and non-exposed periods, we performed conditional Poisson regressions to generate incidence rate ratios (IRR) and 95% confidence intervals, with adjustment of patients’ baseline covariates including age, sex, HBV, HCV and related medication. Of 54,267 RA patients and 137,889 AS patients identified between 2000 and 2015, 11,221 (20.7%) RA and 4,208 (3.1%) AS patients underwent TNFi therapy, with 722 (5%) receiving isoniazid for latent tuberculosis. We identified 31 incident cases (4.3%) of hospitalization due to severe hepatitis. Of these hospitalization events, 5 occurred in the exposed periods, 25 occurred in the INH unexposed periods, and 1 occurred in the pre-exposure period. Compared with non-exposure, the risk of severe hepatitis was higher in exposed periods (incidence rate ratio [IRR]: 5.1, 95% CI: 1.57–16.55), especially 57–84 days (IRR: 17.29, 95% CI: 3.11–96.25) and 85–168 days (IRR:10.55, 95% CI: 1.90–58.51). The INH related fatal hepatotoxicity was not identified in our study. Our findings suggest an association between risk of severe hepatitis and exposure to isoniazid in patients with RA or AS under TNFi therapy, particularly within the exposed period 57–168 days. A close monitoring of liver function is mandatory to minimize the risk, especially within the first 6 months after initiation of 9 months isoniazid.

Correction possibilities of drug-induced liver toxicity in the treatment of patients with blood system tumors

Background. In modern oncohematology achieved notable success due to the intensification and development of new chemotherapy regimens. However, the side effects of anticancer drugs, due to low selectivity of most of them, are a serious limitation to achieve their maximal therapeutic effect. Although doctors are aware of the possibility of hepatotoxic reactions to various drugs, in clinical practice, the diagnosis of drug-induced liver injury is formulated unreasonably rarely. This speculation is due to several factors: in some cases, the latent course of drug-induced liver injury, often inadequate interpretation of clinical symptoms and laboratory parameters, and sometimes insufficiently thorough collection of anamnesis. A particularly difficult problem for a doctor is the development of drug-induced hepatotoxicity in patients for whom the “causal” drug is prescribed for vital indications, in particular, polychemotherapy in cancer patients, complex antimicrobial therapy and antiviral therapy for febrile neutropenia or sepsis, etc. In these situations, on the one hand, treatment cancellation is impossible due to the risk of disease progression, on the other hand, its continuation is undesirable due to the risk of severe hepatitis. In addition, multicomponent therapy, which is a complex of potentially hepatotoxic substances, often does not allow specifying the substance that caused the pathological reaction. At the same time, it is obvious that the hepatocyte, the main cell of the hepatic parenchyma, remains the center of the organ pathology. The variety of biochemical processes occurring with ademetionine participation served as the basis for conducting clinical studies in order to correct drug-induced liver toxicity in the treatment of patients with blood system tumors.The objective of the study is to assess laboratory and clinical parameters of drug-induced liver injury (DILI), intrahepatic cholestasis in the study of homeostasis disorders in patients with hematological malignancies and chemotherapy-induced hepatotoxicity.Materials and methods. The study involved 45 patients with blood system tumors, who had chemotherapy-induced hepatocellular failure. To describe the population of DILI patients, we collected demographic data, clarified the underlying liver disease in each patient, and analyzed the diagnostic criteria for chronic liver disease due to DILI. Clinical signs and symptoms of cholestasis (jaundice, pruritus, weakness), as well as manifestations of a depressive state and asthenic syndrome – mood (mild, moderate and severe), normalization of sleep rhythm, memory improvement, general health were assessed. Changes in laboratory parameters of liver function were studied. In 20 patients with blood system tumors, the biochemical parameters associated with cell metabolism were analyzed – lipid peroxidation, nitric oxide (NOx ) level, impaired liver detoxification capacity by glutathione level and glutathione-S-transferase activity. The treatment regimens for drug-induced hepatotoxicity included the Heptral, which was prescribed until stable normalization of liver function.Results. All patients with developed liver failure showed metabolic disorders. The use of ademetionine has shown significant effect. The NO and superoxide dismutase in most patients decreased significantly and almost corresponded to the norm. Normalization of the glutathione system parameters was also observed. One of the mechanisms of Heptral protective effect is an increase in the glutathione synthesis. The improvement in laboratory parameters was accompanied by the disappearance of DILI and intrahepatic cholestasis symptoms. This is confirmed by significant statistical correlations between them and indicates the ademetionine efficacy to recovery of hepatocytes function. When using ademetionine, the most pronounced reduction among biochemical parameters was observed in alkaline phosphatase and γ-glutamyl transpeptidase, markers of cholestasis syndrome. In addition, serum bilirubin concentration and alanine and aspartic transaminases activity (albeit to a lesser extent) decreased significantly. Clinical and biochemical effects, as a rule, persisted for several months after completion of therapy. Decrease in biochemical parameters characterizing cholestasis and cytolysis (positive dynamics of alanine and aspartic transaminases, alkaline phosphatase, γ-glutamyl transpeptidase, bilirubin) was accompanied by an improvement and normalization of patients’ well-being. When assessing the depression and asthenic syndrome, it was noted that the duration of Heptral therapy is important.Conclusion. The results obtained were the basis for the development of supportive therapy programs to prevent and reduce liver toxicity during chemotherapy. Rational approaches to the liver metabolic disorders correction – a real way to increase the treatment efficacy and improve the quality of life of patients with blood system tumors.

Modeling the hepatitis A epidemiological transition in Brazil and Mexico

ABSTRACTBackground: Many low- to middle-income countries have completed or are in the process of transitioning from high or intermediate to low endemicity for hepatitis A virus (HAV). Because the risk of severe hepatitis A disease increases with age at infection, decreased incidence that leaves older children and adults susceptible to HAV infection may actually increase the population-level burden of disease from HAV. Mathematical models can be helpful for projecting future epidemiological profiles for HAV.Methods: An age-specific deterministic, dynamic compartmental transmission model with stratification by setting (rural versus urban) was calibrated with country-specific data on demography, urbanization, and seroprevalence of anti-HAV antibodies. HAV transmission was modeled as a function of setting-specific access to safe water. The model was then used to project various HAV-related epidemiological outcomes in Brazil and in Mexico from 1950 to 2050.Results: The projected epidemiological outcomes were qualitatively similar in the 2 countries. The age at the midpoint of population immunity (AMPI) increased considerably and the mean age of symptomatic HAV cases shifted from childhood to early adulthood. The projected overall incidence rate of HAV infections decreased by about two thirds as safe water access improved. However, the incidence rate of symptomatic HAV infections remained roughly the same over the projection period. The incidence rates of HAV infections (all and symptomatic alone) were projected to become similar in rural and urban settings in the next decades.Conclusion: This model featuring population age structure, urbanization and access to safe water as key contributors to the epidemiological transition for HAV was previously validated with data from Thailand and fits equally well with data from Latin American countries. Assuming no introduction of a vaccination program over the projection period, both Brazil and Mexico were projected to experience a continued decrease in HAV incidence rates without any substantial decrease in the incidence rates of symptomatic HAV infections.

Fulminant hepatitis in patients with chronic liver disease.

The changing epidemiology of hepatitis A virus (HAV) in the UK has led to a decline in natural immunity against the virus. It is estimated that in the UK, HAV is responsible for 10%-20% of cases of liver failure, and an overall mortality rate of 0.1%. It is clear that certain factors predispose patients to more severe HAV disease and increased mortality, although the reasons for this have yet to be elucidated. The age at which infection occurs clearly influences the outcome, with the risk of severe hepatitis increasing sharply after the age of 40 years. Intravenous drug users, homosexual men, individuals with an excessive alcohol intake or patients with chronic liver disease are also at increased risk of severe disease. An analysis of data from King's College Hospital was performed to determine the factors that influence the outcome or clinical course of HAV infection in at-risk patients. Data compiled from 1991 to 1998 revealed 187 cases with confirmed HAV, 45 of whom developed severe hepatitis. Outcomes were varied, eight (17.7%) patients developed acute liver failure and two (4.4%) died.