Use of intravenous N-acetylcysteine in acute severe hepatitis due to severe dengue infection: a case series

Background Dengue fever is a common mosquito borne viral infection. Severe dengue fever associated severe hepatitis carries high mortality. Based on the beneficial effect of N-acetylcysteine (NAC) in paracetamol poisoning and non-acetaminophen induced liver failure, it is used in dengue fever associated hepatitis in clinical practice. We aim to study the reversal of liver enzymes with NAC in the setting of severe hepatitis due to severe dengue infection. Methods A retrospective analysis was conducted on hospitalized 30 adults with severe dengue fever with severe hepatitis. These 30 patients had aspartate transaminase (AST) and alanine transaminases (ALT) more than 500 U/L and/or PT INR (prothrombin time and international normalized ratio) more than 1.5. They were treated with NAC infusion of 100 mg/h for 3 to 5 days. Results The mean age of the group was 49.9 ± 11.46 years and 18 (60%) patients were males. Nineteen patients (63%) developed dengue shock. Of them 12 patients (40%) developed hepatic encephalopathy. Median AST on the day of administration of NAC was 1125 U/L interquartile range (IQR) 1653.25 while median ALT was 752 (IQR 459.25). There was a statistically significant reduction of both ALT (p = 0.034) and AST (p = 0.049) from day 1 to 4 after NAC infusion. Rise of platelet count between day 1 and day 4 also showed statistically significant difference (p = 0.011) but the reduction of prothrombin time and international normalized ratio (PT/INR) from 1 to day 4 did not show statistical significance difference. Mean duration of treatment with NAC was 3.61 ± 0.75 days while mean length of hospital stay was 6.2 ± 1.27 days. Only one patient died (3.3%). None of the patients reported adverse drug reaction due to NAC. Conclusion Majority of patients demonstrated marked clinical and biochemical improvements and they recovered fully. We observed faster and significant recovery of liver enzymes following administration of NAC. Based on the above findings, this study provides preliminary evidence for the beneficial effect of NAC in severe hepatitis in dengue infection with greater survival benefits.

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.

Recurrent Severe Hepatitis of Autoimmune Origin

The autoimmune liver disease constituent conditions include autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis and IgG-4 associated cholangitis. They remain a diagnostic challenge to the practicing physician due to their close resemblance in clinical course, and laboratory and imaging findings to the vast array of other etiologies of liver injury. We report a case of recurrent severe hepatitis of autoimmune origin in a female patient. The disease course was marked by initial onset at age 39, followed by nearly four years of remission, and a second flare with a more exaggerated severity. Systemic lupus erythematosus was initially deemed as the culprit, however formal diagnostic criteria were not fulfilled and the serological findings were not reproduced at a later date. With the aim of ascertaining the underlying process, the patient underwent an extensive array of testing with regards to infectious, genetic, systemic and autoimmune disease. Positive anti-dsDNA (double stranded DNA) and an antinuclear antibody titer of 1:160 provided the strongest support for an autoimmune etiology, specifically autoimmune hepatitis or possibly an overlap syndrome. An excellent outcome was achieved via treatment with corticosteroids, ursodeoxycholic acid and plasmapheresis.

Q fever: a rare but potentially life-threatening zoonotic disease

Q fever can present as a fever of unknown aetiology and can be challenging to diagnose because of the rare incidence. It can present as an acute illness with manifestations, including influenza-like symptoms, hepatitis, pneumonia or chronic disease involving the cardiovascular system. We present a case of a 39-year-old woman in the USA, who developed acute Q fever with associated sepsis and severe hepatitis. She received treatment with recovery from acute infection but currently has symptoms of post Q fever syndrome.