Regular Liver Function Monitoring Research Articles

Tirzepatide-Related Acute Liver Injury.

Tirzepatide should be used cautiously, with regular monitoring of liver function tests.If patients develop severe gastrointestinal symptoms or worsening abdominal pain, immediate hospital admission is necessary for further work-up, including a CT abdomen.Daily liver function tests, renal function tests and international normalised ratio (INR) tests should be conducted to identify and manage potential complications.

Comparison of Liver Injury in Patients Taking Methotrexate and Leflunamide in Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints, leading to inflammation and potential joint damage. Methotrexate (MTX) and Leflunomide (LEF) are commonly used disease-modifying antirheumatic drugs (DMARDs) for RA, but their hepatotoxic effects require careful monitoring. Objective: This study aimed to compare the incidence of liver injury in RA patients treated with Methotrexate versus Leflunomide. Methods: This prospective study was conducted from January 2023 to June 2023 and included 80 RA patients aged 20 years or older, who reported to the Medicine Department at Combined Military Hospital (CMH) Lahore. Patients were divided into two groups: Group A received 20 mg/day Methotrexate (n=40), and Group B received 20 mg/day Leflunomide (n=40). Exclusion criteria included pregnant females, patients with hepatitis B or C, those with known allergies to Methotrexate or Leflunomide, and alcoholics. Baseline investigations, including liver enzyme levels (ALT/AST), were performed, and patients were monitored every three months. Hepatotoxicity was defined as an increase in ALT/AST levels to at least twice the upper limit of normal (ULN). Data were analyzed using SPSS version 25.0, with mean and standard deviation for quantitative data and frequency and percentage for qualitative data. The Chi-square test was used to compare variables, with p<0.05 considered statistically significant. Results: Out of 80 patients, 43 (53.75%) were female, and 37 (46.25%) were male. In Group A, 7 patients (17.5%) had elevated ALT/AST levels, while 6 patients (15%) in Group B exhibited elevated liver enzymes. The mean age was 52.4 ± 8.3 years in Group A and 50.6 ± 9.1 years in Group B. The mean BMI was 26.7 ± 3.5 kg/m² in Group A and 27.1 ± 3.8 kg/m² in Group B. No statistically significant difference in hepatotoxicity was observed between the two groups (p>0.05). Conclusion: Methotrexate and Leflunomide were equally effective in treating RA, with no significant difference in liver toxicity observed between the two groups. Both medications have comparable risks for hepatotoxicity, necessitating regular liver function monitoring during treatment.

CDK4/6 inhibitors in drug-induced liver injury: a pharmacovigilance study of the FAERS database and analysis of the drug-gene interaction network.

The aim of this study was to investigate the potential risk of drug-induced liver injury (DILI) caused by the CDK4/6 inhibitors (CDK4/6is abemaciclib, ribociclib, and palbociclib by comprehensively analyzing the FDA Adverse Event Reporting System (FAERS) database. Moreover, potential toxicological mechanisms of CDK4/6is-related liver injury were explored via drug-gene network analysis. In this retrospective observational study, we collected reports of DILI associated with CDK4/6i use from the FAERS dated January 2014 to March 2023. We conducted disproportionality analyses using the reporting odds ratio (ROR) with a 95% confidence interval (CI). Pathway enrichment analysis and drug-gene network analyses were subsequently performed to determine the potential mechanisms underlying CDK4/6i-induced liver injury. We found positive signals for DILI with ribociclib (ROR = 2.60) and abemaciclib (ROR = 2.37). DILIs associated with liver-related investigations, signs, and symptoms were confirmed in all three reports of CDK4/6is. Moreover, ascites was identified as an unlisted hepatic adverse effect of palbociclib. We isolated 189 interactive target genes linking CDK4/6 inhibitors to hepatic injury. Several key genes, such as STAT3, HSP90AA1, and EP300, were revealed via protein-protein analysis, emphasizing their central roles within the network. KEGG pathway enrichment of these genes highlighted multiple pathways. Our study revealed variations in hepatobiliary toxicity among the different CDK4/6 inhibitors, with ribociclib showing the highest risk of liver injury, followed by abemaciclib, while palbociclib appeared relatively safe. Our findings emphasize the need for cautious use of CDK4/6 inhibitors, and regular liver function monitoring is recommended for long-term CDK4/6 inhibitor use.

Causal Relationship between Angina and Hepatic Failure as Revealed by Mendelian Randomization.

Patients with angina are often suffering from comorbidities such as varying degrees of hepatic dysfunction. However, the impact of angina on the incidence of hepatic failure (HF) remains unclear. The genetic data were retrieved from genome-wide association studies. Five Mendelian randomization methods were used to investigate the causal relationship between unstable angina (UA), stable angina (SA), and HF. The result of the Inverse variance weighted (IVW) method was deemed the principal result. In addition, we performed a comprehensive sensitivity analysis to verify the robustness of the results. The IVW results showed that UA (Odds ratio (OR): 2.055, 95% confidence interval (CI): 1.171-3.606, p = 0.012) was causally associated with the incidence of HF. SA (OR: 1.122, 95% CI: 0.738-1.706, p = 0.591) was not causally associated with the incidence of HF. Sensitivity analysis did not identify any bias in the results. UA turned out to be a risk factor for HF. SA does not have a significant causal effect on HF. Therefore, it is highly recommended that patients with chronic liver disease seek prompt medical attention and undergo regular monitoring of liver function when experiencing UA. This may help them to reduce the risk of HF.

Consequence of Antivirals Versus Standard Care on Clinical Situation in Patients With COVID-19

Abstract Favipiravir and remdesivir have recently received more clinical interest for the management of COVID-19. The study aimed to explore the effectiveness of favipiravir or remdesivir on the clinical outcome of SARS-CoV-2 patients in comparison with standard care. All patients were given standard care before being randomized into the following 3 groups: standard care group (standard care only), remdesivir group (remdesivir and standard care), and favipiravir group (group 3, favipiravir and standard care). The primary endpoint of the study was time to recovery or the clinical condition of patients on day 14. A total of 156 patients underwent randomization (53 assigned to standard care group, 51 to favipiravir group, and 52 to remdesivir group). The percentage of death in favipiravir and remdesivir groups was higher than those in the standard care group and likewise the liver enzymes. Studying the time to starting therapy showed that early administration of antivirals resulted in lower percentage of mortality. The ratio of hazard for early favipiravir and remdesivir was lower in comparison with those treated with late administration of the same drugs (hazard ratio, 0.62; 95% confidence interval [CI], 0.62–0.73 vs 3.22; 95% CI, 3.21–3.44, respectively, for favipiravir and 0.11; 95% CI, 0.10–0.12 vs 3.44; 95% CI, 3.43–3.55, respectively, for remdesivir). For favipiravir or remdesivir to have more beneficial effects than standard care alone for SARS-CoV-2 patients, they need to be started as early as possible. However, regular monitoring of liver function is required.

Aripiprazole-induced liver injury: a spontaneous reporting database study.

Background: There have been individual case reports of aripiprazole in recent years, both domestically and internationally, but no analysis of the characteristics of the occurrence of adverse reactions/events of drug-induced liver injury with aripiprazole using spontaneous reports has been seen. Methods: Using a retrospective study approach, the 452 adverse reaction/event reports of aripiprazole-induced liver injury collected by the China Adverse Drug Reaction Monitoring System from 1 January 2012 to 31 December 2016 were analyzed and evaluated, and exploring it's the clinical characteristics and related risk factors for liver injury occurrence. Results: Among 452 cases of aripiprazole-induced liver injury ADR/ADE reports, there were 121 cases classified as serious, accounting for 26.8% of the total. There were 250 male and 202 female patients, with a male-to-female ratio of 1.24:1. The age of patients ranged from 11 to 77years old, with an average age of (34.56 ± 12.81)years old, and a high proportion of young adults in the total population. Some patients had used the drug off-label or at a higher than recommended dosage. The onset of liver injury was generally within 15-90days after continuous use, while some patients are also accompanied by nausea, vomiting, and weight gain. 70% of the combined drug instructions listed that may cause liver injury. Conclusion: In clinical practice, healthcare professionals should pay closely attention to the adverse reactions and risk factors of liver injury caused by aripiprazole. If there are potential risk factors for liver injury, early and regular monitoring of liver function should be carried out to reduce the occurrence of adverse reactions.

P300 The effect of Highly Effective Modulator therapy (HEMT) on liver function tests of adult patients with cystic fibrosis-related liver disease at one year: the Welsh experience

One of the important potential adverse reactions of HEMT is hepatobiliary disorders, and regular liver function monitoring is essential practice. This study aims to evaluate the effect of the triple CFTR-modulator therapy Kaftrio (elexacaftor/tezacaftor/ivacaftor) on liver function tests (LFT’s) of patients with cystic fibrosis-related liver disease (PwCFLD) one year after starting therapy.

Management of Pulmonary Tuberculosis in Liver Cirrhosis: A Case Report

Background: Anti-tuberculosis drugs (OAT) are metabolized in the liver and have a high potential for hepatotoxicity, and will increase the risk of drug-induced liver injury (DILI). This study aimed to describe the management of pulmonary tuberculosis in patients with cirrhosis of the liver.
 Case presentation: 45 years old male patient with cough with phlegm for 5 months, weight loss. The patient is also known to have cirrhosis of the liver. From the results of the bacteriological examination, it was found that TCM mtb was detected as high. The patient has risk factors for low BMI, a history of alcohol, hypo albumin, and comorbid hepatic cirrhosis. This patient was given a hepatoprotection. After liver function improved, the patient was started on anti-tuberculosis drugs with a regimen of 2 hepatotoxic drugs, namely isoniazid, rifampin, and ethambutol, given gradually and planned to be given for 9 months, with regular monitoring of liver function in the first 2 months.
 Conclusion: Effective management of pulmonary tuberculosis infection depends on giving OAT at the appropriate dose and duration. The selection of regimen and duration of therapy can be considered based on the condition of chronic liver disease. Careful assessment and periodic evaluation of liver function are required.

Incidence and Temporal Trend of Antituberculosis Drug-Induced Liver Injury: A Systematic Review and Meta-Analysis.

Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed, and the protocol was registered in PROSPERO (CRD42020200077). Five electronic databases were searched to identify eligible studies published between 1990 and 2022. Search terms included anti-TB treatment and drug-induced liver injury. Studies that reported the incidence of ATLI or provided sufficient data to calculate the incidence of ATLI were included, and duplicate studies were excluded. Meta-analysis was conducted on the basis of logit-transformed metrics for the incidence of ATLI with 95% confidence intervals (CIs), followed by a predefined subgroup meta-analysis. Temporal trend analyses were performed to describe the change in pooled incidence over time. A random effects metaregression was conducted to explore the source of heterogeneity. All statistical analyses were carried out using R 4.0.1. Results A total of 160 studies from 156 records with 116147 patients were included in the meta-analysis. Based on the random effects model, the pooled incidence of ATLI was 11.50% (95% CI: 10.10%–12.97%) and showed an upward trend over time (P < 0.001). Patients who received first-line anti-TB drugs, patients in South America, and patients with hepatitis B and C virus coinfection had a higher incidence of ATLI (13.66%, 18.16%, and 39.19%, respectively). Sensitivity analyses also confirmed this robust incidence after the exclusion of some studies. The metaregression showed that different anti-TB regimens and geographical regions were important explanatory factors of the heterogeneity between studies. Conclusions The present systematic review provided a basis for estimating the incidence of ATLI worldwide, which varied among patients with different anti-TB regimens in different geographical regions and with different coinfections and had an upward trend. Regular liver function monitoring is imperative for patient safety during the anti-TB treatment course.

Evaluation of the Hepatic effects of Caladium hortulanum Leaf Extract on Wistar Albino Rats

This study evaluates the hepatic effects of caladium hortulanum leaf extract on wistar albino rats. A total of twenty-four (24) rats were randomly divided into 4 groups labeled A, B, C and D and kept in a well-ventilated room. Group A served as control and these rats were fed distilled water. Rats in the groups B, C, and D were given three (3) different doses of the leaf extract (1.5, 3.5 and 5.0mL/Kgbw) respectively. They were administered once daily for 14 and 28 days consecutively. Animals were sacrificed 24 hours after the last treatment. Blood samples were collected into heparinized sample bottles for analysis. All liver enzymes and histology results were normal for short term use in this study. Alkaline phosphatase was increased in a dose dependent manner when used in the long term. Histopathological changes were seen in all doses when Caladium hortulanum leaf extract was used in the long term. This suggests that this medicinal plant cause some degree of hepatic damage when used for continuously for long periods at a time. Care should therefore be taken with their use, prescriptions reviewed as needed and regular monitoring of liver function should be instituted.

Gastrointestinal and hepatic side effects of potential treatment for COVID-19 and vaccination in patients with chronic liver diseases

The outbreak of coronavirus disease 2019 (COVID-19) is a global pandemic. Many clinical trials have been performed to investigate potential treatments or vaccines for this disease to reduce the high morbidity and mortality. The drugs of higher interest include umifenovir, bromhexine, remdesivir, lopinavir/ritonavir, steroid, tocilizumab, interferon alpha or beta, ribavirin, fivapiravir, nitazoxanide, ivermectin, molnupiravir, hydroxychloroquine/chloroquine alone or in combination with azithromycin, and baricitinib. Gastrointestinal (GI) symptoms and liver dysfunction are frequently seen in patients with COVID-19, which can make it difficult to differentiate disease manifestations from treatment adverse effects. GI symptoms of COVID-19 include anorexia, dyspepsia, nausea, vomiting, diarrhea and abdominal pain. Liver injury can be a result of systemic inflammation or cytokine storm, or due to the adverse drug effects in patients who have been receiving different treatments. Regular monitoring of liver function should be performed. COVID-19 vaccines have been rapidly developed with different technologies including mRNA, viral vectors, inactivated viruses, recombinant DNA, protein subunits and live attenuated viruses. Patients with chronic liver disease or inflammatory bowel disease and liver transplant recipients are encouraged to receive vaccination as the benefits outweigh the risks. Vaccination against COVID-19 is also recommended to family members and healthcare professionals caring for these patients to reduce exposure to the severe acute respiratory syndrome coronavirus 2 virus.

Relative risk of hepatotoxicity associated with cyclin-dependent kinase inhibitors (CDK4/6i): A systematic review and meta-analysis of phase 3 randomized controlled trials.

e13037 Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) such as palbociclib, abemaciclib, and ribociclib have changed the landscape of management of estrogen receptor-positive and HER2-negative breast cancer in recent years. We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of hepatic dysfunction associated with the use of CDK4/6i. Methods: We conducted a systematic search using PRISMA guidelines in PubMed, EMBASE, American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer Symposium meeting abstracts from inception through Jan 30, 2021. Phase 3 RCTs using CDK4/6i in the intervention arm and reporting the number of events for elevation of liver enzymes were included in the analysis. The Cochran-Mantel-Haenszel method and random effects model were used to calculate the pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested by Cochran’s Q test and I2 value. Results: Nine phase 3 RCTs — MONALEESA-2, MONALEESA-3, MONALEESA-7, MONARCH 2, MONARCH 3, MONARCH plus, monarchE, PALOMA-2, and PALOMA-3 — randomizing 5,809 patients in the CDK4/6i arms and 4,638 patients in the control arms were included in the analysis. The CDK4/6i arms used CDK4/6i such as palbociclib, abemaciclib, or ribociclib in combination with one of the standard-of-care endocrine therapies such as letrozole, anastrozole, tamoxifen, or fulvestrant. The control arms received placebo along with respective endocrine therapies. The incidence of any grade alanine aminotransferase (ALT) elevation was 13.1% in the CDK4/6i arm and 5.4% in the control arm, pooled RR: 2.18, 95% CI: 1.74-2.72, P &lt; 0.00001, I2 = 45%. The incidence of any grade aspartate aminotransferase (AST) elevation was 12.5% in the CDK4/6i arm and 5.3% in the control arm, pooled RR: 2.00, 95% CI: 1.57-2.54, P &lt; 0.00001, I2 = 57%. The incidence of grade 3/4 ALT elevation was 4.1% in the CDK4/6i arm and 0.8% in the control arm, pooled RR: 4.43, 95% CI: 3.08-6.37, P &lt; 0.00001, I2 = 0%. The incidence of grade 3/4 AST elevation was 2.9% in the CDK4/6i arm and 0.9% in the control arm, pooled RR: 2.70, 95% CI: 1.75-4.19, P &lt; 0.00001, I2 = 29%. No fatal case of hepatotoxicity has been reported. Conclusions: Cyclin-dependent kinase 4/6 inhibitors are associated with significant risk of any grade and grade 3/4 hepatic enzymes elevation. Regular monitoring of liver function is a key to early detection and initiation of appropriate management.

ADVERSE DRUG REACTION MONITORING OF FLUCONAZOLE IN A TERTIARY CARE HOSPITAL

Objective: To study the incidence and pattern of adverse effects of Antifungal drug Fluconazole and to assess the severity of its adverse effects.&#x0D; Methodology: The study was approved by Institutional ethics committee and informed consent was obtained from all willing participants. Patients fulfilling inclusion and exclusion criteria were enrolled. Age sex, diagnosis, dose and duration of treatment were recorded. 2ml of blood was collected for liver function test. The adverse drug reaction (ADR) was documented. The causality assessment was done by WHO assessment scale and severity assessment by using modified Hartwig severity assessment scale.&#x0D; Results: In this study, most of the patients were in 31-40 years age group. Among the 100 patients who were on Fluconazole 58 developed adverse drug reactions. 64 percentage of ADRs were reported in patients with treatment duration of more than 12 weeks. The most common adverse drug effect documented was abdominal pain followed by headache. Increase in serum transaminases was noted in 7 percentage of patients who were taking Fluconazole for more than 12 weeks, which did not require treatment termination or dosage alteration. Most of the ADRs were in possible category of causality assessment scale. In severity assessment most of the ADRs were in mild category.&#x0D; Conclusion: Adverse drug reaction to Fluconazole was mostly noted in patients who were on treatment for more than12 weeks of which elevated serum transaminases were observed in 8 patients. Hence regular liver function monitoring is advised in all patients receiving Fluconazole for more than 12 weeks to prevent further liver damage.&#x0D; Keywords: Adverse drug reaction, Fluconazole

Moderate Risk of Hepatitis B Virus Reactivation in HBsAg\u2212/HBcAb+ Carriers Receiving Rituximab for Rheumatoid Arthritis

To investigate the incidence and risk factors of hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)−/ HBV core antibody (HBcAb)+ patients who underwent rituximab (RTX) therapy for rheumatoid arthritis (RA). From January 2000 through December 2017, a total of 134 RA patients with various HBV serostatuses who received RTX at Dalin Tzu Chi Hospital were screened. Finally, 50 HBsAg−/HBcAb+ patients were enrolled in this retrospective study. Baseline characteristics, comedications, and the occurrence of HBV reactivation were recorded. Four HBsAg−/HBcAb+ RA patients (8%; 4/50) experienced HBV reactivation after treatment with RTX. Hepatitis flare-up occurred in 2 of these 4 patients, with a fatal outcome in one. HBV reactivation occurred approximately 1–4 years after the first dose of RTX and 0.5–1.5 years after the last one. In HBsAg−/HBcAb+ patients, HBV reactivation was significantly more common in those who were HBV surface antibody (HBsAb)− at baseline than in those who were HBsAb+ (30% vs 4%; p = 0.02). A history of adalimumab use was associated with HBV reactivation (100% vs 39%; p = 0.02). A moderate risk of HBV reactivation was observed in HBsAg−/HBcAb+ RA patients receiving RTX therapy. The reactivation may induce acute hepatitis and even death. To reduce the risk of HBV reactivation, regular monitoring of liver function is insufficient; monitoring of viral load and HBsAg or prophylaxis with antiviral therapy should be considered.

Resolution of grossly discrepant inter-analyser bilirubin results in patients on eltrombopag therapy: A hepatotoxic drug that affects bilirubin measurement

Background: Eltrombopag is a thrombopoietin receptor agonist that is increasingly being prescribed for the treatment of chronic thrombocytopenic conditions. Hepatotoxicity occurring in ∼15% of patients necessitates regular monitoring of liver function. Depending in which hospital a patient is followed-up, serum bilirubin concentration for a single sample can vary by more than 8-fold, or 64 μmol/L, with the true concentration unknown. Methods: Bilirubin was measured using up to nine assays including the Doumas Reference method and HPLC, for 66 samples from patients on 25–150 mg daily. Plasma/serum eltrombopag concentrations were determined using LC-MS/MS. Results: There was a positive correlation between inter-analyser total bilirubin difference and plasma eltrombopag concentration (r=0.679). Spike-in experiments demonstrated that methods including the Doumas reference method were susceptible to positive interference. HPLC quantified bilirubin after separating eltrombopag, and results show that different analysers are affected to varying degrees by eltrombopag and its metabolites. Conclusions: We are the first to demonstrate which bilirubin assays can accurately quantitate bilirubin concentration in patients on eltrombopag therapy. We are also the first to provide evidence that metabolites likely contribute to the interference. Resolution of inter-analyser discrepancies may prevent misdiagnosis of hepatotoxicity and improve our understanding of the prevalence of hyperbilirubinaemia in patients on eltrombopag therapy.

Re-evaluation of liver injury associated with Buguzhi Preparations based on passive monitoring data and hospital cases

In this paper,the case reports on rug-induced liver injury( ADR cases) related to Gukang Capsules containing Psoralea corylifolia( Buguzhi,BGZ) were collected from the adverse reaction monitoring database from January 1,2012 to December 31,2016,and the in-patients cases with drug-induced liver injury admitted to a tertiary Class A liver disease hospital from January 1,2010 to December 31,2016 were also collected. These collected cases were re-evaluated and analyzed. 110 cases with liver injury related to this preparation were collected from adverse reaction monitoring database,and 55 cases of them received the preparation alone,mainly for fracture treatment( 52. 74%). Ninty one cases( 82. 72%) met the standard of the biochemical diagnostic criteria for drug-induced liver injury. 89. 01% of patients were over the age of 41 and women accounted for 60. 9%. The time from administration to liver injury was 1-208 days,with the median of 29 d. The dose of the preparation was 2. 4-4. 8 g per day,with a cumulative dose ranging from 3. 6-699. 6 g. The recovery and improvement rate reached 96. 70% after positive treatment. Seven inpatient cases related to the preparation were collected in a tertiary Class A liver disease hospital,6 females and 1 male. All of them were over 40 years old. Two cases reached the " suspicious diagnosis" standard and 5 cases reached the " clinical diagnosis" standard in Guidelines for the diagnosis and treatment of herb-induced liver injury. Six patients had a good prognosis effect,but another one had liver failure. This preparation is commonly used in fracture,osteoarthritis and other diseases,with remarkable curative effect. However,ADR cases and hospital cases all indicated the risk of liver injury. There was no significant correlation between the time and dose of drug use and the occurrence of liver injury.The induced-liver injury may have immunological heterogeneity,thus regular monitoring of liver function should be taken during clinical use.

The role of regular liver function monitoring in antituberculosis drug-induced liver injury.

Antituberculosis (TB) drug-induced liver injury (ATLI) is a common adverse effect of anti-TB drugs. Whether regular monitoring of liver function can ameliorate ATLI has been widely debated. The current study aimed to investigate the liver test monitoring status of patients receiving anti-TB treatment in Taiwan, as well as the impact of scheduled liver function monitoring on the risk of ATLI. Patients who received anti-TB treatment at our hospital between 2009 and 2017 were enrolled for retrospective analysis. A total of 1062 patients were included, and of them 469 (44.2%) received regular liver function monitoring (good monitoring group). ATLI was recognized in 100 (9.4%) patients. The good monitoring group detected more ATLI cases early compared with the poor monitoring group (14.7% vs 5.2%, and 21.4 vs 61.6 days, p < 0.01), with a lower peak serum alanine aminotransferase (276.1 vs 507.1 IU/L, p = 0.05). In the current study, less than half of all patients who received anti-TB drugs had their liver function monitored regularly. Scheduled monitoring of liver function could facilitate the early identification of more ATLI cases, thus leading to less liver injury. The implementation of periodic liver function monitoring tests in patients receiving anti-TB treatment should be re-emphasized and encouraged.

Co-infection with hepatitis B virus among tuberculosis patients is associated with poor outcomes during anti-tuberculosis treatment

BackgroundTuberculosis (TB) and chronic Hepatitis B virus (HBV) infection are common in China. Fist-line anti-TB medications often produce drug-induced liver injury (DILI). This study sought to investigate whether TB patients with chronic HBV co-infection are more susceptible to liver failure and poor outcomes during anti-TB treatment.MethodsEighty-four TB patients developed DILI during anti-TB treatment and were enrolled, including 58 with chronic HBV co-infection (TB-HBV group) and 26 with TB mono-infection (TB group). Clinical data and demographic characteristics were reviewed. The severity of DILI and incidences of liver failure and death were compared. Risk factors of clinical outcomes were defined.ResultsThe patterns of DILI were similar in both groups. Compared with patients in the TB group, patients in the TB-HBV group who did not receive anti-HBV therapy before anti-TB treatment were more susceptible to Grade-4 severity of DILI (36.2% vs. 7.7%, P = 0.005), liver failure (67.2% vs. 38.5%, P = 0.013) and poor outcomes (37.9% vs. 7.7%, P = 0.005). Age > 50 years (48.1% vs. 22.6%, P = 0.049), cirrhosis (50.0% vs. 15.4%, P = 0.046) and total bilirubin > 20 mg/dl (51.6% vs. 14.8%, P = 0.005) were independent risk factors for the rate of death in the TB-HBV group, and HBV DNA > 20,000 IU/ml had borderline significance (44.1% vs. 20.8%, P = 0.081). In the TB-HBV group, nucleos(t)ide analogues as rescue therapy were not able to reduce short-term death (33.3% vs. 36.8%, P = 0.659) once liver failure had occurred.ConclusionsPatients on anti-TB therapy with chronic HBV co-infection are more susceptible to developing liver failure and having poor outcomes during anti-TB treatment. Regular monitoring of liver function and HBV DNA level is mandatory. Anti-HBV treatment should be considered in those with high viral levels before anti-TB treatment.

Hepatotoxicity in hyperthyroid patient after consecutive methimazole and propylthiouracil therapies

SummaryMethimazole (MMI) and propylthiouracil (PTU) are widely used antithyroid drugs (ATD) that have been approved for the treatment of hyperthyroidism. Hepatotoxicity may be induced by these drugs, though they exert dissimilar incidence rates of hepatotoxicity and, possibly, with different underlying pathogenic mechanisms. We report the case of a 55-year-old woman with no relevant medical history diagnosed with hyperthyroidism due to Graves’ disease, who developed two episodes of acute hepatitis concurrent with the consecutive administration of two different ATDs, first MMI and then PTU. Given the impossibility of administering ATDs, it was decided to perform a total thyroidectomy because the patient was found to be euthyroid at that point. Pathological anatomy showed diffuse hyperplasia and a papillary thyroid microcarcinoma of 2 mm in diameter. Subsequent clinical check-ups were normal. This case suggests the importance of regular monitoring of liver function for hyperthyroid patients. Due to the potential severity of this side effect, it is recommended to determine baseline liver function prior to initiation of treatment.Learning points:We present a rare case of two acute hepatitis episodes concurrent with two different consecutive ATD therapies.Our results highlight the relevance of a liver function monitoring during the treatment with MMI or PTU.A baseline assessment of the liver function before starting an ATD treatment should be recommendable.

Effect of scheduled monitoring of liver function during anti-Tuberculosis treatment in a retrospective cohort in China

BackgroundData on effect of regular liver function monitoring during anti-TB treatment is limited in China. This study aimed to evaluate the effects of scheduled liver function monitoring on identification of asymptomatic liver damage and anti-TB treatment outcomes during anti-TB treatment.MethodsA retrospective analysis was performed based on a national-level cohort study. A total of 273 patients developing liver dysfunction were divided into two groups, 111 patients who were diagnosed through scheduled liver function test within two months after initiation of anti-TB treatment formed scheduled monitoring group, others who were diagnosed due to developing symptoms formed passive detection group (n = 162). The two groups were compared through clinical features, prognosis of liver dysfunction and impact on anti-TB treatment using propensity score weighting analysis.Results33.3% of 273 patients did not have any clinical symptoms, including 8 with severe hepatotoxicity. 1.8% in scheduled monitoring group and 11.1% in passive detection group required hospitalization (P = 0.004). Regarding the prognosis of liver dysfunction, most patients recovered, no death happened in scheduled monitoring group while 3 died in passive detection group. In terms of impact on anti-TB treatment, 35.1% in scheduled monitoring group and 56.8% in passive detection group changed their anti-TB treatment (P = 0.001).ConclusionsScheduled monitoring is effective in identifying asymptomatic liver damage, reducing hospitalization rate and improving compliance of anti-TB treatment.