Occurrence Of Liver Damage Research Articles

Effect of HBV DNA load on the safety and prognosis of systematic therapy in advanced hepatocellular carcinoma

Objective: To study the effect of hepatitis B virus (HBV) infection on the occurrence of liver damage, HBV reactivation (HBVr) and the influence of HBVr on the prognosis of patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. Methods: The clinical data of 403 patients with HBV-related HCC at the Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University et al, from July 2018 to December 2020 were collected. The incidence of liver damage and HBVr during systematic therapy, and the influence of HBVr on survival prognosis were analyzed. Results: Of the 403 patients, 89.1% were male (n=359), with a median age of 51 years (51.5±12.1). Before propensity score matching (PSM), the proportion of patients with cirrhosis, TNM and advanced BCLC stage was higher in high HBV-DNA (baseline HBV-DNA>1000 U/ml, n=147) group comparing with the low HBV-DNA (baseline HBV DNA≤1000 u/ml, n=256) group (P<0.05). There was no significant difference in baseline indexes between the two groups after PSM. In 290 patients after PSM, there was no significant difference in the incidence of liver damage and HBVr between high HBV-DNA group and low HBV-DNA group (P>0.05). Survival analysis was performed on 169 patients with survival data, the median overall survival (OS) was found to be 11.49 months (95%CI: 7.77-12.89) and 16.65 months (95%CI: 10.54-21.99, P=0.008) in the high and low HBV-DNA groups, respectively. And median progression-free survival (PFS) was 7.41 months (95%CI: 5.06-8.67) and 10.55 months (95%CI: 6.72-13.54, P=0.038), respectively, with a statistically significant difference. There were no differences in overall survival (OS) and progression-free survival (PFS) between patients with and without HBVr and those with or without liver damage (P>0.05). Conclusions: HBV-DNA levels above 1 000 U/ml before systemic therapy do not increase the risk of liver damage or HBVr during systemic therapy in patients with HBV-related hepatocellular carcinoma, and such patients can safely receive systemic therapy.

Clinical and laboratory diagnostics of drug-induced liver injury by antibiotics

Liver damage in a patient can precede the prescribing of antibiotics for the treatment of an infectious disease, may occur during their use or after their discontinuation. Liver damage before the start of treatment limits the choice and affects the dosage of antimicrobial agents. The occurrence of liver damage during antimicrobial treatment or after discontinuation of antibiotics can be both a consequence of this intake and independent of treatment with antibacterial drugs. Diagnosis of such lesions requires the use of many clinical, laboratory and instrumental investigations. The key element of diagnosis is the determination of the biochemical variant of liver damage, which makes it possible to plan the sequence of differential diagnosis. In case of suspicion of drug-induced damage to the liver, it is necessary to stop taking immediately the drugs that allegedly caused it. The next step is finding out the connection between the use of the antibiotic and the occurrence of the disease, taking into account the data of the literature regarding this possibility. Then it is necessary to estimate compatibility in time between the start of the use of drugs and the appearance of signs of liver damage, to assess the severity of the injury and, if possible, to prescribe appropriate medicines. There are several methods to assess causality between drugs and liver injury with RUCAM on the head. LiverTox is a well-known database on medicines, which are capable to cause liver damage. Antimicrobial agents belong to the most frequent causes of drug-induced liver injury. Most of such injuries are idiosyncratic. There was used a clinical example of possible drug-induced liver damage to illustrate decisions and difficulties in proving the etiological role of an antibiotic in a case, when liver damage arose during management of a patient with community-acquired pneumonia. This artic­le is a clinical lecture. Keywords: toxic action, biochemical variant, antimicrobials.

Incidence of and risk factors for liver damage in patients with HIV-1 mono-infection receiving antiretroviral therapy.

The study aimed to investigate the incidence of and risk factors for liver damage in patients with human immunodeficiency virus type-1 (HIV-1) mono-infection receiving antiretroviral therapy (ART). We retrospectively analyzed the clinical data of patients who were diagnosed with HIV-1 infection and initiated ART from January to December 2017. Among them, 382 patients with HIV-1mono-infection and normal baseline liver function were included in the analysis. The incidence of liver damage at each follow-up point, and possible risk factors for liver damage were evaluated via COX regression survival analyses. The overall incidence of liver damage (grade I-IV) was 27.23% (interquartile range [IQR]: 26.38%-28.72%). Grade I liver damage was most common and accounted for 22.13% of cases (IQR: 21.06%-24.04%), while grade II liver damage accounted for 3.40% of cases (IQR: 3.19%-4.26%). COX regression and survival analyses revealed that baseline body mass index (BMI), alanine aminotransferase (ALT) level, CD4+ T cell count, HIV-1 viral load, and the antiretroviral regimen were significantly correlated with the occurrence of liver damage. Moreover, baseline ALT levels and HIV-1 viral load were identified as independent risk factors for liver damage in patients with HIV-1mono-infection. Liver damage is common in patients with HIV-1mono-infection undergoing ART. Patients with risk factors for liver damage should be well-informed before the initiation of ART, and liver function should be closely monitored during ART even in patients with normal liver function before ART.

Adherence with methotrexate in polish patients-Survey research results.

Methotrexate (MTX) is the first-line medicine used in most inflammatory joint diseases. It is highly effective but, it's burdened with common side effects and the result of treatment is not immediately visible. This fact significantly increases the risk of unsatisfying patients' compliance. It may lead to difficulties in achieving disease remission and unjustified escalation of treatment. The aim of the study was to evaluate the methotrexate treatment schemes and to assess the patients' compliance with the treatment. The study was based on an online questionnaire distributed to rheumatic patients treated with MTX. The questions about MTX therapy, treatment monitoring, patients' compliance and causing of skipping drug doses were asked. The questionnaire was filled up by 415 patients (21 men, 394 women and average age 36±12.3). In 238 cases the MTX therapy was discontinued, in 148 the decision was taken by the physician, the others discontinued treatment on their own (90 subjects). From the group of patients who stopped taking MTX, 140 returned to the previous treatment. The most common cause of stopping treatment was gastrointestinal (GI) side effects. Self-discontinuation was more often explained by unbearable side-effects (63.33% vs 44.59%; P=.005) such as GI complaints, headaches and bad mood. The doctor's decision to stop treatment was more often caused by the occurrence of liver damage and the improvement of the patient's condition. Good compliance was declared by 346 patients. Most of them (61.69%) admit to skipping MTX doses. The most common reasons for missing a dose were: infectious disease and forgetfulness. The group of patients with good adherence to therapy was significantly older with longer disease duration. High adherence with prescribed MTX is associated with good treatment tolerance, while the occurrence of side effects significantly increases the risk of discontinuation, often without consulting the physician.

Carbimazole Drug-Induced Hepatitis during Treatment of Graves’ Disease: About Four Cases at Dakar Teaching Hospital

Introduction: Mostly reported common side effects of carbimazole are cutaneous allergies and severe agranulocytosis. However, hepatotoxicity is rarely described. Thus, we report four observations of carbimazole drug-induced hepatitis during the treatment of Graves’ disease, which imputability is likely and probably an immuno-allergic mechanism. Observations: They were four women whose average age was 43 years, with extreme ages of 32 and 54. Patients were monitored and treated with carbimazole in doses contained between 40 mg and 60 mg per day. Clinical manifestations of liver injury were mainly dominated by cholestatic jaundice, found in 100% of our patients. A painful sensitivity of the right hypochondrium was concomitant with jaundice for two patients. The jaundice time to onset after the beginning of treatment with carbimazole varies between 1 month and 6 months. They all had acute hepatitis. The biological assays used to determine the type of liver injury showed, in all cases, a mixed, cholestatic and cytolytic hepatitis. Therapeutically, in all patients, carbimazole was stopped as soon as the suspicion of its incrimination in the occurrence of liver damage was set up. They all had a substitution of carbimazole with benzylthiouracil. Evolution was favorable for all patients, after therapeutic substitution. It was marked by disappearance of jaundice and normalization of the liver biological parameters within a maximum delay of two months after stopping carbimazole use. Conclusion: Treatment with synthetic antithyroid drugs, particularly carbimazole that is most widely used in our regions, requires clinical and biological monitoring. This surveillance, which is often difficult in Africa because of the limited economic resources, can lead to the occurrence of side effects such as potentially serious drug-induced hepatitis, but which has been favorable in our observations.

Clinical analysis of acute liver damage in children with acute Epstein-Barr virus infection

Objective To study the clinical manifestations and laboratory findings like liver function, immunoglobulin and peripheral blood lymphocyte subsets, and to provide evidence for diagnosing and the therapy for acute Epstein-Barr virus (EBV) infection. Methods From July 2012 to June 2015, clinical data from 321 patients with acute EBV infection admitted to Children′s Hospital of Fudan University for treatment were retrospectively analyzed.The clinical characteristics and the findings by liver function test, detection of virus, immunoglobulin and lymphocyte subsets were analyzed.The patients were divided into an abnormal liver function group (186 cases) and the normal liver function group (135 cases). The copy number of EBV-DNA, serum EBV-IgM, immunoglobulin, CD series between the 2 groups were analyzed.Stata 12.0 software was used for statistical analysis. Results (1) There were 321 cases diagnosed with acute EBV infection.Among them, the gender of 183 cases were boys, 138 cases were girls, male to female ratio was 1.33∶1.00.The average age of onset was (52.07±35.05) months.There were 186 cases (57.94%) with abnormal liver function and 135 cases (42.06%) with normal liver function.(2) Clinical course was (9.11±8.21) days, and period of fever lasted (7.12±5.00) days; 281 cases (87.54%) had fever, and the highest temperature reached (39.04±0.69) ℃; lymphadenectasis occurred in 267 cases (83.18%), 245 cases (76.32%) had angina, hepatomegaly occurred in 235 cases (73.21%), 142 cases (44.24%) had splenomegaly, and rash occurred in 60 cases (18.69%); 155 cases (48.29%) occurred trilogy of fever, lymphadenectasis and angina.(3) There were 186 cases had abnormal liver function without jaundice, and their levels of total bilirubin, direct bilirubin, total bile acid, albumin and coagulation function were normal.Alanine aminotransferase (ALT) increased from 40 to 400 IU/L in 125 cases, 400 to 800 IU/L in 2 cases, and more than 800 IU/L in 6 cases.Aspartate aminotransferase(AST) increased from 40 to 400 IU/L in 157 cases, 400 to 800 IU/L in 5 cases, more than 800 IU/L in 1 case.Ninety-seven cases were followed up for liver function, and the recovery time was 21-74 days.(4) In comparison of the abnormal liver function group to the normal liver function group, the differences were statistically significant in age, IgG, IgA, CD4+ T cell, the ratio of CD4+ T cell and CD8+ T cell (all P 0.05). Conclusions Children with acute EBV infection may have a high incidence of liver damage.The clinical manifestations are characterized by elevated transaminase and self-limiting.The occurrence of liver damage may be related to case of cell-mediated immunity Key words: Epstein-Barr virus; Liver function damage; Child

184 Evaluation of the impact of SERPINA gene mutation on the occurrence of liver damage and cholestasis in patients diagnosed with cystic fibrosis

SERPINA1 gene is present in about 2% of patients with cystic fibrosis, but more frequently, in approximately 5% of patients with cystic fibrosis (CF) and concomitant changes in the liver. Aim: The aim of this study was to assess the impact of SERPINA gene mutation on the occurrence of liver damage and cholestasis in patients diagnosed with cystic fibrosis. Patients and Methods: The analysis included 30 children, 13 girls (43.3%) and 17 boys (56.6%), aged from 6 months to 18 years, with diagnosed CF. All patients underwent genetic testing for SERPINA gene mutation. The analysis included age, sex, clinical symptoms, type of mutation of the CFTR protein, laboratory abnormalities (levels of transaminases, GGTP, FA, protein, acid steatocrit) and ultrasound examination of the abdomen. Results: Elevated transaminases were found in 9/30 (30%), whereas elevated levels of gamma-glutamyl transferase in 6/30 (20%) children. In 5/30 patients the ultrasound examination demonstrated liver enlargement with increased echogenicity. The mutation in SERPINA gene was found in 1/30 (3.3%) patient with cystic fibrosis. Currently, this patient has normal values of transaminases, GGTP and FA, whereas, a significant worsening of respiratory symptoms is observed. There was no correlation between the occurrence of SERPINA gene mutation and clinical symptoms, type of CFTR protein mutation, results of laboratory tests of liver function and hepatocyte damage, and ultrasound examination of the abdomen. Conclusions: There was no correlation between the occurrence of SERPINA gene mutation and the presence of features of liver damage and cholestasis in children diagnosed with cystic fibrosis.

Propylthiouracil-Induced Hepatotoxicity: A Case Report

Purpose: Case Presentation: A 61-year-old Hispanic male with a history of Graves Disease and CHF presented with three days of diffuse abdominal pain, localized to the epigastric and periumbilical areas. History revealed the patient had been taking propylthiouracil (PTU) for five months with no prior known toxicity. Exam revealed jaundice and voluntary guarding without rebound. There was no hepatosplenomegaly, ascites, or palpable masses. Labs revealed elevated total bilirubin, lactic acid, PT (39.7), INR (4.02), LDH, and markedly elevated AST (2054 U/L), ALT (1697 U/L). Other major causes of transaminitis, such as acetominophen toxicity, viral hepatitis, and ischemic livery injury were ruled out. Abdominal imaging demonstrated a heterogeneous liver with moderate ascites. Transaminases peaked >5000 U/L after 3 days. The patient symptomatically improved with correction of his liver enzymes and coagulopathy through supportive care and discontinuation of PTU. Discussion: Propylthiouracil is a thiocarbamide used in the treatment of hyperthyroidism, Graves' disease, and multinodular goiter. On rare occasions, PTU can induce serious hepatotoxicity, although a transient increase in aminotransferases has been observed within the first week of treatment in up to 28% of patients 3, 5, 6. In this vignette, we present a case of PTU-induced hepatitis with unusually high liver enzymes. PTU-induced hepatitis was diagnosed based on the occurrence of liver damage within a few months of initiation of therapy, the absence of significantly elevated liver enzymes prior to therapy, and subsequent recovery after discontinuation of the drug. Our patient's condition was complicated by congestive heart failure. Elevated central venous pressure is transmitted to the liver, which can lead to accumulation of deoxygenated blood, hepatocellular hypoxia, necrosis, and fibrosis over time. In such a setting, glucuronidation-dependent metabolism of PTU is compromised. The estimated incidence of antithyroid drug-associated hepatotoxicity is less than 0.5%. PTU-induced hepatitis should be prevented because mortality rate can be as high as 25% due to complications of liver failure 7. Monitoring of liver function and liver transaminases may not necessarily identify those patients who will eventually develop PTU-induced liver failure because it can occur suddenly and be rapidly progressive. This case demonstrates the importance of recognizing such a serious complication in a commonly prescribed medication.

Propylthiouracyl-induced severe liver toxicity: An indication for alanine aminotransferase monitoring

Propylthiouracyl (PTU)-related liver toxicity is likely to occur in about 1% of treated patients. In case of acute or subacute hepatitis, liver failure may occur in about one third. We report two further cases of PTU-induced subacute hepatitis, in whom the delay between occurrence of liver damage after the initiation of treatment, the underestimation of its severity and the delayed withdrawal of the drug were all likely responsible for liver failure. The high incidence of liver toxicity related to PTU, its potential severity and delayed occurrence after initiation of treatment are in favor of monthly alanine aminotransferase monitoring, at least during the first six months of therapy.

Pathophysiology of iron toxicity.

There are several inherited and acquired disorders that can result in chronic iron overload in humans, and the major clinical consequences are hepatic fibrosis, cirrhosis, hepatocellular cancer, cardiac disease, and diabetes. It is clear that lipid peroxidation occurs in experimental iron overload if sufficiently high levels of iron within hepatocytes are achieved. Lipid peroxidation is associated with hepatic mitochondrial and microsomal dysfunction in experimental iron overload, and lipid peroxidation may underlie the increased lysosomal fragility that has been detected in liver samples from both iron-loaded human subjects and experimental animals. Reduced cellular ATP levels, impaired cellular calcium homeostasis, and damage to DNA may all contribute to hepatocellular injury in iron overload. Long-term dietary iron overload in rats can lead to increased collagen gene expression and hepatic fibrosis, perhaps due to activation of hepatic lipocytes. The mechanisms whereby lipocytes are activated in iron overload remain to be elucidated; possible mediators include aldehydic products of iron-induced lipid peroxidation produced in hepatocytes, tissue ferritin, and/or cytokines released by activated Kupffer cells.

Liver damage as a potential source of error in the estimation of myocardial infarct size from plasma creatine kinase activity.

The occurrence of liver damage was investigated in patients with uncomplicated acute myocardial infarction (AMI). Cumulative plasma release of creatine kinase (CK) and alpha-hydroxybutyrate dehydrogenase (HBD) was compared with release of alanine aminotransferase (ALT). Up to 48 h after AMI, the appearance of ALT could be fully explained by myocardial ALT release. Thereafter additional release of ALT occurred, indicating liver damage. A possible effect of liver function on the rate of elimination of CK from plasma was studied in the dog. Complete temporary arrest of hepatic blood supply was obtained after previous implantation of a portacaval shunt, ligation of secondary inflows and blockade of retrograde perfusion. Neither these preliminary haemodynamic interventions nor the acute arrest of hepatic blood flow had any effect on the disappearance rate of CK from plasma. It is concluded that some liver damage commonly occurs in patients after AMI. However, this phenomenon does not interfere with the estimation of infarct size because the elimination of CK from plasma is unaltered during total hepatic ischaemia.

Photosensitivity diseases in New Zealand

Summary An investigation has been undertaken into the effects of toxic extracts of Sporidesmium bakeri, Syd.* Since this paper went to press the toxic fungus has been reclassified as Pithomyces chartarum (Berk. & CurL) M. B. Ellis. administered parenterally in the rabbit, in an attempt to obtain information on the behaviour of the facial eczema toxin within the animal. Lesions characteristic of facial eczema liver damage were found after injection of toxic extracts into the portal system. Macroscopic damage was first observed 48–96 hours after injection. The earliest evidence of histological change was noted 3–6 hours after injection. Liver damage was consistently noted after injection of extracts into the duodenum and gall-bladder, rarely after injection into the systemic circulation via the jugular or ear vein, but never after injection into the caecum. The significance of these findings is discussed in relation to the occurrence of liver damage in animals in the field. It is concluded that the toxin is...

Alteration of copper metabolism in chlorpromazine-treated cases.

The purpose of this paper is to demonstrate that some cases treated with chlorpromazine show alterations of copper metabolism, and a syndrome similar perhaps in some respects to Wilson's disease (hepatolenticular degeneration). Azima and Ogle,1Lehman and Hanrahan,2and others have previously reported a 5% incidence of extrapyramidal complications, or what appears to be a Parkinson-like syndrome, in chlorpromazine-treated cases. The development of extrapyramidal signs, and the occurrence of liver damage, which also is found in 5% to 15% of persons treated with chlorpromazine,* led us to the supposition that perhaps the phenomenon represented a hepatolenticular disturbance similar to Wilson's disease. Although the hepatic lesions associated with chlorpromazine therapy appear to be cholangiolitic in nature,3whereas in Wilson's disease they are parenchymal, there is no definite evidence that the hepatic lesions in the early stages of Wilson's disease are solely parenchymal, or that the continuation of chlorpromazine

EFFECT OF STILBESTROL UPON LIVER AND BODY GROWTH IN RATS

MANY WORKERS have reported the effects of chronic administration of stilbestrol in experimental animals. Undoubtedly, different species of animals vary greatly in their susceptibility to the toxic effects of this substance. The rat has been studied most intensively, the toxic effects upon the liver and body growth having received particular attention. This paper adds our observations of the effects of chronic stilbestrol administration upon certain organ changes, especially the liver and body growth of rats. If the review of the literature is confined to a limited number of representative papers, we find no agreement regarding the occurrence of liver damage in rats. Grumbrecht and Loeser (1, 2) reported necrossis in the liver after 54 doses of 1 mg. of stilbestrol daily, while this dose could be given 25 days without causing such symptoms.