Acute hepatitis B or exacerbation of chronic hepatitis B-that is the question

Hepatitis B virus (HBV) infection constitutes a serious global health problem. In countries with intermediate or high endemicity for HBV, exacerbations of chronic hepatitis B may be the first presentation of HBV infection. Some of these patients may be diagnosed mistakenly as having acute hepatitis B. Accurate diagnosis in these cases is very important for deciding whether to start treatment or not, because acute hepatitis B does not require therapy, while exacerbation of chronic hepatitis may benefit from it. Clinical and routine laboratory findings cannot help distinguishing between these two conditions. Therefore, several assays have been proposed for this purpose during the last few years. The presence of high levels of anti-HBe antibodies, HBsAg and HBV DNA are typical of chronic disease, whereas high titers of IgM anti-HBc, together with their high avidity index, characterize acute HBV infection. Starting from the description of a patient with acute hepatitis B-who recently came to our observation-we critically review the currently available assays that may help distinguishing between the different conditions and lead to the optimal management of each patient.

Ceftriaxone-induced toxic hepatitis

Toxic hepatitis or drug-induced liver injury encompasses a spectrum of clinical disease ranging from mild biochemical abnormalities to acute liver failure.The advantages of a long half-life,wide spectrum,high tissue penetration rate,and a good safety profile,make ceftriaxone,a third-generation cephalosporin,a frequent choice in the treatment of childhood infections.Previous studies have reported a few cases of high aspartate aminotransferase and alanine aminotransferase levels,along with three cases of hepatitis caused by ceftriaxone.Here,we report a case of drug-induced toxic hepatitis in a patient who was treated with ceftriaxone for acute tonsillitis.

Defensive nature of Sargassum polycystum (Brown alga) against acetaminophen-induced toxic hepatitis in rats: Role of drug metabolizing microsomal enzyme system, tumor necrosis factor-a and fate of liver cell structural integrity

AIM： To assess the defensive nature of Sargassum polycystum （S. polycystum） （Brown alga） against acetaminophen （AAP）-induced changes in drug metabolizing microsomal enzyme system, tumor necrosis factor （TNF-α） and fine structural features of the liver during toxic hepatitis in rats. METHODS： Male albino Wistar strain rats used for the study were randomly categorized into 4 groups. Group Ⅰ consisted of normal control rats fed with standard diet. Group II rats were administered with acetaminophen （800 mg/kg body weight, intraperitoneally）. Group Ⅲ rats were pre-treated with S. polycystum extract alone. Group IV rats were orally pre-treated with S. polycystum extract （200 mg/kg body weight for 21 d） prior to acetaminophen induction （800 mg/kg body weight, intraperitoneally）. Serum separated and liver was excised and microsomal fraction was isolated for assaying cytochrome P450, NADPH Cyt P450 reductase and bs. Serum TNF-α was detected using ELISA. Fine structural features of liver were examined by transmission electron microscopy. RESULTS： Rats intoxicated with acetaminophen showed considerable impairment in the activities of drug metabolizing microsomal enzymes, such as cytochrome P450, NADPH Cyt P450 reductase and bs when compared with the control rats. The rats intoxicated with acetaminophen also significantly triggered serum TNF-a when compared with the control rats. These severe alterations in the drug metabolizing enzymes were appreciably pretreated with S. polycystum. prevented in the rats The rats pretreated withS. polycystum showed considerable inhibition in the elevation of TNF-α compared to the rats intoxicated with acetaminophen. The electron microscopic observation showed considerable loss of structural integrity of the endoplasmic reticulum, lipid infiltration and ballooning of mitochondria in the acetaminophen-intoxicated rats, whereas the rats treated with S. polycystum showed considerable protection against acetaminophen-induced alterations in structural integrity. CONCLUSION： These observations suggest that the animals treated with S. polycystum extract may have the ability to protect the drug metabolizing enzyme system and mitochondrial functional status from free radical attack, thereby showing its defense mechanism in protecting hepatic cells from acetaminophen toxic metabolite N-acetyl-para-benzoquinone-imine （NAPQI）.

Efficacy and safety of tenofovir alafenamide in patients with chronic hepatitis B exhibiting suboptimal response to entecavir

BACKGROUND Entecavir(ETV)is a potent and safe antiviral agent for patients with chronic hepatitis B(CHB);however,some patients may exhibit suboptimal response or resistance to ETV.Tenofovir alafenamide(TAF)is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate.AIM To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV.METHODS A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia[Hepatitis B virus(HBV)DNA≥20 IU/mL]or partial virologic response(HBV DNA<20 IU/mL,but detectable)were enrolled in the study.The patients were randomly assigned to either continue ETV(0.5 mg)daily or switch to TAF(25 mg)daily for 48 wk.The primary endpoint was the proportion of patients who achieved a virologic response(HBV DNA level<20 IU/mL)at week 48.Secondary endpoints included changes in serum alanine aminotransferase(ALT),hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg),and anti-HBe levels,and renal and bone safety parameters.RESULTS At week 48,the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group(93.3%vs 66.7%,P=0.012).The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group(-3.8 vs-2.4 Log10 IU/mL,P<0.001).The rates of ALT normalization,HBeAg loss,HBeAg seroconversion,and HBsAg loss were not found to significantly differ between the two groups.None of the patients developed genotypic resistance to ETV or TAF.Both drugs were well tolerated,with no serious adverse events or discontinuations caused by adverse events.No significant changes were observed in the estimated glomerular filtration rate,serum creatinine level,or urine protein-to-creatinine ratio in either group.The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group(-0.8%vs-2.1%,P=0.004;-0.6%vs-1.8%,P=0.007,respectively).CONCLUSION Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.

Experimental substantiation of the platelet-rich plasma usage in toxic hepatitis treatment

The paper presents the investigation of the possibility of hepatic tissue restoration by the platelet-rich plasma(PRP)in case of toxic hepatitis.It is shown PRP injection into liver reduced an amount of connective tissue and collagen fibers at the places of hepatocytes necrosis after experimental toxic influence.PRP administration leads to rapid regeneration of hepatic tissues with restoration of its normal structure.As PRP is concentrate of autologous blood cells,it doesn't cause any side effects and doesn't require immunosuppressive therapy.

Hepatitis C virus and diffuse large B-cell lymphoma: Pathogenesis, behavior and treatment

A significant association between hepatitis C virus (HCV) infection and B-cell lymphoma has been reported by epidemiological studies, most of them describing a strong relationship between indolent lymphomas and HCV. Furthermore, the curative potential of antiviral therapy on HCV related indolent lymphomas supports a specific role for the virus in lymphomagenesis. These observations are reinforced by numerous laboratory experiments that led to several hypothetical models of B-cell transformation by HCV. Diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype in the western countries, has been associated to HCV infection despite its aggressive nature. This association seems particularly prominent in some geographical areas. Clinical presentation of HCV-associated DLBCL has consistently been reported to differ from the HCV-negative counterpart. Nevertheless, histopathology, tolerance to standard-of-care chemo-immunotherapy (R-CHOP or CHOP-like regimens) and final outcome of HCV-positive DLBCL patients is still matter of debate. Addition of rituximab has been described to enhance viral replication but the probability of severe hepatic complications remains low, with some exceptions (i.e., hepatitis B virus or immune immunodeficiency virus co-infected patients, presence of grade &#x0003e; 2 transaminases elevation, cirrhosis or hepatocarcinoma). HCV viral load in this setting is not necessarily directly associated with liver damage. Overall, treatment of HCV associated DLBCL should be performed in an interdisciplinary approach with hepatologists and hematologists with close monitoring of liver function. Available reports reveal that the final outcome of HCV-positive DLBCL that receive standard immunochemotherapy is not inferior to their HCV-negative counterpart. This review summarizes data on epidemiology, pathogenesis and therapeutic approach on HCV-associated DLBCL. Several issues that are matter of debate like clinical management of patients with transaminase elevation, criteria for discontinuing or starting immuno-chemotherapy, as well as the exact role of monoclonal antibodies will be analyzed.

Acute hepatitis secondary to parenteral amiodarone does not preclude subsequent oral therapy

Amiodarone chlorhydrate is a diiodated benzofuran derivative used to treat cardiac rhythm abnormalities. Hepatotoxicity is a relatively uncommon side effect of amiodarone and symptomatic hepatic dysfunction occurs in less than 1% to 3% of patients taking amiodarone. We report here on an unusual case of amiodarone-induced hepatotoxicity. A 29 year old woman with normal liver function was given amiodarone intravenously to treat her atrial fibrillation. She developed acute toxic hepatitis after 24 h. The intravenous form of amiodarone was immediately avoided and replaced by the oral form, using conventional loading doses as soon as the deranged liver function tests had normalized, without recurrence of the hepatitis. These observations show that the occurrence of acute hepatic impairment with intravenous amiodarone does not necessarily preclude the use of this drug by mouth and the necessity of monitoring the hepatic function of patients treated with amiodarone.

Alverine citrate induced acute hepatitis

Alverine dtrate is a commonly used smooth muscle relaxant agent.A MEDLINE search on January 2004 revealed only 1 report implicating the hepatotoxicity of this agent.A 34- year-old woman was investigated because of the finding of elevated liver function tests on biochemical screening.Other etiologies of hepatitis were appropriately ruled out and elevated enzymes were ascribed to alverine citrate treatment. Although alverine citrate hepatotoxicity was related to an immune mechanism in the first case,several features such as absence of predictable dose-dependent toxicity of alverine citrate in a previous study and absence of hypersensitivity manifestations in our patient are suggestive of a metabolic type of idiosyncratic toxicity.

Risk factors for ribavirin treatment failure in Asian organ transplant recipients with chronic hepatitis E infection

BACKGROUND Hepatitis E virus(HEV)infection is a cause of chronic hepatitis in immunosuppressed patients.Sustained virologic response rates to a 12-wk course of ribavirin therapy were reported to be>70%in the West.This study describes the outcome of HEV treatment in a transplant center in Singapore.AIM To study the outcome of ribavirin treatment in a series of chronic HEV patients,and the cause of treatment failure.METHODS We studied all of the transplant recipients who were diagnosed with HEV infection between 2012 to 2015.The outcome of therapy and virologic relapse are monitored for three years after the end of therapy.RESULTS Ten transplant recipients(4 liver,5 kidney,and 1 bone marrow transplantation)with positive HEV RNA were studied.Nine patients received at least 12 wk of ribavirin therapy,and the remaining patient resolved after reducing immunosuppression therapy.Two subjects had prolonged viremia that lasted more than one year,despite continuous ribavirin therapy.Four ribavirin-treated patients(44.4%)had HEV RNA relapse after achieving a virologic response by the end of treatment.The overall failure rate is 66.7%.Being a kidney transplant recipient is the strongest risk factor for not achieving an initial sustained virologic response(0/5 treated,Chi-Square test,P<0.05).The most common side effect of ribavirin is anemia(100%)(haemoglobin reduction of 3-6.2 g/dL).Seven patients required either a blood transfusion or erythropoietin therapy.CONCLUSION The sustained virologic response rate of 12-wk ribavirin therapy for HEV infection in this Asian series was lower than expected.Kidney transplant recipients had a higher rate of treatment failure due to higher immunosuppression requirements and adverse effects.

Stereological and cytochemical study on the pathogenesis of hepatitis induced by halothane in rats

This study was designed to investigate the relationship between hepatotoxicity of halothane and altered hepatic calcium homeostasis in enzyme-induced hypoxic rats by means of Ca2+ cytochemical location and EDX microanalysis combined with stereology of liver and ultrastructural analysis by computer. It was found that more calcium precipitated in the cytoplasm and mitochondria of liver than that in the controls following halothane exposure. This alteration appears to be the result of accelerated uptake of Ca2+ by hepatocytes and decreased output of loaded Ca2+ on the one hand, and increased release of reserved Ca2+ on the other hand. These results suggest that change in cullular Ca2+ balance plays an important role in the mechanism of hepatotoxicity induced by halothane exposure.

Trimethoprim-Sulfamethoxazole-Induced Hepatitis in Mixed Connective Tissue Disease

Trimethoprim-Sulfamethoxazole (TMP-SMZ) is associated with severe hepatic toxicity or liver failure. We present a case of severe hepatic toxicity for whom TMP-SMZ was prescribed as part of treatment for mixed connective tissue disease (MCTD). TMP-SMZ was used to prevent complications from steroid therapy, but fever and hepatic toxicity developed with repeated TMP-SMZ medication. While the drug lymphocyte stimulation test (DLST) for TMP-SMZ showed negative, the genotype for N-acetyltransferase 2 (NAT2) showed type *6/*7, which is the slow acetylating type for NAT2 activity. This finding for NAT2 genotype and the patient’s clinical history lead us to speculate that her fever and hepatic toxicity were caused by TMP-SMZ.

Hydroxycut hepatotoxicity:A case series and review of liver toxicity from herbal weight loss supplements

Dietary supplements represent an increasingly common source of drug-induced liver injury. Hydroxycut is a popular weight loss supplement which has previously been linked to hepatotoxicity, although the individual chemical components underlying liver injury remain poorly understood. We report two cases of acute hepatitis in the setting of Hydroxycut exposure and describe possible mechanisms of liver injury. We also comprehensively review and summarize the existing literature on commonly used weight loss supplements, and their individual components which have demon-strated potential for liver toxicity. An increased effort to screen for and educate patients and physicians about supplement-associated hepatotoxicity is warranted.

Hepatotoxicity associated with glucosamine and chondroitin sulfate in patients with chronic liver disease

Glucosamine and chondroitin sulfate are molecules involved in the formation of articular cartilage and are frequently used for symptom relief in patients with arthrosis.These molecules are well tolerated with scarce secondary effects.Very few cases of possible hepatotoxicity due to these substances have been described.The aim of this paper is to report the frequency of presumed glucosamine hepatotoxicity in patients with liver disease.A questionnaire was given to 151 consecutive patients with chronic liver disease of different etiology(mean age 59 years,56.9%women)attended in an outpatient clinic with the aim of evaluating the frequency of consumption of these drugs and determine whether their use coincided with a worsening in liver function test results.Twenty-three patients(15.2%)recognized having taken products containing glucosamine or chondroitin sulfate previously or at the time of the questionnaire.Review of the clinical records and liver function tests identified 2 patients presenting an elevation in aminotransferase values temporarily associated with glucosamine treatment;one of the cases simultaneously presented a skin rash attributed to the drug.Review of these two patients and the cases described in the literature suggest toxicity of glucosamine and chondroitin sulfate.The clinical spectrum is variable,and the mechanism of toxicity is not clear but may involve reactions of hypersensitivity.The consumption of products containing glucosamine and/or chondroitin sulfate is frequent among patients with chronic liver diseases and should be taken into account on the appearance of alterations in liver function tests not explained by the underlying disease.

Hepatotoxicity Induced by High Dose of Methylprednisolone Therapy in a Patient with Multiple Sclerosis: A Case Report and Brief Review of Literature

Toxic hepatitis due to drugs is an important and frequent drug adverse reaction in clinical practice. Here, we report a case of high dose methylprednisolone-induced acute hepatitis in a 51-year-old woman that suffers from multiple sclerosis while steroids are usually safe drugs with regards to liver injury and even they are the treatment choice of autoimmune hepatitis, but the literatures about corticosteroids showed are not entirely safe to liver injury and they have occasionally linked to hepatotoxicity. Although recent reports have demonstrated that prednisolone may cause hepatitis. This case report includes a brief review of the relevant literature on corticosteroids-induced hepatitis that is presented.

Evaluation of the hepatoprotective and antioxidant effects of Tegillarca granosa flesh body extract against potassium bromide toxicity via targeting the histomorphometry,chromosomal and expressions of TGF-β1,VEGF and COX-2 genes in rats

The hepatotoxic effect of potassium bromide(KBr)on rat liver tissues were determined,as well as the potential protective effect of Tegillaraca granosa(T.granosa)flesh body extract.Twenty adult male albino rats were equally distributed into four groups;Group(I)treated with physiological saline(control group),Group(II)was orally gavaged by 200 mg/kg of T.granosa body extract day after day,Group(III)was intoxicated by KBr(150 mg/kg bwt day after day orally)and finally,Group(IV)was given a combination of T.granosa flesh body extract plus KBr with similar doses in the second and third groups.At the end of one month,blood,liver tissue and bone marrow samples were collected to be used for the required laboratory examinations.In response to KBr toxicity,there was a significant increase in serum antioxidant biomarkers,which was accompanied by a significant change in hepatocyte ultrastructure and a significant change in carbohydrate and protein levels within the liver organ.In addition,KBr intoxication resulted in a substantial increase in the incidence of chromosomal aberrations such as holes,splits,deletions,fragments,ploidy,and ring chromosomes,as well as significant upregulation of TGF-1,VEGF,and COX-2 gene expression.The hepatotoxic effect of KBr was counteracted by treatment with T.granosa flesh body extract.T.granosa flesh body extract has a curative antioxidant and numerous protective effects against KBr hepatotoxicity.

Hepatoprotective effects of S-adenosyl-L-methionine against alcohol-and cytochrome P450 2E1-induced liver injury

S-adenosyl-L-methionine (SAM) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione. SAM is also a key metabolite that regulates hepatocyte growth, differentiation and death. Hepatic SAM levels are decreased in animal models of alcohol liver injury and in patients with alcohol liver disease or viral cirrhosis. This review describes the protection by SAM against alcohol and cytochrome P450 2E1-dependent cytotoxicity both in vitro and in vivo and evaluates mechanisms for this protection.

Liver toxicity of rosuvastatin therapy

We report here a case of clinically significant liver toxicity after a brief course of rosuvastatin, which is the first statin approved by the regulatory authorities since the withdrawal of cerivastatin. Whether rosuvastatin has a greater potential compared with other statins to damage the liver is unclear and the involved mechanisms are also unknown. However, rosuvastatin is taken up by hepatocytes more selectively and more efficiently than other statins, and this may reasonably represent an important variable to explain the hepatotoxic potential of rosuvastatin. Our report supports the view that a clinically significant risk of liver toxicity should be considered even when rosuvastatin is given at the range of doses used in common clinical practice.

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

Propylthiouracyl (PTU)-related liver toxicity is likely to oc- cur 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 sub- acute hepatitis, in whom the delay between occurrence of liver damage after the initiation of treatment, the un- derestimation 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 aminotrans- ferase monitoring, at least during the first six months of therapy.

肝动脉插管化疗栓塞术患者的经济毒性现状及其影响因素分析

目的调查肝动脉插管化疗栓塞术(TACE)患者的经济毒性现状并分析其影响因素。方法选取251例TACE患者作为研究对象,采用一般资料调查表、癌症患者报告结局的经济毒性量表、癌症患者恐惧疾病进展简化量表进行调查,采用多元线性回归模型分析TACE患者经济毒性的影响因素。结果TACE患者经济毒性得分为(15.52±6.62)分,其中高经济毒性患者占比为79.3%。多元线性回归结果显示,职业、对治疗费用的了解程度、恐惧疾病进展总分、文化程度是TACE患者经济毒性的影响因素(P<0.05)。结论TACE患者经济毒性普遍存在且处于高水平。临床医护人员应针对高风险人群及时进行经济毒性评估,为其制订早期、有效、个性化的干预策略,从而降低其经济毒性,提高生活质量。

An Experimental Study on Drugs for Improving Blood Circulation and Removing Blood Stasis in Treating Mild Chronic Hepatic Damage

Large and small doses of drugs for improving blood circulation and removing blood stasis were used in model rats to treat mild chronic hepatic damage induced by carbon tetrachloride (CCl4). The results show that large dose of Dang Gui ([symbol: see text] Radix Angelicae Sinensis) and Dan Shen ([symbol: see text] Radix Salviae Miltiorrhizae) (drugs for regulating blood flow) and small dose of Yu Jin ([symbol: see text] Radix Curcumae) and Niu Xi ([symbol: see text] Radix Achyranthis Bidentatae) (drugs for activating blood flow) can significantly elevate the activity of SOD (P