Drug-Induced Hepatitis

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Predictors, Outcome, Profile of Anti-Tubercular Drug Induced Hepatitis: A Prospective Nested Case- Control Study in a South Indian Tertiary Hospital

Predictors, Outcome, Profile of Anti-Tubercular Drug Induced Hepatitis: A Prospective Nested Case- Control Study in a South Indian Tertiary Hospital

One of the recent studies from India was published in Journal of Postgraduate Medicine (March 2014) by SM Pore from Maharashtra(30). It was a retrospective study including 893 patients admitted in a tertiary care hospital from 2005 to 2009. Baseline characteristics revealed predominant male population (70%) with mean age of 40 years. Significant number of people had past history of ATT intake (30.36% among cases and 44 % among controls). 56 patients developed drug induced hepatitis with most of them requiring hospitalization. Incidence of drug induced hepatitis from that study was 6.27% which was lower compared to other Indian studies. Significant risk factors for drug induced hepatitis from univariate analysis were female gender, past history of ATT intake and alcohol abuse. However in the multivariate analysis, only female gender and alcohol abuse were significant. Effect of other risk factors on drug induced hepatitis like Hepatitis B and C virus infection, pregnancy, hypoalbuminemia and malnutrition were not studied probably because of inadequate data.

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 CLINICAL EVALUATION OF KODIPAVALA CHUNNAM IN THE TREATMENT OF INFECTIVE HEPATITIS, DRUG INDUCED HEPATITIS AND ALCOHOLIC HEPATITIS

 CLINICAL EVALUATION OF KODIPAVALA CHUNNAM IN THE TREATMENT OF INFECTIVE HEPATITIS, DRUG INDUCED HEPATITIS AND ALCOHOLIC HEPATITIS

Overall results revealed that out of 40 patients 10 patients had excellent relief, 26 had good relief, 3 cases showed satisfactory result and only one case showed fair response (Table 6 and Figure 3). There were no new or unexpected safety events noticed during the course of the treatment. The results clearly shown that the Kodipavala Chunnam treatment to the jaundice patients helped in cutting down the course of the disease and relieving jaundice earlier. The trial drugs Kodipavala Chunnam showed definitive hepatoprotective effect over the trial period of one month and re-establish the normal liver function which is essential for normal metabolism and physiological function of other organs. From the above result, if prolonged administration of Kodipavala Chunnam treatment is given would definitely protect the liver and prevent the development of infective hepatitis, drug induced hepatitis and alcoholic hepatitis and it will help to maintain the normal liver architecture and its function effectively.

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Care strategies for patients with severe drug induced hepatitis

Care strategies for patients with severe drug induced hepatitis

Objective: The aim of this study is to analyse the clinical characteristics of 32 patients with severe drug-induced hepatitis, reinforce the practice of unique nursing and holistic nursing, improve the therapeutic effect, reduce the pa- tients’ mortality, and increase their quality of life. Methods: We give patients individualized dietary guidance, medication nursing, and psychologi- cal care according to the characteristics of se- vere hepatitis and its complications, using com- prehensive medical treatment and combined signs of Traditional Chinese Medicine. Results: Overall, 22 (68.8%) out of 32 cases were im- proved, 8 (25.0%) cases died, and 2 (6.2%) cases were discharged of free will. In addition, the av- erage hospital stay was 28.75 days. Conclusion: This study indicates that dietary guidance for the patients with severe drug-induced hepatitis varies with the individual. The result embodies the concept of Traditional Chinese Medicine that different treatment for the same disease and different diet for the same disease. Special nursing enriches the connotation of holistic nursing. Both of them are vital for improving the survival rate and promoting rehabilitation of patients with severe drug-induced hepatitis. Keywords: Drug-Induced Liver Injury; Severe Hepatitis; Diet Nursing; Holistic Nursing

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Drug induced hepatitis mimicking Wilson’s disease secondary to the use of complex naturopathic regimens: a case report

Drug induced hepatitis mimicking Wilson’s disease secondary to the use of complex naturopathic regimens: a case report

Ultrasound showed a liver with nodularity, with no evidence of hepatic vein or inferior vena cava throm- bosis. However, an ultrasound completed months prior in February showed normal hepatic architecture without evidence of cirrhosis. A follow up ultrasound in March revealed a thin rim of fluid around the liver and gallbladder, favoring a reactive cause and interval liver parenchymal edema, consistent with acute hepatitis. She also had a magnetic resonance cholangiography (MRCP) in March, which was also unremarkable. Computed Tomography (CT) studies revealed a lobulated liver contour and lobar redistribution. There was also evidence of portal hypertension with splenomegaly. The liver paren- chyma had a nodular morphology, suggestive of re- generation, seen in Fig. 2. The pattern of disease on CT is often seen in Budd Chiari syndrome, but can also be consistent with liver necrosis and regeneration after fulminant hepatitis due to drug toxicity. A bi- opsy was completed at another institution in April, a month prior to our admission and revealed subacute severe hepatitis with areas of confluent panacinar dropout (about 50% of specimen area affected) with no pathological features of Budd-Chiari. There was also no evidence of fibrosis or cirrhosis from this bi- opsy. The pathologist ’ s report suggested drug induced liver injury as a possible diagnosis. Portal hyperten- sion was confirmed by measuring the wedge pressure

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Drug users in Hanoi, Vietnam: factors associated with membership in community-based drug user groups

Drug users in Hanoi, Vietnam: factors associated with membership in community-based drug user groups

characteristics confounded or modified the associations examined. There is no way of knowing if the differences we observed between groups of members and non- members existed before members joined their CBG. Second, the sampling was not done at random, although several reports have indicated that snowball sampling can yield relatively representative samples of hidden populations [51]. However, our results may not be generalizable to drug-using populations outside of Hanoi. Third, many of the behaviors reported on are considered socially undesirable, and our reliance on self-report in face-to-face interviews may result in under-reporting of all behaviors, and of the riskiest behaviors in particular. Fourth, serological data confirming HIV and hepatitis B and C infection status were not collected. Although these data were not a direct interest in this study, it has been shown that HIV status can alter subject responses about self-efficacy and risk behaviors [29,35]. Additionally, it has been reported that injection risk behaviors may dif- fer between HIV-infected and non-infected individuals in Vietnam, with HIV-positive individuals more willing to receive borrowed needles and share with other infected users [52]. Finally, there were challenges in measuring the degree of participation in the CBGs by those individuals we have characterized as members. Two CBGs were stud- ied, and although they have largely identical structures, services, and programming, we were not able to analyze the CBGs separately to determine if characteristics and be- haviors of members differed between the CBGs. Intensity of participation in the CBGs was also difficult to quantify but may provide important information in explaining the impact of the groups.

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A case report of nifedipine induced hepatitis with jaundice

A case report of nifedipine induced hepatitis with jaundice

Conclusion: Not much is known about nifedipine-induced hepatitis due to its rare occurrence. Its prevalence is unknown. The disease appears to afflict older men and women. It can present acutely (within days) or subacutely (within 4–8 weeks after medication start) and in an idiosyncratic manner. Chronic or latent cases have also been described, some diagnosed as late as 3 years after medication start. Common symptoms include jaundice, nausea, chills, rigors, diaphoresis, fatigue, and abdominal pain. Laboratory investigations often reveal profound elevations in AST, ALT, GGT, and conjugated bilirubin. Peripheral blood smear may demonstrate eosinophilia. Histology from liver biopsy typically demonstrates infiltration of immune cells, cholestasis, and a picture of steatohepatitis. Treatment involves immediate discontinuation of the drug with supportive care. Thus far, all published instances of nifedipine- induced hepatitis were self-limiting without mortality due to fulminant liver failure. However, this disease can take months to resolve. There is no randomized evidence for other treatments such as corticosteroids.

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HIV seroprevalence among participants at a Supervised Injection Facility in Vancouver, Canada: implications for prevention, care and treatment

HIV seroprevalence among participants at a Supervised Injection Facility in Vancouver, Canada: implications for prevention, care and treatment

As part of a comprehensive evaluation strategy, a repre- sentative cohort of SIF users (SEOSI) was recruited and followed prospectively. The methods have been described previously [5]. Briefly, the cohort includes SIF users who were selected through a random number generation strat- egy. Each week between 16 and 32 two-hour time blocks were designated for recruitment between the opening hours of 10:00 a.m. and 4:00 a.m. seven days per week. During these random time periods 10 cards were distrib- uted to consecutive SIF users who were invited to visit the SEOSI cohort study office located one block from the SIF. There was a CAN$20 compensation provided if they were willing to participate in the prospective study following a full explanation, providing a written informed consent, completing an interviewer-administered questionnaire and supplying a blood sample for HIV and hepatitis C testing. All SEOSI participants provide informed consent to link to the Insite database so that SIF use can be tracked, as well as informed consent to access administrative health record databases in the community. The study was closed to new participants as of March 31, 2005 at which time 1,035 people were enrolled in the cohort from 4,764 individuals who had ever visited the SIF. A comparison between all SIF users and SEOSI cohort participants has shown statistically similar socio-demographic variables (all p > 0.5)[5]. The study was approved by the University of British Columbia/Providence Health Care Ethics Board.

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Review Article Drug-induced megaloblastic, aplastic, and hemolytic anemias: current concepts of pathophysiology and treatment

Review Article Drug-induced megaloblastic, aplastic, and hemolytic anemias: current concepts of pathophysiology and treatment

Drug-induced aplastic anemia is the most seri- ous acquired blood dyscrasia because of its associated high mortality which averages ab- out 50% [22, 23]. In drug-induced aplastic ane- mia, multipotent hematopoietic stem cells undergo damage before their differentiation to committed stem cells [24]. Therefore, the num- ber of circulating neutrophils, platelets, and erythrocytes is reduced [24]. Previous reports have showed that the incidence of drug-induced aplastic anemia is 2/million in Europe and North America which is two or three times greater in Asian countries. These findings point to the relationship between the risk and envi- ronmental factors [25, 26]. Table 2 summariz- es a list of drugs that induce aplastic anemia. Symptoms of drug-induced aplastic anemia are of variable in onset. They may appear from days to months after initiation of the therapy with the causative drug [27]. Symptoms include fatigue, pallor, and weakness (signs of anemia), and pharyngitis, fever and chills (signs of neu- tropenia). Symptoms can also appear as neu- tropenia followed by thrombocytopenia after the discontinuation of the causative drug, [1, 27] while anemia develops slowly because of the longer life span of erythrocytes [28].

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Original Article Drug-drug interaction potential of 1,5-dicaffeylquinic acid, a new herbal drug for the treatment of hepatitis B and human immunodeficiency virus infection, based on the inhibition of cytochrome P450s in human and rat liver microsomes

Original Article Drug-drug interaction potential of 1,5-dicaffeylquinic acid, a new herbal drug for the treatment of hepatitis B and human immunodeficiency virus infection, based on the inhibition of cytochrome P450s in human and rat liver microsomes

Abstract: The inhibition of cytochrome P450s (CYPs) is regarded as one of the most important causes for drug-drug interactions. 1,5-Dicaffeylquinic acid (1,5-DCQA) is currently being evaluated in a phase II clinical study in China for the treatment of hepatitis B and human immunodeficiency virus infections. The purpose of this study was to investigate the in vitro inhibitory effect of 1,5-DCQA on six major CYP enzymes to assess its safety through its po- tential to interact with co-administered drugs. Seven CYP probe substrate metabolites (acetaminophen for CYP1A2, 6α-hydroxypaclitaxel for CYP2C8, 4-hydroxydiclofenac for CYP2C9, 4-hydroxymephenytoin for CYP2C19, dextrorphan for CYP2D6, and 6β-hydroxytestosterone and 1-hydroxymidazolam for CYP3A4) were measured simultaneously by LC-MS/MS. 1,5-DCQA was incubated with human and rat liver microsomes in the presence of seven CYP450 iso- form substrates, and the in vitro inhibitory effects were evaluated by determining the IC 50 values. 1,5-DCQA showed negligible inhibitory effects on the six major human (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and rat CYP isozymes (Cyp1a2, Cyp2c7, Cyp2c11, Cyp2c79, Cyp2d4, and Cyp3a2). All IC 50 values exceeded 100 μM. Our study demonstrates that 1,5-DCQA is unlikely to cause significant drug-drug interactions in humans when co-administered with drugs metabolized by the six CYP isozymes.

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Manganese Superoxide Dismutase Therapy in a Murine Hepatitis Associated Injury

Manganese Superoxide Dismutase Therapy in a Murine Hepatitis Associated Injury

This study does have several limitations, the largest being its short-term nature. While oxidative stress is at- tenuated in the short term, we do not have any longer term data. A more realistic long-term hepatic injury model, such as chronic ethanol ingestion or carbon tetra- chloride-induced liver fibrosis, would be advantageous. Another limitation is the mechanism study of oxidative stress by Con A. It is highly unlikely to perform an in vitro study regarding Con A-induced hepatocytes injury since this is an acute injury model. However, pretreat- ment with gadolinium chloride to block the Kupffer cells can help to clarify whether the oxidative damage is from Kupffer-cell-released superoxide. Further study regard- ing the injurious and protective mechanisms is needed.

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Drug Induced Parkinsonism: A Causality, Severity, and Preventability Assessment study in a Tertiary Care Hospital

Drug Induced Parkinsonism: A Causality, Severity, and Preventability Assessment study in a Tertiary Care Hospital

CDSCO (Central Drugs Standard Control Organization), under the aid of Ministry Of Health & Family Welfare (MoHFW), Government of India (GOI) in collaboration with All India Institute of Medical Sciences, New Delhi as the National Coordination Centre (NCC), has initiated a nationwide pharmacovigilance programme for protecting the health of the patients by ensuring drug safety in July 2010. To ensure the effective implementation of the programme, the NCC was shifted from AIIMS to Indian Pharmacopeia Commission (IPC), Ghaziabad on 15

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DETECTION OF HEPATITIS C VIRUS IN BLOOD DONORS; CORRELATION OF HEPATITIS C WITH INTRAVENOUS DRUG USE/ABUSE/ADDICT, TYPE OF BLOOD DONOR AND MULTIPLE-PRICKS

DETECTION OF HEPATITIS C VIRUS IN BLOOD DONORS; CORRELATION OF HEPATITIS C WITH INTRAVENOUS DRUG USE/ABUSE/ADDICT, TYPE OF BLOOD DONOR AND MULTIPLE-PRICKS

of the donor was taken regarding to their infectious dis- eases, smoking, alcohol user, anaemic condition, HIV, hepatitis in previous history, Intravenous drug abuser or addict, venepuncture, allergic reaction, Cardiovascular disorder, Diabetes mellitus, Epilepsy condition, Malar- ia, Hyperthyroidism, haemophilia (abnormal bleeding tendency), unexpected weight loss, severe diarrhoea, because these conditions are the helpful parameters for blood donation criteria.

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Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure

Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure

ABSTRACT Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to increasing use of the glycopeptide antibi- otic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may ne- cessitate concurrent treatment with a second antibiotic that targets the coinfecting pathogen. While investigating factors that affect bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus to vancomycin is reduced by concurrent expo- sure to colistin, a cationic peptide antimicrobial employed to treat infections by Gram-negative pathogens. We show that colistin-induced vancomycin tolerance persists only as long as the inducer is present and is accompanied by gene expression changes similar to those resulting from mutations that produce stably inherited reduction of vancomycin sensitivity

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Use of Massively Parallel Ultradeep Pyrosequencing To Characterize the Genetic Diversity of Hepatitis B Virus in Drug-Resistant and Drug-Naive Patients and To Detect Minor Variants in Reverse Transcriptase and Hepatitis B S Antigen

Use of Massively Parallel Ultradeep Pyrosequencing To Characterize the Genetic Diversity of Hepatitis B Virus in Drug-Resistant and Drug-Naive Patients and To Detect Minor Variants in Reverse Transcriptase and Hepatitis B S Antigen

The overall distribution of all substituted codons detected by UDPS within the RT gene from each patient, according to their position in the functional and the interdomain regions, is shown in Fig. 1A. On the whole, the pattern of changes versus the genotype consensus sequence varied according to patient source and treatment schedule, including some substitutions with a frequency of ⬎ 20% and several additional changes spread along the gene occurring with low frequency. Interest- ingly, both functional and interfunctional domains presented variant positions in both treated and drug-naive patients. The total number of changes in treated patients was always higher than in drug-naive patients, both in functional domains (48 versus 19, ratio of 2.5) and in interdomains (96 versus 63, ratio of 1.5). Generally, HBV genotype D presented a higher num- ber of substitutions compared to genotype A in both treated and drug-naive patients. However, due to the small number of TABLE 2. Comparison of UDPS, DR v2, and direct sequencing for HBV from eight patients under treatment

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Lactate dehydrogenase is a prognostic indicator in patients with hepatocellular carcinoma treated by sorafenib: results from the real life practice in HBV endemic area

Lactate dehydrogenase is a prognostic indicator in patients with hepatocellular carcinoma treated by sorafenib: results from the real life practice in HBV endemic area

LDH: Lactate dehydrogenase; HCC: hepatocellular carcinoma; FDA: Food and Drug Administration; OS: overall survival; PFS: progression-free survival; HBV: hepatitis B virus; HCV: hepatitis C virus; AFP: alpha- fetoprotein; RFA: radiofrequency ablation; TACE: transcatheter hepatic arterial chemoembolization; BCLC: Barcelona Clinic Liver Cancer stage; AASLD: American Association for the Study of Liver Diseases; ECOG PS: Eastern Cooperative Oncology Group performance status; IFCC: International Federation of Clinical Chemistry and  Laboratory  Medicine;  mRECIST:  modified  Response  Evaluation Criteria in Solid Tumors.

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Drug-induced uveitis

Drug-induced uveitis

The hepatitis B virus (HBV) vaccine is approved by the FDA for the prevention of hepatitis B infection in children and for at-risk populations. A few case reports have impli- cated HBV vaccination in the development of uveitis, in- cluding a single case report of post-vaccination APMPPE [208-211]. The bulk of our information regarding hepatitis B vaccine-related uveitis comes from a review of 32 cases reported to a national database [211]. In this series, the mean age of patients was 29 years (1 to 57 years), with a predominance of female patients (24 females vs. 8 males). The majority of cases developed within a few days follow- ing vaccination and more often after the initial vaccination than subsequent vaccinations, although several patients developed recurrent inflammation with each vaccination. A majority of patients (75%) also reported a flu-like illness. It was hypothesized that this reaction represented either an immune-mediated delayed-type hypersensitivity reac- tion or a reaction to the vaccine carrier meant to potenti- ate the vaccine's immunogenic activity [211].

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Role of CYP2E1 Immunoglobulin G4 Subclass Antibodies and Complement in Pathogenesis of Idiosyncratic Drug-Induced Hepatitis

Role of CYP2E1 Immunoglobulin G4 Subclass Antibodies and Complement in Pathogenesis of Idiosyncratic Drug-Induced Hepatitis

Further evidence suggesting a vital role for complement activation in the pathogenesis of AH, and possibly IDDIH, is the detection of CYP2E1-specific IgG4 autoantibodies in AH patients. IgG4 autoantibodies can form immune complexes that are smaller and may escape clearance (45). More impor- tantly, previous studies have shown that IgG4 autoantibodies can inhibit complement activation and thus prevent clearance of immune complexes (44). In fact, we found that C4a, C3a, and C5a in AH patients were similar to the levels in controls. Additionally, in spite of elevated levels of CYP2E1-specific IgG4 autoantibodies, significantly elevated levels of immune complexes were not demonstrated. Low levels of complement components have been previously reported in persons with drug-induced liver injury (13, 15, 38, 50). Finding elevated levels of IgG4 autoantibodies in AH or any other form of IDDIH to our knowledge has not previously been demon- strated. Our data suggest that hypocomplementemia in drug- induced IDDIH may occur because of inhibition of comple- ment activation. In addition liver injury in IDDIH may occur through IgG4-containing immune complexes by mechanisms similar to those suggested in idiopathic membranous nephrop- athy (32). We are in the process of verifying these mechanisms in our animal model of drug-induced IDDIH (31).

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Identification of a Shared Cytochrome p4502E1 Epitope Found in Anesthetic Drug-Induced and Viral Hepatitis

Identification of a Shared Cytochrome p4502E1 Epitope Found in Anesthetic Drug-Induced and Viral Hepatitis

FIG 2 Covalent modification of JHDN-5 is critical for induction of hepatitis and antibodies in BALB/c mice. After 3 weeks, mice immunized on days 0 and 7 with CFA ⫾ JHDN-5, JHDN-1, or TFA-JHDN-5 (100 ␮ g) were evaluated for hepatitis and serum antibodies by ELISA (405 nm) using CYP2E1 test antigens (0.5 ␮ g/100 ␮ l), sera (1:100), and AKP-conjugated IgG, IgG1, and IgG2a secondary antibodies (1:1,000). (A) Inflammation/injury scores of liver sections from immunized BALB/c mice demonstrating that JHDN-1 (1.8 ⫾ 0.9) induced more hepatitis than JHDN-5 (0.7 ⫾ 0.3; *, P ⬍ 0.05) but not compared to mice immunized with CFA (1.4 ⫾ 0.4) (mean ⫾ SD). (B) Inflammation/ injury scores of liver sections from immunized mice demonstrating that TFA-JHDN-5 induced more severe hepatitis (2.8 ⫾ 0.9) than did CFA (1.6 ⫾ 0.7); mean ⫾ SD; ***, P ⬍ 0.001. (C) Representative liver sections (5 ␮ m thick) stained with hematoxylin and eosin comparing CFA- and TFA-JHDN-5-immunized BALB/c mice, demonstrating increased hepatitis in the form of granulocytic (blue) infiltration in TFA-JHDN-5-immunized mice (64 ⫻ magnification). (D) TFA-JHDN-5 increased TFA IgG, TFA IgG1, and CYP2E1 IgG more than did CFA; *, P ⬍ 0.05. (E and F) Hepatic levels of IL-1 ␤ , IL-2, IL-4, IL-5, IL-6, IL-17, IFN- ␥ , and TNF- ␣ (E) as well as mRNA expression of Casp1, Jak 3, CXCL14, IL-28ra, and Pdgfb (F) were upregulated compared to CFA-immunized mice; *, P ⬍ 0.05; **, P ⬍ 0.01.

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Autoantibodies in liver disease: important clues for the diagnosis, disease activity and prognosis

Autoantibodies in liver disease: important clues for the diagnosis, disease activity and prognosis

Abstract It has been well established that numerous kinds of autoantibodies have been detected in liver disease. Some kinds of autoantibodies may be helpful in the diag- nosis of autoimmune liver diseases including autoimmune hepatitis, primary biliary cirrhosis or primary sclerosing cholangitis. However, these autoantibodies are present even in sera of patients with viral hepatitis, drug-induced hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease and hepatocelluar carcinoma as well as in sera of patients with autoimmune liver diseases. Other kinds of autoantibodies are recognized as predictive hallmarks for disease activity or prognosis in liver diseases. On the other hand, treatment with interferon initiates the production of several types of autoantibodies in patients with chronic hepatitis C virus infection. Some of autoantibodies induced by interferon may postulate the treatment outcome in those patients. Recent studies also revealed the close correlation between oxidative stress and the production of autoanti- bodies in liver diseases. This article primarily reviews the recent advances of autoantibodies in the liver diseases and discusses the clinical significance of these autoantibodies. Keywords Autoantibodies Autoimmune liver diseases Diagnosis Disease activity Prognosis

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NIMESULIDE INDUCED CHOLESTATIC HEPATITIS

NIMESULIDE INDUCED CHOLESTATIC HEPATITIS

Transaminase(ALT) = 33 IU/L, Alkaline phosphatase(ALP) = 390 IU/L with associated reversal of Albumin : Globulin(A:G) ratio. Blood tests forHBsAg, Hepatitis C were negative. Ultrasound abdomen showed hepatomegaly with fatty infiltrates and CT scan abdomen reported the presence of omental infarcts. Upper GI endoscopy confirmed the absence of any varices. Doppler scan of hepatic vein showed absence of portal or hepatic vein thrombosis and thereby ruling out the diagnosis of a Budd Chiari syndrome. For further evaluation, an ultrasound guided liver biopsy was done which showed effacement of liver architecture by extensive macrovesicularsteatosis with intrahepatic cholestasis and thereby confirming the diagnosis as cholestatic hepatitis. The biopsy sample was sent for pathology review and was reported as cholestasis with steatohepatitis (Figure 2) associated with periportal fibrosis (Figure1, 3) with absence of any bridging

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