Episode Of Hepatitis Research Articles

Treatment of HBV–HCV coinfection

Hepatitis B and C viruses are the most frequent causes of chronic disease worldwide. Chronic liver disease can progress to cirrhosis and develop into hepatocarcinoma (HCC). Coinfection with both viruses may occur because they share the same transmission routes. Coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is a more serious disease with a higher risk of progression to HCC than HCV infection alone. According to estimates of the World Health Organization (WHO), approximately 350 million people are infected with HBV and 170 million are infected with HCV. The number of HBV–HCV-coinfected patients is unknown, but it is estimated that it is in between 9%–30%, depending on the geographical region. In Western Europe, the frequency of HBV–HCV coinfection is 0.68% in a selected healthy population. In an Italian study, it was found that the possibility of coinfection is increased with age, being most frequent in patients older than 50 years. At present, there are large trials, therefore the prevalence may be overor underestimated. In all patients presenting with a first episode of acute hepatitis, serological studies must be carried out for various hepatotropic viruses, including HBV and HCV. HBV superinfection may exist in patients with HCV and HCV superinfection may exist in patients with HBV. The possibility of coinfection should be considered for patients with chronic HBV or HCV infection who have been exposed to risk factors such as intravenous drug use.

Hépatite cytolytique due à l’ésoméprazole au cours d’une chimiothérapie anticancéreuse

Esomeprazole, the pure S isomer form of omeprazole, is indicated for the treatment of peptic esophagitis. We report here a major episode of cytolytic hepatitis following a single administration. A 41-year-old woman with infiltrating ductal carcinoma of the breast was undergoing chemotherapy with paclitaxel and trastuzumab. On the fourth day of the second course, she took 1 tablet of esomeprazole 20 mg for epigastric pain. Liver pain and asthenia followed, and liver function tests showed substantial cytolysis. These tests returned to normal levels despite continuation of the chemotherapy. This cytolytic hepatitis is very probably imputable to esomeprazole, but a synergistic hepatic toxicity of the chemotherapy with esomeprazole cannot be ruled out.

Hepatotoxicity of NONI juice: Report of two cases

NONI juice (Morinda citrifolia) is an increasingly popular wellness drink claimed to be beneficial for many illnesses. No overt toxicity has been reported to date. We present two cases of novel hepatotoxicity of NONI juice. Causality of liver injury by NONI juice was asses-sed. Routine laboratory tests and transjugular or percutaneous liver biopsy were performed. The first patient underwent successful liver transplantation while the second patient recovered spontaneously after cessation of NONI juice. A 29-year-old man with previous toxic hepatitis associated with small doses of paracetamol developed sub-acute hepatic failure following consumption of 1.5 L NONI juice over 3 wk necessitating urgent liver transplantation. A 62-year-old woman without evidence of previous liver disease developed an episode of self-limited acute hepatitis following consumption of 2 L NONI juice for over 3 mo. The most likely hepatotoxic components of Morinda citrifolia were anthraquinones. Physicians should be aware of potential hepatotoxicity of NONI juice.

A Case of Acute Toxic Hepatitis induced by brief exposure to Dimethylformamide

Dimethylformamide (DMF), a widely used industrial solvent, has been reported to induce subtle to clinically overt hepatotoxicity. Liver injury due to occupational exposure through inhalation and skin contact has been sporadically reported. We report a 23-year-old male who developed intermittent abdom inal pain, anorexia, nausea, vomiting, chest discomfort, and general weakness for 4 days after working in a plastic-coated -glove factory. An acute hepatitis episode occurred after working in an enclosed work place for 3 days. Other causes of hepatitis such as viral, drug induced or alcoholic hepatitis, could be excluded or were considered to be unlikely. Based on occupational history, serological examination and serial liver function examinations, the case was compatible with DMF-induced acute toxic hepatitis. Hepatotoxicity due to occupational exposure to solvents (e.g., DMF) should be considered in any patient with unexplained hepatitis. The fast improvement of the clinical symptoms and the progressive normal ization of the liver function tests once the DMF exposure has been stopped, supports the diagnosis.

Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases.

The centrilobular liver cell necrosis observed in hypoxic hepatitis is generally attributed to failure of hepatic blood perfusion. Accordingly, this injury of the liver is commonly recognized under the terms "shock liver" or "ischemic hepatitis." During a 10-year period, 142 episodes of hypoxic hepatitis were consecutively identified in the intensive care unit of a general hospital, and the clinical, biological, and hemodynamic parameters were prospectively collected on individual files. We conducted the current study to assess retrospectively the role of the hemodynamic mechanisms of tissue hypoxia: ischemia, passive venous congestion, and hypoxemia. Among the 142 episodes of hypoxic hepatitis, 138 were separated in 4 main groups based on clinical features: decompensated congestive heart failure (80 cases), acute cardiac failure (20 cases), exacerbated chronic respiratory failure (19 cases), and toxic/septic shock (19 cases). An elementary hemodynamic evaluation, including blood pressure, central venous pressure, and arterial blood gas analysis, was carried out in every episode and a more complete hemodynamic assessment through pulmonary artery catheterization was performed in 61 episodes. The hemodynamic mechanisms responsible for hypoxic hepatitis were different in the 4 groups. In congestive heart failure and acute heart failure, the hypoxia of the liver resulted from decreased hepatic blood flow (ischemia) due to left-sided heart failure and from venous congestion secondary to right-sided heart failure. In chronic respiratory failure, liver hypoxia was mainly due to profound hypoxemia. In toxic/septic shock, oxygen delivery to the liver was not decreased but oxygen needs were increased, while the liver was unable to use oxygen properly. In all conditions underlying hypoxic hepatitis, except toxic/septic shock, a shock state was observed in only about 50% of the cases. Therefore, the expressions "shock liver" or "ischemic hepatitis" are misleading and should be replaced by the more general term "hypoxic hepatitis."

Determinants of viral clearance and persistence during acute hepatitis C virus infection.

The virological and immunological features of hepatitis C virus (HCV) infection were studied weekly for 6 months after accidental needlestick exposure in five health care workers, four of whom developed acute hepatitis that progressed to chronicity while one subject cleared the virus. In all subjects, viremia was first detectable within 1-2 weeks of inoculation, 1 month or more before the appearance of virus-specific T cells. The subject who cleared the virus experienced a prolonged episode of acute hepatitis that coincided with a CD38+ IFN-gamma- CD8+ T cell response to HCV and a small reduction in viremia. Subsequently, a strong CD4+ T cell response emerged and the CD8+ T cells became CD38- and started producing IFN-gamma in response to HCV, coinciding with a rapid 100,000-fold decrease in viremia that occurred without a corresponding surge of disease activity. Chronic infection developed in two subjects who failed to produce a significant T cell response and in two other subjects who initially mounted strong CD4+ T cell responses that ultimately waned. In all subjects, viremia was higher at the peak of acute hepatitis than it was when the disease began, and the disease improved during the viremia. These results provide the first insight into the host-virus relationship in humans during the incubation phase of acute HCV infection, and they provide the only insight to date into the virological and immunological characteristics of clinically asymptomatic acute HCV infection, the commonest manifestation of this disease. In addition, the results suggest that the vigor and quality of the antiviral T cell response determines the outcome of acute HCV infection, that the ability of HCV to outpace the T cell response may contribute to its tendency to persist; that the onset of hepatitis coincides with the onset of the CD8+ T cell response, that disease pathogenesis and viral clearance are mediated by different CD8+ T cell populations that control HCV by both cytolytic and noncytolytic mechanisms, and that there are different pathways to viral persistence in asymptomatic and symptomatic acute HCV infection.

Acute Alcoholic Hepatitis

Acute alcoholic hepatitis characterised histologically by a florid inflammatory lesion and liver injury is part of a spectrum of liver damage resulting from alcoholic excess (Figure [1]). Although many cases of alcoholic cirrhosis develop insidiously, others will pass through one or more episodes of acute alcoholic hepatitis (AH). Clinically AH is manifest by acute onset of jaundice with fever and other signs of constitutional upset and with the rapid development of signs of acute liver failure, including renal impairment and encephalopathy. Very often it follows an acute alcoholic binge. It may be the first presentation of liver disease for that particular patient. Some episodes of AH can resolve without the development of cirrhosis if abstinence is maintained and acute alcoholic hepatitis is to be distinguished from acute episodes of decompensation in patients with an established underlying cirrhosis. AH carries a high mortality more than 50 % when the MADDREY index is > 32. The MADDREY index which has proved to be of considerable value as a prognostic tool and in estimating the need for particular methods of treatment such as corticosteroids, is based on the following formula which includes the height of the bilirubin and degree of prolongation of prothrombin time.

Natural history of chronic hepatitis B virus infection in adults with emphasis on the occurrence of cirrhosis and hepatocellular carcinoma.

The natural course of perinatally acquired hepatitis B virus (HBV) infection has three phases. In the first 'immune tolerance phase', patients are HBeAg positive and have high serum levels of HBV DNA, but have no symptoms, normal ALT levels and minimal histological activity. The second 'immune clearance phase' usually occurs between 15 and 35 years of age, during which HBV replication declines, accompanied by increased serum ALT levels and inflammatory activity in the liver; HBeAg to anti-HBe seroconversion is then observed, frequently preceded by a flare of the ALT level. The average rate of spontaneous HBeAg seroconversion is 10% per year. In the third 'low-replicative phase', serum HBsAg persists, but HBeAg is no longer detectable and HBV DNA can only be detected by PCR assay. During this phase, patients are usually asymptomatic and liver disease is inactive; some patients, however, may progress to cirrhosis and hepatocellular carcinoma (HCC). The ultimate outcome of chronic HBV infection appears to depend on the duration and severity of liver injury during the immune clearance phase. About 2.1% of patients with chronic type B hepatitis develop cirrhosis each year. Patients who have a severe acute exacerbation complicated by subacute hepatic failure or who have recurrent episodes of acute exacerbations with bridging hepatic necrosis are more likely to develop cirrhosis. A significant proportion of those with HBsAg eventually develop HCC; they have a 100-fold increased risk of HCC relative to those without. The development of HCC, however, is closely related to the severity of the underlying liver disease. The annual incidence of HCC is only 0.1% in asymptomatic HBsAg individual, 1% in patients with chronic hepatitis B, but increases to 3-10% in patients with cirrhosis. Some anti-HBe-positive patients continue to have active liver disease and they should be tested for HBV DNA by hybridization assay to determine whether the disease results from replicative precore mutant HBV infection or other causes of liver disease, such as superinfection with HCV and HDV. A substantial number of apparently healthy HBV-infected individuals are first recognized when they present with episodes of acute hepatitis. About 30% of these cases could be attributed to other hepatotropic virus superinfection. Acute viral hepatitis in patients with concurrent HBV infection is associated with an increased risk of fulminant hepatic failure. Finally, HBsAg disappears from serum in about 1% of patients each year. HCV superinfection can enhance the termination of HBsAg positivity. HCV, however, replaces HBV as the dominant cause of chronic viral hepatitis. The outcome of HBV-infected persons with 'spontaneous' seroclearance of HBsAg is usually favourable, though progress to cirrhosis and HCC is still possible.

Changes in portal venous hemodynamics in patients with severe acute hepatitis over one year

Purpose A wide range of portal vein blood flow velocity (PVV) values can be found in acute hepatitis. We studied course and medical significance of PVV changes in patients with severe acute hepatitis over a 1-year period. Methods Portal venous hemodynamics were studied by Doppler sonography in 90 patients at study enrollment and 3, 6, and 12 months following an episode of severe acute hepatitis. Results Forty-one survivors who had a maximum PVV at enrollment greater than or equal to the value measured at the third month were classified as the “declining PVV” group. Thirty-six survivors who had a maximum PVV at enrollment less than the value measured at the third month were classified as the “rising PVV” group. Thirteen patients died of acute hepatic failure and were classified as the fatality group. The fatality group had significantly lower maximum PVV, worse liver biochemical test results, and a higher prevalence of ascites at enrollment. In contrast, the declining PVV group showed significantly better liver biochemical test results and a lower prevalence of ascites. There was no significant difference in portal vein blood flow between the rising and declining PVV groups since portal vein diameter increased while PVV decreased. Conclusions An initially decreased PVV can be found in some patients with severe acute hepatitis and is inversely correlated with the severity of liver damage. © 2000 John Wiley & Sons, Inc. J Clin Ultrasound 28:83–88, 2000.

Assessment of Needs for Plasma for Fractionation in Europe

In the early 1990s, a series of outbreaks of hepatitis C (HCV) infections clustering among recipients of certain lots of plasma-derived medicinal products (PDMP) alarmed regulatory authorities, manufacturers and the public alike. Also, a few episodes of Hepatitis A (HAV) infections occurred in haemophiliacs receiving solvent–detergent-treated factor VIII concentrates. Thus, several measures were brought into effect to reestablish the safety of the incriminated products and to further increase the margin of safety of PDMP in general. Therefore, intramuscular immunoglobulins had to be free of HCV RNA as shown by nucleic acid amplification technology (NAT) in the final products. Furthermore, the manufacturing process of PDMP had to be validated for both viral inactivation and elimination. Finally, HCV-NAT was to be standardised and implemented as a validated test of plasma pool samples.In 1994, a joint meeting of EPFA, EAPPI and Regulatory Authorities was held in Brussels to outline the state of the art and to delineate the actions to be taken. Five years later, in 1999, the incidence rates of HIV, HBV and HCV in unpaid blood donors have been minimized, especially in European countries. With probabilities for window period donations as low as 0·6 in 1 million for both HIV and HCV and 2·1 in 1 million for HBV in Switzerland, labile blood products have reached extreme, but not absolute safety. The introduction of HCV-NAT roughly doubles this safety resulting in a 1 in 3 million probability of a window donation.Concomittantly, extensive viral validation studies document effective inactivation and removal of viruses in PDMP. The demonstrated margins of safety, expressed as logarithmical reduction factors (LRF), range from 4 to over 20 log10, depending on product, virus, and inactivation procedure used. Further progress to even safer PDMP shall be acomplished by consolidating the GMP processes, abandoning of obsolete requirements and harmonising national regulations within Europe. Before introducing new measures for additional agents such as HAV or Parvovirus B 19, gains and risks and even potential new threats have to be carefully assessed. Alternative efforts for the safeguard of patients, e.g. vaccination for HAV, need to be balanced against the risks of changing established and validated manufacturing procedures of PDMP with long-lasting safety records.

Prevalence and implication of TT virus infection: minimal role in patients with non-A-E hepatitis in Taiwan.

TT virus (TTV) is a newly identified human DNA virus and little is known about its clinical significance. The aim of the study was to explore the prevalence of TTV infection in different risk populations and in patients with various liver diseases. Viral DNA was studied in 190 high-risk individuals, 97 household contacts, 52 patients with acute hepatitis A, 32 patients with non-A-E hepatitis including 13 fulminant hepatitis, 200 asymptomatic hepatitis B surface antigen (HBsAg) carriers, 100 patients with chronic hepatitis C, and 100 healthy adults. TTV infection was more frequent in high-risk groups (26-70%), patients with acute or fulminant non-A-E hepatitis (42-45%), and hepatitis C carriers (36%) than in healthy adults (10%) and hepatitis B carriers (15%). However, most of subjects with TTV infection alone had no or only mild hepatitis, and the same rate of TTV DNA in pre-hepatitis serum samples and constant serum TTV titers during hepatitis episodes were observed in two patients with acute non-A-E hepatitis. Phylogenetic analysis of the Taiwanese TTV isolates showed genetic heterogeneity and most (68%) isolates were TTV type 1. No particular strain was found to be associated with fulminant non-A-E hepatitis.

Réactions systémiques secondaires à la prise de minocycline. À propos de quatre observations et revue de la littérature

We report four cases of the side effects of minocycline seen during the last two years in our department. There was one case of drug-related lupus and three cases of hypersensitivity reactions, including one eosinophilic pneumopathy with pericarditis, one nephropathy and one severe, pseudo-infectious episode of high fever, rash, lympadenopathy, hepatitis and eosinophilia. Minocycline is a tetracycline agent widely used for acne therapy in France and all over the world. During the last few years, there has been an increasing number of reports concerning systemic adverse reactions to minocycline, with on the one hand auto-immune disorders (lupus, autoimmune hepatitis, vascularitis with ANCA), occurring after a prolonged course of therapy and reported recently in the last few years, and on the other hand, hypersensitivity reactions (eosinophilic pneumopathies, hepatitis, nephropathies, myocarditis, serum sickness or pseudo-infectious reactions), occurring precociously in the course of therapy, and potentially severe. Although these side effects are uncommon in the context of the high number of patients who have been prescribed the drug, the first-line antibiotic therapy in acne must probably be reconsidered.

Experimental transmission of hepatitis C virus-associated fulminant hepatitis to a chimpanzee.

Hepatitis C virus (HCV) was transmitted from a patient with fulminant hepatitis C to a chimpanzee. The patient had developed two episodes of fulminant hepatitis C, each occurring after a separate liver transplantation. Serial serum and liver samples from the patient and the chimpanzee were analyzed for HCV replication, genotype, quasispecies heterogeneity, and antibodies. In the patient, the levels of HCV replication in serum and liver correlated with the degree of hepatocellular necrosis and the clinical expression of fulminant hepatitis. The same HCV strain, genotype 1a, was recovered from both episodes of fulminant hepatitis. An unusually severe acute hepatitis was also observed in the chimpanzee. The viruses recovered from the patient and the chimpanzee were almost identical and displayed relatively little quasispecies heterogeneity. Thus, the same HCV strain induced two episodes of fulminant hepatitis in a single patient and severe hepatitis in a chimpanzee, suggesting that the pathogenicity or virulence of a specific HCV strain may be important in the pathogenesis of fulminant hepatitis C.

Hepatitis C virus infection in special groups

Hepatitis C virus (HCV) infection is associated with a wide spectrum of clinical manifestations which may influence the choice of diagnostic assays, especially in haemodialysis patients, the clinical course of infection with possible multiple and sequential episodes of hepatitis in multiple transfused patients, and the severity of liver disease, especially in patients with HBV-HCV co-infection. The consequences of HCV infection in patients with organ graft are not completely understood due to the complexity of the clinical situations and the unavailability of long-term follow-up. Furthermore, current antiviral therapy is not very effective in these populations. Thus, it is especially important to protect patients at risk for HCV infection, using universal precautionary procedures.

Simultaneous pancreatitis and hepatitis associated with trimethoprim-sulfamethoxazole

A 34-yr-old woman developed simultaneous pancreatitis and hepatitis following exposure to trimethoprim-sulfamethoxazole (TMP/SMX). The episode occurred 4 yr after a previous episode of hepatitis associated with TMP/SMX. This patient represents the second case of concurrent TMP/SMX-induced pancreatitis and hepatitis reported in the literature. However, it is the first in which the adverse reaction was documented following an inadvertent rechallenge with the drug.

Hepatitis virus infection in haemodialysis patients from Moldavia.

Although the epidemiology of hepatitis B (HBV) and C (HCV) now seems well established for Western European countries, in Central and Eastern Europe < 50% of all dialysis centres routinely test for hepatitis C antibodies since testing is not available or is not applied to all patients. This study describes the prevalence, risk factors and clinical significance of HBV and HCV infection for the haemodialysis population of the North Eastern region of Romania, Moldavia. The presence of HBV antigens was determined with an ELISA kit (Wellcome, Abbot) and HCV antibodies with the ELISA-3 Ortho-HCV, third generation test. The following individual data were collected: gender, age, duration of dialysis, rural/urban domicile, actual and previous HBV status, actual HCV status, known acute, clinically evident hepatitis episodes in the last 3 years, monthly alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) levels, complete biochemical hepatic assessment at the time of the study, transfusions for the past 3 years and family history. HBV and HCV prevalences were 17% (stable over the last 3 years) and 75%, respectively; co-infection was seen in 10% of the subjects. Hospitalization (nosocomial infection) for HBV, blood transfusions and duration on dialysis for HCV, emerged as the main risk factors for hepatitis infection. Socio-economic conditions appear to be equally important for HCV infection, since the prevalence was significantly higher among patients from rural, underdeveloped areas than urban areas (80.8 vs 60.3%), and infection was already present in a large proportion of patients (47%) before starting dialysis, without being related to previous disease duration or blood transfusions. HBV and/or HCV was not associated with a worse clinical or biochemical profile at the time of the study. However, infected patients had significantly more previous cytolytic episodes, with higher, transient increases in ALAT and ASAT levels. HCV infection is endemic among dialysis centres in Moldavia. Apart from previously well-known risk factors for hepatitis infection, our study demonstrates the negative impact of socio-economic underdevelopment. Simple measures such as enforced general asepsia rules, careful disinfection and equipment sterilization, routine testing of patients from economically disadvantaged areas and monthly, serial determination of hepatic enzymes should be the common practice in dialysis centres in Romania.

A Simple Mathematical Method to Predict the Course of a First Episode of Liver Viral Cytolysis

Early detection of the self‐limiting or chronic tendency towards disease at the beginning of the hepatitis process is a canonical element of the analysis and synthesis to formulate the diagnosis and to decide the most useful and economic therapeutic strategy. Early treatment with antiviral drugs before liver functions undergo deterioration may reduce death and disability especially in young patients.A formula suggested by a Max Planck equation provides mathematical curves that can be obtained very early during the course of hepatitis using just a few initial serum measurements of the alanine‐aminotransferase (ALT) enzyme. The clinical ALT data forming the unpredictable early natural curve of ALT can be transformed into mathematical values capable of providing a deterministic curve that intersects the normal ALT value at what is known as the G point, and allows some predictions to be made concerning the acute or chronic evolution of the disease.The G point seems to be a good predictor of whether or not a patient with clinically evident first episode of viral hepatitis will develop chronic liver disease as it revealed the initial phase of the first cytolytic episode in 56 untreated patients of our 59 cases; the three wrong predictions involved patients being treated with interferon.

Hepatitis in haemophilia.

Hepatitis in haemophilia.

Disease of the liver following bone marrow transplantation in children: incidence, clinical course and outcome in a long-term perspective.

Sixty-four consecutive cases of allogeneic (n = 16), autologous (n = 47) or syngeneic (n = 1) bone marrow transplantation (BMT) in children with haematological or lymphoid malignancy, aplasia or metabolic disease were reviewed to assess the incidence, clinical presentation and outcome of liver disease. Median follow-up time was 5 y (1.0-10). No liver diagnosis was established at the pre-transplant check-up. During the first 100 d post-transplant, 81% of the patients had impaired liver function as documented by various biochemical parameters. Three of 64 patients (5%) met diagnostic criteria for veno-occlusive disease. Four (25%) of the 16 receiving allografts were diagnosed as having acute graft vs host disease (GVHD) with liver involvement (grades II-III). No patient died of liver disease. During the late post-transplant follow-up, one patient developed HCV hepatitis after packed erythrocyte transfusion. Four patients were diagnosed as having chronic GVHD with liver involvement; three of them also had an episode of CMV hepatitis. At their latest follow-up, the patients with chronic GVHD had aminotransferase values 1.5-3 times the normal, whereas all other long-term survivors had normal or near-normal liver function tests. We conclude that the incidence of serious liver disease was low in this paediatric population of bone marrow recipients.

Disease of the liver following bone marrow transplantation in children: incidence, clinical course and outcome in a long‐term perspective

Sixty‐four consecutive cases of allogeneic (n= 16), autologous (n= 47) or syngeneic (n= 1) bone marrow transplantation (BMT) in children with haematological or lymphoid malignancy, aplasia or metabolic disease were reviewed to assess the incidence, clinical presentation and outcome of liver disease. Median follow‐up time was 5 y (1.0‐10). No liver diagnosis was established at the pre‐transplant check‐up. During the first 100d post‐transplant, 81% of the patients had impaired liver function as documented by various biochemical parameters. Three of 64 patients (5%) met diagnostic criteria for veno‐occlusive disease. Four (25%) of the 16 receiving allografts were diagnosed as having acute graft vs host disease (GVHD) with liver involvement (grades II‐III). No patient died of liver disease. During the late post‐transplant follow‐up, one patient developed HCV hepatitis after packed erythrocyte transfusion. Four patients were diagnosed as having chronic GVHD with liver involvement; three of them also had an episode of CMV hepatitis. At their latest follow‐up, the patients with chronic GVHD had aminotransferase values 1.5–3 times the normal, whereas all other long‐term survivors had normal or near‐normal liver function tests. We conclude that the incidence of serious liver disease was low in this paediatric population of bone marrow recipients.