Severe hepatitis with prolonged cholestasis and bile duct injury due the long-term use of ornidazole

Nitroimidazole derivatives are commonly used in the treatment of protozoal and anaerobic infections, and reports of their hepatotoxicity are rare. We report a case of severe hepatitis due to the long-term (8 weeks) use of ornidazole. A 27-year-old woman presented for evaluation of elevated serum transaminase and total bilirubin levels. Liver biopsy revealed portal inflammation, hepatocellular and canalicular cholestasis, porto-portal and portocentral bridging fibrosis, and a tendency to form nodules. No aetiological factors associated with chronic liver disease were identified. The abdominal ultrasonographic findings were compatible with chronic liver disease. We therefore made the diagnosis of severe hepatitis resulting from the long-term use of ornidazole. We conclude that nitroimidazole derivatives may lead to serious liver damage, especially in female patients.     

Ornidazole‐induced liver damage: report of three cases and review of the literature

Abstract: Metronidazole and ornidazole, synthetic nitroimidazole derivatives, are used in the treatment of infections caused by anaerobic bacteria and protozoa. The drugs are well tolerated and serious side effects are very rarely encountered. Hepatotoxicity is a rare side effect and hitherto only six cases have been reported. We describe three patients who developed hepatitis after ornidazole use and review the previously reported cases. All three cases used ornidazole in conventional doses and developed hepatitis and associated cholestasis. They improved 1–2 months after discontinuation. We concluded that nitroimidazole derivatives may cause hepatotoxic damage resembling acute cholestatic hepatitis. Early recognition and withdrawal of the drug may prevent further damage.     

What Would We Do Without Metronidazole?

Metronidazole is a treatment of choice for several types of infections, but coexisting conditions or concomitant medications may preclude its use. Although tinidazole, a newer nitroimidazole, may be an option in cases where drug interactions make the use of metronidazole inadvisable, similar absolute contraindications exist. In situations where nitroimidazole use is contraindicated or inadvisable, clinicians may have difficulty deciding on efficacious treatment options. For the treatment of trichomoniasis, alternatives include furazolidone, clotrimazole, nonoxynol-9 or paromomycin. Alternatives for bacterial vaginosis include clindamycin topically or systemically. For giardiasis, alternative options include paromomycin, nitazoxanide or the antihelminthic benzimidazoles. Alternatives for Clostridium difficile are varied, including oral vancomycin, nitazoxanide and rifaximin. Although options are limited, alternative therapies for treatment of patients with absolute contraindications to the nitroimidazole antibiotics are available.     

Combined branched-DNA and conventional HBV PCR assays for detection of serum HBV-DNA in hepatitis B e antigen-positive chronic hepatitis B patients

BACKGROUND/AIMS: Monitoring of HBV replication level is very useful for the management of patients with chronic HBV. However, the use of the correct tools to quantify HBV-DNA levels in serum and monitor the replication of HBV is of paramount importance in terms of diagnosis, and antiviral treatment of patients with chronic HBV infection. The aim of this study was to combine the bDNA assay and HBV PCR to improve detection of viremia the patients with HBeAg-positive chronic hepatitis B infection. METHODOLOGY: In this study, 67 HBeAg-positive chronic hepatitis B patients were analyzed to determine viremia level using bDNA and HBV PCR assays. RESULTS: Sixty-four patients with HBeAg-positive chronic hepatitis B showed positivity by conventional HBV PCR, whereas 56 subjects with HBeAg-positive chronic hepatitis B showed HBV-DNA levels by bDNA. CONCLUSIONS: The results indicated that it is reasonable to use the bDNA assay to determine HBV replicative activity first, and use conventional HBV-PCR for HBeAg-positive chronic hepatitis B patient samples that are negative in bDNA assay.     

Hepatitis B in pregnancy

In countries with a high prevalence of chronic hepatitis B, perinatal transmission from mother to infant accounts for the majority of cases of chronic hepatitis B. Passive-active immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine at birth is 95% efficacious in reducing the risk of HBV transmission but is less effective in HBeAg-positive mothers with very high serum HBV DNA levels. In the last 4 weeks of pregnancy lamivudine may provide additional protection in pregnant women who have high-level viremia. Further studies are needed to evaluate the use of nucleos(t)ide analogues to treat chronic hepatitis B during pregnancy.     

Future aspects of therapy for hepatitis B virus infection: value of surrogate markers,innovative therapy,and global collaboration

Both optimism and frustration exist regarding therapy for patients with chronic hepatitis B virus infection. Due to the recent advent of several drugs with potent antiviral capacities and comparatively low rates of adverse effects, considerable optimism has developed regarding the treatment of these patients. Chronic hepatitis B is now a treatable disease, and suppression of hepatitis B virus replication, normalization of alanine aminotransferase levels, seronegativity/seroconversion of hepatitis B e antigen and hepatitis B surface antigen, and decreased hepatic inflammation and liver fibrosis have been documented in chronic hepatitis B virus-infected patients treated with antiviral therapy. In contrast, many frustrations regarding antiviral therapy for chronic hepatitis B have arisen, because the disease, although treatable, is not curable. The present regimens of antiviral therapy modulate some intermediate parameters or so-called surrogate markers in chronic hepatitis B virus-infected patients, but usually fail to improve all intermediate parameters or ultimate clinical outcomes. In addition, major concerns remain about the applicability and use of antiviral drugs in developing and resource-constrained countries in which healthcare delivery systems do not support the proper use of antiviral therapy. New and more effective therapeutic regimens for chronic hepatitis B patients are needed that take into account potential surrogate markers of treatment outcomes and allow for effective collaboration between resource-constrained and advanced countries.     

Is Hepatitis A More Severe in Patients with Chronic Hepatitis B and Other Chronic Liver Diseases?

There are several published case series of acute hepatitis A, with coverage ranging from epidemics to case reports, that provide information regarding the clinical course and outcome of hepatitis A in patients with underlying chronic hepatitis B virus (HBV) infection (1–12). Only a few reports have addressed the outcome of hepatitis A in patients with other chronic liver diseases (2, 13). Some, but not all, of these reports suggest that hepatitis A superimposed on chronic hepatitis B or other chronic liver diseases is associated with higher peak laboratory abnormalities, more severe disease, including fulminant hepatic failure, and a higher case fatality rate. In addition, analysis of HBsAg titer and serum markers of HBV replication, including HBeAg, HBV DNA, and DNA polymerase, reveals suppression of HBV replication. With the availability of hepatitis A virus (HAV) vaccine in many countries and its imminent approval for use in the United States, the issue of whether or not patients with chronic liver diseases, including chronic HBV infection, should be a target group for vaccination to prevent hepatitis A warrants consideration. The purpose of this review is to analyze the published literature addressing the clinical course and outcome of acute hepatitis A in patients with chronic HBV infection and other chronic liver diseases to determine if hepatitis A is more severe in these patients.     

Hepatitis C Plus Alcohol or Marijuana: Which Is Worse?

Despite advances in hepatitis C therapy and better knowledge of viral/host factors related to disease progression, the hepatitis C virus remains the leading cause of chronic liver disease, causing progression to end-stage liver disease (ESLD) as well as the development of hepatocellular carcinoma. Because hepatitis C virus acquisition is linked to an addictive behavior (ie, injection drug use), any perceived dependence has been a major reason for treatment denial as well as exclusion from clinical trials. Of special interest are two such dependences: drinking alcohol and smoking marijuana (cannabis). We review the available evidence for the effects of alcohol and cannabis on liver disease progression in chronic hepatitis C, and conclude with recommendations regarding the use of these two substances in the setting of chronic hepatitis C.     

The use of silymarin in patients with toxic and viral liver diseases

Effective use of Silybum marianum medicines is still urgent in hepatology practice. Data about effectiveness and safety of silymarin in patients with acute and chronic toxic injuries including drug-induced ones and patients with acute and chronic viral hepatitis is reviewed in the article. An attempt of trials limitations and disadvantages systematization is made and methods of their solvation are discussed. A possibility of silymarin use as antiviral agent in patients with chronic hepatitis C is also reviewed and perspectives of this drug clinical use in future is discussed.     

Diagnosis of chronic hepatitis C after liver transplantation by the detection of viral sequences with polymerase chain reaction.

Chronic hepatitis frequently occurs after liver transplantation. The role of hepatitis C virus infection in patients after liver transplantation is unknown, although antibodies to HCV are detected in some of these cases. The use of polymerase chain reaction techniques for the detection of hepatitis C virus RNA should improve sensitivity and specificity, particularly in these immunosuppressed patients. Our goal was to further clarify the role of hepatitis C virus infection in chronic hepatitis occurring after liver transplantation. Patients with chronic hepatitis of uncertain origin after transplantation were identified. Serum samples taken at the time of the most recent liver biopsy that showed chronic hepatitis were tested for anti-hepatitis C virus using enzyme-linked immunoassay and supplemented by recombinant immunoblot assay (recombinant immunoblot assay I and recombinant immunoblot assay II). The samples were also tested for the presence of hepatitis C virus RNA using polymerase chain reaction. Of the 25 patients with chronic hepatitis, 15 (60%) had hepatitis C virus RNA present. Only seven (47%) of these 15 patients had anti-hepatitis C virus detected. Hepatitis C virus is a major cause of chronic hepatitis occurring after liver transplantation. The magnitude of hepatitis C virus infection will be underestimated if only currently available assays for anti-hepatitis C virus are used.     

拉米夫定治疗后慢性乙型肝炎患者的生活质量测评

目的　评价拉米夫定对慢性乙型肝炎患者生活质量的影响 ,探讨临床防治重点。方法　应用健康状况调查问卷 ,对中南大学湘雅第二医院传染科 2 0 0 2 - 0 7～ 2 0 0 3- 0 7的 15 0例慢性乙型肝炎患者及 5 0名健康者生活质量研究 ,并对拉米夫定治疗前后的临床客观指标和生活质量主观指标进行对照分析 ,综合评价拉米夫定的疗效。结果　慢性乙型肝炎患者生活质量评分与对照组相比差异有显著意义 (P <0 0 1) ;拉米夫定治疗前后临床症状、血液学和病原学检查等客观指标及生活质量评分均差异有显著意义 (P <0 0 1)。结论　慢性乙型肝炎患者的生活质量普遍下降 ,拉米夫定能改善临床客观指标和提高患者的生活质量 ;在慢性乙型肝炎的防治中 ,生活质量可以作为效果评价指标 ,指导临床治疗方法的选择和决策。     

Role of liver biopsy in chronic hepatitis C

At the present time liver biopsy is the most reliable method to determine the grade of necroinflammatory lesion and the amount of fibrosis in chronic hepatitis C. Therefore the liver biopsy should always be performed before initiating therapy. It is suggested to use the METAVIR histological activity to grade chronic hepatitis because it is simple, the reproducibility has been validated, the criteria used to define different lesions has been clearly stated, and there is a significant association between ALT levels and this index. The use of semi-quantitative systems in routine reports of liver biopsies is unnecessary. In these cases the schematic diagrams from Batts and Ludwig can be used, as visual analogue scales, in order to grade and stage chronic hepatitis.     

Analysis of acute to chronic hepatitis E: 6-10 year follow-up

Hepatitis E as a self-limiting disease and is generally not chronic, although in a small number of cases it appears to be so. Complete data were collected from 1104 cases of hepatitis E out of which 28 did not heal after liver treatment. These 28 cases were followed-up for 6-10 years. It was found that hepatitis can be chronic. Chronic hepatitis cases are more common in males, but a high degree of inflammatory activity and fibrosis were not evident. After 6-10 years of follow-up observation, cirrhosis or liver cancer did not appear. This is significantly different from the hepatitis B and hepatitis C viruses. Further, most cases of chronic hepatitis E occurred in older patients, in which the ability to remove the virus may decline, contributing to the more than six months duration, along with other important reasons. In addition, we also observed that several cases were unhealed or chronic because of a combination with other viruses. Chronic disease or the long-term use of immune agents may be one of the causes for chronic hepatitis E.     

Alcohol abuse and chronic hepatitis C

AbstractChronic infection with hepatitis C virus (HCV) and alcohol abuse are two of the most common causes of chronic liver disease in the United States. These two entities often coexist and contribute to accelerated development of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Although the effect of one drink per day in the setting of chronic HCV infection is unclear, there is overwhelming evidence for the deleterious effects of heavy alcohol use on HCV liver disease. The mechanisms by which alcohol increases liver injury in hepatitis C are poorly understood. Potential pathways include impaired host immune systems and increased viral replication. Alcohol use may decrease the success of treatment. Physicians should encourage patients with chronic hepatitis C to abstain from regular alcohol use.     

The management of chronic viral hepatitis: A Canadian consensus conference 2004.

Several government and nongovernment organizations held a consensus conference on the management of acute and chronic viral hepatitis to update previous management recommendations. The conference became necessary because of the introduction of new forms of therapy for both hepatitis B and hepatitis C. The conference issued recommendations on the investigation and management of chronic hepatitis B, including the use of lamivudine, adefovir and interferon. The treatment of hepatitis B in several special situations was also discussed. There were also recommendations on the investigation and treatment of chronic hepatitis C and hepatitis C-HIV coinfection. In addition, the document makes some recommendations about the provision of services by provincial governments to facilitate the delivery of care to patients with hepatitis virus infection. The present document is meant to be used by practitioners and other health care providers, including public health staff and others not directly involved in patient care.     

Hepatitis viruses under immunosuppressive agents

Clinical and experimental studies have shown that T cell-mediated immune mechanisms are involved in the pathogenesis of hepatitis B virus (HBV) and hepatitis C virus infection. Immunosuppressants may impair T cell function and thereby reduce immune-mediated hepatocytolysis and virus clearance. In addition, corticosteroid may activate the glucocorticoid responsive element in the HBV genome to enhance HBV replication and gene expression. These combined effects result in an increase of viraemia in association with a decrease of serum aminotransferase and hepatic necroinflammation. In acute infection, use of immunosuppressants will increase the incidence of chronic evolution. In chronic infection, withdrawal of immunosuppressants will be followed by a clinical flare due to a rebound of immune attack to hepatocytes with increased viral load. This may lead to a subsequent decrease of the viraemia. Therefore, short-term use of immunosuppressant before antiviral therapy may be beneficial in the treatment of chronic viral hepatitis. However, the clinical rebound may be extremely severe and lead to hepatitis failure; thus, the patients should be monitored closely upon tapering and after the withdrawal of immunosuppressants. Long-term use of immunosuppressants in patients with hepatitis virus infection is usually deleterious, particularly in patients after organ transplantation. These findings suggest that clinicians should be cautious in the use of immunosuppressants in patients with hepatitis virus infection.     

Alcoholic hepatitis and concomitant hepatitis C virus infection

Hepatitis C virus(HCV)infection and alcohol abuse are two most important causes of chronic liver disease in the United States.Alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active alcohol abuse with a potential for high short-term mortality.About 20%of patients presenting with alcoholic hepatitis have concomitant HCV infection.Mortality from alcoholic hepatitis is increased in the presence of concomitant hepatitis C due to synergistic interaction between HCV and alcohol in causing hepatocellular damage.Large prospective randomized studies are needed to develop guidelines on the use of corticosteroids among patients with alcoholic hepatitis and concomitant HCV infection.The impact of antiviral therapy on mortality and outcome in the setting of alcoholic hepatitis remains a novel area for future research.     

The management of chronic viral hepatitis: a Canadian consensus conference 2004.

Several government and nongovernment organizations held a consensus conference on the management of acute and chronic viral hepatitis to update previous management recommendations. The conference became necessary because of the introduction of new forms of therapy for both hepatitis B and hepatitis C. The conference issued recommendations on the investigation and management of chronic hepatitis B, including the use of lamivudine, adefovir and interferon. The treatment of hepatitis B in several special situations was also discussed. There were also recommendations on the investigation and treatment of chronic hepatitis C and hepatitis C-HIV coinfection. In addition, the document makes some recommendations about the provision of services by provincial governments to facilitate the delivery of care to patients with hepatitis virus infection. The present document is meant to be used by practitioners and other health care providers, including public health staff and others not directly involved in patient care.     

Silymarin treatment of viral hepatitis: a systematic review

Silymarin from the milk thistle herb (Silybum marianum) is used by many patients with chronic viral hepatitis, but its efficacy remains unknown. We performed a systematic review of silymarin for the treatment of chronic viral hepatitis B and C. An exhaustive search strategy identified 148 papers that studied silymarin compounds in liver disease. Of these, four trials included patients with hepatitis C, one included hepatitis B patients, and two, unspecified chronic viral hepatitis. However, only one trial exclusively studied patients with hepatitis C, and none involved patients with only hepatitis B. Silymarin treatment resulted in a decrease in serum transaminases compared with baseline in four studies, and compared with placebo in only one study. There is no evidence that silymarin affects viral load or improves liver histology in hepatitis B or C. No studies were found that investigated the use of silymarin concomitantly with interferon, nucleoside analogues, or other conventional treatments for hepatitis B or C. In conclusion, silymarin compounds likely decrease serum transaminases in patients with chronic viral hepatitis, but do not appear to affect viral load or liver histology. Nevertheless it may be worthwhile to determine its effects in conjunction with standard antiviral treatment.     

The implications of antiviral drugs with activity against hepatitis B virus and HIV

PURPOSE OF REVIEW: Around 10% of individuals infected with HIV suffer from chronic hepatitis B virus infection. This represents at least 4 million people worldwide. HIV infection modifies the course of hepatitis B virus associated liver disease with faster progression to cirrhosis. The number of anti-hepatitis B virus drugs has increased within the last few years, and some of them also exert activity against HIV-1. The aim of this article is to update the current knowledge on antiviral therapy for chronic hepatitis B in HIV-infected patients. RECENT FINDINGS: In the absence of successful anti-hepatitis B virus therapy, morbidity and mortality associated with liver disease are increased in hepatitis B virus/HIV coinfected individuals. Data derived from studies using new more potent anti-hepatitis B virus drugs are very promising, and strategies to use these antivirals sequentially and/or in combination are being developed. Hopefully, this success will help bring a halt to liver-related complications and death in the hepatitis B virus/HIV coinfected population. SUMMARY: Appropriate diagnosis and monitoring of chronic hepatitis B, including the use of noninvasive tools for assessing liver fibrosis, measurement of serum hepatitis B virus-DNA, and drug resistance testing, along with wise use of antivirals may convert hepatitis B virus/HIV coinfection into a manageable disease.