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 j...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 acutehepatitis 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.展开更多
Immunological checkpoint inhibitors(ICIs)have revolutionized therapy of many different malignanices.Concomitant immune-mediated adverse effects are common and can affect many organs such as the skin,lungs,gastrointest...Immunological checkpoint inhibitors(ICIs)have revolutionized therapy of many different malignanices.Concomitant immune-mediated adverse effects are common and can affect many organs such as the skin,lungs,gastrointestinal and endocrine organs as well as the liver.Liver injury has been reported in 3%-8%of patients with grade III-IV hepatitis in retrospective studies.The liver injury is characterized by hepatocellular injury resembling autoimmune hepatitis biochemically but not immunologically as patients with ICI induced hepatoxicity rarely have auto-antibodies or IgG elevation.The role for liver biopsy(LB)in patients with suspected liver injury due to ICIs is controversial and it is not clear whether results of a LB will change clinical management.LB can be helpful when there is diagnostic uncertainty and pre-existing liver disease is suspected.Although there are no distinctive histological features,the finding of granulomas and endothelitis may suggest a specific type of hepatitis induced by ICIs.The natural history of hepatotoxicity of ICI therapy is not well known.Recent studies have demonstrated that 33%-50%of patients improve spontaneously with discontinuation of ICIs.In patients with jaundice and/or coagulopathy corticosteroids are used.The high doses of corticosteroids with 1-2 mg/kg/d of methylprednisolone recommended by the oncological societies are controversial.Recently it has shown that initial treatment with 1 mg/kg/d provided similar liver tests improvement which was also associated with a reduced risk of steroid-induced adverse effects in comparison with higher-dose regimens.Secondary immunosuppression mostly with mycophenolate mofetil has been reported to be helpful.展开更多
Drug-induced liver injury(DILI)is an uncommon event in clinical practice,which makes knowing its true incidence difficult.Prospective,retrospective and registry-based studies are the most important methods to obtain e...Drug-induced liver injury(DILI)is an uncommon event in clinical practice,which makes knowing its true incidence difficult.Prospective,retrospective and registry-based studies are the most important methods to obtain epidemiological data on DILI.Latin America(LA)has a historical lack of prospective studies on this topic.New definitions and the creation of hepatotoxicity registries have significantly improved the epidemiological understanding of hepatic drug reactions in several regions of the world.The Latin American DILI network,referred to as LATINDILI,has been created in 2011,and recently published its own DILI recommendations describing the most relevant issues on the management of hepatotoxicity in general,and those based on findings from our own LA experience in particular.Although most of the registries do not carry out population-based studies,they may provide important data related to the prevalence of DILI.The joint work among researchers and the corresponding health and regulatory authorities should be stimulated due to the high impact that hepatotoxicity represents for public health.展开更多
Abnormal liver biochemical tests are present in up to30%of patients with inflammatory bowel disease(IBD),and therefore become a diagnostic challenge.Liver and biliary tract diseases are common extraintestinal manifest...Abnormal liver biochemical tests are present in up to30%of patients with inflammatory bowel disease(IBD),and therefore become a diagnostic challenge.Liver and biliary tract diseases are common extraintestinal manifestations for both Crohn’s disease and ulcerative colitis(UC),and typically do not correlate with intestinal activity.Primary sclerosing cholangitis(PSC)is the most common hepatobiliary manifestation of IBD,and is more prevalent in UC.Approximately 5%of patients with UC develop PSC,with the prevalence reaching up to 90%.Cholangiocarcinoma and colon cancer risks are increased in these patients.Less common disorders include autoimmune hepatitis/PSC overlap syndrome,IgG4-associated cholangiopathy,primary biliary cirrhosis,hepatic amyloidosis,granulomatous hepatitis,cholelithiasis,portal vein thrombosis,liver abscess,and non-alcoholic fatty liver disease.Hepatitis B reactivation during immunosuppressive therapy is a major concern,with screening and vaccination being recommended in serologically negative cases for patients with IBD.Reactivation prophylaxis with entecavir or tenofovir for 6to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen(HBsAg)positive,independently from viral load.HBsAg negative and anti-HBc positive patients,with or without anti-HBs,should be closely monitored,measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy,and should be treated if the viral load increases.On the other hand,immunosuppressive therapy does not seem to promote reactivation of hepatitis C,and hepatitis C antiviral treatment does not influence IBD natural history either.Most of the drugs used for IBD treatment may induce hepatotoxicity,although the incidence of serious adverse events is low.Abnormalities in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically relevant.Methotrexaterelated hepatotoxicity has been described in 14%of patients with IBD,in a dose-dependent manner.Liver biopsy is not routinely recommended.Biologics-related hepatotoxicity is rare,but has been shown most frequently in patients treated with infliximab.Thiopurines have been associated with veno-occlusive disease,regenerative nodular hyperplasia,and liver peliosis.Routine liver biochemical tests are recommended,especially during the first month of treatment.All these conditions should be considered in IBD patients with clinical or biochemical features suggestive of hepatobiliary involvement.Diagnosis and management of these disorders usually involve hepatologists and gastroenterologists due to its complexity.展开更多
Novel biological agents including cytokines and recombinant fusion proteins are increasingly prescribed for cancer,rheumatologic,autoimmune,and inflammatory diseases,and are currently being evaluated in hepatocellular...Novel biological agents including cytokines and recombinant fusion proteins are increasingly prescribed for cancer,rheumatologic,autoimmune,and inflammatory diseases,and are currently being evaluated in hepatocellular carcinoma(HCC).They are classified by their mechanism of action and include tumor necrosis factor-alpha(TNF-α)antagonists,T cell mediated antitumor inhibitors,interleukin receptor antagonists,and immune checkpoint inhibitors(ICIs).Some ICIs cause frequent hepatotoxicity with a variable clinical,biochemical,and serological presentation,especially in patients receiving another immunomodulatory agent.Half of the cases of liver damage induced by biological agents spontaneously regress after drug withdrawal,but the others require steroid therapy.Unfortunately,there are no widely accepted recommendation for the use of corticosteroids in these patients,even though international cancer societies have their own guidelines.Differentiating drug-induced autoimmune hepatitis(DIAIH)from classic AIH is challenging for pathologists,but liver biopsy is valuable,particularly in cases with unclear clinical presentation.Interesting,novel histological patterns have been described in liver damage induced by these agents(i.e.,endothelitis,ring granuloma and secundary sclerosing cholangitis associated with lymphocytic infiltration of cytotoxic CD8+T cells).Here,we describe the clinical and biochemical characteristics of patients with hepatotoxicity induced by TNF-αantagonists and ICIs.Controversial issues involved in the administration of corticosteroid therapy,and hepatitis B virus(HBV)reactivation induced by immunosuppressive therapy are also discussed.展开更多
In order to analyze the causative drugs,clinical manifestation and pathological characteristics of the patients with acute drug-induced liver disease,from January 2000 to December 2005,275 cases diagnosed as acute dru...In order to analyze the causative drugs,clinical manifestation and pathological characteristics of the patients with acute drug-induced liver disease,from January 2000 to December 2005,275 cases diagnosed as acute druginduced liver diseases according to Maria Criterion and hospitalized in Zhongshan Hospital of Fudan University were retrospectively reviewed.Each was determined by drug history,clinical symptoms and signs,laboratory tests and therapeutic effects.In 41 cases,the diagnosis was confirmed by liver biopsy.The proportion of acute drug-induced liver disease among all of the acute liver injuries was annually increased.The most common drugs which induced acute liver injuries were traditional Chinese herb medicine(23.3%,64/275 cases),antineoplastics(15.3%,42/275),hormones and other immunosuppressant agents(13.8%,38/275),antihypertensive drugs and other cardiovascular drugs(10.2%,28/275),NSAIDs(8.7%,24/275)respectively.Hepatocellular injury was the predominant type in these cases(132 cases,48%).The principal clinical manifestation included nausea(54.8%),fatigue(50.2%),jaundice(35.6%).27.9%patients were asymptomatic.Most patients were cured with good prognosis.The total effective rate was 94.2%after treatment.The clinicians should pay attention to the prevention,diagnosis and therapy of drug-induced liver disease.展开更多
Autoimmune hepatitis is a chronic liver disease putatively caused by loss of tolerance to hepatocyte- specific autoantigens. It is characterized by female predilection, elevated aminotransferase levels, autoantibodies...Autoimmune hepatitis is a chronic liver disease putatively caused by loss of tolerance to hepatocyte- specific autoantigens. It is characterized by female predilection, elevated aminotransferase levels, autoantibodies, increased y-globulin or IgG levels and biopsy evidence of interface hepatitis. It is currently divided into types 1 and 2, based on expression of autoantibodies. Autoantigenic epitopes have been identified only for the less frequent type 2. Although autoimmune hepatitis occurs in childhood, this review focuses on disease in adults. In the absence of pathognomonic biomarkers, diagnosis requires consideration of clinical, biochemical, serological and histological features, which have been codified into validated diagnostic scoring systems. Since many features also occur in other chronic liver diseases, these scoring systems aid evaluation of the differential diagnosis. New practice guidelines have redefined criteria for remission to include complete biochemical and histological normalization on immunosuppressive therapy. Immunosuppression is most often successful using prednisone or prednisolone and azathioprine; however, the combination of budesonide and azathioprine for non-cirrhotic patients offers distinct advantages. Patients failing standard immunosuppression are candidates for alternative immunosuppressive regimens, yet none of the options has been studied in a randomized, controlled trial. Overlap syndromes with either primary sclerosing cholangitis or primary biliary cirrhosis occur in a minority. Liver transplantation represents a life-saving option for patients presenting with acute liver failure, severely decompensated cirrhosis or hepatocellular carcinoma. Transplant recipients are at risk for recurrent autoimmune hepatitis in the allograft, and de novo disease may occur in patients transplanted for other indications. Patients transplanted for AIH are also at risk for recurrent or de novo inflammatory bowel disease. Progress in our understanding of the immunopathogenesis should lead to identification of specific diagnostic and prognostic biomarkers and new therapeutic strategies.展开更多
BACKGROUND Drug-induced liver injury(DILI)is the leading cause of acute liver failure in the United States.DILI is mainly caused by painkillers and fever reducers,and it is often characterized by the type of hepatic i...BACKGROUND Drug-induced liver injury(DILI)is the leading cause of acute liver failure in the United States.DILI is mainly caused by painkillers and fever reducers,and it is often characterized by the type of hepatic injury(hepatocellular or cholestatic).This report presents a case of fenofibrate-induced severe jaundice in a 65-year-old Korean male with no prior history of liver disease.We offer a strategy for patients who present signs of severe liver injury with jaundice and high elevations in serum transaminases.CASE SUMMARY A 65-year-old male visited the gastroenterology outpatient clinic of a tertiary hospital due to increased levels of liver enzyme and total bilirubin which were incidentally detected through a preoperative screening test.Abdominal ultrasound and computed tomography showed no biliary obstruction or nonspecific findings in the liver.Liver biopsy was performed and the patient was finally diagnosed with acute cholestatic hepatitis.Following the biopsy,steroid therapy was initiated and after 3 wk of treatment,the total bilirubin level was reduced to 7.22 mg/dL.CONCLUSION In patients with hyperlipidemia,treatment including fenofibric acid induces rare complications such as severe jaundice and acute cholestatic hepatitis,warranting clinical attention.展开更多
文摘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 acutehepatitis 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.
文摘Immunological checkpoint inhibitors(ICIs)have revolutionized therapy of many different malignanices.Concomitant immune-mediated adverse effects are common and can affect many organs such as the skin,lungs,gastrointestinal and endocrine organs as well as the liver.Liver injury has been reported in 3%-8%of patients with grade III-IV hepatitis in retrospective studies.The liver injury is characterized by hepatocellular injury resembling autoimmune hepatitis biochemically but not immunologically as patients with ICI induced hepatoxicity rarely have auto-antibodies or IgG elevation.The role for liver biopsy(LB)in patients with suspected liver injury due to ICIs is controversial and it is not clear whether results of a LB will change clinical management.LB can be helpful when there is diagnostic uncertainty and pre-existing liver disease is suspected.Although there are no distinctive histological features,the finding of granulomas and endothelitis may suggest a specific type of hepatitis induced by ICIs.The natural history of hepatotoxicity of ICI therapy is not well known.Recent studies have demonstrated that 33%-50%of patients improve spontaneously with discontinuation of ICIs.In patients with jaundice and/or coagulopathy corticosteroids are used.The high doses of corticosteroids with 1-2 mg/kg/d of methylprednisolone recommended by the oncological societies are controversial.Recently it has shown that initial treatment with 1 mg/kg/d provided similar liver tests improvement which was also associated with a reduced risk of steroid-induced adverse effects in comparison with higher-dose regimens.Secondary immunosuppression mostly with mycophenolate mofetil has been reported to be helpful.
文摘Drug-induced liver injury(DILI)is an uncommon event in clinical practice,which makes knowing its true incidence difficult.Prospective,retrospective and registry-based studies are the most important methods to obtain epidemiological data on DILI.Latin America(LA)has a historical lack of prospective studies on this topic.New definitions and the creation of hepatotoxicity registries have significantly improved the epidemiological understanding of hepatic drug reactions in several regions of the world.The Latin American DILI network,referred to as LATINDILI,has been created in 2011,and recently published its own DILI recommendations describing the most relevant issues on the management of hepatotoxicity in general,and those based on findings from our own LA experience in particular.Although most of the registries do not carry out population-based studies,they may provide important data related to the prevalence of DILI.The joint work among researchers and the corresponding health and regulatory authorities should be stimulated due to the high impact that hepatotoxicity represents for public health.
文摘Abnormal liver biochemical tests are present in up to30%of patients with inflammatory bowel disease(IBD),and therefore become a diagnostic challenge.Liver and biliary tract diseases are common extraintestinal manifestations for both Crohn’s disease and ulcerative colitis(UC),and typically do not correlate with intestinal activity.Primary sclerosing cholangitis(PSC)is the most common hepatobiliary manifestation of IBD,and is more prevalent in UC.Approximately 5%of patients with UC develop PSC,with the prevalence reaching up to 90%.Cholangiocarcinoma and colon cancer risks are increased in these patients.Less common disorders include autoimmune hepatitis/PSC overlap syndrome,IgG4-associated cholangiopathy,primary biliary cirrhosis,hepatic amyloidosis,granulomatous hepatitis,cholelithiasis,portal vein thrombosis,liver abscess,and non-alcoholic fatty liver disease.Hepatitis B reactivation during immunosuppressive therapy is a major concern,with screening and vaccination being recommended in serologically negative cases for patients with IBD.Reactivation prophylaxis with entecavir or tenofovir for 6to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen(HBsAg)positive,independently from viral load.HBsAg negative and anti-HBc positive patients,with or without anti-HBs,should be closely monitored,measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy,and should be treated if the viral load increases.On the other hand,immunosuppressive therapy does not seem to promote reactivation of hepatitis C,and hepatitis C antiviral treatment does not influence IBD natural history either.Most of the drugs used for IBD treatment may induce hepatotoxicity,although the incidence of serious adverse events is low.Abnormalities in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically relevant.Methotrexaterelated hepatotoxicity has been described in 14%of patients with IBD,in a dose-dependent manner.Liver biopsy is not routinely recommended.Biologics-related hepatotoxicity is rare,but has been shown most frequently in patients treated with infliximab.Thiopurines have been associated with veno-occlusive disease,regenerative nodular hyperplasia,and liver peliosis.Routine liver biochemical tests are recommended,especially during the first month of treatment.All these conditions should be considered in IBD patients with clinical or biochemical features suggestive of hepatobiliary involvement.Diagnosis and management of these disorders usually involve hepatologists and gastroenterologists due to its complexity.
文摘Novel biological agents including cytokines and recombinant fusion proteins are increasingly prescribed for cancer,rheumatologic,autoimmune,and inflammatory diseases,and are currently being evaluated in hepatocellular carcinoma(HCC).They are classified by their mechanism of action and include tumor necrosis factor-alpha(TNF-α)antagonists,T cell mediated antitumor inhibitors,interleukin receptor antagonists,and immune checkpoint inhibitors(ICIs).Some ICIs cause frequent hepatotoxicity with a variable clinical,biochemical,and serological presentation,especially in patients receiving another immunomodulatory agent.Half of the cases of liver damage induced by biological agents spontaneously regress after drug withdrawal,but the others require steroid therapy.Unfortunately,there are no widely accepted recommendation for the use of corticosteroids in these patients,even though international cancer societies have their own guidelines.Differentiating drug-induced autoimmune hepatitis(DIAIH)from classic AIH is challenging for pathologists,but liver biopsy is valuable,particularly in cases with unclear clinical presentation.Interesting,novel histological patterns have been described in liver damage induced by these agents(i.e.,endothelitis,ring granuloma and secundary sclerosing cholangitis associated with lymphocytic infiltration of cytotoxic CD8+T cells).Here,we describe the clinical and biochemical characteristics of patients with hepatotoxicity induced by TNF-αantagonists and ICIs.Controversial issues involved in the administration of corticosteroid therapy,and hepatitis B virus(HBV)reactivation induced by immunosuppressive therapy are also discussed.
文摘In order to analyze the causative drugs,clinical manifestation and pathological characteristics of the patients with acute drug-induced liver disease,from January 2000 to December 2005,275 cases diagnosed as acute druginduced liver diseases according to Maria Criterion and hospitalized in Zhongshan Hospital of Fudan University were retrospectively reviewed.Each was determined by drug history,clinical symptoms and signs,laboratory tests and therapeutic effects.In 41 cases,the diagnosis was confirmed by liver biopsy.The proportion of acute drug-induced liver disease among all of the acute liver injuries was annually increased.The most common drugs which induced acute liver injuries were traditional Chinese herb medicine(23.3%,64/275 cases),antineoplastics(15.3%,42/275),hormones and other immunosuppressant agents(13.8%,38/275),antihypertensive drugs and other cardiovascular drugs(10.2%,28/275),NSAIDs(8.7%,24/275)respectively.Hepatocellular injury was the predominant type in these cases(132 cases,48%).The principal clinical manifestation included nausea(54.8%),fatigue(50.2%),jaundice(35.6%).27.9%patients were asymptomatic.Most patients were cured with good prognosis.The total effective rate was 94.2%after treatment.The clinicians should pay attention to the prevention,diagnosis and therapy of drug-induced liver disease.
文摘Autoimmune hepatitis is a chronic liver disease putatively caused by loss of tolerance to hepatocyte- specific autoantigens. It is characterized by female predilection, elevated aminotransferase levels, autoantibodies, increased y-globulin or IgG levels and biopsy evidence of interface hepatitis. It is currently divided into types 1 and 2, based on expression of autoantibodies. Autoantigenic epitopes have been identified only for the less frequent type 2. Although autoimmune hepatitis occurs in childhood, this review focuses on disease in adults. In the absence of pathognomonic biomarkers, diagnosis requires consideration of clinical, biochemical, serological and histological features, which have been codified into validated diagnostic scoring systems. Since many features also occur in other chronic liver diseases, these scoring systems aid evaluation of the differential diagnosis. New practice guidelines have redefined criteria for remission to include complete biochemical and histological normalization on immunosuppressive therapy. Immunosuppression is most often successful using prednisone or prednisolone and azathioprine; however, the combination of budesonide and azathioprine for non-cirrhotic patients offers distinct advantages. Patients failing standard immunosuppression are candidates for alternative immunosuppressive regimens, yet none of the options has been studied in a randomized, controlled trial. Overlap syndromes with either primary sclerosing cholangitis or primary biliary cirrhosis occur in a minority. Liver transplantation represents a life-saving option for patients presenting with acute liver failure, severely decompensated cirrhosis or hepatocellular carcinoma. Transplant recipients are at risk for recurrent autoimmune hepatitis in the allograft, and de novo disease may occur in patients transplanted for other indications. Patients transplanted for AIH are also at risk for recurrent or de novo inflammatory bowel disease. Progress in our understanding of the immunopathogenesis should lead to identification of specific diagnostic and prognostic biomarkers and new therapeutic strategies.
基金Supported by Soonchunhyang University Research Fund,No.20200037.
文摘BACKGROUND Drug-induced liver injury(DILI)is the leading cause of acute liver failure in the United States.DILI is mainly caused by painkillers and fever reducers,and it is often characterized by the type of hepatic injury(hepatocellular or cholestatic).This report presents a case of fenofibrate-induced severe jaundice in a 65-year-old Korean male with no prior history of liver disease.We offer a strategy for patients who present signs of severe liver injury with jaundice and high elevations in serum transaminases.CASE SUMMARY A 65-year-old male visited the gastroenterology outpatient clinic of a tertiary hospital due to increased levels of liver enzyme and total bilirubin which were incidentally detected through a preoperative screening test.Abdominal ultrasound and computed tomography showed no biliary obstruction or nonspecific findings in the liver.Liver biopsy was performed and the patient was finally diagnosed with acute cholestatic hepatitis.Following the biopsy,steroid therapy was initiated and after 3 wk of treatment,the total bilirubin level was reduced to 7.22 mg/dL.CONCLUSION In patients with hyperlipidemia,treatment including fenofibric acid induces rare complications such as severe jaundice and acute cholestatic hepatitis,warranting clinical attention.
