Clinical characteristics of tuberculosis in patients with liver cirrhosis

BACKGROUND AND OBJECTIVES: Patients with liver cirrhosis are likely to be susceptible to tuberculosis (TB) because of immune system dysfunction. The aim of this study was to elucidate the clinical characteristics and treatment responses in TB patients with cirrhosis. METHODS: Cases were patients with TB detected during their follow up for liver cirrhosis over a 4-year period. Controls were randomly selected patients with TB but no liver disease, matched to cases by age and gender in a 3:1 ratio. RESULTS: Thirty-six cases and 108 controls were enrolled. Extrapulmonary TB was more common in cases than controls (31% vs 12%, P = 0.02). Clinical and radiographic manifestations and response to treatment did not differ between the two groups. The frequency of hepatotoxicity was higher in the cases than in the controls who were treated with a regimen containing rifampicin and isoniazid, although the difference was not statistically significant (27% vs 10%, P = 0.079). CONCLUSIONS: TB patients with liver cirrhosis show extrapulmonary involvement more frequently. Patients with pulmonary TB and cirrhosis usually respond well to anti-TB treatment although appear to present more frequently with treatment-related hepatotoxicity.     

Effect of anti-tuberculosis therapy on liver function of pulmonary tuberculosis patients infected with hepatitis B virus

AIM: To observe the effect of anti-tuberculosis therapy on liver function of pulmonary tuberculosis patients with hepatitis B virus (HBV) infection, and to compare the differences of liver function by two treatments of anti-tuberculosis. METHODS: Forty-seven TB patients with HBV infection and 170 TB patients without HBV infection were divided into HPBE(S) and HLAMKO treatment groups. Liver function tests before and after the treatments were performed once in 2 wk or monthly, and their clinical manifestations were recorded. RESULTS: The rate of hepatotoxicity occurred in 26 (59%) TB patients with HBV during anti-TB treatment, higher than that in 40 (24%) TB patients without HBV. Hepatotoxicity occurred in 66 out of 217 patients, and the incidence of liver dysfunction was 46.1% in HPBE(S) group, significantly higher than that in HLAMKO group (12.7%) (P<0.01). CONCLUSION: TB patients with HBV should choose HLAMKO treatment because of fewer hepatotoxicity.     

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

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

Use of statins in patients with liver disease

Opinion statement  Cardiovascular disease is as common in individuals with chronic liver disease as in the general population. Moreover, recent data suggest that patients with nonalcoholic fatty liver disease (NAFLD) may have a cardiovascular risk greater than that conferred by the conventional risk factors. There is unequivocal evidence that cardiovascular disease is an important cause of morbidity and mortality in this patient population and thus requires consideration of aggressive therapy with lipid-lowering agents such as statins. Because all statins are hepatically cleared and can cause elevations in liver biochemistries, there is a concern that patients with underlying liver disease may be at increased risk for hepatotoxicity. However, recent data, along with an assessment of statin safety by the Liver Expert Panel, suggest that statins are generally well tolerated in patients with chronic liver disease such as NAFLD, primary biliary cirrhosis, and hepatitis C virus. These drugs also appear to be safe in patients with stable/compensated cirrhosis. However, decompensated cirrhosis and acute liver failure should be considered contraindications for lipid-lowering therapy as these patients are unlikely to benefit because of their generally grave prognosis. Although routine hepatic biochemical test monitoring is recommended, the cost-effectiveness of this approach has been questioned. The benefit of statins in patients with underlying liver disease who are otherwise important candidates for statin therapy far outweighs the risk of a very rare event of serious liver injury.     

抗结核治疗对携带HBV的肺结核病患者肝功能的影响

目的　探讨抗TB治疗过程中HBV携带与肝功能损害的关系 ,比较HPBE(S)和HLAMKO两种化疗方案对肝功的影响。方法　选择HBV携带的TB患者 47例 ,非HBV携带的TB患者 170例 ,随机分成HPBE(S)和HLAMKO两个治疗组 ,于治疗前和治疗后每 2wk检测肝功能 ,并观察临床症状。结果　 47例HBV携带的TB患者发生肝功损害 2 6例 ( 5 9% ) ,明显高于非HBV携带者40例 ( 2 4% ) ;在所有 2 17例患者中 ,不同程度肝功能损害者共 66例 ( 3 0 4% ) ,其中应用HPBE(S)方案组 115例发生肝损害 5 3例( 4 6 1% ) ,HLAMKO方案组 10 5例发生肝功异常者 13例 ( 12 7% )。结论　HBV携带的TB患者应选肝损害小的HLAMKO抗结核治疗方案 ,同时应用保肝药物     

Orthotopic liver transplantation for subacute hepatic failure following partial treatment of isoniazid-resistant tuberculosis

Abstract: The management of patients with pre-existing tuberculosis (TB) undergoing liver transplantation is challenging. Cautious immunosuppression is required to prevent reactivation of disease, and second-line anti-tuberculous treatment may be necessary to prevent graft hepatotoxicity. Furthermore, liver transplantation in the context of isoniazid-resistant TB has seldom been reported. We report on a 44-year-old man with recent isoniazid-resistant extra-pulmonary TB who developed subacute hepatic failure requiring emergency liver transplantation and treatment with second-line anti-tuberculous therapy. We demonstrate that patients who have pre-existing TB can be successfully treated with alternative anti-tuberculous medication while under immunosuppression post transplantation. Pre-existing TB, including resistant strains, should not be an absolute contraindication to liver transplantation.     

HCV and Chemotherapy: Does Infection Change Management?

Hepatitis C infects 1.6% of the United States adult population, and the peak prevalence of infection is present in the Baby Boomer generation. HCV infection predisposed patients to both hepatic and non-hepatic malignancies, leading to an increasing number of HCV infected patients needing chemotherapy. Since the liver is the most important site of drug metabolism, it is critical to understand how HCV impacts chemotherapy. Clinical decisions regarding chemotherapy dosing are traditionally based on serum biochemical tests; however these do not measure liver function, and liver biopsy combined with the Child classification are better measures of true liver function. Fortunately, patients without cirrhosis have intact synthetic function. However, patients with cirrhosis, some of whom have normal liver function tests, may not. Not only can HCV infection increase the risk of hepatotoxicity from chemotherapy, but chemotherapy can accelerate the progression of HCV related liver disease.     

Hepatobiliary manifestations in inflammatory bowel disease: The gut,the drugs and the liver

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-depen     

HIV／TB病人抗结核治疗强化期发生药物性肝炎的研究

目的了解广西地区人类免疫缺陷病毒（HIV）及结核（TB）双重感染病人（HIV／TB病人）,在标化抗结核治疗强化期药物性肝炎的发生情况,分析发生药物性肝炎的影响因素。方法以同期HIV阴性的TB病人作对照,选择16个可能对发生药物性肝炎产生影响的因素进行Spearman相关性分析,对单因素分析有统计学意义的影响因素进行Logistic回归模型多因素分析。结果符合观察条件的HIV／TB病人共369例,药物性肝炎发生率为22．8％（84例）;HIV阴性的TB共350例,药物性肝炎发生率为13．1％（46例）,两组比较差异有统计学意义（Pd0．001）。HIV／TB组治疗失败47例,其中与药物性肝炎相关占63．8％。单因素分析HIV／TB病人药物性肝炎的危险因素为女性、体质量减少、合并乙型肝炎病毒（HBV）或／和丙型肝炎病毒（HCV）感染、既往有肝损伤病史、血清蛋白降低、低CD4^＋T淋巴细胞计数、静脉途径用药、用药后嗜酸性粒细胞计数升高;多因素分析显示：体质量减少、既往有肝损伤病史、低CD4^＋T淋巴细胞计数、静脉用药、用药后嗜酸性粒细胞计数升高,是导致药物性肝炎的危险因素。结论HIV／TB病人抗结核治疗易出现药物性肝炎,对预后影响大;HIV感染后体质下降和免疫异常是导致药物性肝炎发生率高的主要原因。     

Accumulating awareness on the clinical significance and relevance of frailty in cirrhosis: Time to dig deeper into mechanistic basis!

Frailty corresponds to an emerging construct in the hepatology which is originally introduced as a validated geriatric syndrome regarding increased vulnerability to pathophysiological stressors. As for patients with cirrhosis, the presence of frailty is indicative of debilitating conditions that subjects are prone to deleterious acute insults and have difficulties to restore even if the underlying liver function partially returned to normal levels. Since this conceptual development, a variety of tools assessing frailty have been proposed and evaluated in the context of cirrhosis. A recent performance-based metric for frailty, designated as Liver Frailty Index, has broadly been applied in patients with cirrhosis and exhibited acceptable predictive ability in relation to disease progression, mortality and hospitalization. However, those functional tests measuring frailty may be impossible to perform in circumstance that patients are critically ill or undergoing detrimental events. An interesting modality indicates the use of alternative tests to evaluate frailty, which may be more adaptable and of choice for specific subgroups. The interrelation between frailty and various cirrhosis-associated pathological entities is of clinical importance and implication. Noticeably, it is imperative to clarify these complex linkages to highlight novel therapeutic targets or interventional endpoints. The efficient and effective management of frailty is still challenging, but many attempts have been made to overcome barriers of affordability and availability. Some clinical trials on small scale revealed that home-based exercise and individualized nutrition therapy show benefits in patients with cirrhosis, and high adherence to the treatment regimen may direct better efficacy and performance.     

Liver abnormalities in drug and substance abusers

Drug and substance abuse remains a major medical problem. Alcohol use, abuse and dependence are highly prevalent conditions. Alcohol related liver disease can present as simple steatosis, steatohepatitis, alcoholic hepatitis or liver cirrhosis. Paracetamol hepatotoxicity secondary to accidental or deliberate overdose is another common problem. While the adverse cardiovascular, neurological, renal and psychiatric consequences of various illicit substance abuses are widely studied and publicized, less attention has been directed towards possible hepatotoxic effects. Illicit drug abuse can cause a range of liver abnormalities ranging from asymptomatic derangement of liver function tests to fulminant hepatic failure. This article reviews the epidemiology, risk factors, clinical manifestations, pathogenesis, investigations, management and prognostic factors of alcohol related liver disease and paracetamol hepatotoxicity as well as the current knowledge pertaining to hepatotoxicity of the more commonly used illicit substances including cannabis, amphetamine type stimulants, cocaine, khat chewing and complementary and alternate medicine.     

DDI and liver tests in HIV-1 seropositive haemophiliacs

Many patients with haemophilia who are HIV-1 seropositive are co-infected with the hepatitis C virus with variable degrees of underlying liver disease. To evaluate whether the use of the antiretroviral agent Dideoxyinosine (DDI) causes worsening of hepatic dysfunction as measured by liver enzyme tests, we reviewed our cohort of patients previously treated with monotherapy with Zidovudine (AZT) and subsequently changed to DDI. Seventeen patients (median age: 34 years, median absolute CD4 lymphocyte cell count: 86 cells μL⁻¹) were included in this study. None had coincident use of other hepatotoxic agents. The median duration of treatment with AZT and DDI was 18 and 15 months, respectively. There was no significant change in liver function tests with the use of DDI and no development of clinical signs of hepatotoxicity. Neither duration of treatment, absolute CD4 lymphocyte cell count, pre-existing elevation of baseline aminotransferase levels nor the use of Pneumocystis carinii prophylaxis therapy resulted in further elevation of liver function tests. Monotherapy with DDI was well tolerated in this cohort of HIV-1-seropositive haemophiliacs with coincident hepatitis C infection.     

Enfermedad hepática por alcohol. Guías de práctica clínica. Documento de consenso auspiciado por la AEEH

Alcohol-related liver disease (ARLD) is the most prevalent cause of advanced liver disease and liver cirrhosis in Europe, including Spain. According to the World Health Organization the fraction of liver cirrhosis attributable to alcohol use in Spain is 73.8% among men and 56.3% among women. ARLD includes various stages such as steatohepatitis, cirrhosis and hepatocellular cancer. In addition, patients with underlying ARLD and heavy alcohol intake may develop alcoholic hepatitis, which is associated with high mortality. To date, the only effective treatment to treat ARLD is prolonged withdrawal. There are no specific treatments, and the only treatment that increases life expectancy in alcoholic hepatitis is prednisolone. For patients with alcoholic hepatitis who do not respond to treatment, some centres offer the possibility of an early transplant. These clinical practice guidelines aim to propose recommendations on ARLD taking into account their relevance as a cause of advanced chronic liver disease and liver cirrhosis in our setting. This paper aims to answer the key questions for the clinical practice of Gastroenterology, Hepatology, as well as Internal Medicine and Primary Health Centres, making the most up-to-date information regarding the management and treatment of ARLD available to health professionals. These guidelines provide evidence-based recommendations for the clinical management of this disease.     

Nodular regenerative hyperplasia of the liver: a rare differential diagnosis of cholestasis with response to ursodeoxycholic acid

Nodular regenerative hyperplasia of the liver (NRHL) is an uncommon non-malignant finding typically associated with haematological or auto-immune disease. The main clinical symptom is portal hypertension in the absence of underlying liver cirrhosis. The pathogenesis of NRHL remains unknown. We report a case of NRHL with cholestasis and progression to liver insufficiency without any underlying disease and no association with systemic disease or drug intake. Cholestasis and liver function tests improved significantly during treatment with ursodeoxycholic acid (750 mg per day). Based on this case, it may be concluded that treatment with ursodeoxycholic acid might be beneficial in patients with NRHL and progression to liver insufficiency.     

Hepatitis C virus infection and hepatotoxicity during antituberculosis chemotherapy

BACKGROUND: The risk of drug-induced hepatotoxicity (DIH) during treatment for tuberculosis (TB) in patients who are seropositive for the hepatitis C virus (HCV) is not clear. We evaluated whether HCV-seropositive patients are at a higher risk of DIH than control subjects during treatment for TB with standard short-course regimens. METHODS: Fifty-four HCV-seropositive patients with newly diagnosed active TB who were treated with isoniazid, rifampin, ethambutol, and/or pyrazinamide were included in the study population. Ninety-seven HCV-seronegative patients were selected as control subjects. RESULTS: Forty HCV-seropositive patients (74%) and 82 control subjects (85%) received an initial treatment regimen that included pyrazinamide. Twenty-two HCV-seropositive patients (41%) and 19 control subjects (20%) exhibited elevated liver enzyme levels during TB treatment, including transient elevation of transaminase. DIH, defined as a liver transaminase level >/= 120 IU/L, occurred more frequently in HCV-seropositive patients (7 of 54 patients, 13%) than in control subjects (4 of 97 patients, 4%). Isoniazid and rifampin were reintroduced after the liver transaminase level returned to baseline in five HCV-seropositive patients exhibiting DIH, and all these retrials proved to be successful. CONCLUSIONS: These findings suggest that treatment for TB in HCV-seropositive patients could be pursued in the usual manner, using standard short-course regimens, with the condition that monthly liver function tests are carefully performed.     

27例儿童原发性肝癌的临床特点分析

目的总结儿童原发性肝癌(primary liver cancer,PLC)临床特点,探讨其防治策略。方法回顾总结我院收治的27例儿童PLC相关资料。结果在我院确诊的27例PLC的患儿中,有18例(66.7%)为HBV感染者。有18例存在肝硬化基础,其中失代偿期12例。22例有不同的肝病背景,但另外5例无任何肝病基础。Child-Pugh分级A级15例,B级11例,C级1例;临床肝癌巴塞罗那(Barcelona clinic liver cancer,BCLC)分期A期8例,B期3例,C期14例,D期2例。27例中行肝切除术的仅有2例,行肝动脉化疗栓塞术者3例,行射频消融术者3例,患者经治疗后预后较好。结论 27例PLC儿童基础疾病大多数为慢性乙型肝炎(67%),有肝硬化基础者更易发生。儿童PLC恶性度高、进展快,致其手术切除率低。防止感染HBV,积极治疗慢性乙型肝炎患者尤其是肝硬化患者,加强高危人群肝癌的筛查和监管,对于儿童PLC的防治至关重要。     

NAT2＊6A, a haplotype of the N-acetyltransferase 2 gene, is an important biomarker for risk of anti-tuberculosis drug-induced hepatotoxicity in Japanese patients with tuberculosis

AIM： To investigate an association between N-acetyltransferase 2 （NAT2）-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS： We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS： Statistical analysis revealed that the frequency of a variant haplotype, NAT2^＊6A, was significantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio （OR） = 3.535]. By contrast, the frequency of a wild-type （major） haplotype, ＂NAT2＊4＂, was significantly lower in TB patients with hepatotoxicity than those without hepatotoxicity （P 〈 0.001, OR = 0.265）. There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION： The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2^＊4 and NAT2^＊6A, are useful new biomarkers for predicting antiTB drug-induced hepatotoxicity.     

Hepatic abnormalities in adult onset Still's disease

Five patients with adult onset Still's disease are reported. Three had abnormal liver function tests (LFT) prior to receiving salicylates. Liver biopsy in 1 of these 3 and in another with normal LFT was abnormal. The elevated LFT returned to normal with high dose salicylate therapy coincident with remission of disease activity. It is proposed that hepatic abnormalities in Still's disease frequently reflect the underlying disease and not salicylate hepatotoxicity (SH).     

Hepatogenous diabetes. Current views of an ancient problem

Diabetes developed as a complication of cirrhosis is known as «hepatogenous diabetes» (HD). Around 30% to 60% of cirrhotic patients suffer from this metabolic disorder. Insulin resistance in muscular, hepatic and adipose tissues as well as hyperinsulinemia, seem to be pathophysiologic bases for HD. An impaired response of the islet β-cells of the pancreas and the hepatic insulin resistance are also contributing factors. Diabetes develops when defective oxidative and nonoxidative muscle glucose metabolism develops. Non-alcoholic fatty liver disease (NAFLD), alcoholic cirrhosis, chronic hepatitis C (CHC), and hemochromatosis are more frequently associated with HD. HD in early cirrhosis stages may be sub clinical. Only insulin resistance and glucose intolerance may be observed. As liver disease advances, diabetes becomes clinically manifest, therefore HD may be considered as a marker for liver function deterioration. HD is clinically different from that of type 2 DM since it is less frequently associated with microangiopathy and patients suffer complications of cirrhosis more frequently as well as increased mortality. Insulin resistance and HD associate to a decrease in the sustained response to antiviral therapy and an increased progression of fibrosis in patients with CHC. Diabetes treatment is complex due to liver damage and hepatotoxicity of oral hypoglycemic drugs that are frequently prescribed to these patients. This paper will review current concepts in relation to the pathopysiolo-gy, the impact on the clinical outcome of cirrhosis, and the therapy of HD. Finally, the role of HD as a risk factor for the occurrence and exacerbation of hepatocel-lular carcinoma (HCC) will also be reviewed.     

Chronic active hepatitis and liver cirrhosis in association with combined tamoxifen/tegafur adjuvant therapy

Summary Two female breast cancer patients who received combined tamoxifen and tegafur as postsurgical adjuvant therapy developed severe hepatotoxicity after being treated for three and eight months, respectively. Shortly after the cessation of the treatment, routine liver tests showed gradual recovery, but liver biopsies revealed chronic active hepatitis in one patient and liver cirrhosis in the other. Four and five years, respectively, after the cessation of the treatment, the results of liver tests were normal and distinct histological improvement was observed in both patients. Because these patients had no viral and immunoserological markers nor any history of alcohol abuse, this study suggested that the tamoxifen and tegafur regimen induced reversible chronic active liver disease.