Mild Liver Function Abnormalities Research Articles

Analysis of occurrences and causes of abnormal liver function in 109 patients with COVID-19

ABSTRACT Context: COVID-19 is a novel coronavirus pneumonia, which is related to abnormal liver function. Thus, it is important to explore the occurrences and causes of abnormal liver function with COVID-19. Methods: We chose 109 patients with COVID-19 in 2020 and studied the relationship between gender, age, basic diseases, antiviral drug treatment, disease classification, and abnormal liver function, and analyzed the causes of abnormal liver function in patients with COVID-19 Results: Among patients, 46 (42.20%) had abnormal liver function at admission; 37 (80.43%) had mild abnormal liver function; and 9 (19.57%) had severe liver function. Compared with other age groups, the abnormal rate of serum ALP in the group younger than 21 years old were the highest (P < 0.05). The abnormal rates and concentrations of serum ALT, AST and γ-GT in the male groups were higher than in female groups (P < 0.05), basic disease group were higher than those in the non-basic disease group (P < 0.05). Serum γ-GT concentration after 1 week of antiviral treatment was higher than that before treatment (P < 0.05). The abnormal rate of ALT and AST at discharge was lower than that after antiviral treatment for 1 week (P < 0.05). Serum TB and AST concentrations at discharge were lower than those before treatment (P < 0.05). Serum AST and γ-GT concentrations in severe/critical type group were higher than those in mild or ordinary type group (P < 0.05) Conclusions: In this study, we found male sex, basic diseases, antiviral drugs, and severe/critical types are related to the occurrence of abnormal liver function in COVID-19 patients.

A case of Legionella pneumonia after robot‐assisted radical prostatectomy

IntroductionPostoperative Legionella pneumonia is very rare.Case presentationA 71‐year‐old male patient with prostate cancer (cT2bN0M0) underwent a robotic‐assisted radical prostatectomy. On the 5th postoperative day, the patient developed chills and a fever of 39.2°C. Chest radiography revealed decreased permeability in the right middle lung field, leading to the diagnosis of postoperative pneumonia. Antimicrobial therapy was initiated immediately. Blood tests on postoperative day 10 revealed mild liver function abnormalities, electrolyte abnormalities, and a markedly elevated inflammatory response. Legionella pneumonia was suspected based on blood sample results and systemic symptoms, such as diarrhea and nausea. Furthermore, Legionella antigens were detected in the patient's urine, prompting further administration of levofloxacin. The patient's subsequent clinical course was favorable.ConclusionWhen bacterial pneumonia fails to respond to antimicrobial therapy and systemic symptoms develop, atypical pneumonia, caused by pathogens such as Legionella pneumophila, should be considered even in cases of postoperative pneumonia.

Efficacy and safety of molnupiravir in patients with Omicron variant vaccine breakthrough COVID-19 infection: a randomized, controlled trial.

Introduction: Randomized, controlled trials of molnupiravir in real-world use during the Omicron wave are scarce. The frequency of hospitalization and death is low, so further research is needed to confirm the virological efficacy of molnupiravir. Methods: A single-center, randomized, controlled clinical trial was conducted, and 111 hospitalized coronavirus disease 2019 (COVID-19) patients were randomly assigned at a ratio of 1:1. Fifty-three patients in the molnupiravir group were administered 800mg of molnupiravir twice daily for 5 days in addition to the standard therapy, and 58 patients in the control group only received the standard therapy in accordance with local guidelines. The antiviral effect and adverse events were evaluated during the follow-up. Results: The median viral clearance time in the molnupiravir group was significantly shorter than that in the control group (p = 0.003). Furthermore, patients who started molnupiravir therapy within 3 days had significantly shorter viral clearance time than the controls (p = 0.003). In the vaccinated subgroup, molnupiravir therapy was also associated with a shorter viral clearance time (p = 0.003). A total of three adverse events, which were minor, were reported in the molnupiravir group. One of the patients had mild liver function abnormalities, and all of them were resolved without intervention. However, the remission time was similar between the two tested groups. Conclusion: Molnupiravir exhibited good viral replication inhibitor efficacy in patients with Omicron variant vaccine breakthrough COVID-19 infection. Clinical Trial Registration: [https://www.chictr.org.cn/], identifier [ChiCTR2200059796].

Antibody response and safety of inactivated SARS-CoV-2 vaccines in chronic hepatitis B patients with and without cirrhosis.

The immune response and safety of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic hepatitis B (CHB), especially those with cirrhosis, are not clear. Therefore, this study was conducted to evaluate the efficacy and safety of inactivated SARS-CoV-2 vaccines among CHB patients with and without cirrhosis. A total of 643 CHB patients who received two doses of inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) were enrolled. Serum samples were collected and tested for SARS-CoV-2 S-receptor-binding domain (S-RBD) immunoglobulin G (IgG) at enrollment. Data on adverse events (AEs) within 7days after the second dose were obtained using a questionnaire. A total of 416 non-cirrhotic and 227 cirrhotic patients were included in the analysis. Cirrhotic patients had lower antibody titers than non-cirrhotic patients after adjusting for age, sex, and time interval (2.45 vs. 2.60ng/ml, p=0.034). Furthermore, the study revealed that cirrhotic patients demonstrated a slower rate of seropositivity increase, with the highest rate being recorded at week4 and reaching 94.7%. On the other hand, among non-cirrhotic patients, the seropositivity rate peak was observed at week2 and reached 96.0%. In addition, cirrhotic patients displayed a more rapid decline in the seropositivity rate, dropping to 54.5% after ≥16weeks, while non-cirrhotic patients exhibited a decrease to 67.2% after the same time period. The overall incidence of AEs was low (18.4%), and all AEs were mild and self-limiting. In addition, 16.0% of participants had mild liver function abnormalities, and half of them returned to normality within the next 6months without additional therapy. The participants who experienced liver function abnormalities showed a higher seropositivity rate and antibody titer than those who did not (91.6% vs. 79.5%, p=0.005; 2.73 vs. 2.41ng/ml, p<0.001). Cirrhotic CHB patients had lower antibody titers to inactivated SARS-CoV-2 vaccines than non-cirrhotic patients. The vaccines were generally well tolerated in both non-cirrhotic and cirrhotic CHB patient groups. Patients with abnormal liver function may have a better antibody response than those without.

The Liver Injury and Coagulation Dysfunction in the Patients with Severe/Critical COVID-19

The clinical data of 53 COVID-19 patients were collected from a single center in Wuhan from February 8, 2020 to March 25, 2020. The patients were divided into severe type group (38 patients) and critical type group (15 patients). The clinical characteristics, indexes of liver function, coagulation function and inflammatory markers were analyzed retrospectively. According to the degree of abnormal liver function in the process of diagnosis and treatment, the patients were divided into three groups: combined liver injury, mild abnormal liver function and normal liver function group. Statistical analysis was performed by using Student t test, Mann-Whitney U test, Kruskal-Wallis test and Chi-square test. Among the 53 patients, 29 were male (54.7%) and 24 were female (45.3%), the median age was 57(27－80) years old. The time from onset to admission was (11.5±7.7) days. The levels of AST, TBIL, DBIL, ALP, GGT, LDH, D-dimer, PCT and hsCRP in critical patients were higher than those in severe patients (P<0.05). The levels of Alb in critical patients was lower than those in severe patients (P<0.05). Among the 53 patients, 34 (64%) patients showed abnormal elevation of ALT, AST or TBIL, while 4 (7.5%) patients showed the criteria of COVID-19 with liver injury. After the patients were grouping according to the degree of liver dysfunction, the levels of ALP, GGT and D-dimer of the patients in the liver injury group were significantly higher than those in the normal liver function group, D-dimer levels of the patients in the liver injury group was significantly higher than those in the mild abnormal liver function group, while the levels of ALP and GGT in the mild abnormal liver function group were significantly higher than those in the normal liver function group, and the differences were statistically significant(P<0.05). In this group, the patients with COVID-19 severe/critical type have a certain proportion of liver injury accompanied by significantly increased D-dimer levels, critical type patients have more severe liver function and coagulation dysfunction, which may promote the progression of COVID-19.

Aromatase inhibitors combined with growth hormone in treatment of adolescent boys with short stature

To assess the efficacy and safety of aromatase inhibitors (AIs) combined growth hormone in treatment of adolescent boys with short stature. One hundred and fifty-one short stature pubertal boys with age of 10-14 years and bone age of 13-15 years, who were admitted to the Department of Pediatrics, the First Affiliated Hospital, Zhejiang University School of Medicine, were included in this trial. According to their own or parents' intention, the children were divided into recombinant human growth hormone (rhGH)+AI group ( n=108) and rhGH group ( n=43). All children were injected subcutaneously with rhGH 0.15-0.2 IU·kg -1·d -1, and those in rhGH+AI group were additionally given 2.5 mg/d letrozole or 1 mg/d anastrozole, orally for 12 months or longer. The children were followed-up every 3 months. During the follow-up visit, the predicted adult height (PAH), sex hormone level, glucose and lipid metabolism, and other indicators were measured, and adverse reactions were monitored. After intervention, there were significant differences in ΔBA(bone age)/ΔCA(chronological age), ΔHtSDS BA(height standard deviation score based on bone age)and ΔPAH between rhGH+AI group and the rhGH group( P &lt; 0.05 or P &lt; 0.01). During follow-up, 63.9%of the children in the rhGH+AI group had elevated uric acid and 51.9%had decreased high-density lipoprotein (HDL); 25.9%showed severe acne, excitement, hyperactivity and irritability, 11.1%had knee pain; 4.6%had fracture; 2.8%had mild renal dysfunction; 1.9%had inactivity, drowsiness, memory loss and performance decline; 1.9%showed mild abnormal liver function; 0.9%showed impaired fasting glucose; 0.9%showed granulocytopenia. In the rhGH group, 11.6%of the children presented with knee pain and 2.3%with impaired fasting glucose. AI combined with rhGH can delay the growth of BA and effectively improve the PAH of adolescent boys with larger bone age. However, the occurrence of adverse reactions of AI should be closely monitored during treatment.

Screening of serum susceptibility biomarkers in patients with mild liver function abnormalities based on non-targeted metabolomics

In the present study,non-targeted metabolomics technique was used to screen potentially susceptibility biomarkers in patients with mild liver function abnormalities during long-term use of Chinese herbal compound. According to the inclusion and exclusion criteria,we collected 7 cases of patients with abnormal liver function during the period of complete taking Chinese herbal medicine( 60 days),and 18 cases of patients with normal liver function in re-examination from the reproductive medicine center in our hospital. Ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOF/MS~E) technique combined with Progenesis QI software was used to analyze the differential biomarkers in serum of patients with wild liver function abnormalities and normal liver function. 11 potential biomarkers such as bilirubin,pantothenic acid,hippuric acid,sphingomyelin,palmitic acid,and oleic acid were tentatively identified. Metabolic disorders in patients with herbal-induced mild liver abnormality were mainly related to two pathways: pantothenic acid and coenzyme A biosynthesis and linoleic acid metabolism. It could provide a reference for the early warning of mild liver function abnormalities of patients that may be caused by long-term use of Chinese medicine compound in clinical application,and will lay a foundation for further understanding the endogenous substance changes in different levels of liver injury.

Hepatic safety of ketoconazole in Cushing's syndrome: results of a Compassionate Use Programme in France.

Ketoconazole (KTZ) is one of few available treatments for Cushing's syndrome (CS). Although KTZ has been associated with severe hepatotoxicity, little information is available about hepatic safety in CS. The aim of this study was to document changes in liver function in patients with CS treated with KTZ. An observational prospective French cohort study (Compassionate Use Programme (CUP)). Enrolled patients were stratified into a KTZ-naive cohort and a cohort already treated by another formulation of ketoconazole (KTZ-switch cohort). Liver function markers (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, γ-glutamyltransferase and bilirubin) were monitored at regular intervals. Patients with ALT > 3 × ULN (upper limit of normal), total bilirubin > 2 × ULN or both ALP > 2 × ULN and ALT > ULN were considered to have liver injury. Overall, 108 patients were analysed (47 KTZ-naïve; 61 KTZ-switch). The median KTZ dose was 600 mg/day. Most abnormalities observed were asymptomatic mild increases of liver enzymes. Four patients in the KTZ-naïve cohort (8.5%) and two in the KTZ-switch cohort (3.3%) developed liver injury, considered related to KTZ in three cases (all KTZ-naïve in the first month of treatment). Five patients had mild liver function abnormalities at baseline and two had proven liver metastases. Two patients recovered on discontinuation of KTZ and the remaining patient died of unrelated causes. These findings highlight the need for close monitoring of liver enzymes especially during the first six months of treatment. Liver enzyme abnormalities usually occurred within four weeks were asymptomatic and could be reversed on timely discontinuation of KTZ.

Clinical investigation of sequential therapy with micafungin and reduced-dose voriconazole in prevention of fungal in patients after allogeneic hematopoietic stem cell transplantation

Objective To observe the clinical effect of sequential therapy with micafungin and reduced-dose voriconazole in prevention of invasive fungal infections in patients received allogeneic hematopoietic stem cell transplantion (Allo-HSCT). Methods 28 patients received the treatments for prevention of fungal infection with micafungin 50 mg per day from pretreatment to 30 days, then oral voriconazole at a dose of 100 mg two times per day until 90 days after Allo-HSCT.The occurrence of invasive fungal infection and the side effects of both medicine were observed during 180 days after Allo-HSCT. Results 8 patients(28.6%) developed above grade 2 acute graft verse host disease(GVHD), 2 patients developed grade 3 GVHD among the 8 patients.Two case with GVHD were cured by voriconazole with the therapeutic dose who occurred probably pulmonary invasive fungal infection at two months after Allo-HSCT.There were no other patients diagnosed fungal infection.No toxic efect were observed during the clinical observation during treatment with micafungin.5 patients appeared mild liver function abnormalities during treatment with voriconazole, and liver dysfunction were improved by symptomatic treatment.2 cases developed transient auditory hallucination and visual impairment induced by voriconazole. Conclusion Micafungin and reduced-dose voriconazole are effective and safe prophylaxis in prevention early invasive fungal infection after HSCT. Key words: Micafungin; Voriconazole; Hematopoietic stem cell transplantation; Fungal infection

Acute acalculous cholecystitis due to breast cancer metastasis to the cystic duct.

BackgroundAcute acalculous cholecystitis (AAC) is a relatively rare disorder of the gallbladder. Breast cancer recurrence more than 10 years after curative surgery is also infrequent.Case presentationHere, we report a case of a 59-year-old woman who presented with right flank pain. Her medical history included a lumpectomy for cancer of the left breast 12 years prior. Laboratory tests showed a severe inflammatory reaction and mild liver function abnormalities. Ultrasonography and computed tomography revealed an enlarged gallbladder and inflammation of the surrounding tissues; however, no gallstone was present. She was diagnosed with AAC. We performed an emergency laparoscopic cholecystectomy, and histopathological examination revealed a poorly differentiated adenocarcinoma in the cystic duct. Both metastatic and primary tumor cells were positive for estrogen and progesterone receptors on immunohistochemistry. The final pathological diagnosis was acute cholecystitis due to breast cancer metastasis to the cystic duct.ConclusionAlthough AAC secondary to metastatic breast cancer is rare, it should be included in the differential diagnosis for abdominal pain in patients with a previous history of breast cancer.

Establishing population distribution of drug‐metabolizing enzyme activities for the use of salivary caffeine as a dynamic liver function marker in a Singaporean Chinese population

The salivary paraxanthine/caffeine molar ratio has been proposed as a novel dynamic liver function test to guide dose adjustments of drugs hepatically cleared by CYP1A2. Its usability requires an established population norm as well as the factors influencing the ratio and actual concentrations. To address this knowledge gap, salivary caffeine and paraxanthine concentrations were measured at 4h post caffeine dose in healthy Chinese individuals who had undergone 24h of caffeine abstinence. The metabolic ratio was calculated and statistical analysis was performed. From the 52 participants (26 males; 30 regular caffeine consumers) recruited, the salivary paraxanthine/caffeine molar ratio was normally distributed with a mean and SD of 0.5±0.2. No statistically significant factors (BMI, body weight, gender and regularity of caffeine intake) affecting the metabolic ratio were found. The caffeine concentration and total caffeine plus paraxanthine concentrations were lower in males than in females, and lower in regular caffeine consumers than in non-regular caffeine consumers. The 4h salivary metabolic ratio (mean: 0.5) was generally not significantly different from the literature reported salivary, serum and plasma ratios measured at 4-9h in healthy individuals (mean range 0.4-0.7) but was significantly higher than the literature reported 6h plasma ratio and salivary ratios measured at 1-6h in patients with liver disease or mild abnormal liver function tests (mean range 0.03-0.2). Overall, the population norm of the salivary metabolic ratio in a Singaporean Chinese population established in this study is distinct from individuals with liver disease or mild abnormal liver function tests and provides the benchmark for dosage adjustments of drugs metabolized by CYP1A2. Copyright © 2016 John Wiley & Sons, Ltd.

Short Term Treatment With Thrombopoietin-Receptor Agonists For Patients With Immune Thrombocytopenic Purpura (ITP) Before Splenectomy

The thrombopoietin-receptor agonists (romiplostim and eltrombopag) were approved recently as treatments for patients with immune thrombocytopenic purpura (ITP). Splenectomy remains a common second line treatment for ITP with the highest remission rate compared with alternative therapies. It has been reported that splenectomy can be safely performed in patients with a platelet count of 40-50,000 per cubic millimeter but many patients do not reach these values. Intravenous immune globulins (IVIG) are often used before splenectomy in order to increase the platelet count before surgery.The aim of this study was to determine whether a short course of thrombopoietin-receptor agonists can be used as a reliable and safe treatment to increase the platelet count in patients with ITP before splenectomy.Between 2010 and 2012, fifteen patients with ITP, all refractory to steroids, were scheduled for splenectomy. Treatment with thrombopoietin-receptor agonists (romiplostim or eltrombopag) was started 3 weeks before splenectomy. Eight patients received eltrombopag at a dose of 50 mg/day orally until 3 days before splenectomy. For romiplostim, a subcutaneous injection of 3 mcg/kg was given weekly to 7 patients. The last injection was given one week before splenectomy. Complete blood count was repeated every week and the dose of romiplostim was adjusted (up to 10 mcg/kg or down to 1 mcg/kg) based on the platelet count increment. Response was defined as a platelet count of 50,000 or more per cubic millimeter.Mean platelet count before treatment was 11,000±8,000 cells per cubic millimeter. All patients, except one patient on romiplostim, responded to the treatment with a mean platelet count of 74± 25 cells per cubic millimeter on the day of splenectomy (p<0.01). Similar effect was noticed among responders of the two drugs. Four patients from the romiplostim group responded to a 3 mcg/kg dose. Two patients responded to increased doses of 7 and 10 and 10 mcg/kg. One patient did not respond to 10 mcg/kg of romiplostim but later responded to IVIG. The two drugs were well tolerated with no side effects except for mild liver function abnormalities in one patient in the eltrombopag group. No thromboembolic complications or excessive bleeding were reported for these patients.In summary, we report that a short course of thrombopoietin-receptors agonists can effectively and safely increase the platelet count in steroid resistant ITP patients before splenectomy. Disclosures:No relevant conflicts of interest to declare.

Exemestane Versus Anastrozole in Postmenopausal Women With Early Breast Cancer: NCIC CTG MA.27—A Randomized Controlled Phase III Trial

In patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss. We designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety. In the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms. This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer.

Laparoscopic Habib 4X bipolar radiofrequency device in laparoscopic liver resection

Objective To evaluate the efficacy of laparoscopic Habib 4X (Habib 4X,Angio Dynamics US),a new bipolar radiofrequency (RF) device,in laparoscopic liver resection.Methods Thirty one patients who underwent laparoscopic liver resection using the laparoscopic Habib 4X from Sept 2009 to Apr 2012 were studied retrospectively.Results The laparoscopic Habib 4X was success fully used in 30 patients (malignant,n=18; benign,n=12).The procedures performed included left lateral sectionectomy (n=12),left hemi-hepatectomy (n=1),Ⅴ or Ⅵ segmentectomy (n=9),Ⅴ and Ⅵ bi-segmentectomy (n=2) and wedge exclusion (n=6).The time required for precoagulation and resection was 10～68 min (median 24 min).The mean intraoperative blood loss was 145±75ml (range 8-370 ml).Mild abnormal liver function which returned to normal in 3 to 5 days was detected postoperatively.The mean hospital stay was 7.8±2.6 d (range 3～12 days).There was no patient who developed postoperative bleeding,bile leakage or abdominal abscess.For cancer patients,there was no local recurrence on follow-up.Conclusion Laparoscopic Habib 4X,a device when used in laparoscopic liver resection,resulted in minimal blood loss and quick recovery.It had only mild effect on liver function and it had low morbidity.In addition,it might reduce the risk of local recurrence in malignant tumours. Key words: Laparoscopic liver resection; Habib 4X; Blood loss

Human isolates of Bartonella tamiaeinduce pathology in experimentally inoculated immunocompetent mice

BackgroundBartonella tamiae, a newly described bacterial species, was isolated from the blood of three hospitalized patients in Thailand. These patients presented with headache, myalgia, anemia, and mild liver function abnormalities. Since B. tamiae was presumed to be the cause of their illness, these isolates were inoculated into immunocompetent mice to determine their relative pathogenicity in inducing manifestations of disease and pathology similar to that observed in humans.MethodsThree groups of four Swiss Webster female mice aged 15-18 months were each inoculated with 106-7 colony forming units of one of three B. tamiae isolates [Th239, Th307, and Th339]. A mouse from each experimental group was sampled at 3, 4, 5 and 6 weeks post-inoculation. Two saline inoculated age-matched controls were included in the study. Samples collected at necropsy were evaluated for the presence of B. tamiae DNA, and tissues were formalin-fixed, stained with hematoxylin and eosin, and examined for histopathology.ResultsFollowing inoculation with B. tamiae, mice developed ulcerative skin lesions and subcutaneous masses on the lateral thorax, as well as axillary and inguinal lymphadenopathy. B. tamiae DNA was found in subcutaneous masses, lymph node, and liver of inoculated mice. Histopathological changes were observed in tissues of inoculated mice, and severity of lesions correlated with the isolate inoculated, with the most severe pathology induced by B. tamiae Th239. Mice inoculated with Th239 and Th339 demonstrated myocarditis, lymphadenitis with associated vascular necrosis, and granulomatous hepatitis and nephritis with associated hepatocellular and renal necrosis. Mice inoculated with Th307 developed a deep dermatitis and granulomas within the kidneys.ConclusionsThe three isolates of B. tamiae evaluated in this study induce disease in immunocompetent Swiss Webster mice up to 6 weeks after inoculation. The human patients from whom these isolates were obtained had clinical presentations consistent with the multi-organ pathology observed in mice in this study. This mouse model for B. tamiae induced disease not only strengthens the causal link between this pathogen and clinical illness in humans, but provides a model to further study the pathological processes induced by these bacteria.

Long‐term clinical outcome of living‐donor liver transplantation for primary biliary cirrhosis

We described the recurrence of primary biliary cirrhosis (PBC) after living donor liver transplantation (LDLT) (Liver Transplantation, 7, 2001: 588). However, since the follow-up period in that study was insufficiently long (median 35.5 months), we performed a long-term study to further characterize recurrence of PBC after LDLT. From 1991 to 2006, 15 patients with end-stage PBC underwent LDLT at Tokyo Women's Medical University. Of these patients, we studied 8 PBC patients (age 29 to 51 years, all females) who survived LDLT for more than 5 years. The follow-up period for these patients ranged form 68 to 120 months. Immunosuppression was maintained with tacrolimus and prednisone. Laboratory examinations performed in every patient and donor before LDLT included routine biochemical studies, antimitochondrial antibody (AMA) by immunofluorescence (IF), anti-M2 by enzyme-linked immunosorbent assay as well as antinuclear antibody (ANA) by IF, and immunoglobulin. After LDLT, the same laboratory examinations were performed in patients every 6 months. Liver biopsy was performed when patients exhibited clinical or biochemical signs of graft dysfunction. In addition, protocol biopsy was performed every 1 to 2 years after LDLT. At the time of LDLT, all patients had end-stage cholestatic liver failure. Seven patients were positive for AMAand anti-M2 while 1 patient was negative for these markers but strongly positive for ANA. Donors were blood relatives in 6 cases, and 2 donors who were not blood relatives still exhibited multiple HLA matches with the recipients. At the end of the study in May 2006, all patients were doing well. On laboratory examination, mild abnormal liver function test results were found in 4 patients: 3 were probably due to recurrence of PBC, 1 resulted from nonalcoholic steatohepatitis. Comparison of the AMA titer between before LDLT and the most recent follow-up visit showed an increase in three patients, a decrease in two patients and no change in three patients. In contrast, the ANA titer increased in five patients. Histologically, strong evidence of recurrent PBC was found in 4 patients, and findings compatible with PBC were present in 2 additional patients. Although the number of our patients is small, our findings confirm that PBC can recur at high frequency after LDLT. However, this complication has not developed to advanced stages and has not caused appreciable symptoms in our patients, all of whom have a good quality of life.

Nimesulide-induced acute hepatitis.

To report the occurrence of nimesulide-induced acute hepatitis confirmed by biopsy and an in vitro lymphocyte toxicity assay. A 54-year-old Arabic woman treated with nimesulide for chronic low back pain was admitted to the hospital with acute hepatitis confirmed by biopsy. Her liver function test results returned to normal within one month after nimesulide discontinuation. An in vitro lymphocyte toxicity assay confirmed that the liver injury was due to nimesulide exposure. A case of acute hepatitis secondary to nimesulide, confirmed by biopsy and a laboratory in vitro assay, is described. Although the occurrence of clinically significant liver damage due to nonsteroidal antiinflammatory drugs (NSAIDs) is low, the enormous consumption of these drugs has made them an important cause of liver damage. Nimesulide, a relatively new NSAID commonly used in Europe, with a relative selectivity to cyclooxygenase type 2, can cause a wide range of liver injuries, from mild abnormal liver function to severe liver injuries. These effects are usually reversible on discontinuation of the drug, but occasionally can progress to fatal hepatic failure. Drug-induced acute hepatitis is a well-recognized adverse effect of many drugs, including nimesuilde. Identification of a drug as a cause for this life-threatening disease is important because the discontinuation of it may be life saving. This article confirms the occurrence of nimesulide-induced hepatitis. It also highlights the importance of monitoring liver function test results after initiating therapy with such a drug.

Gravesʼ hyperthyroidism in a patient with primary sclerosing cholangitis. Coincidence or combined pathogenesis?

Several autoimmune disorders have been associated with the diagnosis of primary sclerosing cholangitis (PSC). We report on a 19-year-old male PSC patient with a history of ulcerative colitis who developed hyperthyroidism consistent with Graves' disease. In contrast to primary biliary cirrhosis, hyperthyroidism appears to be very uncommon in PSC patients. Nevertheless, the rarity of Graves' disease in young males, the presence of a human leucocyte antigen (HLA) phenotype often encountered in both Graves' disease and PSC and the presence of several autoantibodies suggest a common immunogenetic predisposition, rather than mere coincidence, of both diseases in this patient. Since many patients with thyroid disease exhibit mild cholestatic liver function abnormalities but few of them undergo cholangiographic examination, PSC may be underdiagnosed. Physicians should therefore be aware of the potential association between thyroid disease and PSC.

Alternating floxuridine and 5-fluorouracil hepatic arterial chemotherapy for colorectal liver metastases minimizes biliary toxicity

The goals of this study of a hepatic arterial infusion (HAI) regimen of alternating floxuridine and 5-fluorouracil were to evaluate the treatment-related toxic effects, the antitumor response rate, and patient survival. Fifty-seven consecutive patients were treated with implanted HAI pumps and received a regimen of alternating floxuridine (0.1 mg/kg/day continuous HAI for 7 days) followed by a weekly HAI pump bolus of 5-fluorouracil (15 mg/kg for 3 weeks). Any changes in treatment plan because of toxicity, antitumor response, and survival were recorded. Thirty-one (54.4%) patients responded to this HAI regimen; 14 (24.5% )patients had stable disease, and 12 (21.1%) progressed during treatment. Responders or patients with stable disease had a significantly (P < 0.05) improved survival rate (19 months median) compared with patients in whom disease progressed (12 months median). Two (3.5%) patients developed biliary sclerosis and 12 (21.1%) had mild transient liver function abnormalities. The liver alone or in combination with another area was the site of first progression of disease in 40 (70.2%) patients. This regimen had reversible or no hepatobiliary toxicity in more than 95% of patients. Tumor reduction or stabilization of disease was observed in 79% of the patients, who had a median survival of 19 months. Reduced toxicity and more effective chemotherapeutic regimens may increase the likelihood of survival after HAI chemotherapy for unresectable colorectal liver metastases.

Eosinophilia-Myalgia Syndrome

We reviewed 21 cases of eosinophilia-myalgia syndrome to describe the range of clinical findings in these patients. Most patients were women (20 [95%]) and middle-aged (mean, 46 years) and had taken the food supplement L-tryptophan (95%). All cases involved eosinophilia (eosinophil count, 2.0 × 10⁹/L) and incapacitating myalgias. Fourteen (88%) of the 16 patients tested had mild liver function abnormalities. Aldolase levels were abnormal in all patients tested. Muscle biopsies were done in five patients; four showed eosinophilic perimyositis, and one had interstitial inflammation. No physical finding was pathognomonic or universal, but muscle tenderness, tachycardia, and rash were the most common signs found during physical examinations. Seven patients were treated with prednisone, and six showed improvement in muscle pain and a decrease in eosinophilia. The cause of this disorder is still unknown. (<i>Arch Intern Med.</i>1991;151:533-537)