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Background: Bone marrow transplantation (BMT) is a standard treatment for several haematologic conditions. Following BMT, patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischaemic hepatitis, and fulminant hepatitis., Aims: To evaluate the frequency, clinical characteristics, and outcomes of patients with hepatobiliary alterations associated with BMT in a tertiary referral centre., Methods: This was a cross-sectional study with data collected from the medical records of patients undergoing BMT between January 2017 and June 2022. We diagnosed hepatobiliary complications based on established criteria., Results: We included 377 patients; 55.7% had hepatobiliary complications. Female gender, pre-BMT hepatobiliary alteration, and haploidentical allogeneic transplantation were associated with increased risk with odds ratios (OR) of 1.8 (p = 0.005), 1.72 (p = 0.013) and 3.25 (p = 0.003), respectively. Patients with hepatobiliary complications spent longer in the hospital than those without (27.7 × 19.3 days, respectively; p < 0.001). Among 210 patients with hepatobiliary complications, 28 died compared to 5 of 167 without complications (OR 4.98; p = 0.001)., Conclusions: Hepatobiliary complications are frequent in patients undergoing BMT. There is a greater risk of their occurrence in women, people with pre-BMT liver alterations, and in haploidentical transplants. The occurrence of these complications increases the length of stay and is associated with a higher risk of death., (© 2023 John Wiley & Sons Ltd.)

Inflammation and fibrosis are major consequences of autoimmune hepatitis, however, the therapeutic mechanism remains to be investigated. USP4 is a deubiquitinating enzyme and plays an important role in tissue fibrosis and immune disease. Vialinin A is an extract from mushroom and is a specific USP4 inhibitor. However, there is lack of evidences that Vialinin A plays a role in autoimmune hepatitis. By employing S100-induced autoimmune hepatitis in mice and AML12 cell line, therapeutic mechanism of Vialinin A was examined. Inflammation was documented by liver histological staining and inflammatory cytokines. Fibrosis was demonstrated by Masson, Sirius red staining and fibrotic cytokines with western blot and real-time RT-PCR. In experimental animal, there were increases in inflammation and fibrosis as well as USP4, and which were reduced after treatment of Vialinin A. Vialinin A also reduced Rheb and phosphorylated mTOR. Moreover, in LPS-treated AML12 cells, LPS-induced USP4, inflammatory and fibrotic cytokines, phosphorylated mTOR and Rheb. Specific inhibitory siRNA of USP4 reduced USP4 level and the parameters mentioned above. In conclusion, USP4 was significantly elevated in autoimmune hepatitis mice and Vialinin A reduced USP4 level and attenuate inflammation and fibrosis in the liver. The mechanism may be related to regulation of Rheb/mTOR signalling., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: This study aimed to investigate the protective effect of 5-aminolevulinic acid (5-ALA) and sodium ferrous citrate (SFC) against binge alcohol-induced gut leakiness and inflammatory liver disease in HIV transgenic (TG) rats., Methods: TG rats were treated with 3 consecutive doses of binge ethanol (EtOH) with or without 5-ALA/SFC. Blood and liver tissue samples were collected at 6 hours following the last dose of EtOH., Results: Compared with the wild-type (WT) rats, the TG rats showed increased sensitivity to alcohol-mediated inflammation, as evidenced by the significantly elevated levels of serum endotoxin, AST, ALT, ED1, and ED2 staining in liver. In contrast, 5-ALA/SFC improved the above biochemical and histochemical profiles. 5-ALA/SFC also attenuated the up-regulated mRNA expression of leptin and CCL2. Furthermore, down-regulated intestinal ZO-1 protein expression was also inhibited by 5-ALA/SFC. Moreover, the expressions of HO-1, HO-2, Sirt1, and related signal transduction molecules in liver were increased by 5-ALA/SFC. These results demonstrated that 5-ALA/SFC treatment ameliorated binge alcohol exposure liver injury in a rat model of HIV-infected patients by reducing macrophage activation and expression of inflammatory cytokines/chemokines, and by inducing HO-1, HO-2, and Sirt1 expression., Conclusions: Taken together, these findings suggested that treatment with 5-ALA/SFC has a potential therapeutic effect for binge alcohol exposure liver injury in HIV-infected patients., (© 2019 by the Research Society on Alcoholism.)

Background: A significant proportion of cases of acute liver failure (ALF) do not have an identifiable cause; so called "non A-E," "non A, non B, non C," "seronegative" or "indeterminate" hepatitis. However, this entity is clinically not well described., Aim: To collate the known incidence and outcomes in indeterminate hepatitis. This systematic review sought to identify potential aetiologies that ought to be considered, and identify likely future objectives in classification and treatment strategies for indeterminate hepatitis., Methods: Literature review to determine aetiological factors, prevalence and outcomes relating to indeterminate hepatitis., Results: There is significant heterogeneity within the reported cases of indeterminate hepatitis in the literature. Some of the potential infective aetiologies which are reviewed here include: parvovirus B19 (PVB19), herpes simplex virus (HSV), Toga-Like Virus and the Annelloviridae (including SEN-V). Interestingly, this condition predominately affects middle aged women, with subacute progression of the liver failure. In addition, the prognosis of indeterminate hepatitis is poor, with reduced spontaneous survival compared with other causes of acute liver failure and increased need for emergency liver transplantation., Conclusions: Whilst various pathological processes have been implicated in the development of indeterminate hepatitis, the specific cause remains elusive. There is an urgent need for general consensus on a specific definition and exclusion of confounding aetiologies with coordinated multicentre investigation of this rare condition to identify aetiology and develop therapies to reduce the significant mortality and need for emergency liver transplantation associated with this condition., (© 2018 John Wiley & Sons Ltd.)

Hepatitis-associated aplastic anemia (HAA) is a variant of acquired aplastic anemia (AA) in which immune-mediated bone marrow failure (BMF) develops following an acute episode of seronegative hepatitis. Dyskeratosis congenita (DC) is an inherited BMF syndrome characterized by the presence of short telomeres, mucocutaneous abnormalities, and cancer predisposition. While both conditions may cause BMF and hepatic impairment, therapeutic approaches are distinct, making it imperative to establish the correct diagnosis. In clinical practice, lymphocyte telomere lengths (TL) are used as a first-line screen to rule out inherited telomeropathies before initiating treatment for AA. To evaluate the reliability of TL in the HAA population, we performed a retrospective analysis of TL in 10 consecutively enrolled HAA patients compared to 19 patients with idiopathic AA (IAA). HAA patients had significantly shorter telomeres than IAA patients (P = 0.009), including four patients with TL at or below the 1st percentile for age-matched controls. HAA patients had no clinical features of DC and did not carry disease-causing mutations in known genes associated with inherited telomere disorders. Instead, short TLs were significantly correlated with severe lymphopenia and skewed lymphocyte subsets, features characteristic of HAA. Our results indicate the importance of caution in the interpretation of TL measurements in HAA, because, in this patient population, short telomeres have limited specificity., (© 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.)

Severe psoriasis is a systemic inflammatory disease involving major arteries and internal organs. The association between psoriasis and arterial inflammation, however, has been noted mostly in patients with moderate to severe psoriasis. Therefore, it is still not clear whether mild psoriasis also increases the arterial inflammation and cardiovascular disease. In this study, we aimed to investigate systemic inflammation using (18) F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in patients with mild psoriasis. In a nested case-control study, FDG-PET/CT findings of 10 patients with mild chronic plaque psoriasis involving a body surface area of less than 5% were compared with those of 10 age- and sex-matched healthy controls. The degree of FDG uptake in the large arteries (ascending aorta, aortic arch, descending aorta, suprarenal abdominal aorta and infrarenal abdominal aorta,) and liver were analyzed using the maximum target-to-background ratios (TBR). There were no significant demographic differences between the psoriasis patients and the control subjects (P > 0.05). Patients with psoriasis showed higher maximum TBR than healthy controls in all examined arterial segments, with statistical significance reached in the suprarenal abdominal aorta (P < 0.05), ascending thoracic aorta (P < 0.01) and infrarenal abdominal aorta (P < 0.05), and in the liver (P < 0.05). The "candy cane sign", which represents typical arterial inflammation of the thoracic aorta, was noted upon PET in the majority of psoriasis cases. In conclusion, mild psoriasis is also associated with arterial and hepatic inflammation, which can be readily demonstrated by using FDG-PET/CT., (© 2015 Japanese Dermatological Association.)

Background & Aims: Early recognition of prediabetes can lead to timely clinical interventions to prevent type 2 diabetes. Both Latino ethnicity and chronic hepatitis C (HCV) have been identified as diabetic risk factors. We aimed to investigate predictors of impaired fasting glucose (IFG), a common prediabetic state, among Latinos with and without HCV., Methods: One hundred Latino adults with no history of diabetes or cirrhosis underwent clinical, laboratory, and metabolic evaluation, including oral glucose tolerance testing (OGTT) and insulin suppression testing to quantify directly measured insulin resistance (IR). Isolated IFG was defined as fasting glucose ≥100 mg/dl and <140 mg/dl at 2 h during normal glucose tolerance during OGTT., Results: Overall subject characteristics included median age 44 years, 64% male, 40% HCV-positive and 32% with isolated IFG. Factors associated with isolated IFG included subject age (OR 2.42 per decade, 95%CI 1.40-3.90, P = 0.001), HCV infection (OR 4.0, 95%CI 1.71-9.72, P = 0.002) and alanine aminotransferase (ALT) (OR 2.35 per doubling, 95%CI 1.46-3.77, P < 0.0001). Multipredictor logistic regression analysis identified ALT (OR 2.05 per doubling, P = 0.005, 95% CI 1.24-3.40) and age (OR 2.20 per 10 years, P = 0.005, 95%CI 1.27-3.80) as factors independently associated with IFG. While HCV was associated with 4-fold higher odds of IFG, this entire effect was mediated by ALT., Conclusions: We found strong evidence that liver inflammation is a risk factor for prediabetes among Latinos with and without HCV. Among HCV-infected individuals, early antiviral therapy could mitigate the effect of inflammation and represent an important intervention to prevent diabetes in this at-risk population., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The relationship between relative adrenal insufficiency (RAI) and chronic liver disease is unclear., Aim: To determine the frequency with which RAI is observed in noncritically ill patients at various stages of chronic liver disease, and the correlation between RAI and disease severity and long-term mortality., Methods: In total, 71 non-critically ill patients with liver cirrhosis (n = 54) and chronic hepatitis (n = 17) were evaluated prospectively. A short stimulation test (SST) with 250 μg of corticotrophin was performed to detect RAI. RAI was defined as an increase in serum cortisol of <9 μg/dL in patients with a basal total cortisol of <35 μg/dL., Results: RAI was observed in only 13 (24.1%) of 54 patients with cirrhosis. Compared to those without RAI, cirrhotic patients with RAI had significantly higher Child-Turcotte-Pugh score (10.3 ± 1.7 vs. 7.1 ± 1.8, mean ± s.d., P < 0.001) and Model for End-Stage Liver Disease score (14.5 ± 6.6 vs. 9.4 ± 3.7, P = 0.017). The cortisol response to corticotropin was negatively correlated with the severity of cirrhosis (P < 0.05). In addition, the mortality rate was higher in cirrhotic patients with RAI (69.2%) than in those without RAI (4.9%; P < 0.001) during the follow-up period of 20.1 ± 13.5 months (range, 5.8-51.1 months). The cumulative 1-year survival rates in cirrhotic patients with and without RAI were 69.2% and 95.0%, respectively (P = 0.05), while the corresponding cumulative 3-year survival rates were 0% and 95.0% (P < 0.001)., Conclusions: Relative adrenal insufficiency is more commonly observed in those with severe cirrhosis, and is clearly associated with more advanced liver disease and a shortened long-term survival. This suggests that relative adrenal insufficiency is an independent prognostic factor in non-critically ill patients with cirrhosis., (© 2014 John Wiley & Sons Ltd.)

The objective of this study was to demonstrate the clinical profiles of Stevens-Johnson syndrome (SJS) in Thai patients, and to compare those clinical features between younger and older patients. Medical records of all patients with SJS who were admitted to Srinagarind Hospital Medical School, Khon Kaen, Thailand, from January 2002 to December 2014 were reviewed. Epidemiological features, etiologies, treatment and clinical outcomes were collected. There were 45 patients with SJS during the 10-year period. Females were the majority (57.8%) and the median age was 49 years. Hepatitis was the most frequent complication (67.5%). Phenytoin (15.6%), sulfonamide drugs (15.6%) and allopurinol (13.3%) were implicated as leading causes of SJS. Steroids were prescribed in 37 cases (82.2%). The mortality rate was 4.4%. Comparing older patients to younger patients, allopurinol appeared to be the main instigating drug to develop SJS with an odds ratio of 5.6 (95% confidence interval, 2.8-10.6). In conclusion, clinical features of Thai patients with SJS were similar to other reports. Allopurinol had the strongest association with SJS in older patients as compared to the younger ones., (© 2014 Japanese Dermatological Association.)

Background & Aims: Precisely what type of cells mainly contributes to portal fibrosis, especially in chronic viral hepatitis, such as hepatic stellate cells (HSCs) in the parenchyma or myofibroblasts in the portal area, still remains unclear. It is necessary to clarify the characteristics of cells that contribute to portal fibrosis in order to determine the mechanism of portal fibrogenesis and to develop a therapeutic target for portal fibrosis. This study was undertaken to examine whether LRAT+/CRBP-1+ HSCs contribute to portal fibrosis on viral hepatitis., Methods: Antibodies to lecithin:retinol acyltransferase (LRAT), cellular retinol-binding protein-1 (CRBP-1) and widely ascertained antibodies to HSCs (alpha-smooth muscle actin, neurotrophin-3) and endothelial cells (CD31) were used for immunohistochemical studies to assess the distribution of cells that contribute to the development of portal fibrosis with the aid of fluorescence microscopy. A quantitative analysis of LRAT+/CRBP-1+ HSCs was performed., Results: The number of LRAT+/CRBP-1+ HSCs was increased in fibrotic liver in comparison with normal liver in the portal area and fibrous septa. The number of double positive cells was less than 20% of all cells/field in maximum., Conclusion: This study provides evidence that functional HSCs coexpressing both LRAT and CRBP-1 that continue to maintain the ability to store vitamin A contribute in part to the development of portal fibrogenesis in addition to parenchymal fibrogenesis in patients with viral hepatitis., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Denis Parsons Burkitt was born in 1911, and in the late 1950s, described the disease that has come to be known as Burkitt lymphoma based on cases he observed in Uganda. Subsequently, Burkitt lymphoma was recognized as the first human tumour associated with an infectious agent when Epstein-Barr virus was isolated from samples supplied by Burkitt. It is now recognized that over one-quarter of cancers worldwide are tied to infections. Notably, liver cancer is linked to hepatitis B virus and hepatitis C virus infections, and cervical cancer to infections involving the human papilloma viruses. In addition, immunocompromise arising from infection with the human immunodeficiency virus allows tumours (e.g., Kaposi sarcoma) caused by other viruses to arise. More than 50 years after the seminal paper by Burkitt based on his work in Africa, it is appreciated that the contribution of viral infections to cancers remains considerably higher in sub-Saharan Africa than in the rest of the world., (© 2012 Blackwell Publishing Ltd.)

Introduction: Differentiation between steatosis and non-alcoholic steatohepatitis (NASH) in non-alcoholic fatty liver disease (NAFLD) is important as NASH progress to cirrhosis. No specific laboratory/imaging technique exists either to diagnose NASH or to select patients for liver biopsy., Patients and Methods: We evaluated serum ferritin and the features of metabolic syndrome with respect to histological inflammation and/or fibrosis in NAFLD patients. The Kleiner scoring system was used to classify NAFLD in consecutive liver biopsies. One hundred and eleven patients: median age 52.6, 64 males, obesity 62, diabetes mellitus (DM) 58, arterial hypertension 26 and hyperlipidaemia 40%., Results: Histologically, 40.7 had fatty liver, 30.6% had borderline NASH, 28.7% had NASH and 11% had cirrhosis. Multivariate regression showed that diabetes, serum ferritin concentrations, body mass index (BMI) and AST were independently associated with NASH: together, the areas under the receiver operating characteristic (AUROC) was 0.91 (95% confidence interval 0.86-0.96); fibrosis was associated with ferritin concentrations and BMI: AUROC 0.87, portal inflammation with ferritin and DM: AUROC 0.82, while lobular inflammation was associated with BMI, DM and ferritin: AUROC 0.85., Conclusion: Serum ferritin concentrations and BMI are strongly associated with fibrosis, portal and lobular inflammation in NAFLD patients. Both ferritin and BMI are potential discriminant markers to select patients for liver biopsy and are associated with inflammation and fibrosis., (© 2011 John Wiley & Sons A/S.)

In order to assess the epidemiology of Hepatitis-Associated Aplasia (HAA) and compare treatment outcome of HAA with non-HAA patients, we evaluated 3916 aplastic anaemia patients reported to the European Registry between 1990 and 2007. Year, month, season of diagnosis, type and outcome of first-line therapy were analysed. Prevalence of HAA (n = 214) in Europe was 5%. Compared to non-HAA patients, HAA patients were younger (15 vs. 20 years, P < 0.001), with a male prevalence (68% vs. 58% P = 0.002), and were treated earlier after diagnosis (46 vs. 62 d; P < 0.001). No significant differences were found regarding the year or month of diagnosis. No geographic clusters could be identified. Actuarial survival at 10 years after first-line immunosuppression was 69%, and did not differ according to aetiology. The 10-year actuarial survival after transplantation was 70%, and was comparable in HAA and non-HAA patients, when stratified for age and donor type. In a multivariate Cox analysis, increasing age and delayed treatment were significant negative indicators for survival. In conclusion, the incidence of HAA was 5% and was evenly distributed over time and geographic areas in Europe. Treatment outcome and predictive variables, were comparable in patients with or without HAA.

Background: Hepatitis-associated aplastic anaemia is a syndrome in which marrow failure follows the development of hepatitis., Aim: To review systematically the aetiology, immunopathogenesis, clinical presentation, diagnosis and treatment of hepatitis-associated aplastic anaemia., Methods: Literature searches were undertaken on the MEDLINE electronic database up to December 2008. Twenty-four relevant studies were identified. The clinical and laboratory characteristics of the patients were analysed and reviewed., Results: Hepatitis-associated aplastic anemia is a variant of acquired aplastic anemia in which an episode of hepatitis precedes the onset of aplastic anemia. The hepatitis may be acute and severe, even fulminant; it may be self-limiting or chronic. The pathology is often not attributable to a recognized cause of viral hepatitis. The syndrome occurs in 28 percent of young adults after liver transplantation for non-A, non-B, non-C hepatitis. Several features of the syndrome suggest that the marrow aplasia is mediated by immunological mechanisms, possibly mediated by gamma interferon or the cytokine cascade. Survival of patients treated with hematopoietic cell transplantation has been 82%, and the response rate to immunosuppressive therapy 70%., Conclusions: Hepatitis-associated bone marrow aplasia is mediated by immunological mechanisms. Treatment options include hematopoietic cell transplantation and immunosuppressive therapy.

Aim: To study the accuracy of various clinical and investigational parameters to differentiate biliary atresia (BA) from neonatal hepatitis (NH)., Methods: It was a prospective study, conducted in a tertiary care hospital. A total 101 infants with neonatal cholestasis (NCS) were included in this study. Following a baseline hepatobiliary scintigraphic study (HBS), it was repeated after giving UDCA (40 mg/kg/day for 48-72 h). The sensitivity and specificity of clinical and investigational parameters were calculated with peroperative cholangiogram as gold standard., Results: The mean age was 2.8 +/- 1.7 months and 82 were male. Of these, 35 were diagnosed to have BA and 66 had NH (idiopathic 25, sepsis/UTI 20, galactosaemia 11, TORCH 2 and others 8). Persistently clay stool was found to have modest accuracy (79%) and the accuracy of HBS improved significantly following UDCA therapy (91% from 77%, p < 0.01) whereas liver biopsy was 100% accurate in differentiating BA from NH. The outcome of BA cases with ductal plate malformation (DPM) was worse., Conclusion: One-third of all NCS in India is due to BA and among the intrahepatic causes acquired infection and galactosaemia are common. Liver biopsy is the best method to differentiate NH from BA.

Aim: Aplastic anaemia following hepatitis may develop in as many as 1 of 3 patients with non-A, non-B and non-C hepatitis. Several causative factors have been discussed, such as viral infections and autoimmunity. Here we describe the natural history of this condition in 7 children and investigate possible hepatitis-causing agents., Methods: We reviewed the medical records, bone marrow and liver biopsies of 7 children with severe hepatitis, with or without liver failure, who subsequently had developed aplastic anaemia., Results: The median time from onset of hepatic symptoms until diagnosed onset of aplasia was 54 days. No associated viral infections could be identified. On liver biopsy, a majority had lobular inflammation but lacked signs of autoimmune hepatitis, findings compatible with a viral aetiology. Three of 6 children had low reticulocyte counts already at onset of hepatitis. All, but one patient is alive at median follow-up of 8 years., Conclusion: The unknown pathogenetic mechanism appears to target liver and bone marrow simultaneously, because half of the children concomitantly had low reticulocyte counts and severe liver failure.

Objectives: The variability in phenotypic expression of hereditary hemochromatosis (HH) is not fully understood. We sought to examine whether the metabolic syndrome, hepatic steatosis or steatohepatitis influenced hepatic fibrosis among patients with HH and iron overload., Methods: We identified 86 patients with C282Y/C282Y or C282Y/H63D HH and iron overload (hepatic iron concentration (HIC) >2,200 microg/g for males, >1,600 microg/g for females). Features of the metabolic syndrome were assessed at the time of liver biopsy. Biopsies were scored by a blinded pathologist. Significant fibrosis was defined as peri-portal fibrosis or greater., Results: The mean (+/-SD) age of the study population was 53+/-12 years and 68 (79%) were male. The median (range) values of ferritin and HIC were 1,125 (253-9,530) microg/l and 9963 (1926-50 887) microg/g, respectively. The metabolic syndrome was present in 23 (27%), hepatic steatosis in 43 (50%), steatohepatitis in 18 (21%) and significant fibrosis in 38 (44%). Overall, neither the metabolic syndrome nor any of its components were associated with significant fibrosis or a higher mean fibrosis stage. Hepatic steatosis but not steatohepatitis was associated with a lower fibrosis stage. C282Y/H63D compound heterozygous individuals who had glucose intolerance had more severe fibrosis compared with those without glucose intolerance (1.0+/-1.0 vs. 0.1+/-0.3, P=0.01)., Conclusions: Overall, the metabolic syndrome and fatty liver were not associated with hepatic fibrosis among individuals with HH and iron overload. However, glucose intolerance may be important risk factor for the development of hepatic fibrosis in subjects with the C282Y/H63D HFE genotype.

Autoimmune hemolytic anemia (AIHA) associated with giant cell hepatitis (GCH) is a rare disorder in infants. AIHA usually precedes the development of liver disease by months to years. Early recognition of the disease and prompt institution of immunosuppressive therapy results in clinical remission and prevents liver disease progression.

Papillon-Lefevre syndrome (PLS) is an autosomally recessive palmoplantar keratoderma accompanied by psoriasiform plaques on the extensor surfaces of extremities and leading to premature loss of deciduous and permanent teeth by progressive periodontitis. Patients with PLS may exhibit mental retardation, intracranial ectopic calcifications, nail dystrophies and a tendency to various infectious disorders, in addition to skin and oral findings. Herein, we report a 26-year-old man with PLS, who had experienced xanthogranulomatous pyelonephritis and hepatitis during childhood and adolescence. To the best of our knowledge, this is the first report of PLS associated with xanthogranulomatous inflammation.

Non-alcoholic steatohepatitis has been recognized as a significant cause of end-stage liver disease and hepatic decompensation. Despite the growing interest in this condition, the molecular mechanisms underlying the development of fibrosis in this setting are only partially understood. In this article, the cellular and molecular basis of fibrosis in chronic liver disease are briefly outlined. In addition, mechanisms specifically operating in the context of fatty liver and steatohepatitis are examined, including: insulin resistance, oxidative stress, and inflammation. Finally, recent developments indicating the possible contribution of cytokines derived from adipose tissue (adipokines) to liver fibrosis is discussed.

The authors present a case report of a 60-year-old man with a hepatic unknown mass. For diagnosis, they used ECO, CT (with and without contrast), MR (with and without contrast) and an ultrasound-assisted percutaneous lesion biopsy. Thus the mass-lesion in the liver appeared to be an intrahepatic accessory spleen in a patient afflicted with chronic hepatitis., (Copyright 2004 Blackwell Munksgaard)

Background: Previous studies have identified the association between diabetes mellitus and liver cancer. However, the detail of this association is still unclear, in terms of confounding factors, the trend according to the duration of diabetes, and the interaction between diseases associated with the liver cancer and this association. The purpose of the present study was to examine the association between diabetes and liver cancer in view of the trend and the interaction., Methods: The baseline survey was conducted during the period 1986-1989 among the general population of Fukuoka Prefecture, Japan (15 417 persons aged 30-79 years). The respondents were assessed for history of diabetes, age at which they had had diabetes, and other covariates by means of a baseline questionnaire. A total of 7308 persons aged 40-79 years were retrieved for the main analysis and 4902 persons for a subcohort from which the information on history of diseases associated with liver cancer were obtained. The relative risks (RRs) and their 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model., Results: After adjustment for smoking, alcohol and the diseases associated with liver cancer, the RR for liver cancer was 2.06 (95% CI=1.01-4.19). Diabetes increased the risk of liver cancer in persons with hepatitis and/or cirrhosis (RR=2.90, 95% CI=1.13-7.41). However, the RR of diabetes for liver cancer was 1.35 (95% CI=0.41-4.43) in persons without hepatitis and cirrhosis. The trend according to the duration of diabetes was not seen., Conclusions: A significant association between diabetes and liver cancer was observed. Moreover, this association was modified by hepatitis and cirrhosis., (Copyright 2001 John Wiley & Sons, Ltd.)

Unlabelled: Congenital hypopituitarism is a recognized cause of neonatal hepatitis, but the diagnosis may be difficult to establish even if clinically suspected. In order to determine the natural history of this disorder, the outcome of 12 infants with neonatal hepatitis secondary to hypopituitarism is reviewed. The clinical diagnosis of hypopituitarism was established on a combination of features, which include dysmorphism (4 infants), optic nerve hypoplasia (8 infants), micropenis (5 male infants) and recurrent hypoglycaemia (blood glucose < 2.4 mmol/l (8 infants)). Endocrine investigation revealed low free thyroxine (T4) levels (< 10 pmol/l), with normal thyroid stimulating hormone (TSH) levels (0.4-4.5 mU/l) (11 infants), and serum cortisol levels which were inappropriately low (< 200 nmol/l). In 9 of 12 infants, liver disease resolved within 6 wk following treatment with thyroxine, hydrocortisone and, where appropriate, growth hormone, including Cases 9 and 1 in whom diagnosis and treatment were delayed until 3 mo and 3 y of age, respectively. Liver disease resolved spontaneously in two infants prior to starting hormone replacement therapy (Cases 11, 12), and one male infant (Case 10), in whom the diagnosis and hormone replacement therapy were delayed until 5 y of age, developed cirrhosis and portal hypertension and later underwent liver transplantation., Conclusion: The diagnosis of hypopituitarism should always be considered in infants with unexplained neonatal hepatitis. Delay in diagnosis and appropriate treatment was associated with persistently abnormal liver function tests and may lead to irreversible liver disease.

The purpose of this study was to assess changes in liver enzyme levels among opioid-dependent patients treated with buprenorphine. Liver enzyme levels were evaluated among 120 individuals before treatment and following a minimum of 40 days of buprenorphine treatment (2, 4, or 8 mg/70 kg/day). Among patients with a history of hepatitis, AST and ALT levels significantly increased (p < .05) with buprenorphine treatment. The odds of observing an increase in AST were determined to be dependent upon buprenorphine dose (p < .05; odds ratio = 1.23 per 1 mg increase in dose). These results suggest that liver enzyme levels should be monitored carefully when patients with hepatitis are treated with buprenorphine.

A method and approach are described to differentiate classic autoimmune thrombocytopenia (ATP) from immune complex-associated thrombocytopenia in systemic lupus (SLE), hepatitis/chronic liver disease (LIV-ITP) and HIV-1 related thrombocytopenia (HIV-1-ITP). The platelet immunologic profile of IgG, C3C4 and IgM was measured with a solid-phase ELISA, employing 125I-staphylococcal protein A to detect indicator antibody binding. Polyethylene glycol was employed to precipitate immune complexes (PEG-IC). Platelet-associated IgG (PAIgG) was 2.8-, 5.6- and 5.8-fold higher in SLE, LIV-ITP and HIV-1-ITP patients respectively compared to ATP patients: platelet C3C4 was 3.2-, 4.8- and 4.5-fold higher respectively; platelet IgM was 2.2-, 3.7- and 3.8-fold higher respectively; serum PEG-IC levels were 4.2-, 4.8- and 2.1-fold higher respectively. With all parameters measured, there was no overlap between the 75th percentile for ATP patients and the 25th percentile for all three cohorts. The likelihood of having a platelet C3C4 level higher than the highest ATP level was 69% for SLE, 90% for LIV-ITP and 94% for HIV-1-ITP respectively; with PEG-IC measurements the likelihood was 83%, 100% and 100% respectively. Serum IgG, C3, C4, IgM and PEG-IC were examined for a possible relationship with platelet measurements. Except for a positive correlation between serum and platelet IgM in ATP, r = 0.5, P < 0.04, there was no positive correlation with any of the parameters measured. An inverse correlation was noted between PEG-IC level and platelet C3C4 in SLE, r = 0.7, P < 0.04. Thus platelet immunologic profile and serum PEG-IC level measurements differentiated classic ATP from immune complex-associated thrombocytopenias (SLE, LIV-ITP, HIV-1-ITP). Except for IgM measurements in ATP, platelet measurements could not be attributed to their respective serum concentration.

We describe a systemic lupus erythematosus (SLE) patient who for several years had typical SLE features and positive antinuclear antibodies (ANA), including anti-native DNA. Over the course of a year, 4 years after the SLE was diagnosed, the ANA disappeared and antibodies to cytoplasmic component ribosomal P protein (anti-P) appeared. Associated with the appearance of anti-P antibodies was the development of biochemical evidence of liver disease, later shown histologically to be chronic active hepatitis. The temporal relationship between the occurrence of anti-P antibodies and the development of liver disease raises the possibility of a role for anti-P antibodies in liver disease.

1. The activities of microsomal glucuronyltransferase and thiomethyltransferase, and those of cytosolic sulphotransferase, acetyltransferase, glutathione transferase and thiomethyltransferase were measured in abnormal (cirrhosis and chronic hepatitis) and normal livers. 2. Glucuronyltransferase and sulphotransferase were investigated with 2-naphthol and ethinyloestradiol as substrates. p-Aminobenzoic acid, benzo(a)pyrene-4,5-epoxide and 2-mercaptoethanol were the substrates of acetyltransferase, glutathione transferase and thiomethyltransferase, respectively. 3. Enzyme activities are expressed as nmol min-1 incubation mg-1 protein and the averages (+/- s.d.) are given. With 2-naphthol as substrate, the glucuronyltransferase activity was 6.55 +/- 4.10 (abnormal liver, n = 33) and 7.81 +/- 4.02 (normal liver, n = 26) (NS); whereas sulphotransferase activity was 0.28 +/- 0.18 (abnormal liver, n = 35) and 0.68 +/- 0.43 (normal liver, n = 26) (P less than 0.01). Glucuronyltransferase activity towards ethinyloestradiol was 102.5 +/- 56.9 (abnormal liver, n = 30) and 107 +/- 59.9 (normal liver, n = 26) (NS), whereas sulphotransferase activity was 57.2 +/- 36.0 (abnormal liver, n = 35) and 122 +/- 67.6 (normal liver, n = 28) (P less than 0.01). Acetyltransferase activity was 0.84 +/- 0.83 (abnormal liver, n = 35) and 3.84 +/- 1.65 (normal liver, n = 26) (P less than 0.01). Glutathione transferase activity was 0.83 +/- 0.68 (abnormal liver, n = 35) and 2.90 +/- 1.59 (normal liver, n = 25) (P less than 0.01) and thiomethyltransferase activity was 1.00 +/- 0.69 (abnormal liver, n = 34) and 3.99 +/- 1.49 (normal liver, n = 25) (P less than 0.01). 4. Liver disease lowers the activities towards the substrates studied of sulphotransferase, acetyltransferase, glutathionetransferase and thiomethyltransferase but not that of glucuronyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)

A patient with seropositive rheumatoid arthritis developed ascites while taking weekly doses of methotrexate (MTX). Her serum transaminase and albumin levels were normal. A liver biopsy revealed chronic hepatitis with bridging fibrosis and piecemeal necrosis. Upon discontinuation of MTX, her ascites resolved, and her arthritis became more active. This is the third report of reversible hepatic decompensation associated with prolonged MTX therapy in patients with rheumatoid arthritis.

The clinical course of a patient with chronic hepatitis and previous ulcerative colitis who subsequently developed pure red cell aplasia (PRCA) is described. The PRCA remitted initially with corticosteroid therapy. A subsequent relapse responded to cyclophosphamide therapy following splenectomy. This was followed by a fatal third episode of red cell aplasia associated with megakaryocyte aplasia.

A 36-year-old woman visited our hospital with a five month history of persistent pustulation, crusting, and alopecia on the vertex of the scalp. No pathological organisms were isolated from the lesions. Histological examination revealed non-specific changes of chronic inflammation with destroyed follicles. Antibiotic therapy produced no response, but steroid therapy was effective. From these observations, a diagnosis of erosive pustular dermatosis of the scalp (EPDS), as described by Pye et al., was made. The patient also had Hashimoto's thyroiditis, autoimmune hepatitis, and Takayasu's aortitis. The laboratory studies revealed an increased erythrocyte sedimentation rate, C-reactive protein 3+, hypergammaglobulinemia, and various auto-antibodies, suggesting the possibility of a pathogenesis common to both this dermatosis and the autoimmune diseases.

We recently observed a increase in factor-VIII clot promoting activity as measured by a one-stage assay (VIII AHF) in a haemophiliac with hepatitis. However, VIII AHF as measured by a two-stage assay (VIII AHF) was 0.013 u/ml at a time when VIII AHF measured 0.38 u/ml. We then studied seven non-haemophiliacs with liver disease, and attempted to correlate the lvels of VIII AHF and VIII AHF with factor VIII-like antigen (VIII AGN) as measured by quantitative immunoelectrophoresis. In four of the seven patients, disproportionate elevations of VIII AHF compared to VIII AHF were found. Furthermore, VIII AHF values correlated well with VIII AGN vales . No such discrepancy was apparent in four normal control subjects. These findings emphasize the necessity for performing two-stage assays in haemophiliacs as well as non-haemophiliacs with liver disease to assess factor-VIII levels. In addition, they suggest that confirmation of the diagnosis of haemophilia may not be possible in the haemophiliac with hepatitis unless VIII AHF determinations are performed. The reason for the disparity between VIII ahf and VIII AHF levels is not apparent. However, the correlation of VIII AGN and VIII AHF levels in the non-haemophiliacs with liver disease provides further support for the concept that VIII AGN and VIII AHF are closely related or identical molecular entities.

A double-blind controlled trial of prophylactic factor VIII therapy has been carried out on nine severe haemophiliacs at the Lord Mayor Treloar College. Infusions were given once weekly and calculated to give a post-infusion plasma concentration of at least 0.25 I.U./ml of factor VIII. This regime reduced the overall bleeding frequency by 15%. The bleeding frequency in the first 3 days post-infusion was reduced by 66%. A moderate overall reduction in morbidity was also achieved. It is calculated that to reduce the incidence of bleeding in severe haemophiliacs by 15% would require a 73% increased usage of therapeutic materials. More than twice this amount of material is likely to be needed to reduce the bleeding frequency of the same group by 66%.

A case of sudden onset facial swelling which occurred in association with extubation is presented. Factors are suggested that may have made this patient--a known sufferer from chronic liver disease--more susceptible to the development of such a reaction, but the principle cause is thought to have been the changes in capillary hydrostatic pressure induced by the patient 'fighting' on the tracheal tube whilst regaining consciousness after an anaesthetic for the injection of her esophageal varices.