Increased ALT Levels Research Articles

Comparison of clinical, biochemical and morphological parameters in patients with chronic hepatitis B

Introduction: Hepatitis B virus is primarily hepatotropic, causing chronic hepatitis B in 5-10% of patients. Chronic hepatitis B (CHB) infection is a dynamic process, which may have five phases: immunotolerant, immunoactive, latency phase, reactive and HBsAg negative phase. Aim: Analyze clinical and biochemical parameters in relation to morphological condition of the liver. Material and Methods: The study enrolled 35 patients diagnosed with CHB, 24 males and 11 females, aged between 12 and 62 years, in the period 2015-2016. The diagnosis was based on serological, biochemical results, and liver biopsy. In patients in an ELISA assay demonstrated the presence of HBsAg in serum. Results: The study shows that middle-aged male patients are more prone to chronic hepatitis B infection. Most patients have one or two symptoms.Fatigue and right subcostal pain are most commonly present in the groups with fibrosis in second- and third-degree, and hepatomegaly in the group with fibrosis in first-degree. Splenomegaly is present only in groups with fibrosis in third and fourth degree. Elevated average aminotransaminase levels reflected the degree of fibrosis. Significant statistical difference in aminitransaminase levels was confirmed between the group of patients with third- and forth-degree and patients without fibrosis. Conclusion: The increase in ALT levels reflect the degree of fibrosis and cirrhosis of the occurrence. ALT levels may be a predictor of the process of the fibrogenesis, as well as to indicate the degree of fibrosis in HHB infection. Due to frequent discrepancies between clinical manifestations and results of laboratory tests, liver biopsy has been considered 'gold standard' for establishing the diagnosis, staging chronic hepatitis B, making therapeutic decisions, monitoring the course of the disease, and assessing prognosis.

The protective effects of CHIR99021 against oxidative injury in LO2 cells.

Hepatic ischemia-reperfusion injury is one of the most important factors for the prognosis of liver transplantation and hepatic surgery. It was reported that glycogen synthase kinase-3 (GSK-3) regulated injury response during ischemia-reperfusion. In this study, we investigated the protective effects of the GSK-3 inhibitor CHIR99021 against hepatic ischemia-reperfusion injury. A H2O2-induced oxidative injury model using LO2 cells was established. LO2 cells were divided into four groups, including blank control group, CHIR99021 control group treated with CHIR99021 alone, H2O2-injury group treated with H2O2 and protection group treated with H2O2 plus CHIR99021. Cell viability, cell apoptosis or necrosis was determined. Meanwhile, mitochondrial membrane potential, lipid peroxidation, cellular ROS levels, SOD activity, and serum contents of ALS and AST were measured. Protein and mRNA expressions were also detected. The results showed that a cell oxidative injury model was established by treating LO2 cells with 200 μmol/L H2O2 for 6 h. Cells exposed to H2O2 resulted in a significant decrease of cell viability and increase of cell apoptosis, which was accompanied by increasing ROS levels, disruption of mitochondrial membrane potential, excessive lipid peroxidation, reduction of SOD activity, and increased levels of ALT and AST. Treatment with CHIR99021 significantly protected LO2 cells against H2O2-induce oxidative injury by inhibiting the changes of above oxidative injury related indicators. Moreover, CHIR99021 treatment significantly reversed H2O2-induced decrease in p-GSK-3βSer9 , Bcl-2, Bcl-xl, survivin and β-catenin expression, whereas it significantly attenuated H2O2-induced increase in caspase-3, cleaved caspase-3 and p-JNK protein expression. In conclusion, CHIR99021 protected LO2 cells against H2O2-induced oxidative injury through reducing GSK-3β activity and apoptosis, with underlying mechanisms involved in stabilizing mitochondrial membrane potential, attenuating cellular ROS generation, suppressing mitochondria-mediated apoptotic pathway, and activation of GSK-3β/β-catenin signaling pathway.

Ursodeoxycholic acid therapy in intrahepatic cholestasis of pregnancy: Results in real-world conditions and factors predictive of response to treatment

BackgroundUrsodeoxycholic acid (UDCA) therapy is commonly used in intrahepatic cholestasis of pregnancy (ICP). AimTo evaluate the efficacy and tolerance of UDCA in real-world conditions and to search for factors predictive of response to treatment. MethodsThis observational study included 98 consecutive patients suffering from pruritus during pregnancy associated with increased ALT levels or total bile acid (TBA) concentrations, without other causes of cholestasis. The entire ABCB4 gene coding sequence was analyzed by DNA sequencing. ResultsUDCA was prescribed until delivery in all patients (mean dose 14.0mg/kg/day; mean duration 30.4 days). Pruritus improved in 75/98 (76.5%) patients, and totally disappeared before delivery in 25/98 (25.5%). After 2–3 weeks of treatment, ALT levels decreased by more than 50% of base line in 67/86 (77.9%) patients and normalized in 34/86 (39.5%), and TBA concentrations decreased in 28/81 (34.6%). Only one patient stopped the treatment before delivery. On multivariate analysis, ALT >175IU/l before treatment was associated with improvement of pruritus (OR 2.97, 95% CI 1.12–7.89, P=0.029) and with decreased ALT (OR 18.61, 95% CI 3.94–87.99, P=0.0002). ABCB4 gene mutation was not associated with response to treatment. ConclusionThis study supports the use of UDCA as first line therapy in ICP.

Liver biopsy in Type 2 Diabetes Mellitus: Steatohepatitis represents the sole feature of liver damage

Recent studies report a prevalence of non-alcoholic fatty liver disease (NAFLD) of between 70% and 80% in patients with metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM). Nevertheless, it is not possible to differentiate between simple steatosis and non-alcoholic steatohepatitis (NASH) with non-invasive tests. The aim of this study was to differentiate between simple steatosis and NASH by liver biopsy in patients with hypertransaminasemia and MS or T2DM. Two hundred and fifteen patients with increased ALT levels and MS, and 136 patients at their first diagnosis of T2DM regardless of ALT values were consecutively admitted to a tertiary hepatology center between January 2004 and November 2014. Exclusion criteria were other causes of liver disease/ALT increase. Each patient underwent a clinical, laboratory and ultrasound evaluation, and a liver biopsy. Gender distribution, age, and body mass index were similar in the two groups of patients, whereas cholesterol levels, glycemia and blood pressure were significantly different between the two groups. The prevalence of NAFLD was 94.82% in MS patients and 100% in T2DM patients. NASH was present in 58.52% of MS patients and 96.82% of T2DM. Consequently, this study reveals that, by using liver biopsy, almost all patients with T2DM or MS have NAFLD, which in patients with T2DM means NASH. Importantly, it suggests that NASH may be one of the early complications of T2DM due to its pathophysiological correlation with insulin resistance.

N-ACYTEL CYSTEINE AMELIORATES METHOTREXATE INDUCED HEPATIC TOXICITY AND GENOTOXICITY IN MALE ALBINO RATS

Background: Methotrexate (MTX) is widely used as a cytotoxic chemotherapeutic agent for malignancies as well as in the treatment of various inflammatory diseases. MTX treatment has been associated with hepatic toxicity and genotoxicity. The current study was conducted to assess the potential protective role of N-acetylcysteine in attenuation of methotrexate–induced hepatic damage and genotoxicity in MTX intoxicated male albino rats. Methods: Forty, apparently healthy adult male albino rats weighed 150+10 gm were randomly divided into four groups; [group 1: negative control group, group 2: positive control (NAC treated) group, group 3: MTX treated group, group 4: MTX/NAC treated group]. The rats were treated once daily for 12 weeks by I.V injection of Methotrexate in a dose of 2 mg/kg (1 /7 LD50) and N-acetylcysteine in a dose of 80 mg/kg (1 /14 LD50) in the tail veins of rats. Blood samples were obtained at the end of the 4th, 8th and 12th weeks and were prepared for ALT levels and BAX gene expression value examination. At the end of the study, liver samples were obtained for histopathological examination. Results: A significant constant increase in ALT levels and BAX gene expression value of the MTX-treated group (group 3) was observed throughout the study. Supplementation of NAC concomitantly with MTX in group 4 reduced significantly ALT levels and BAX gene expression value when compared to the non-supplemented group 3 that treated with MTX at the 4th, 8th and 12th weeks (P< 0.000).The previous chemical results were confirmed by the histopathological studies of the liver that revealed the presence of dilatation and congestion of the central veins, hepatic sinusoids, hepatic arteries, portal veins with increased number of Kupffer cells and pyknosis of the hepatic nuclei in group 3: MTX treated group. On the other hand, the liver sections showed the normal hepatic architectures with addition of NAC with MTX in group 4. Conclusion: The present study showed that NAC has a good protective effect against the hepatic damage and genotoxicity induced by MTX in male albino rats.

Cytotoxic potentials of thiocyanate administration on the liver of male wistar rats ( RattusNorvegicus )

The use of thiocyanate as an anti-sickling drug is currently on the increase among sickle cell disease (SCD) patients. The continuous use of this substance without sufficient toxicity data does not guaranty continuously functional and healthy internal organs among the SCD patients that are susceptible to multi-organ failure such as hepatic failure. Hence this study was performed to elucidate the consequence(s)of thiocyanate administration on the liver of adult male wistar rats. Twenty adult male wistar rats with an average weight of 234.5g were used. The rats were grouped into four (A, B, C & D) with five animals in each group. Group A represented the control and was given only 1ml of distilled water daily while B,C,&D received 1ml of thiocyanate solution at doses of 10mg/Kg/day, 20mg/Kg/day, & 30mg/Kg/day for twenty-eight (28) days. The administration was carefully done with the use of an oral cannula. Thereafter, the rats were sacrificed via cervical dislocation. The rats were dissected and blood samples were immediately collected from the apex of the heart for the analysis of serum total bilirubin. A fraction of the liver was cut to prepare homogenates for biochemical enzymes (alanine aminotransferase-ALT, aspartate aminotransferase- AST) analysis. Thereafter the animals were wholly perfused with normal saline and then fixed with 4% paraformaldehyde. The fixed liver tissues were then taken for histological assessments. The slide sections (H&E and PAS stains) in the treated groups showed varying degrees (mild to severe disruption of hepatocellular morphology plus prominence and widening of sinusoids) of thiocyanateinduced liver damage. But hepatocellular appearance was normal in the control group. Biochemical assays of serum total bilirubin and tissue AST increased fairly with increasing dose although this was not significant. The increase in tissue level of ALT in group B was also not significant with respect to the control. But increase in ALT level was found to be significant in groups C&D when compared with the control. Therefore, this study can be used to infer that SCN use in sickle cell disease management regimen can cause hepatocellular damage in wistar rats. Key Words : Thiocyanate,Biochemical enzymes,Hepatocellular morphology, Anti-sickling

JSH Guidelines for the Management of Hepatitis C Virus Infection: A 2016 update for genotype 1 and 2.

JSH Guidelines for the Management of Hepatitis C Virus Infection: A 2016 update for genotype 1 and 2.

Equine Sporotrichosis and Iatrogenic Hypothyroidism

Background: Sporotrichosis is a subacute or chronic granulomatous fungal infection that affects the dermis and subcutane­ous tissue. Its etiology is related to a complex of Sporothrix spp. species of worldwide distribution. Usually, sporotrichosis results from traumatic inoculation of Sporothrix spp. into the dermis, affecting humans and other mammals, but a greater number of cases have been reported in felines, a fact increasingly important in the zoonotic transmission of diseased animals to man. In horses, there may be multiple ulcerated wounds covered with scabs and slightly elevated plaques or nodules that occur along lymphatic chains in limbs and can be unique and located. Iodides are considered drugs of choice for the treatment of sporotrichosis in horses. The main side effect of prolonged use of these substances is iodism and thyroid dysfunction. The aim of this study was to report a clinical case of sporotrichosis in an equine treated in the state of Paraná, southern Brazil, which showed secondary iatrogenic hypothyroidism with prolonged use of sodium and potassium iodide.Case: A female, 3-year-old, Quarter Horse, with 400 kg of liveweight presented at clinical examination of the cutaneous tissue elevated lesions of nodular aspect, with 2 to 4 cm in diameter, absence of itching and some nodules presenting alo­pecia areas in the chest and abdominal region, and in the anterior, posterior and internal regions of the hindlimbs, featuring diffuse distribution of lesions. Biopsy was performed for histological examination of affected tissue and microbiological culture in the attempt to isolate the etiologic agent. Treatment consisted of the use of intravenous potassium iodide (KI) at a dose of 2 mg / kg for 2 weeks, followed by oral sodium iodide (NaI) at a dose of 5 mg / kg, 10 days later and 20 mg / kg for a period of 65 days, totaling 100 days of treatment, during which hepatic, renal and thyroid functions were evaluated.Discussion: In the case described, empiric treatment with dexamethasone carried by the owner might have triggered the diffuse presentation of the disease restricted to the skin, as glucocorticoids interfere with immunity. The histopathological analysis of skin fragments obtained by biopsy and prepared with H.E. staining found mononucleate inflammatory infil­trate with the presence of lymphocytes and macrophages in deep dermis and necrotic foci. No microbiological isolation of S. schenckii was possible. They were described as a common side effect of the prolonged use of iodinated compounds, iodism and thyroid dysfunction. There were no changes in renal function; however, there was an increase in serum levels of ALT, GGT and FA, featuring liver dysfunction. Thyroid gland dysfunction was observed due to the low levels of thyroid hormones found in the bloodstream, featuring hypothyroidism. The animal of the present case report did not show clinical signs associated with hypothyroidism, which required no specific treatment, since normalization occurs with the gradual decrease of the body iodine levels after removal of the source. It was conclude that, despite the diffuse characteristic of the disease in the animal of this report, it was possible to obtain the clinical cure of sporotrichosis. Therapy with sodium and potassium iodide proved to be effective, but caution is recommended in the use of these drugs, as secondary iatrogenic hypothyroidism and liver dysfunction were observed due to the prolonged period of the required treatment.Keywords: hypothyroidism, fungal infection, sodium iodide, Sporothrix spp.

Development of a database and processing method for detecting hematotoxicity adverse drug events.

Adverse events are detected by monitoring the patient's status, including blood test results. However, it is difficult to identify all adverse events based on recognition by individual doctors. We developed a system that can be used to detect hematotoxicity adverse events according to blood test results recorded in an electronic medical record system. The blood test results were graded based on Common Terminology Criteria for Adverse Events (CTCAE) and changes in the blood test results (Up, Down, Flat) were assessed according to the variation in the grade. The changes in the blood test and injection data were stored in a database. By comparing the date of injection and start and end dates of the change in the blood test results, adverse events related to a designated drug were detected. Using this method, we searched for the occurrence of serious adverse events (CTCAE Grades 3 or 4) concerning WBC, ALT and creatinine related to paclitaxel at Osaka University Hospital. The rate of occurrence of a decreased WBC count, increased ALT level and increased creatinine level was 36.0%, 0.6% and 0.4%, respectively. This method is useful for detecting and estimating the rate of occurrence of hematotoxicity adverse drug events.

Patatin-like phospholipase 3 (rs738409) gene polymorphism is associated with increased liver enzymes in obese adolescents and metabolic syndrome in all ages.

Obesity is associated with non-alcoholic fatty liver disease (NAFLD), and the patatin-like phospholipase 3 (PNPLA3) rs738409 (Ile148Met, C>G) gene polymorphism is one of the most important genetic determinants of NAFLD. Carriers have been reported to better respond to lifestyle modification. To investigate the effect of rs738409 on overweight/obese adolescents and adults with and without metabolic syndrome (MetS). Two hundred and eighty-eight overweight/obese and 209 normal weight participants of the STYJOBS/EDECTA cohort (NCT00482924) were analysed for PNPLA3 genotypes. Compared to overweight/obese without MetS, in overweight/obese study participants with MetS, the presence of the G allele (148Met) was significantly higher (CC: 5.0% vs. 9.2%, Spearman's correlation, 0.12; P=0.038). Persons with CG (heterozygote for the risk allele) and with GG (homozygote for the risk allele) genotypes showed significantly higher ALT levels than those with CC genotypes. Even young individuals aged below 20years had significantly increased ALT levels if they were homozygote with the G allele. The PNPLA3 rs738409 polymorphism is associated already in youths with increased ALT, and is more frequent in obese with MetS of all ages. Hence, overweight/obese rs738409 carriers should be identified early in life and treated with a rigorous life style intervention.

Age-related sensitivity to endotoxin-induced liver inflammation: Implication of inflammasome/IL-1β for steatohepatitis.

Aging is associated with increased vulnerability to inflammatory challenge. However, the effects of altered inflammatory response on the metabolic status of tissues or organs are not well documented. In this study, we present evidence demonstrating that lipopolysaccharide (LPS)-induced upregulation of the inflammasome/IL-1β pathway is accompanied with an increased inflammatory response and abnormal lipid accumulation in livers of aged rats. To monitor the effects of aging on LPS-induced inflammation, we administered LPS (2 mg kg−1) to young (6-month old) and aged (24-month old) rats and found abnormal lipid metabolism in only aged rats with increased lipid accumulation in the liver. This lipid accumulation in the liver was due to the dysregulation of PPARα and SREBP1c. We also observed severe liver inflammation in aged rats as indicated by increased ALT levels in serum and increased Kupffer cells in the liver. Importantly, among many inflammation-associated factors, the aged rat liver showed chronically increased IL-1β production. Increased levels of IL-1β were caused by the upregulation of caspase-1 activity and inflammasome activation. In vitro studies with HepG2 cells demonstrated that treatment with IL-1β significantly induced lipid accumulation in hepatocytes through the regulation of PPARα and SREBP1c. In summary, we demonstrated that LPS-induced liver inflammation and lipid accumulation were associated with a chronically overactive inflammasome/IL-1β pathway in aged rat livers. Based on the present findings, we propose a mechanism of aging-associated progression of steatohepatitis induced by endotoxin, delineating a pathogenic role of the inflammasome/IL-1β pathway involved in lipid accumulation in the liver.

Effect of kidney-tonifying and spleen-strengthening prescription on PD-1 and PD-L1 expression in HBeAg-positive chronic hepatitis B patients with slightly increased ALT levels

Effect of kidney-tonifying and spleen-strengthening prescription on PD-1 and PD-L1 expression in HBeAg-positive chronic hepatitis B patients with slightly increased ALT levels

Disruption of CD8-Coreceptor Binding Abrogates Tolerance Induction Via Liver-Directed Expression of Donor MHC Class I - A Role for PD-L1?

Introduction. We previously used an adeno-associated viral (rAAV) vector to express donor MHC (H-2Kb) in recipient livers and induce donor-specific tolerance in a mouse skin transplant model. Kb expression in B10.BR mice led to impaired production of IFN-γ in response to Kb, but no substantial deletion of CD8 T cells, suggesting that tolerance was associated with functional silencing. Methods. To determine the role of direct recognition of class I by CD8-dependent T cells in tolerance induction, we generated rAAV encoding a mutant Kb (rAAV-D227K), where Asp at position 227 of the α3 domain is replaced with Lys, abrogating CD8 binding. Expression of Kb, D227K-Kb and PD-L1 on hepatocytes was assessed by FACS and IHC. Kb-bearing 178.3 skin was grafted onto uninjected recipients and mice injected with rAAV-D227K or rAAV-Kb ± PD-L1 blockade. Results. Uninjected B10.BR mice rejected 178.3 skin (MST=16 d, n=6), while grafts onto rAAV-Kb-injected mice survived long term (MST>250, n=5). Survival of 178.3 grafts onto mice injected with rAAV-D227K was only slightly prolonged (MST=27, n=6), suggesting that CD8 coreceptor engagement is needed for tolerance induction. Kb expression in B10.BR livers resulted in increased PD-L1, but this was not seen following Kb-D227K expression, or with Kb expression in C57BL/6 livers, suggesting that alloreactive CD8 T cell activation results in PD-L1 upregulation. Antibody blockade of PD-L1 plus rAAV-Kb treatment resulted in increased ALT levels (721±73) compared to treatment with rAAV-Kb (33±4) or anti-PD-L1 (35±2) alone. Experiments to determine the effect of PD-L1 blockade on skin graft survival are ongoing. Conclusion. Disruption of CD8 coreceptor engagement abolishes tolerance induction via liver-directed expression of donor MHC class I, indicating that direct recognition by CD8-dependent T cells is essential for the process. PD-L1 upregulation accompanied alloreactive CD8 T cell activation and blockade of PD-L1 resulted in hepatitis, suggesting that this molecule might play a role in the functional silencing of CD8 T cells in this model.

Variation of Transaminases, HCV-RNA Levels and Th1/Th2 Cytokine Production during the Post-Partum Period in Pregnant Women with Chronic Hepatitis C

This study analyses the evolution of liver disease in women with chronic hepatitis C during the third trimester of pregnancy and the post-partum period, as a natural model of immune modulation and reconstitution. Of the 122 mothers recruited to this study, 89 were HCV-RNA+ve/HIV-ve and 33 were HCV-RNA-ve/HIV-ve/HCVantibody+ve and all were tested during the third trimester of pregnancy, at delivery and post-delivery. The HCV-RNA+ve mothers were categorized as either Type-A (66%), with an increase in ALT levels in the post-partum period (>40 U/L; P<0.001) or as Type-B (34%), with no variation in ALT values. The Type-A mothers also presented a significant decrease in serum HCV-RNA levels in the post-delivery period (P<0.001) and this event was concomitant with an increase in Th1 cytokine levels (INFγ, P = 0.04; IL12, P = 0.01 and IL2, P = 0.01). On the other hand, the Type-B mothers and the HCV-RNA-ve women presented no variations in either of these parameters. However, they did present higher Th1 cytokine levels in the partum period (INFγ and IL2, P<0.05) than both the Type-A and the HCV-RNA-ve women. Cytokine levels at the moment of delivery do not constitute a risk factor associated with HCV vertical transmission. It is concluded that differences in the ALT and HCV-RNA values observed in HCV-RNA+ve women in the postpartum period might be due to different ratios of Th1 cytokine production. In the Type-B women, the high partum levels of Th1 cytokines and the absence of post-partum variation in ALT and HCV-RNA levels may be related to permanent Th1 cytokine stimulation.

194th ENMC international workshop. 3rd ENMC workshop on exon skipping: Towards clinical application of antisense-mediated exon skipping for Duchenne muscular dystrophy 8–10 December 2012, Naarden, The Netherlands

194th ENMC international workshop. 3rd ENMC workshop on exon skipping: Towards clinical application of antisense-mediated exon skipping for Duchenne muscular dystrophy 8–10 December 2012, Naarden, The Netherlands

NONINVASIVE ULTRASOUND EVALUATION OF THE PARENCHYMA OF THE PARENCHYMA OF LIVER AND SPLEEN IN CHILDREN WITH INFECTIOUS MONONUCLEOSIS

The data of the examination of 73 children aged 1 to 18 years with mononucleosis of Epstein-Barr virus etiology are presented. The use of non-invasive quantitative assessment methodology of the parenchyma (Acoustic Structure Quantification) was shown to allow objectify the examination and to found that infectious mononucleosis in 1st Group patients with a minimum degree of diffuse changes of the liver proceeded without structural changes in the liver parenchyma. In the 2nd group patients the estimation of density index according to Acoustic Structure Quantification allowed to reveal the signs of cholestasis. The heterogeneity of the structure of the liver and the elevation of the parenchymal density index indicated on signs of acute hepatitis and was confirmed by the increase in ALT level in blood serum. Despite the pronounced splenomegaly no structural changes in the spleen were found in any patients.

MIS5-3 - Expanded Treatment Efficacy and Safety Study of Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma with Epirubicin/ Doxorubicin–Lipiodol Emulsion and Gelatin Particles: A Cooperative Study between Korea and Japan

ABSTRACT Background A single-arm expanded treatment efficacy and safety study of TACE in Japan and Korea was conducted to confirm the reproducibility of the results in the phase III study carried out by Llovet et al., which showed a significant survival advantage of TACE, compared with conservative treatment, for unresectable HCC. Methods Patients with unresectable HCC who had no indications for curative treatment and who had not received prior therapy for HCC were enrolled. The patients underwent TACE using an emulsion of epirubicin HCl or doxorubicin HCl and Lipiodol, followed by the injection of gelatin sponge particles. The treatment was repeated on an as-needed basis. The primary end point was the 2-year survival rate, and the secondary end points were the incidence and grade of adverse events and the response rate. Results The study accrued 102 patients enrolled at 27 institutions in both countries between January 2008 and January 2009, but three patients withdrew their informed consent. The 2-year survival rate of the 99 evaluable patients was 75.0% (95% CI, 65.2–82.8%). The median time-to-progression and the median overall survival period were 7.6 months and 3.1 years, respectively. Among the 99 evaluable patients, 42 (42%) achieved a complete response and 31 (31%) had a partial response, and the response rate was 73% (95% CI: 63–82%) using the modified response evaluation criteria for solid tumors. The major grade 3–4 toxic effects were an increased AST level (35%) and an increased ALT level (36%), thrombocytopenia (12%), and abdominal pain (4%); all other toxic effects were generally transient. Conclusion In Japan and Korea, TACE exerted a marked favorable efficacy in patients with unresectable HCC who were not suitable for curative treatment, and this treatment modality may be regarded as a standard therapy for unresectable HCC.

Serum levels of Th17 associated cytokines in chronic hepatitis C virus infection

The Th17-mediated immune response was investigated in patients chronically infected with hepatitis C virus (HCV) by determining the serum levels of the cytokines involved in the induction of the Th17 response (TGF-β and IL-6), the cytokines produced by Th17 cells (IL-17A, IL-17F and IL-22) and the cytokines whose production is stimulated by Th17 lymphocytes (IL-8 and GM-CSF). We investigated the relationships among the levels of these cytokines by assessing clinical findings, liver histology and viremia. Sixty untreated patients and 28 healthy individuals were included in the study. Cytokine levels were determined using ELISA. Differences between HCV and control groups were identified in the median levels of IL-17F (controls=172.4pg/mL; HCV=96.8pg/mL, p<0.001) and IL-8 (controls=30.1pg/mL; HCV=18.1pg/mL, p<0.05). IL-6 levels were higher in patients presenting moderate liver necroinflammation than in patients with mild or no liver necroinflammation (p<0.05). IL-17F levels were increased in patients that had increased ALT levels. Additionally, a strong positive correlation was observed between IL-17F and IL-22 levels in the two groups investigated, and the IL-17F/IL-22 ratio was lower in the patients infected with HCV (p<0.0001). Patients with low HCV viral loads had higher median levels of IL-8 (32.5pg/mL) than did patients with high HCV loads (16.7pg/mL, p<0.05). These results suggest that in chronic hepatitis C infection, IL-17F and IL-8 could be associated with the control of liver injury and infection, respectively.

Patterns of hepatitis B viral load level (HBV DNA), hepatitis B e antigen (HBeAg) status and risk factors of cirrhosis and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients in Thailand

Background: There is a strong relationship between HBeAg sero-status, HBV DNA level and CHB-associated complications, especially cirrhosis and HCC. However, the distribution of HBV DNA and HBeAg seroprevalence and risk factors of cirrhosis among Thai CHB patients have not been adequately described. We aim to determine the patterns of HBV DNA level, HBeAg status, and risk factors of cirrhosis and HCC in Thai CHB patients. Methods: A cross-sectional study was conducted at Chulabhorn Hospital in 2010. CHB patients, aged 20-65 years, were tested for liver function test , HBeAg, HBV DNA, alpha fetoprotein and ultrasound upper abdomen. Results: 2,293 CHB patients (1,086 (47.36%) males) with the mean age (SD) of 41.25 (10.95) years were included. Mean HBV DNA was 3.62(2.22) log 10 IU/ml, and 47.71% had HBV DNA > 2,000 IU/ml. HBeAg positivity was present in 17.2% and most cases (96.19%) had high HBV-VL > 2,000 IU/ml. The majority of CHB (82.8%) were HBeAg negative, and only 37.6% of them had HBV DNA > 2,000 IU/ml. ALT level was 35.5(40.1) IU/L, of which 22.5% had ALT > 40 IU/ml. Higher HBV DNA and increased ALT levels were significantly associated with male gender, HBeAg-seropositivity and cirrhosis (p< 0.001). Liver cirrhosis by liver biopsy, transient elastography and US was found in 180 (7.8%) cases. HBeAg-seropositivity was more frequently found in cirrhosis patients than HBeAg-seronegativity (23.33% vs 16.67%, p=0.023). High prevalence of cirrhosis was found in HBV DNA level 2-3 and 5-6 log 10 IU/ml in 18.33% and 18.89%, respectively (p<0.001). Multivariate analysis showed factors associated with cirrhosis, including male gender, age > 50 years and HBV DNA> 2000 IU/ml. Logistic regression analysis revealed HBV DNA level of 200,000-1,999,999 IU/ml, which significantly associated with cirrhosis (OR 5.84). Conclusion: Higher HBV DNA level, HBeAg-seropositivity and risk factors for cirrhosis were commonly found in Thai CHB patients. HBeAg negative with 39.34% viremic regardless of ALT were observed in most CHB cases. The predominant trend towards HBeAg –seronegativity CHB has also been observed as in western countries. Hence, the active national surveillance policy should be implemented in those with high HBV DNA and HBeAg-seropositivity to provide effective treatment and prevent complications.

Predictors of HBeAg status and hepatitis B viraemia in HIV-infected patients with chronic hepatitis B in the HAART era in Brazil

BackgroundHBV-HIV co-infection is associated with an increased liver-related morbidity and mortality. However, little is known about the natural history of chronic hepatitis B in HIV-infected individuals under highly active antiretroviral therapy (HAART) receiving at least one of the two drugs that also affect HBV (TDF and LAM). Information about HBeAg status and HBV viremia in HIV/HBV co-infected patients is scarce. The objective of this study was to search for clinical and virological variables associated with HBeAg status and HBV viremia in patients of an HIV/HBV co-infected cohort.MethodsA retrospective cross-sectional study was performed, of HBsAg-positive HIV-infected patients in treatment between 1994 and 2007 in two AIDS outpatient clinics located in the São Paulo metropolitan area, Brazil. The baseline data were age, sex, CD4 T+ cell count, ALT level, HIV and HBV viral load, HBV genotype, and duration of antiretroviral use. The variables associated to HBeAg status and HBV viremia were assessed using logistic regression.ResultsA total of 86 HBsAg patients were included in the study. Of these, 48 (56%) were using combination therapy that included lamivudine (LAM) and tenofovir (TDF), 31 (36%) were using LAM monotherapy, and 7 patients had no previous use of either one. Duration of use of TDF and LAM varied from 4 to 21 and 7 to 144 months, respectively. A total of 42 (48. 9%) patients were HBeAg positive and 44 (51. 1%) were HBeAg negative. The multivariate analysis revealed that the use of TDF for longer than 12 months was associated with undetectable HBV DNA viral load (serum HBV DNA level < 60 UI/ml) (p = 0. 047). HBeAg positivity was associated with HBV DNA > 60 UI/ml (p = 0. 001) and ALT levels above normality (p = 0. 038).ConclusionProlonged use of TDF containing HAART is associated with undetectable HBV DNA viral load. HBeAg positivity is associated with HBV viremia and increased ALT levels.