Cases Of Chronic Hepatitis Research Articles

The Amino-Terminal Region of Hepatitis E Virus ORF1 Containing a Methyltransferase (Met) and a Papain-Like Cysteine Protease (PCP) Domain Counteracts Type I Interferon Response.

Hepatitis E virus (HEV) is responsible for large waterborne epidemics of hepatitis in endemic countries and is an emerging zoonotic pathogen worldwide. In endemic regions, HEV-1 or HEV-2 genotypes are frequently associated with fulminant hepatitis in pregnant women, while with zoonotic HEV (HEV-3 and HEV-4), chronic cases of hepatitis and severe neurological disorders are reported. Hence, it is important to characterize the interactions between HEV and its host. Here, we investigated the ability of the nonstructural polyprotein encoded by the first open reading frame (ORF1) of HEV to modulate the host early antiviral response and, in particular, the type I interferon (IFN-I) system. We found that the amino-terminal region of HEV-3 ORF1 (MetYPCP), containing a putative methyltransferase (Met) and a papain-like cysteine protease (PCP) functional domain, inhibited IFN-stimulated response element (ISRE) promoter activation and the expression of several IFN-stimulated genes (ISGs) in response to IFN-I. We showed that the MetYPCP domain interfered with the Janus kinase (JAK)/signal transducer and activator of the transcription protein (STAT) signalling pathway by inhibiting STAT1 nuclear translocation and phosphorylation after IFN-I treatment. In contrast, MetYPCP had no effect on STAT2 phosphorylation and a limited impact on the activation of the JAK/STAT pathway after IFN-II stimulation. This inhibitory function seemed to be genotype-dependent, as MetYPCP from HEV-1 had no significant effect on the JAK/STAT pathway. Overall, this study provides evidence that the predicted MetYPCP domain of HEV ORF1 antagonises STAT1 activation to modulate the IFN response.

Epidemiological features of acute and chronic hepatitis B in the Kyrgyz Republic over the 20-year period (1997-2017)

Aim. To determine epidemiological features of acute and chronic viral hepatitis B in the Kyrgyz Republic over the period 1997-2017. Меthоds. Analysis was performed on data bases of the National accounting forms on treated cases of acute and chronic hepatitis B cumulated by the Medical Information Centre of the Ministry of Health of Kyrgyz Republic for the period of 1997 to 2017 as well as 384 medical records of patients with chronic hepatitis B treated in the Hepatologic Centre “Tsadmir”. Results. In the Kyrgyz Republic among all acute cases of acute viral hepatitides, hepatitis A comprises 60.5 %, hepatitis B - 16.9 %, the ratio of unverified non-A non-C viral hepatitis - 15.2%. With the introduction of HBV vaccination of children (2000) and improvement of infectious control in healthcare settings, a decline of acute HBV incidence is observed - from 26.7 0/0000 to 5.3 0/0000 due to the decrease of acute hepatitis B among children and adolescents to isolated cases, adults from risk groups. The highest incidence of acute hepatitis B is recorded in Osh and Bishkek, in Jalal-Abad and Chuy Regions. This can be explained by that in the southern and northern capitals of the Kyrgyz Republic and in the near lying areas with high population density, access to laboratory and instrumental methods of diagnosis of viral hepatitides is better, along with the higher awareness of its inhabitants regarding the prevention compared to other regions. At the same time an increase of chronic hepatitis B incidence is observed. Predominant modes of transmission are medical-parenteral exposure and household contact (60.9 %), with frequent formation of family clusters (23.8 %). Imperfections were found in the early detection, reporting and accounting of cases of chronic viral hepatitides as well as in examination of hepatitis B virus carriers. Conclusion. The performed analysis of the incidence and prevalence of acute and chronic hepatitis B in the Kyrgyz Republic allowed assessing the dynamics of the epidemiologic situation in the country regarding this disease, revealed shortcomings in the detection and examination of viral hepatitis B carriers, contributed to development of a new guide for epidemiological surveillance of viral hepatitides.

Expressions of MiR-132 in patients with chronic hepatitis B, posthepatitic cirrhosis and hepatitis B virus-related hepatocellular carcinoma.

To explore the expressions of miR-132 in patients with chronic hepatitis B, posthepatitic cirrhosis and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and to investigate its possible mechanism affecting the function of the body. Among 125 patients with HBV, there were 44 cases of chronic hepatitis, 42 cases of liver cirrhosis and 39 cases of liver cancer. Their liver function and HBV-deoxyribonucleic acid (HBV-DNA) viral load as well as the expressions of micro ribonucleic acid-132 (miR-132), phosphoinositide 3-kinase (PI3K), phosphorylated-protein kinase B (p-Akt) and hepatitis B X protein (HBx), were detected. There were significant differences in some liver function indexes and the HBV-DNA level among the three groups of patients (p < 0.05). The HBV-DNA level was 6.91 Lg copies/mL in the liver cancer group and 5.34 Lg copies/mL in the chronic hepatitis B group. Differences in the expression level of miR-132 among the three groups were notable (p < 0.05), but this expression level had a negative correlation with the HBV-DNA level. The expressions of PI3K and p-Akt proteins and messenger ribonucleic acids (mRNAs) were markedly different among the three groups (p < 0.05). HBx was expressed in the three groups of patients, and liver cancer patients with the highest expression degree of HBx accounted for 46%. Differences in the expression of miR-132 among the three groups are evident, which may be associated with differences in liver function, the HBV-DNA level, HBx and the expressions of PI3K and p-Akt proteins to a certain degree.

Iron metabolism disorders in patients with hepatitis B-related liver diseases.

AIMTo investigate the relationship between levels of iron metabolism markers and hepatitis B virus (HBV)-related chronic liver diseases.METHODSThis case-control study with 318 participants included 78 cases of chronic hepatitis B, 85 cases of HBV-related liver cirrhosis, 77 cases of HBV-related hepatocellular carcinoma, and 78 healthy controls. Markers of iron metabolism were detected in participants. Hematological and biochemical parameters and HBV-DNA were assessed. Child-Pugh grade and Barcelona Clinic Liver Cancer stage were determined for each hepatocellular carcinoma patient. Perls’ staining was performed on liver sections. The SPSS program was used for all statistical analyses, and statistical significance was considered if a P-value < 0.05.RESULTSSignificantly higher serum ferritin and lower serum hepcidin levels were detected in all groups of HBV-infected patients compared with healthy controls. Serum iron, total iron binding capacity, and serum transferrin levels were significantly lower in patients with cirrhosis and hepatocellular carcinoma, whereas the hepcidin level was higher than that in chronic hepatitis B patients. Correlation analysis indicated that serum hepcidin was negatively correlated with HBV-DNA load (P < 0.01). Serum ferritin and transferrin saturation levels increased proportionally to the extent of liver cirrhosis and poorer Child-Pugh scores (P < 0.05). The decreased serum iron and transferrin saturation levels were significantly correlated with a smaller hepatocellular carcinoma tumor burden according to Barcelona Clinic Liver Cancer staging. Liver histology showed a clearly increasing trend in iron deposition in the liver tissues with increased fibrosis, which became prominent at stages 3 (severe liver fibrosis) and 4 (cirrhosis).CONCLUSIONIron metabolism disorders occur in patients with HBV-related liver diseases. The serum markers of iron metabolism disorders vary in different stages of HBV-related liver diseases.

Expression Analysis of Long Non-Coding RNA HAR1A and HAR1B in HBV-Induced Hepatocullular Carcinoma in Chinese Patients.

To determine the clinical relevance of long noncoding RNA (lncRNA) HAR1A and HAR1B expression in hepatocellular carcinoma (HCC). In this study, we enrolled 50 cases of chronic hepatitis B (CHB) without cirrhosis, 50 cases of CHB and liver cirrhosis (LC), and 100 cases of HBV and HCC. The expression profiles of lncRNA HAR1A and HAR1B were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of HAR1A and HAR1B were significantly lower in the HCC group, compared with the CHB and LC groups (P <.01). HAR1A and HAR1B were negatively associated with histologic grade and TNM (tumor/nodes/metastasis) stage (all P <.05). Univariable multivariable analysis showed that decreased HAR1A (HR = 0.753, P = .02) and HAR1B (HR = 0.551, P = .01) levels were independent predictors for shorter overall survival (OS) in HCC. Decreased HAR1A and HAR1B expression in HCC indicates poor prognosis.

Unusual Cause of Acute Drug-Induced Hepatitis

Rivaroxaban is an oral anticoagulant used in non-valvular A-fib, as well as treatment and prevention of DVT and pulmonary embolism (PE). We present a case of reversible acute liver injury; a rare adverse reaction of rivaroxaban. A 62-y.o. female presented to ER with a 2-week history of nausea, early satiety, dull aching RUQ pain, dark urine and normal colored stool. She has history of GERD and recurrent PE, the latest was a month earlier and she was started on rivaroxaban. She has no history of alcohol/acetaminophen use, substance abuse, liver disease, blood transfusion, recent travel or infection. The only positive physical exam finding was mild RUQ tenderness. Initial work up showed markedly elevated LFTs (table). Acute hepatitis profile, monospot test, acetaminophen/alcohol levels, EBV, CMV, CPK, TSH, urine/blood drug screen, autoimmune workup, liver ultrasound with Doppler, CT and MRI abdomen; all were negative. The patient was discharged home with GI follow-up. Few days later, she presented with worsening symptoms including dizziness, poor appetite and nausea. Repeat blood test showed worsening LFTs. Patient was admitted and started on supportive therapy while efforts to determine the cause of elevated LFTs continued. Rivaroxaban-induced acute liver injury was entertained. The drug was stopped and she was switched to enoxaparin for anticoagulation. Her LFTs and symptoms continued to improve over few months after her discharge. The Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between rivaroxaban use and acute liver injury. Rivaroxaban is a direct factor Xa inhibitor that may cause bleeding, rash and liver injury. Rivaroxaban is associated with moderate ALT elevation in 1.5% to 3% of patients. Most cases have an onset within 1 to 8 weeks of starting therapy. All patients recover 2 to 4 weeks after stopping rivaroxaban. Cases of acute liver failure, chronic hepatitis or vanishing bile duct syndrome due to rivaroxaban have not been reported in the literature. The exact mechanism of liver injury is unknown, but may be idiosyncratic or immunologic. Rivaroxaban is metabolized in the liver mainly by CYP3A4 and is susceptible to drug-drug interactions. Clinicians should be made aware of this rare side effect as early discontinuation of the drug is essential to prevent morbidity and even mortality. Future research is needed to determine if routine follow up of LFTs is advised in patients on rivaroxaban.2173 Figure 1 No Caption available.

P061 The number of admissions and the ethiology of cases of acute and chronic hepatitis observed over 5 years in general pediatric ward. The experience of the Ravenna hospital

P061 The number of admissions and the ethiology of cases of acute and chronic hepatitis observed over 5 years in general pediatric ward. The experience of the Ravenna hospital

Hepatocyte expression and prognostic importance of senescence marker p21 in liver histopathology samples from dogs with chronic hepatitis.

BackgroundChronic hepatitis (CH) occurs commonly in dogs but is associated with a variable and largely unpredictable prognosis. p21, a cell‐cycle inhibitor and marker of cellular senescence, is upregulated in human liver disease and is a better prognostic marker than histological or clinical scoring systems.ObjectiveTo quantify hepatocyte p21 immunopositivity in histopathology samples from dogs with CH and determine its association with outcome.AnimalsTwenty‐six client‐owned dogs with histologically confirmed CH, and 15 dogs with normal liver histology.MethodsMedical records and liver histopathology samples were retrospectively reviewed to identify cases of CH. Immunohistochemistry for p21 was performed on all samples and hepatocyte immunopositivity was visually quantified. Relationships between p21 and dog age and dog survival time were statistically evaluated.ResultsHepatocyte p21 immunopositivity in dogs with CH was high (median percentage of positive hepatocytes: 90%, range: 20%‐98%) and exceeded 70% in 23/26 cases with no association with age. In control dogs, p21 immunopositivity was low (≤15% positive hepatocytes in 12/15 cases) and was positively correlated with age (r s = 0.63; P = .011). Dogs with p21 immunopositivity exceeding 91.8% (upper tercile) had significantly shorter survival compared to dogs with less than 88.9% immunopositivity (lowest tercile; 218 versus 874 days, P = .006). Increasing hepatocyte p21 immunopositivity was significantly negatively associated with survival time (HR 4.12; 95% CI 1.34‐12.63; P = .013).Conclusions and Clinical ImportanceMarked p21 immunopositivity in dogs with CH might be indicative of widespread hepatocellular senescence. A significant association with survival time also suggests a potential value for p21 quantification in determining prognosis.

Chronic liver disease increases with damage to intestinal barrier function

Objective: To probe into the correlation between chronic liver disease and intestinal barrier function. Methods: 1 491 cases of hospitalized patients were enrolled, of which 741 cases were of chronic liver diseases, including 397 cases of fatty liver diseases, 230 cases of chronic hepatitis, 114 cases of liver cirrhosis, and 750 cases of non-hepatic diseases. All admitted patients' intestinal barrier function like diamine oxidase (DAO), D-lactate, lipopolysaccharide, and biochemical indicators of liver functions were tested. According to different data, statistical analysis was done using t-test, ANOVA, Dunnett's test, χ (2) test of fourfold table, Pearson's correlation, and binary logistic regression. Results: The intestinal barrier dysfunction was more likely to occur in the chronic liver disease group than that of non-hepatic disease group [54.15% (379/741) vs. 18.53% (139/750), χ (2) = 193.58, P < 0.001]. The correlation analysis between biochemical indicators of liver function and intestinal barrier function in chronic liver disease group showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and total bilirubin levels were more susceptible to intestinal barrier dysfunction than those with normal indexes (P < 0.05 ). GGT had stimulated DAO (P < 0.05, OR > 1), D-lactate (P < 0.05, OR > 1), lipopolysaccharide (P < 0.05, OR > 1), ALT and AST. Conclusion: Chronic liver disease increases with damage to intestinal barrier function.

Histologic features of autoimmune hepatitis: a critical appraisal

We speculate that the "typical" histologic features (lymphoplasmacytic interface hepatitis, emperipolesis, and hepatocyte rosettes) of autoimmune hepatitis (AIH) are related to severity of hepatitis rather than etiology. We critically appraised various histologic features of AIH and compared them with cases of chronic hepatitis with similar inflammatory grade and fibrosis stage. Fifty-one patients with clinically confirmed AIH were identified at our institution, of which 43 biopsies (from 42 patients) were taken before initiation of therapy and formed the study group. Hepatitis C biopsies with similar grade and stage served as controls. Kupffer cell hyaline globules (KcHGs; P = .03), prominence of plasma cells in portal tracts (P = .003), "plasma-lymphocytic" inflammation (defined as plasma cells > lymphocytes), or as clusters (defined as ≥5) within portal tracts (P = .002) or lobules (P = .001) were significantly associated with AIH. Rosettes and emperipolesis lacked significance when controlled for inflammatory grade (rosettes, P = 1; emperipolesis, P = .4), supporting our hypothesis. Based on our findings, we developed a modified scoring system in which typical features require the presence of both (1) prominent plasma cells (plasma cells comprise ≥20% of inflammatory cells or presence of plasma cell clusters) and (2) KcHG. "Compatible" features include prominent plasma cells but lack KcHG, and "atypical" features include the presence of another disease process. Although application of this scoring system in our patients decreased the sensitivity to 77% (from 100%), it increased the specificity to 67% (from 0%). Further studies with different control groups are needed to validate these findings.

Analysis of the complete genome of hepatitis B virus subgenotype C2 isolate NHB17965 from a patient with uncomplicated chronicity

The number of chronic cases of hepatitis B virus (HBV) is increasing rapidly in the world. Herein, we report a complete genome of HBV subgenotype C2 (HBV/C2) with current common amino acid substitutions from a patient with chronic HBV without liver complications. Complete genome analysis revealed that the isolated strain was a non-recombinant wild type and had several regular substitutions in the reverse transcriptase domain and small surface proteins of HBV. The isolated complete sequence could be considered as a chronic reference strain of HBV/C2 in Bangladesh. This study may help clinicians and scientists gain in-depth knowledge on common substitutions of HBV/C2 genome and to identify potential therapies against chronic HBV infections.

The Examination of Hepatitis E after Renal Transplantation

Japan Agency for Medical Research and Development"An oral hepatitic group". Hepatitis E is identified as a zoonosis with a natural reservoir in pigs. Hepatitis E virus (HEV) infection attracted close attention in Japan after the fatal case of patient with hepatitis E was reported in 2002, and after that reports of clinical HEV the hepatitis E infection increased rapidly. Infection via blood transfusion leads to further increased medical concerns. Subclinical infection is the most common situation, while rare cases of HEV infection develop subacute hepatitis, which resultsed in complete recovery. There were no data on chronic hepatitis E until recentlynow. However, in organ- transplantedation patients receiving immunosuppression therapy there is a possibility of chronicityzation and these patients need close attention. Here we report on 4 cases who developedin which hepatitis E developed after kidney transplantation and were diagnosed inat our institution. 2 cases of those remitted as acute hepatitis immediately. However 2 cases (case3 and 4) that take become the chronic hepatitis and do not heal. Chronic hepatitis cases that used an intensive immunosuppressive drug such as Rituximab and FTY720 compared with induction immunosuppressive therapy of the standard cases. Furthermore 2 cases that became the E type chronic hepatitis, lymphocyte counts of the peripheral blood and immunoglobulin were lighter than the standard acute hepatitis cases. For episode time, all cases are 3-6 years after renal transplant. The case that became the chronic hepatitis needed time-temperature tolerance until diagnosis was turned on. Therefore infection time and the route of infection are not clear. It is more difficult a treatment of chronic hepatitis cases than the standard acute hepatitis cases. When the patients of particularly intensive immunosuppression show the increase of the mild liver enzyme, we suspect HEV infection positively and should check HEV RNA. We thoroughly investigated potential route of HEV infection and present detailed clinical course in our cases. There will be the need to elucidate measures, treatment strategy in future by determining the route of infection of the hepatitis E in renal-transplant recipients of our country and presence of the chronicity.

3. X-ray repair cross complementing group 3 polymorphism in association with aflatoxin B1 exposure in chronic hepatitis (B & C) and hepatocellular carcinoma

Background and Aims: X-ray repair cross-complementing group 3 (XRCC3) is a constituent of DNA repair genes involved in the process of DNA double-strand breaks repair pathway. XRCC3 Thr241Met (C > T) polymorphism is a single nucleotide polymorphism (SNP) at codon 241 in exon 7. We aimed to study polymorphisms of XRCC3 Thr241Met in Chronic Hepatitis (B & C) and Hepatocellular carcinoma patients and healthy individuals. This was correlated with total aflatoxin content in various indigenous foods consumed by general population and chronic liver disease patients from Assam, India. Methods: We conducted a hospital based case control study including 70 Chronic Hepatitis (B & C) cases and 70 healthy controls, alongwith 20 Hepatocellular Carcinoma cases and 20 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR- RFLP) assay in Assamese population. Results: Out of 70 cases of chronic liver disease (HBV & HCV) 67.14% patients showed SNP for XRCC3 Thr241Met out of which 32.85% were homozygous (C/C), 50% were heterozygous (C/T) and 17.14% were mutated (T/T). Whereas out of 20 Hepatocellular carcinoma cases 30% were homozygous (C/C), 35% were heterozygous (C/T) and 35% were mutated (T/T). No significant association of SNP's was observed with duration of alcohol consumption, raised transaminase, low platelet count, HBsAg and Anti HCV status. The indigenous food samples were examined by HPLC technique which did not reveal significant aflatoxin content. Conclusions: The XRCC3 codon 241 polymorphism displayed a relationship with HCC and in chronic hepatitis B & C. Codon 241 mutation was significantly increased in patients of HCC and in chronic HBV or HCV. There is increased risk for the individuals with XRCC3 CT genotype [OR = 2.43 (1.17–5.03), p = 0.01*] and TT genotype [OR = 4.17 (1.30–13.34), p = 0.01*]. Hence, presence of mutation in the codon of XRCC3 TT genotype in patients of chronic HBV and HCV could indicate the likelihood of progression to HCC. The authors have none to declare.

MiRNA-221 and miRNA-222 are promising biomarkers for progression of liver fibrosis in HCV Egyptian patients

BackgroundCurrent methodologies used to determine the progression of hepatic fibrosis rely heavily on liver biopsy, a dangerous and invasive procedure, with semi-subjective analysis of the results of the biopsy. Thus, a new approach is immensely needed for monitoring the progression of liver fibrosis in Hepatitis C virus (HCV) patients. Aim of workThe purpose of this study was to find highly specific and sensitive miRNA biomarkers that can be used to detect different stages of liver fibrosis. MethodologyThe study consisted of 42 cases of chronic hepatitis C (CHC) with early-stage fibrosis, 45 cases of CHC with late-stage fibrosis, and 40 healthy subjects with no CHC or fibrosis as controls. Expression patterns of 5 miRNAs (miR-16, miR-146a, miR-214-5p, miR-221, and miR-222) were analyzed in each group using TaqMan real-time PCR. ResultsSerum levels of miRNA-16, miRNA-146a, miRNA-221, and miRNA-222 were all significantly up-regulated in early and late stages of liver fibrosis. miRNA-222 had the highest sensitivity and specificity values in early and late fibrosis. miRNA-221 had the second highest sensitivity and specificity with the late-stage fibrosis group. Furthermore, miRNA-221 showed significant positive correlations with both miRNA-16 and miRNA-146a in the early- and late-stage fibrosis groups, with the early stage having a stronger correlation. ConclusionsThe results indicated that miRNA-16, miRNA-146a, miRNA-221, and miRNA-222 can be used to detect the presence of liver fibrosis. The high sensitivity and specificity of miRNA-222 and miRNA-221 in late-stage fibrosis indicate promising prognostic biomarkers for HCV-induced liver fibrosis.

Hepatitis E virus in South America: The current scenario.

Hepatitis E virus (HEV) is one of the most frequent causes of acute viral hepatitis of enteric transmission worldwide. In South America the overall epidemiology has been little studied, and the burden of the disease remains largely unknown. A research of all scientific articles about HEV circulation in South America until November 2017 was carried out. Human seroprevalences of HEV varied according to the studied population: blood donors presented prevalence rates ranging from 1.8% to 9.8%, while reports from HIV-infected individuals, transplant recipients and patients on hemodialysis showed higher prevalence rates. Only 2 cases of chronic hepatitis in solid-organ transplant patients from Argentina and Brazil have been described. Detection of HEV in the swine population is widely prevalent in the region. Anti-HEV antibodies have also been recently documented in wild boars from Uruguay. Although scarce, studies focused on environmental and food HEV detection have shown viral presence in these kind of samples, highlighting possible transmission sources of HEV in the continent. HEV genotype 3 was the most frequently detected in the region, with HEV genotype 1 detected only in Venezuela and Uruguay. HEV is widely distributed throughout South America, producing sporadic cases of acute hepatitis, but as a possible agent of chronic hepatitis. Finding the virus in humans, animals, environmental samples and food, show that it can be transmitted through many sources, alerting local governments and health systems to improve diagnosis and for the implementation of preventive measures.

Absence of chronic hepatitis E virus infection in liver transplant recipients: Report from a hyperendemic region.

Most cases of chronic hepatitis E virus (HEV) infection in solid organ transplant recipients are attributable to genotype 3. Although India is hyperendemic for HEV genotype 1, chronic infection in transplant patients has not been reported. In this study, 30 liver transplant recipients were followed up by systematic testing for various markers of HEV (IgM, IgG, HEV-Ag, and RNA) on blood and stool samples obtained pre-transplant, and then at 3 and 6months post-transplant to look for HEV exposure and persistence. Evidence of HEV infection was found in 6 (20%) cases post-transplant but none of the recipients demonstrated active viremia or antigenemia. This suggests that the circulating genotype of HEV in our population might have limited potential to cause chronic infections.

Expression analysis of apolipoproteins AI & AIV in hepatocellular carcinoma: A protein-based hepatocellular carcinoma-associated study.

Background & objectives:Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality. The objective of this study was to find out the differential expression of apolipoproteins (ApoAI and ApoAIV) in HCC and cases of liver cirrhosis and chronic hepatitis (controls) without HCC and to compare ApoAI and ApoAIV expression with alpha-foetoprotein (AFP), the conventional marker in HCC.Methods:Fifty patients with HCC and 50 controls comprising patients with liver cirrhosis (n=25) and chronic hepatitis (n=25) without HCC were included in this study. Total proteins were precipitated using acetone precipitation method followed by albumin and IgG depletion of precipitated protein using depletion kit. Proteins were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The expression changes of ApoAI and ApoAIV were confirmed by western blotting using specific primary and secondary polyclonal antibodies followed by densitometric protein semi-quantitative estimation. ApoAI, ApoAIV and AFP were measured in the plasma samples by ELISA method.Results:Semi-quantitative densitometric image analysis of the western blot images and the comparison between HCC patients with those without HCC (control) revealed differential expression of ApoAI and ApoAIV. Levels of ApoAI were significantly higher in patients with HCC compared to controls without HCC (0.279±0.216 vs 0.171±0.091 and 0.199±0.014; P <0.001). Levels of ApoAIV were significantly lower in patients of HCC compared to controls without HCC (0.119±0.061 vs 0.208±0.07 and 0.171±0.16; P <0.01). ELISA assays of apolipoproteins (ApoAI and ApoAIV) revealed similar results of expression of ApoAI and ApoAIV as detected in western blotting densitometric image analysis.Interpretation & conclusions:Increased expression of ApoAI and decreased expression of ApoAIV in HCC patients compared to controls without HCC revealed the abnormalities in HCC. These molecules need to be studied further for their use as potential biomarkers in the future diagnostic tools along with other conventional biomarkers for screening of HCC cases. It needs further analysis in higher number of patient population.

Association of PNPLA3 rs738409 polymorphism with liver steatosis but not with cirrhosis in patients with HBV infection: Systematic review with meta-analysis.

Hepatitis B virus (HBV) infection is a worldwide health issue and is well known for being the main cause of developing secondary liver complications such as cirrhosis and hepatocellular carcinoma (HCC). The PNPLA3 rs738409 polymorphism has been investigated conclusively with occurrence risk of steatosis and cirrhosis. Therefore, performing a meta-analysis of the available studies with the aim of clarifying the association between rs738409 and occurrence risk of steatosis and cirrhosis among HBV-infected patients would be helpful. Chronic HBV infection was defined as the persistence of HBsAg for more than 6months. To gather sufficient data for this meta-analysis, reliable databases were conclusively searched using appropriate keywords. Only studies that satisfied the inclusion criteria were enrolled in the present study. This meta-analysis pooled four studies with 1135 cases of chronic hepatitis B (CHB) to evaluate the impact of PNPLA3 SNP on liver steatosis and also pooled five studies with 3713 cases of CHB to evaluate the impact of PNPLA3 SNP on cirrhosis. The association of rs738409 with each complication was investigated. The rs738409 was found to be associated with steatosis in recessive [p = 4.57 × 10-6 , odds ratio (OR) = 2.85], dominant (p = 4.35 × 10-6 , OR = 1.84), co-dominant (p = 6.18 × 10-8 ; OR = 3.74) and allelic (p = 9.79 × 10-9 ; OR = 1.78) models. No association was found between rs738409 and cirrhosis development in recessive (p = 0.99, OR = 1.00), dominant (p = 0.30, OR = 0.92), co-dominant (p = 0.74; OR = 0.96) and allelic (p = 0.45; OR = 0.96) models. Although the PNPLA3 rs738409 G allele has been associated with the risk of steatosis in CHB patients, no association between this polymorphism and the risk of cirrhosis was seen.

Liver autopsy study – incidental pathological findings

Background: Liver is the site of many diseases, many of which become symptomatic while some are diagnosed only on autopsy. Involvement of liver is secondary to cardiac, metabolic, social problem like alcoholism, drug toxicity, injudicious use of topical applications, herbal remedies and environmental exposures. Aims and Objectives: In apparently healthy individuals autopsy study sometimes reveals liver diseases. Hence this study aims at finding the frequency and the histopathological appearances in random liver autopsy, so as to evoke public awareness against alcoholism, drug toxicity and potential toxins (perfumes, shampoo, cleaning solvents, pesticides fertilizers,). Materials and Methods: The present study was carried out in the Department of Pathology & Department of Forensic Medicine and Toxicology, VIMSAR, Burla, Odisha over a period of 2 years. The liver specimens collected from 64 cases were examined grossly as well as microscopically to establish the presence of liver diseases and also to find out the types of liver diseases. Results: Out of 64 specimens, fatty change, chronic venous congestion, hepatitis, cirrhosis, Steatohepatitis, and drug toxicity cases are reported; fatty change being the predominant finding. Liver diseases predominated in males with male to female ratio of 5:1. Conclusion: Autopsy examination of liver was very helpful to identify silent liver diseases.

Relationship between oxidative stress in patients with HBV-induced liver disease and HBV genotype/drug-resistant mutation

ObjectiveTo explore the correlation of oxidative stress in patients with chronic hepatitis B and degree of severity of the disease with HBV genotype and drug-resistant mutation. MethodsA total of 296 patients with diagnosed chronic hepatitis B were selected from Febuary 2014 to April 2016 in Mianyang Central Hospital, including 145 cases of chronic hepatitis B (CHB), 101 cases of hepatitis B cirrhosis (HBC), and 50 cases of hepatocellular carcinoma (HCC). Three HBV genotypes (B, C and D) and eight drug-resistant mutation genes (rt180L, rt204M, rt207V, rt236N, rt250M, rt181A, rt184T and rt202S) were detected by PCR-reverse dot blot method. In addition, total oxidative stress (TOS), and total antioxidant status (TAS) were measured, on the basis of which oxidative stress index (OSI) was calculated. Furthermore, the differences of TOS, TAS and OSI levels were compared between different liver diseases, different genotypes or drug-resistant mutation, and also the correlations were analyzed between HBV genotype, drug-resistant mutation, patient’s oxidative stress status and disease severity. ResultsSerum TOS and OSI levels, HBV-B/C ratios and drug-resistant mutation rates increased gradually with the severity of liver disease (CHB < HBC<HCC, P < 0.05). Serum TAS levels decreased with degree of severity of the disease, but there was no statistical difference between CHB group and HCC group. Except TAS levels in patients at PHC group, compared with patients without mutation in HBV, the patients with drug-resistant mutation had higher TOS and OSI levels, but lower serum TAS levels (P < 0.05). Drug-resistant mutation rate was positively correlated with TOS (r = 0.476, P < 0.001) and OSI (r = 0.441, P < 0.001) levels, but negatively correlated with TAS level (r = −0.249, P < 0.001), except TAS level in patients at PHC group. In addition, the number of mutation sites was positively correlated with disease severity (γ = 0.614, P < 0.001). ConclusionsThere are different degrees of oxidative damage in patients with HBV-induced liver disease, and the degree of the damage depends on HBV genotypes and drug-resistant mutations. Therefore, oxidative stress parameters might be useful indicators of progression of HBV-induced liver disease in patients.