Hepatitis Activity Index Score Research Articles

Predictors of eligibility for reimbursement of antiviral treatment in HBe-Ag negative chronic hepatitis B patients with high ALT levels

Background/Aim: A liver biopsy is required for the reimbursement of antiviral therapy in Hepatitis B e-antigen (HBe-Ag) negative chronic hepatitis B patients. Liver biopsy is an invasive procedure with potential complications, such as bleeding, pain, pneumothorax, and even death. The study aimed to evaluate simple and non-invasive parameters that may help predict histological criteria that would be eligible for antiviral treatment reimbursement.
 Methods: HBeAg-negative chronic hepatitis B patients with alanine transaminase (ALT) levels > upper normal limit (40 IU/L) and HBV DNA viral load > 2000 IU/ml who underwent liver biopsy were enrolled in this retrospective cohort study. ALT, aspartate aminotransferase (AST), alpha-fetoprotein (AFP) values, hepatitis B virus (HBV) DNA levels, platelet count, and hepato-steatosis grade based on ultrasonography were used to predict the eligibility for antiviral therapy reimbursement. Eligibility for reimbursement of antiviral treatment regarding histological criteria defined by National Social Security Institution is based on the hepatitis activity index (HAI) score ≥ 6 and/or fibrosis score ≥ 2 according to Ishak’s scoring system.
 Results: One hundred and fifteen patients were included in the study; 79 patients (68.7%) were male. The mean age of patients was 46.51 (11.39). Sixty-two patients (53.9%) had a fibrosis score ≥ 2, and 80 (69.6%) patients had an HAI score ≥ 6. Ninety-two (80%) of the patients fulfilled histological criteria for antiviral treatment reimbursement. Multivariate analysis revealed that age and platelet count were independent predictors of eligibility for antiviral treatment reimbursement. The platelet count cut-off point was 198 x 109 /L for predicting eligibility for antiviral treatment reimbursement.
 Conclusion: Most patients (92/115, 80%) with high ALT and DNA viral load were eligible for antiviral treatment reimbursement. Platelet count and age may be used as simple non-invasive parameters for predicting the eligibility for antiviral treatment reimbursement in terms of histological findings.

Hepatitis Activity Index and its Clinical and Biochemical Parameters in Liver Diseases- A Retrospective Study

Introduction: Hepatitis Activity Index (HAI) is a scoring system devised by Ishak K et al., for grading and staging chronic hepatitis. The HAI provides a numerical score that is both objective and reproducible, it may be useful as either an alternative or supplement to the use of conventional pathological terminology in the study and management of chronic hepatitis patients. Aim: To assess the efficiency of HAI scoring in the non neoplastic liver diseases by relating it with the clinical and biochemical parameters. Materials and Methods: This retrospective study was conducted in the Department of Pathology at Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India, from 2010 to 2015. A total of 57 (58%) neoplastic cases and 41 (42%) non neoplastic cases were retrieved. The data was reassessed, HAI score and grade was noted and compared with the clinical and biochemical parameters. Chronic liver disease was classified as chronic viral hepatitis {Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV)} or cirrhosis. Alkaline phosphatase levels, Serum Glutamic Oxaloacetic Transaminase (SGOT) levels , Serum Glutamic Pyruvic Transaminase (SGPT) levels were analysed. Descriptive analysis was done and the data was represented as frequency and percentage in Microsoft Excel. Results: Among the non neoplastic cases, 21 (51%) belonged to hepatitis and cirrhosis and 20 (49%) belonged to others. In patients with high alkaline phosphatase levels, the predominant HAI score was 4. In cases with high SGOT levels, the predominant HAI score was 5 and 6. In cases with high SGPT levels, the HAI score was 5,6, and 7. Conclusion: The HAI is useful in assessing the extent of active inflammation. It gives an objective guideline to the treating physician. The HAI score in combination with clinical and biochemical parameters offers a better insight into disease severity.

Prior Trans-arterial chemoembolization - A protective factor against rapid HCV recurrence post liver transplant in patients with HCV with HCC? - A Retrospective Cohort Study

BackgroundHCV recurrence after liver transplant is nearly universal and results in progressive fibrosis, cirrhosis, graft loss, retransplantation and mortality. There are very few studies comparing impact of pretransplant HCC therapies either as a bridge to transplant or to downstage like TACE, hepatectomy, RFA, PEI on HCV recurrence post transplant. Primary aim of the study was studying prognostic factors associated with HCV recurrence including pre transplant HCC therapies. Material and methodsAll the patients who have undergone living donor liver transplantation at Kaohsiung Chang gung memorial hospital, Taiwan for HCV related HCC between July 2002 and June 2012 were analyzed retrospectively. Severity of HCV histological recurrence was categorized according to the ISHAK hepatitis activity index score. Rapid HCV recurrence was defined ISHAK hepatitis activity index (HAI) score greater than 4 at one year. Statistical analysis was done using SPSS version 21. (IBM). ResultsOne hundred and nine patients with HCC associated with HCV undergo living donor liver transplant from July 2002 to June 2012. Median follow up time was 31 months. Forty nine patient had significant hepatitis c recurrence at the end of one year (HAI >4) and were included in study group.60 patients without significant hepatitis c recurrence were included in control group. On univariate analysis patients who did not undergo pre-transplant trans arterial chemoembolization (0.035), primary transplant (without prior hepatectomy) (p = 0.031), high meld score (p = 0.036), high viral load pretransplant (0.007), High AFP levels (0.013) were significantly associated with rapid histological recurrence of HCV (HAI greater than 4 at one year post transplant). Total 61 patient underwent prior transarterial chemoembolization, 22 of these patients developed significant HCV recurrence while 39 patient did not developed HCV recurrence. On multivariate analysis only patient who did not undergo TACE were significantly associated with rapid histological recurrence of HCV (odds ratio 3.310, p = 0.018 95% confidence interval 1.22–8.94). ConclusionPrior TACE do not increase post transplant HCV recurrence but may be beneficial for it.

Efficacy of autologous mesenchymal stem cell transplantation in patients with liver cirrhosis.

Because of several limitations and complications of liver transplantation, new alternative treatment modalities are required for patients with liver cirrhosis. Many study results encourage the use of autologous bone marrow-derived mesenchymal stem cells for liver diseases. In this study, we assessed the impact of autologous mesenchymal stem cell transplantation on liver tissue and liver chemistry. Twenty-five patients with biopsy-proven liver cirrhosis were enrolled in the study. Patients received 1×106 autologous mesenchymal stem cells/kg via a peripheral vein. Biochemical parameters were checked monthly. Periodical radiological screening and liver biopsies before mesenchymal stem cell transplantation were performed after 6 months. Liver specimens were assessed by a pathologist. No side effect was observed and the mesenchymal stem cell transplantation procedure was well tolerated. Twelve patients completed the study. In 8 patients, improvements in Model for End-Stage Liver Disease (MELD) scores were observed. Serum albumin levels markedly increased in the third month. In patients with non-responder hepatitis C, HCV RNA levels both became negative after mesenchymal stem cell transplantation. Histopathological examinations of liver tissues before and at 6 months after transplantation revealed no change in liver tissue regeneration or fibrosis. However, in 5 patients, hepatitis activity index scores decreased. Autologous mesenchymal stem cell transplantation via peripheral vein is safe and feasible. Consecutive liver biopsy examinations suggested that mesenchymal stem cells could not reach the liver in a sufficient amount. Improvement in patients and clearance of HCV RNA may have occurred through immunomodulatory mediators secreted by transplanted mesenchymal stem cells, namely the "endocrine" effect.

Is Early Recurrence of Hepatitis C Associated With Biliary Anastomotic Stricture After Liver Transplantation?

While the main effect of hepatitis C virus (HCV) is hepatitis, HCV is also known to cause a variety of systemic immunologic inflammatory abnormalities. The effect of HCV infection on the biliary tract after liver transplantation (LT) is not well understood. The aim of the current study is to determine if recurrence of hepatitis C affects biliary complications after LT, with special reference to late biliary anastomotic strictures (LBAS). A total of 688 consecutive adult LT recipients with a choledochocholedochostomy without T-tube placement between 1990 and 2005 were reviewed. Biliary anastomotic stricture was confirmed by endoscopic retrograde cholangiopancreatography. LBAS was defined as stricture that occurred 30 days or more after LT. Early HCV recurrence was defined as recurrence within 6 months after LT. LBAS occurred in 55 patients (8% of total). Patients with HCV infection had a higher occurrence of LBAS than non-HCV patients (11% vs. 5%, P=0.0093). Among HCV patients, those with early HCV recurrence had an exceedingly high rate of LBAS (16%). In multivariate analyses, early recurrence of hepatitis C (P<0.0001), as well as occurrence of hepatic artery thrombosis (P=0.0018) and prolonged cold ischemic time (P=0.034), were independent risk factors affecting LBAS. Among HCV patients, those with LBAS had a significantly higher hepatitis activity index score (3.1 vs. 1.4, P<0.0001) and fibrosis stage (0.9 vs. 0.4, P<0.0001) as compared to patients without LBAS. Patients with early recurrence of HCV have increased occurrence of late biliary anastomotic stricture after liver transplantation.

Significance of hepatitis B virus surface antigen, hepatitis C virus expression in hepatocellular carcinoma and pericarcinomatous tissues

To investigate the correlation between hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) expression in hepatocellular carcinoma (HCC), the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein (AFP) level. The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immuno-histochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index (HAI) score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups: patients positive for HBsAg (HBsAg group), patients positive for HCV (HCV group), patients negative for both HCV and HBsAg (NBNC group) and patients positive for both HBsAg and HCV (BC group). The BC group had significantly higher HAI scores than the other three groups. (BC > HCV > HBsAg > NBNC). HBV and HCV virus infection was positively correlated with HAI (r(s) = 0.39, P = 0.0001). The positive rate of AFP (85.7%) and the value of AFP (541.2 ng/mL) in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate (53.3%) of AFP and the value of AFP ( 53.3 ng/mL) in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP(r(s) = 0.38, P = 0.0001). The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman's rank correlation analysis, we can conclude that the severity of virally induced inflammation is correlated with HBsAg and HCV expression in HCC tissues and noncancerous tissues. Prior co-infection of HBV in HCV patients may be an adverse risk factor for intrahepatic inflammation.

Preoperative assessment of multicentric occurrence in synchronous small and multiple hepatocellular carcinoma based on image-patterns and histological grading of non-cancerous region.

Recent studies have shown that the prognosis of patients with multicentric occurrence (MO) of hepatocellullar carcinoma (HCC) after curative resection, whether synchronous or metachronous, is significantly better than that of patients with intrahepatic metastasis (IM). We attempted to elucidate a group with high probability of MO of HCC by comparing the preoperative ultrasonography (US), computed tomography during arterial portography (CTAP) and CT arteriography (CTA) images with the histological grading of the non-cancerous region of the liver. The imaging and pathological characteristics of 97 nodules in 45 patients diagnosed as having small (<5cm) and oligonodular HCCs preoperatively were investigated. Histological diagnoses were as follows: 18 MO, 23 IM, and 4 unclassified (HCC with benign nodule). Histological grade of the liver tissue was assessed using the hepatitis activity index (HAI) score. No significant differences in tumor location and the mean size of co- or daughter nodules were noticed between the MO and IM patients. Of the 38 nodules in the MO patients, 20 were diagnosed as hyperechoic lesions on US, 20 as negative enhanced lesions on CTA and 12 as having positive portal flow on CTAP. A comparison of image-patterns between the synchronous nodules revealed that the MO group showed different images in at least one imaging technique, whereas in most IM patients similar images were produced by two or three imaging techniques. Moreover, all MO patients had an [Formula: see text], although more than half the IM patients had an [Formula: see text]. In patients with small and oligonodular HCCs, the nodules are highly likely to display MO, when showing both 1 or more different image patterns among US, CTA and CTAP and severe hepatitis such as HAI score >/=8.

Progression of liver fibrosis in patients with chronic hepatitis C after orthotopic liver transplantation.

Hepatitis C virus (HCV)-related cirrhosis is the leading indication for orthotopic liver transplantation (OLTx). HCV recurrence is universal after OLTx, with a highly variable course. This study aimed to find factors that affect progression of fibrosis in recurrent HCV. Fifty-eight HCV patients underwent OLTx at our center who were selected on the basis of available preOLTx serum or explanted liver sample and liver biopsy obtained at least 6 months postOLTx. All liver biopsies were performed when clinically indicated and were scored using the modified Hepatitis Activity Index (HAI). Primary immunosuppression consisted of tacrolimus and prednisone. The group included 41 males (mean age 49.6 years). HCV genotype distribution was 1a, 31 (53%); 1b, 16 (28%), and others 11 (19%). The mean follow-up was 53.1 months. Patients with genotype 1a (n=31; mean 46.3 months) had significantly lower fibrosis-free survival analyzed by the presence of fibrosis stages 5 and 6 when compared with other genotypes (n=27; mean 60.1 months; P=0.0088, log rank test). Mean HAI scores were significantly higher in HCV genotype 1a, although there were no differences in survival between genotypes. Similarly, patients with cytomegalovirus (CMV) infection postOLTx (n=4) had a higher fibrosis progression rate compared with those without CMV (n=54) (mean fibrosis-free survival 29.0 vs. 53.0 months P=0.0004, log-rank test). Human leukocyte antigen matching and rate of acute rejection did not influence progression of fibrosis. Patients with HCV genotype 1a and those developing CMV postOLTx have a higher rate of hepatic fibrosis progression after OLTx for HCV-related chronic liver disease.

Determinants for sustained HBeAg response to lamivudine therapy

There are inconsistent data on the durability of hepatitis B e antigen (HBeAg) seroconversion after lamivudine is discontinued. The aim of this study was to examine the determinants for sustained HBeAg response to lamivudine therapy. Both host and viral factors as well as the drug factor were compared between 43 patients with sustained HBeAg response and 39 patients whose response was not sustained. All of them received a mean period of 16 months (range, 3-55 months) lamivudine therapy and had achieved complete response (HBeAg seroconversion plus HBV DNA seroclearance by hybrid capture assay and normal alanine aminotransferase [ALT]) and were followed-up for a mean period of 44 months (range, 12-88 months). Stepwise logistic regression model was used to estimate the sustained response on the presence of the following variables: age; gender; pretherapy ALT; total bilirubin and HBV DNA levels; time to HBeAg seroconversion; additional lamivudine treatment after HBeAg seroconversion; total duration of treatment; hepatitis activity index scores; periportal, intralobular, and portal inflammation and fibrosis scores; scores excluding fibrosis; status of precore mutation; basal core promoter mutation; and genotype. The results showed that genotype (OR, 5.922; 95% CI, 1.611-21.768; P =.007), age (OR, 0.943; 95% CI, 0.891-0.997; P =.040), and additional treatment (OR, 1.097; 95% CI, 1.028-1.171; P =.005) were independent factors to sustained HBeAg response. Further categorical analysis disclosed that patients with genotype B, age < or =36 years, and additional lamivudine treatment over 8 months have higher sustained response. In conclusion, HBV genotype, age, and additional treatment are the major determinants for the sustained HBeAg response to lamivudine therapy.

Postoperative prediction of and strategy for metastatic recurrent hepatocellular carcinoma according to histologic activity of hepatitis

The hepatitis activity index (HAI) score describes the histologic status of accompanying chronic hepatitis and was established by pathologists. The aim of this study was twofold: 1) to investigate the correlation between intrahepatic metastatic recurrence (IM) and the HAI score of the noncancerous region of the liver and 2) to estimate the usefulness of postoperative preventive chemotherapy in patients with hepatocellular carcinoma (HCC). The study included 158 consecutive patients who underwent curative resection for HCC and had been observed for > 1 year. Based on the HAI scores of the noncancerous region the patients were classified into 3 groups: those with mild hepatitis (n = 33) (i.e., with HAI scores of 0-5), those with moderate hepatitis (n = 77) (with HAI scores of 6-9), and those with severe hepatitis (n = 48) (those with HAI scores of > or = 10). In addition, a prospective randomized trial of postoperative adjuvant chemotherapy was performed for 21 patients with moderate hepatitis. The patients in the moderate hepatitis group were found to be at higher risk for IM recurrence within 2 years after HCC resection compared with those patients in the mild (P = 0.05) and severe (P < 0.01) hepatitis groups. The incidences of more than two tumors and portal vein involvement in patients with moderate hepatitis were much higher than in those patients with mild or severe hepatitis. Multivariate analysis showed that intraoperative bleeding volume, the number of nodules, portal vein involvement, and moderate hepatitis were independent predictive factors for IM recurrence free survival. Ten patients with moderate hepatitis had received postoperative intrahepatic arterial chemotherapy (2-3 courses with a maximum dose of 80 mg of cisplatin and 10 mg of mitomycin C at 1-month intervals) for the last 3 years. Although the number of patients was small, the therapy improved the disease free survival rate significantly compared with 11 patients who received no therapy. The patients with moderate hepatitis (HAI score of 6-9) had the highest rate of IM recurrence among the three HAI groups. Postoperative hepatic arterial chemotherapy may be useful in improving the rate of disease free survival after surgery among these patients.

Outcome of liver transplantation in hepatitis C virus–infected patients who received hepatitis C virus–infected grafts

Background & Aims: The present organ shortage has brought into question the suitability of hepatitis C virus (HCV)-positive grafts. This study reviewed the outcome of such transplantations in our institution. Methods: Twenty-three HCV-positive patients who underwent orthotopic liver transplantation (OLT) for end-stage liver disease with HCV-positive grafts in 1992–1995 were studied. Only patients who survived more than 30 days were included in the analysis. Control group included 169 patients who underwent transplantation for HCV-related cirrhosis and received HCV-negative organs. Results: Patients who received HCV-infected organs had a cumulative survival rate of 89% and 72% at 1 and 5 years, respectively, vs. 88% and 73% for the control group (NS). There was no difference in graft survival, incidence of cirrhosis, mean hepatitis activity index score, fibrosis, or mean activity of serum transaminases. There was a trend toward lower incidence of recurrent hepatitis C in the study group compared with control (21% vs. 23% at 1 year and 47% vs. 64% at 5 years; NS). Patients in whom the donor strain became predominant after transplantation had significantly longer disease-free survival than patients who retained their own HCV strain ( P < 0.003). Conclusions: HCV-infected livers transplanted into HCV-infected recipients do not appear to convey a worse outcome in the initial years after OLT than HCV-negative grafts. GASTROENTEROLOGY 1999;117:149-153

High prevalence of HCV-RNA in the saliva cell fraction of patients with chronic hepatitis C but no evidence of HCV transmission among sexual partners.

The aims of this study were to evaluate the prevalence of HCV-RNA in different fractions of saliva taken from patients with chronic hepatitis C, to establish whether virologic parameters or disease severity exert any influence on the detectability of HCV-RNA in saliva, and to evaluate the prevalence of HCV infection in partners of HCV-infected subjects with respect to the presence of HCV-RNA in saliva. Sera samples and different fractions of saliva (whole saliva, surnatant, and cell fraction) from 48 subjects (45 with chronic hepatitis C and three healthy anti-HCV+ carriers) were examined for HCV-RNA by RT nested PCR and DEIA hybridization. HCV-RNA-positive sera were also tested for genotype and viral titer (bDNA2 method). Twenty-seven stable sexual partners (25 females and 2 males) were screened for anti-HCV antibodies at least twice over a minimum of 12 months. HCV-RNA was detected in the sera of 39/45 patients and of 22/39 viremic patients. In all of the latter, the presence of HCV-RNA was restricted to the cell fraction. Viral titer was significantly higher in patients with HCV-RNA in saliva than in those without (12.3 x 10(6) versus 4.6 x 10(6) eq/ml, P < 0.01). HCV-RNA positivity was unrelated to genotype, duration of disease, Hepatitis Activity Index scores or transaminase levels. Anti-HCV was positive in one of 13 sexual partners of patients with HCV-RNA in saliva and in 1/14 of those without (P = NS). In conclusion, HCV-RNA is detectable in the cell fraction of saliva in a high proportion of highly viremic patients with chronic hepatitis C, but its presence does not seem to be associated with an increased risk of HCV transmission among sexual partners.

The influence of hepatitis C virus genotypes on the outcome of liver transplantation.

The aim of this study was to report the influence of hepatitis C virus (HCV) genotypes and HLA matches on the outcome of liver transplantation, hepatitis recurrence, and progression to cirrhosis after transplantation. HCV genotypes were determined from pretransplantation sera and/or liver explant tissues from 202 patients with HCV-related end-stage liver disease. One hundred fifty patients with known infecting genotype for whom posttransplantation biopsy specimens were available or who had normal results of liver injury tests constituted the group analyzed. Patients were followed up for up to 4.5 years. Hepatitis activity index scores at the time of disease recurrence were used to assess disease activity. Cirrhosis was diagnosed by using histological evidence. The number of HLA matches with respect to A, B, DR, and DQ loci was determined. The rates of hepatitis recurrence were 25% and 75% at 1 year and 4 years, respectively; Kaplan-Meier survival analysis did not reveal significant differences between the infecting genotypes with respect to overall rates of survival or recurrence of hepatitis. At hepatitis recurrence, hepatitis activity index scores did not differ between the genotype groups. The distribution of infecting genotypes among the 7 patients who developed cirrhosis is reflective of pretransplantation distribution. Neither HLA site-specific nor total matches affected the rates of survival or disease recurrence. The infecting HCV genotype had no influence on the incidence or severity of recurrent hepatitis, rate of survival, or development of cirrhosis. HLA matching does not influence transplantation outcome for HCV-related disease.

Repeated Laparoscopy of 27 Patients with Chronic Non‐A, Non‐B Hepatitis Showing a Complete Response to IFN Therapy

Abstract:The laparoscopies and liver histology results of 27 patients with chronic non‐A, non‐B hepatitis who had a complete response to the longterm administration of IFN‐alpha were studied. When comparing the liver surface before IFN therapy, code number 1 using Shimada's classification, i. e., whitish markings, increased from 14.0% to 57.9%, code number 2, i. e., dilated vessels, decreased from 34.9% to 10.6%, code number 4, i. e., reddish markings, decreased from 11.6% to 2.6%, and code number 7, i. e., patchy markings, decreased from 16.3% to 2.6%. Improvement of the liver edge dullness and a decrease of the liver consistency after the IFN therapy were also observed in 40. 7%, and 14. 8% of the patients, respectively. Liver histology after the therapy showed normal liver or liver fibrosis in chronic hepatitis patients, and liver cirrhosis with active hepatitis developed into liver cirrhosis without activity. The hepatitis activity index score decreased significantly after the therapy. The present report seems to be the first which describes detailed changes of the liver surface before and after IFN therapy in patients with chronic non‐A, non‐B hepatitis who had a complete response to the therapy