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BACKGROUND & AIMS: In autoimmune hepatitis (AIH), normal levels of transaminases and IgG define biochemical remission and are considered the best surrogate markers for histological remission. This study assessed whether this also applies to patients with AIH cirrhosis. METHODS: In this European multicentric study, we included 125 biopsies from 113 patients with AIH and histologically proven cirrhosis; 105 biopsies from 104 patients with AIH without cirrhosis served as controls. Biochemical parameters were available within 4 weeks of biopsy. AIH activity was graded according to the modified Hepatitis Activity Index (mHAI), with mHAI ≥4/18 considered to indicate risk of disease progression. RESULTS: In total, 47 out of 125 liver biopsies were obtained from patients with AIH cirrhosis and normal ALT levels at time of biopsy. Only 26% (12/47) of those livers showed histological remission (mHAI <4/18), whereas 36% (17/47) showed moderate to high histological activity (mHAI ≥6/18). In patients with noncirrhotic AIH, 88% (46/52 biopsies) of cases with normal ALT levels had histological remission and only 4% (2/52) had an mHAI ≥6/18 (p <0.001). The addition of IgG to define complete biochemical remission only slightly improved the association with histological remission in the limited number of patients with AIH cirrhosis available for analysis [29% (5/17) of biopsies with mHAI <4/18]. ALT correlated closely with mHAI in AIH without cirrhosis but poorly in AIH with cirrhosis. CONCLUSIONS: In contrast to patients with noncirrhotic AIH, in patients with AIH cirrhosis, who are at risk of disease progression, normal ALT levels and potentially also complete biochemical remission are poor surrogate markers of histological remission. Thus, new biomarkers are needed to monitor disease activity and progression in patients with AIH cirrhosis. LAY SUMMARY: Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that usually responds to immunosuppressive therapy. Serum transaminases and IgG levels within the normal ranges define complete biochemical remission and are considered as surrogate markers for histological disease activity. Here, we show that those biochemical markers are not sufficient to indicate low disease activity in patients with AIH and already established cirrhosis. Consequently, until better biomarkers for disease activity are found, only liver biopsy can reliably indicate disease activity in the presence of cirrhosis. Additional investigations, such as measurements of liver stiffness, should be undertaken to monitor non-invasively for disease progression in patients with AIH and established cirrhosis.

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BACKGROUND: The antiviral immune response is the main cause of hepatocyte damage and inflammatory necrosis. The serum free light chain, reflecting the immune function of B-cells, is strongly associated with inflammation and disease activity. We aimed to investigate the association of serum free light chain with the progression of chronic hepatitis B. METHODS: A total of 208 eligible chronic hepatitis B patients who had undergone a liver biopsy were studied. Serum free light chains of all patients were measured by turbidimetry using an immunoassay. Liver histology was assessed according to the METAVIR scoring system (which grades the stage of fibrosis on a five-point scale, F0 = no fibrosis to F4 = cirrhosis, and histological activity on a four-point scale, A0 = no activity to A3 = severe activity). The association of serum free light chains with histological activity and fibrosis progression was evaluated. RESULTS: The concentration of serum free light chains in CHB patients increased gradually with histological activity and fibrosis progression. The intensity of histological activity was significantly correlated with the serum free kappa chain (r = 0.658, P < 0.001) and the serum free lambda chain (0.675, P < 0.001). The stages of fibrosis were correlated with the serum free kappa chain (r = 0.683, P < 0.001) and serum free lambda chain (0.664, P < 0.001). After adjusting for age, sex and other synergic factors, the serum free kappa chain remained a potential risk factor, but the serum free lambda chain was no longer associated with liver cirrhosis. Similar to FIB-4 and RPR, the serum free kappa chain exhibited excellent performance in the prediction of liver cirrhosis. The AUCs of serum free Kappa chain, FIB-4 and RPR were 0.873, 0.880 and 0.895, respectively, which were significantly higher than those of the AAR and APRI (0.718 and 0.746). CONCLUSION: Our work revealed that serum free light chains were associated with histological activity and cirrhosis in chronic hepatitis B, which could play a crucial role in the immunopathogenesis of HBV-associated cirrhosis. In addition, free kappa light chain could be a useful predictor of liver cirrhosis.

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BACKGROUND: Ulcerative colitis (UC) is an inflammatory disease of the intestine. The genetics factors play an important role in the pathogenesis of UC. SPARC exacerbates colonic inflammatory symptoms in dextran sodium sulphate-induced murine colitis. The aim of the study was to measure the gene expression and intestinal production of SPARC in patients with UC and controls as well as, to determine its correlation with histological activity. METHODS: We included 40 patients with confirmed diagnosis of UC, and 20 controls without endoscopic evidence of any type of colitis or neoplasia. The relative quantification of the gene expression was performed by real time PCR. GAPDH was used as housekeeping gene for normalization purposes and quality controls. Protein expression was determined by immunohistochemistry. RESULTS: The gene expression of SPARC was increased in patients with active UC vs in remission UC and vs. controls (P = 0.005). There was no significant difference between patients with remission UC and controls. The overexpression of SPARC in patients with active UC correlated significantly with mild histological activity (P = 0.06, OR = 7.77, IC = 0.77-77.9) moderate (P = 0.06, OR = 8.1, IC 95%=0.79-82.73), and severe (P = 0.03, OR = 6.5, IC 95%=1.09-38.6). Double positive SPARC+/CD16+ cells were localized mainly in submucosa, muscular layer, and adventitia, and in perivascular inflammatory infiltrates in patients with active UC. CONCLUSION: The gene and protein expression of SPARC is increased in active UC. SPARC could be a marker of intestinal inflammation and its expression correlates with histological activity.

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BACKGROUND AND AIMS: Autoimmune hepatitis presenting as acute on chronic liver failure (AIH-ACLF) is a novel entity with limited data on clinical course and management. We assessed outcomes in patients of AIH-ACLF with no extrahepatic organ dysfunction/failure when administered steroids. METHODS: In this retrospective analysis, clinical data, laboratory parameters, liver biopsy indices and prognostic scores such as model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores at baseline were computed for patients with AIH-ACLF and compared across strata of incident infections and transplant-free survival. The primary outcome was 90-day transplant-free survival. Biochemical remission was assessed, and predictors of end points were identified. RESULTS: Twenty-nine patients of AIH-ACLF were included with a median follow-up of 4 months. The 90- and 180-day transplant-free survival rates of 55.2 [95% confidence interval (CI): 39.7-76.6]% and 30.2(95% CI: 16.7-54.6)%, respectively, were attained on steroids. Three patients (10.3%) underwent liver transplant while 16 (55.2%) deaths occurred. Infections developed in 12 patients (41.3%), leading to worsening prognostic scores, new onset organ dysfunction/failure and 11 deaths. Seven of ten patients (70%) in the transplant-free survivor group attained biochemical remission on follow-up. The MELD score<24 (sensitivity: 68.4%; specificity: 80%) and CTP<11 (sensitivity: 78.9%; specificity: 90%) had best predictive value for survival, in addition to decrease in the MELD score at 2 weeks (sensitivity: 78.9%; specificity: 70%). CONCLUSION: Patients with AIH-ACLF have a morbid disease course despite treatment with steroids. Patients with no extrahepatic organ failure with good baseline prognostic scores may be administered steroids with close monitoring for change in MELD over 2 weeks.

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BACKGROUND AND AIMS: Patients with chronic hepatitis B (CHB) are at an increased risk of disease progression. The influence of hepatic steatosis (HS) to liver fibrosis was controversial. We aim to investigate the association between HS and liver fibrosis and explore the predicting factors for advanced fibrosis. METHODS: CHB patients undergoing liver biopsy with complete assessments of HS, necroinflammation grade [histological activity index (HAI) score], and fibrosis stage were retrospectively recruited. Logistic regression analysis was performed to determine the factors associated with advanced liver fibrosis. RESULTS: In this cohort of 672 patients, 342 (50.9%) had HS and 267 (39.4%) were of advanced liver fibrosis. Age [odds ratio (OR) 1.026, 95% confidence interval (CI) 1.007-1.046, p = 0.008], body mass index (BMI, OR 1.091, 95% CI 1.026-1.159, p = 0.005), genotype (C vs. B) (OR 2.790, 95% CI 1.847-4.214, p < 0.001), platelet (OR 0.986, 95% CI 0.982-0.991, p < 0.001), and HAI score (OR 1.197, 95% CI 1.114-1.285, p < 0.001) were independent factors for advanced liver fibrosis in multivariate logistic regression analysis. HAI score was also a significantly associated factor for significant liver fibrosis in non-cirrhotic subpopulation (OR 1.578, 95% CI 1.375-1.810, p < 0.001). HS was not related to advanced/significant liver fibrosis in overall/non-cirrhotic population (p > 0.05). CONCLUSIONS: Significant or advanced liver fibrosis is associated with grade of necroinflammation but not with HS in CHB patients.

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Objective:To study the intestinal mucosal state of ulcerative colitis (UC) through UC endoscopic scores and to investigate the correlation between the endoscopic scores and clinical activity and histological scores.Methods:A retrospective analysis was performed on data of 152 patients who underwent colonoscopy or sigmoidoscopy in Nanjing Drum Tower Hospital from January 2014 to September 2019. The results were graded with 7 endoscopic scores, namely, Mayo endoscopic score(MES), modified Baron score(MBS), endoscopic activity index(EAI) , Sutherland index(DAI or UCDAI) , Rachmilewitz endoscopic index(REI), Lemann endoscopic index (LEI), and ulcerative colitis endoscopic index of severity(UCEIS). Spearman correlation coefficients between endoscopic score and partial Mayo scores, Truelove-Witts disease severity score and Nancy index (NI), Robarts index (RHI) and Geboes score (GS) were calculated respectively. Consistency of each endoscopic score among different observers was analyzed.Results:Except for the weak correlation between DAI and Truelove - Witts classification ( r= 0.469, P < 0.001), all other endoscopic scores were moderately positively correlated with clinical activity scores with significance( all P<0.001). However, the correlation between 7 endoscopic scores and histological scores was weak ( P<0.001). Except that the consistency of MBS among observers was medium, those of MES, DAI and LEI among observers were poor, and those of UCEIS, EAI and REI among observers were worse ( P<0.001). Conclusion:Endoscopic scores were moderately correlated with clinical activity indexes and weakly correlated with histological scores. However, patients with endoscopic remission may have histologic inflammatory activity, so attention should be paid to histological mucosal healing after endoscopic remission. The consistency of all 7 endoscopic scoring stystems among observers was low, and the repeatability was poor.

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BACKGROUND AND STUDY AIMS: The clinical significance of serum parameters of iron metabolism and hepcidin in liver disease remains unknown. Therefore, this study aimed to evaluate the association of serum hepcidin levels with fibrosis stage and serum iron parameters in patients with chronic hepatitis B (CHB). PATIENTS AND METHODS: This cross-sectional study included 126 treatment-naïve patients with CHB (median age, 39.0 years; 64.3% males) who were positive for hepatitis B surface antigen and 23 healthy controls (median age, 33.0 years; 52.2% males). Data on patient demographics, serum hepcidin levels, liver function tests and serum iron parameters and liver biopsy findings including fibrosis grade, histological activity index (HAI) and liver iron level were recorded. RESULTS: The median (minimum-maximum) serum hepcidin levels were significantly lower in the CHB group than in the control group [71.2 (13.3-672.7) vs. 657.5 (201.7-2714.2) pg/mL, p < 0.001]. Higher fibrosis stage was associated with higher transferrin saturation (p = 0.029), serum ferritin level (p < 0.001) and viral load (p < 0.001). Fibrosis stage and HAI were positively correlated with ferritin (r = 0.407, p < 0.001 and r = 0.415, p < 0.001, respectively) and transferrin saturation (r = 0.219, p = 0.026 and r = 0.290, p = 0.003, respectively) levels, whereas hepcidin level was negatively correlated with fibrosis stage (r = -0.175, p = 0.051), viral load (r = -0.209, p = 0.020) and ferritin level (r = -0.244, p = 0.006) level. There were no significant differences in serum iron level, total iron binding capacity and liver iron level among patients with different stages of fibrosis. CONCLUSION: Reduced hepcidin levels and elevated transferrin saturation and ferritin levels are linked to fibrosis severity and HAI in patients with CHB.

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BACKGROUND AND AIMS: The histological status of ulcerative colitis [UC] patients in clinical and endoscopic remission has gained space as an important prognostic marker and a key component of disease monitoring. Our main aims were to compare two histological indexes-the continuous Geboes score [GS] and the Robarts Histopathology index [RHI]-regarding their definitions of histological remission and response, and the ability of faecal calprotectin [FC] levels to discriminate between these statuses. METHODS: This was an analysis of three prospective cohorts including 422 patients previously enrolled in other studies. RESULTS: The two continuous scores [GS and RHI] were shown to be significantly correlated [correlation coefficient of 0.806, p < 0.001] and particularly close regarding their definition of histological response: 95% and 88% of all patients classified as having/not having [respectively] histological response according to RHI also did so according to GS. Moreover, median FC levels in patients with histological response were lower than those in patients without histological response [GS: 73.00 vs 525.00, p < 0.001; RHI: 73.50 vs 510.00, p < 0.001]; a similar trend was observed when FC levels of patients in histological remission were compared to those of patients with histological activity [GS: 76.00 vs 228.00, p < 0.001; RHI: 73.50 vs 467.00, p < 0.001]. FC levels allowed us to exclude the absence of histological remission [according to RHI] and absence of histological response [according to RHI and GS], with negative predictive values varying from 82% to 96%. However, optimization of the FC cut-off to exclude the absence of histological remission, as for the continuous GS, falls within values that resemble those of the healthy population. CONCLUSION: The continuous GS and RHI histological scores are strongly correlated in their definitions of histological response. An absence of histological remission could only be excluded at physiological levels of FC.

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BACKGROUND: Suppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab. METHODS: We conducted an open-label single-arm multicentre prospective study. At screening/baseline, week 6 (W6) and week 16 (W16), clinical and endoscopic activity (total Mayo score), histologic activity (Geboes index) and biomarkers were evaluated. RESULTS: From 38 patients, 34 (89.5%) completed W6 and 29 (76.3%) completed W16. Mean age (±SD) was 34.6 ± 12.6 years; 55.9% were female. At W16, 62.1% achieved clinical response. Patients with endoscopic activity at W6 (n = 20) had higher baseline sST2 (median, 24.5 versus 18.7 ng/ml, p = 0.026) and no decrease from baseline (median change, 0.8 versus -2.7, p = 0.029). At W6, sST2 levels correlated with endoscopic activity (rs = 0.45, p = 0.007) but not with histological activity (rs = 0.25, p = 0.151). The best cut-offs for endoscopic activity were sST2 = 16.9 ng/ml (sensitivity = 85%; specificity = 71%) and faecal calprotectin (FC) = 353 µg/g (sensitivity = 90%, specificity = 67%). Patients with histological activity at W6 (n = 27) had higher baseline ST2 levels (median, 23.0 versus 13.7 ng/ml, p = 0.035). sST2 did not correlate with FC or serum C-reactive protein. FC levels correlated with histological activity and baseline FC were higher when Geboes ⩾3.1 at W6. CONCLUSIONS: sST2 may be a surrogate biomarker of UC activity and therapeutic response as it correlates with endoscopic and clinical activity at W6 of golimumab treatment, and subjects with endoscopic and histological activity at W6 had higher baseline ST2 levels.

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BACKGROUND/PURPOSE: Dipeptidyl peptidase 4 (DPP-4) expression is directly associated with hepatic lipogenesis and liver injury in nonalcoholic steatohepatitis (NASH). This study has been designed to elucidate the histological improvement of NASH with the DPP-4 inhibitor sitagliptin. MATERIALS AND METHODS: In this open-label randomized control trial, paired liver biopsy was taken from 40 NASH patients. Sitagliptin 100 mg was given once daily to the SL group and no sitagliptin was given to the L group for 1 year. Patients from both groups were encouraged to exercise moderately and advised to avoid saturated fat, excessive sugar, soft drinks, fast food, and refined carbohydrates to reduce weight. RESULTS: Steatosis improved in the SL group (from 2.3±0.6 to 1.2±0.8; P=0.000) and the L group (from 2.1±0.6 to 1.6±0.9; P=0.008), ballooning decreased from 1.8±0.6 to 1.3±06 (P=0.002) in the SL group, but not in the L group. Nonalcoholic fatty liver disease activity score (NAS) attenuated in both groups: the SL group (from 5.8±0.9 to 3.9±1.4; P=0.000) and the L group (from 5.3±0.6 to 4.6±1.2; P=0.009). NAS improvement was much higher in the SL group (1.9±1.4) than in the L group (0.7±1.1) (P=0.006), with NAS improving by ≥2 in 13 patients from the SL group and five patients from the L group (P=0.01). Improvement was irrespective of diabetes. Regression analysis explored that sitagliptin had odds of 6.38 and weight reduction had odds of 4.51 for NAS reduction. CONCLUSION: Sitagliptin 100 mg once daily for 1 year ameliorates NAS by improving steatosis and ballooning, irrespective of diabetes. Sitagliptin has stronger efficacy than that of weight reduction.

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BACKGROUND: The aim of the study was to compare the prognostic value of histological and endoscopic activity in patients with ulcerative colitis (UC). METHODS: Patients in clinical remission for 1 year under treatment with mesalazine underwent a planned colonoscopy with biopsies. Histological activity was scored using the histological activity index (HAI). Endoscopic activity was scored using the Mayo endoscopic subscore (MES). The clinical course was evaluated measuring relapses needing steroids during a follow up of 3 years. RESULTS: A total of 52 patients were enrolled into the study and followed up for 3 years. At baseline 29 patients (55.77%) had no endoscopic lesions, and 17 patients (32.69%) showed no histological alteration. At 3 years of follow up, overall, 26 patients (50%) were still in steroid-free remission. Using univariate logistic regression analysis, both histological (HAI ⩾ 1) and endoscopic activity (MES ⩾ 1) were significantly associated with outcome, showing, respectively, a relapse risk (odds ratio [OR]) 16.4 times higher than histological remission (HAI 0) (96% confidence interval [CI]: 3.2-84.3) and 6.3 times higher with respect to endoscopic remission (MES 0) (96% CI: 1.9-21.3). After multivariate logistic regression analysis, histological activity was the only factor significantly associated with outcome (OR 10.2; 95% CI: 1.7-59.4). CONCLUSIONS: Histological activity has the most powerful prognostic value in predicting the need for steroids in patients with UC in stable clinical remission on mesalazine. It could be considered as a target of therapy in UC.

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A proportion of chronic hepatitis B patients with normal or only minimally elevated alanine aminotransferase (ALT) levels display significant histologic changes and would benefit from antiviral therapy. We aim to evaluate the histologic abnormalities seen in these patients and then determine which of them would most likely respond to peginterferon therapy. One hundred and thirteen hepatitis B e antigen (HBeAg)-positive patients with a normal or minimally elevated ALT level and moderate-to-severe histologic changes in their liver tissue were selected to receive peginterferon monotherapy and participate in a follow-up analysis. A multiple logistic regression analysis indicated that increasing age (P=.049) and lower hepatitis B virus (HBV) DNA levels (P=.038) were associated with significant histological abnormalities in patients with a normal or minimally elevated ALT. Our predictive model which incorporated HBeAg testing at treatment week 12 combined with hepatitis B surface antigen (HBsAg) testing at treatment week 24 was able to identify which patients with a normal ALT level would achieve a sustained virological response (SVR) (positive predictive value [PPV]: 66.7%, negative predictive value [NPV]: 90.0%). Lower HBsAg and HBeAg levels at treatment week 24 were associated with a SVR in patients with a minimally elevated ALT level (PPV: 100.0%, NPV: 100.0%). A liver biopsy and antiviral therapy should be strongly considered when treating HBeAg-positive patients with a normal or minimally elevated ALT level, low HBV DNA level, and aged >35 years. On-treatment quantification of combined HBsAg and HBeAg test results may be useful for predicting a SVR to peginterferon monotherapy in these patients.

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UNLABELLED: Chronic liver diseases may cause inflammation and progressive scarring, over time leading to irreversible hepatic damage (cirrhosis). As a result, the need to assess and closely monitor individuals for risk factors of components of matrix deposition and degradation, as well as the severity of the fibrosis using biomarkers, has been increasingly recognized. AIM: Our aim is to review the use of biomarker for diagnosing and defining the severity of liver fibrosis. METHODS: A systematic literature review was done using the terms "hyaluronic acid" and "liver fibrosis" as well as the name of each biomarker or algorithm known to be employed. PubMed and Google Scholar were searched, and English language articles indexed between January 2010 and October 2014 in which HA was used as a marker of liver fibrosis were retrieved, regardless of the underlying liver disease. Each author read the publications separately and the results were analyzed and discussed. RESULTS: Biomarkers offer a potential prognostic or diagnostic indicator for disease manifestation, progression, or both. Serum biomarkers, including HA, have been used for many years. Emerging biomarkers such as metalloproteinases have been proposed as tools that provide valuable complementary information to that obtained from traditional biomarkers. Moreover, markers of extracellular matrix degradation provide powerful predictions of risk. In order for biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in gender and ethnic origin are a necessity. CONCLUSIONS: This review attempts to provide a comprehensive analysis of the emerging risk biomarkers of liver fibrosis and to describe the clinical significance and analytical considerations of each biomarker pointing out sentinel features of disease progression.

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Objective To study the relationship between histological activity index and serum of tumor nec-rosis factor-α( TNF-α) ,peripheral blood T cell subsets in patients with chronic hepatitis B.Methods Histopatholog-ical examinations were performed in 237 patients with chronic hepatitis B and 12 controls.The histological activity index( HAI) were analyzed by knodels method.These patients were divided into the four groups according to histologi-cal activity index classification:the control group(n=12),mild group(n=67),moderate group(n=89),and severe group(n=81).The serum levels of TNF-αwere determined by ELISA,and peripheral blood T cell subsets were ana-lyzed by flow cytometry.Results The serum level of TNF-αin the mild group[(29.65 ±10.15)μg/L],moderate group[(38.96 ±7.32)μg/L]and severe group[(47.73 ±6.99)μg/L]were higher than those in the control group [(13.78 ±6.40)μg/L](q=14.38,19.97,24.83,all P<0.05),significant positive correlation lied between the histological activity index classification and the serum level of TNF-α(r=0.708,P<0.05).The rate of CD8+cells in the moderate group[(27.66 ±6.63)μg/L]and the severe group[(28.98 ±5.92)μg/L]were higher than those in the control group[(22.32 ±1.84)μg/L](q=3.84,4.76,all P<0.05),and the ratio of CD4+/CD8+in the moderate group(1.32 ±0.37) and the severe group(1.19 ±0.30) were lower than those in the control group(1.67 ±0.14) (q=4.20,5.72,all P<0.05),but the rate of CD8+cells and the ratio of CD4+/CD8+showed no significance among the mild group,moderate group and severe group.Conclusion TNF-αand disorder of cellular immunity may play an important role in the development and progression of intrahepatic vascular lesion.

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BACKGROUND & AIMS: Prevalence of serum autoantibodies in chronic hepatitis C (HCV) patients is higher than that in the general population. Interferon may induce autoimmune manifestations in patients treated with peg-interferon and ribavirin. Effect of autoantibody seropositivity and treatment response are limited and controversial. To detect the prevalence of serum autoantibodies in patients with chronic HCV and impact on histopathology and treatment response. METHODS: Retrospective study including 3673 Egyptian chronic HCV naïve patients enrolled in the Egyptian national programme for HCV treatment with pegylated interferon and ribavirin in the years 2007-2010. Antinuclear antibody (ANA) was determined by ELISA considered positive with a titre ≥ 1:40 by indirect immunofluorescence. ANA-positive patients pre treatment workup including serum aminotransferases, thyroid profile and liver biopsy, follow-up during treatment and sustained virological response (SVR) were assessed compared to ANA-negative patients. RESULTS: Serum ANA was positive in 1.6% of the studied patients. There were no statistically significant differences concerning the demographic, biochemical and histopathological data in ANA positive and negative patients. SVR was comparable between ANA-positive and ANA-negative patients (67.8% and 61.3% respectively). Follow-up treatment; ANA-positive patients' did not experience statistically significant haematological complications, flare-up of serum transaminases, thyroid dysfunction. No systemic autoimmune disorders developed during follow-up. CONCLUSIONS: ANA positivity is not a factor in chronic HCV disease progression and does not affect the treatment response. Pegylated interferon and ribavirin therapy is safe and effective in autoantibodies-positive chronic HCV patients with no need for further follow-up or worry during the treatment in absence of systemic autoimmune disorders.

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BACKGROUND AND AIM: Pegylated-interferon-alfa (PEG-IFN-α) with ribavirin is an established treatment in chronic hepatitis due to hepatitis C virus (HCV) (CH-C). Such treatment is expensive and in resource-poor countries such as India, alternative less expensive therapy is needed. METHODS: Multicenter randomized controlled trial comparing two treatment regimens (interferon-alfa-2b [IFN-α-2b] 3 million unit/day [MU/day] and ribavirin 1000 mg/day [I+R] vs IFN-α-2b 3 MU/day and glycyrrhizin 250 mg [I+G]) in CH-C. Viral, host characteristics and therapeutic responses were assessed (ICMR-6 months trial for chronic hepatitis-CTRI/2008/091/000105). RESULTS: One hundred and thirty-one patients meeting the inclusion criteria were randomized to I + G (n=64) or I+R (n=67) during the period February 2002 to May 2005. About 85% (I+G=53, I+R=58) completed 6 months of treatment and 89% of them (I+G=46, I+R=53) completed 6 months of follow-up after completion of treatment. Hepatitis C virus genotype 3 was the major type detected (71% patients). The mean log10 viral load (copies/mL), histological activity index, and fibrosis stage for all patients were 5.1 ± 0.98, 5 ± 2, and 2± 1.5, respectively. Sustained viral response (SVR) was significantly higher in I + R group than in I + G group (65.7% vs 46.9%, OR=2.2, P = 0.03). Treatment with I + G was associated with significantly lower frequencies of leukopenia (2% vs 17%, P <0.01) and anemia (8% vs 40%, P <0.001) as compared to treatment with I + R. CONCLUSION: Genotype 3 HCV infection with low viral load is prevalent in India. Daily IFN with ribavirin showed significantly better responses. Leukopenia and anemia were significantly more in ribavirin group. Responses observed with IFN + ribavirin were similar to the reported response rates with PEG-IFN suggesting that this modality may be considered as a cheaper alternative of treatment for chronic hepatitis C.

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Hepatitis B is one of the major causes of end-stage liver disease and liver cancer worldwide. A number of host and viral factors influence the disease course and outcomes. One such viral factor is hepatitis B virus (HBV) genotypes. There are eight major HBV genotypes described from various geographic regions of the world. Although direct sequencing appears to be the gold standard for HBV genotyping, it is expensive and laborintensive and therefore cannot be applied for routine clinical use. The newer molecular methods including serotyping have made genotyping easier and simple to apply to large number of samples rapidly. The data collected mainly over the last decade have suggested that HBV genotypes may have a bearing over the natural course of the disease and its response to therapy. This review summarizes the available literature and highlights how genotyping could be incorporated into routine clinical practice in order to improve delivery of care to HBV-infected individuals.

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AIM: To validate the clinical relevance of autofluorescence imaging (AFI) endoscopy for the assessment of inflammatory ulcerative colitis (UC). METHODS: A total of 572 endoscopic images were selected from 42 UC patients: 286 taken with white light imaging (WLI) and 286 with AFI from the same sites. WLI images were assessed for overall mucosal inflammation according to Mayo endoscopic subscore (MES), and for seven characteristic endoscopic features. Likewise, AFI photographs were scored according to relative abundance of red, green and blue color components within each image based on an RGB additive color model. WLI and AFI endoscopic scores from the same sites were compared. Histological evaluation of biopsies was according to the Riley Index. RESULTS: Relative to red (r = 0.52, P < 0.01) or blue (r = 0.56, P < 0.01) color component, the green color component of AFI (r = -0.62, P < 0.01) corresponded more closely with mucosal inflammation sites. There were significant differences in green color components between MES-0 (0.396 ± 0.043) and MES-1 (0.340 ± 0.035) (P < 0.01), and between MES-1 and ≥ MES-2 (0.318 ± 0.037) (P < 0.01). The WLI scores for "vascular patterns" (r = -0.65, P < 0.01), "edema" (r = -0.62, P < 0.01), histology scores for "polymorphonuclear cells in the lamina propria" (r = -0.51, P < 0.01) and "crypt architectural irregularities" (r = -0.51, P < 0.01) showed correlation with the green color component of AFI. There were significant differences in green color components between limited (0.399 ± 0.042) and extensive (0.375 ± 0.044) (P = 0.014) polymorphonuclear cell infiltration within MES-0. As the severity of the mucosal inflammation increased, the green color component of AFI decreased. The AFI green color component was well correlated with the characteristic endoscopic and histological inflammatory features of UC. CONCLUSION: AFI has application in detecting inflammatory lesions, including microscopic activity in the colonic mucosa of UC patients, based on the green color component of images.

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BACKGROUND AND STUDY AIMS: Liver disease in chronic hepatitis C virus (HCV) infection ranges from minimal lesion to liver cirrhosis and sometimes eventually evolving hepatocellular carcinoma. Whether and how HCV determines the different clinical and histological manifestation of the disease is not fully understood. It has not been clearly elucidated whether the extent of liver injury induced by HCV is influenced mainly by direct cytopathic damage or by an immune-mediated response against HCV-infected hepatocytes. The aim of this study is to verify whether the amount of virus in individual patient's serum could be related to the severity of liver injury. PATIENTS AND METHODS: This study was carried out in the Gastroenterology and Hepatology Teaching Hospital, Medical City, Baghdad. Serum levels of HCV-RNA were measured in 27 patients with chronic HCV using b-DNA assay. Core liver biopsies of the patients were evaluated according to Ishak histological activity index system. RESULTS: The serum HCV RNA concentrations in the patients ranged from 3.2×10(3) to 1.2×10(7)copies/ml. In all patients no correlation was observed between the variable levels of viraemia and the age of the patients. Furthermore no correlations were observed between the serum HCV RNA concentrations and the biochemical liver function test levels: Total serum bilirubin, AST, ALT, and alkaline phosphatase. Histologically; patients were categorized into four subgroups: four patients (14.8%) had minimal activity, 17 patients (63%) had mild activity, and six patients (22.2%) had moderate activity. No significant correlation was found between viraemic levels and these histological findings or their individual components: Interface hepatitis, confluent necrosis, intralobular liver cell necrosis and portal inflammation. According to the stage of the fibrosis, the patients were categorized into seven subgroups: one patient (3.7%) with stage zero, seven patients with stage one (25.9%), four patients with stage two (14.9%), eight patients with stage three (29.6%), three patients with stage four (11.1%), two patients with stage five (7.4%), and two patients in cirrhotic stage six (7.4%). There was no correlation between the serum HCV RNA concentration and the stage of fibrosis. Hepatic steatosis was observed in 16/27 patients. It was mild in nine patients, moderate in five patients, and severe in two patients. Correlation has not been observed between the serum HCV RNA viraemic level and the severity of steatosis. CONCLUSION: Serum HCV-RNA level does not determine the degree of hepatic injury precisely and liver biopsy is necessary to accurately evaluate the extent of liver damage.