Imaging Insights into EHPVO Induced Portal Biliopathy and its Grading: Retrospective Study Over A Decade at A Tertiary Care Hospital

Background and Aim: There is limited data on imaging features of extra hepatic portal venous obstruction (EHPVO) induced portal biliopathy. We describe a decade long experience of imaging spectrum of EHPVO induced portal biliopathy using MR/CT in a referral centre for liver diseases. Methods: Retrospective data of patients with primary EHPVO on contrast magnetic resonance imaging MRI/ computed tomography (CT) (n=120) and portal biliopathy (PB) on subsequent magnetic resonance cholangiopancreatography (MRCP) (n=80/120) between June 2009 - 2019 was collected. Categorisation of portal biliopathy was as per the Sarin classification and the corresponding, relevant imaging parameters were studied and analysed. Results: Sarin Type 1 biliopathy was present in 16.3 %, Type 2 in 13.8%, Type 3a in 8.8% and Type 3b in 61.3%patients. The median total serum bilirubin was 1.6 (0.9-3.4) mg/dl with a mean CBD diameter of 6.7 ± 2.9 mm. Bilobar and unilobar IHBRD were observed in 87.5% and 6.3% patients respectively. The mean CBD angle was 138.9 ± 18.8º. CBD showed smooth wall contours (10%), extrinsic indentations (83.8%) and smooth strictures (6.3%). The median CBD stricture length was 26 mm (1.25- 45 mm). Pre-stenotic dilatation was observed in 66.3% with stricture length >16 mm (sensitivity 81.1 % specificity 78%) predisposing to it. Statistically significant associations were tabulated according to the classification of PB. Conclusion: This study provides the decade long experience of imaging findings in EHPVO induced portal biliopathy according to its classification and its clinical implications.

Study of Family Clustering and PNPLA3 Gene Polymorphism in Pediatric Non Alcoholic Fatty Liver Disease

Objectives: To find association of pediatric NAFLD with metabolicrisk factors, and Patatin-like phospholipase domain-containingprotein 3 (PNPLA3) gene polymorphism.Design: Cross-sectional studySetting: Pediatric Hepatology unit of a tertiary care hospitalParticipants: Overweight/obese children (<18 years) with (69patients) or without (30 patients) NAFLD (ultrasonographybased), and their parents.Intervention: Metabolic screening, PNPLA3 gene polymorphism,and transient elastographyOutcome measure: Association of pediatric NAFLD with parentalmetabolic risk factors and PNPLA3 gene polymorphism.Results: In the NAFLD group, there was high parental incidenceof metabolic diseases, fatty liver (80%) and low high-densitylipoproteins levels (84%). Family history of NAFLD (in any parent),higher alanine aminotransferase levels and higher totalcholesterol levels in the child independently predicted possibilityof NAFLD, but similar results could not be replicated for PNPLA3gene polymorphism. Controlled attenuation parametermeasurement (by transient elastography) had high sensitivity andspecificity to diagnose steatosis.Conclusion: There is high familial incidence of metabolicdiseases in children with NAFLD. Controlled attenuationparameter can be useful as a non-invasive modality to screen fattyliver in children.

Immunological mechanisms of hepatitis B virus persistence in newborns.

Chronic hepatitis B virus (HBV) infection affects millions of people worldwide and about a half million people die every year. India represents the second largest pool of chronic HBV infection worldwide with an estimated 40 million infected people. The prevalence of chronic HBV infection in pregnant women is shown to be 0.82 per cent with the risk of mother-to-child vertical transmission. Hepatitis B e antigen (HBeAg) positivity indicates replicative form of HBV which may play a role in immunotolerance in utero by crossing the placenta. In case of HBeAg positivity and high viral load of mother, HBV immunoglobulin is preferably given along with HBV vaccination. Antiviral therapy is recommended for use in the third trimester of pregnancy to reduce the perinatal transmission of HBV, however, use of antiviral therapy should be individualized during pregnancy. Chronic HBV infection in neonates is linked with strong presence of Tregs (T regulatory cells) and defective CD8 T cells pool to produce interferon (IFN)-γ. T cell receptor (TCRζ) chain defects were also associated with decreased CD8 T cell dysfunction. Decreased TCRζ expression could be due to persistent intrauterine exposure of the viral antigens early in embryonic development leading to immune tolerance to HBV antigens in the newborns positive for hepatitis B surface antigen (HBsAg+ve). Therefore, due to HBV infection, T cell tolerance to HBV-antigen may probably leave the newborn as a chronic carrier. However, HBV vaccination may have benefits in restoring acquired immunity and better production of HBV specific antibodies.

Steatosis in chronic hepatitis B: Prevalence and correlation with biochemical, histologic, viral, and metabolic parameters.

Background and Aims: Hepatic steatosis (HS) is highly prevalent in chronic hepatitis C and is an important variable predicting progression of histological injury, insulin resistance, and reduced response to antiviral therapy. There are limited data on HS in patients with chronic hepatitis B (CHB). This is relevant since response to current antiviral therapies for CHB is rather limited. We investigated the spectrum and predictors of HS in CHB patients. Materials and Methods: Liver biopsies of consecutive patients of chronic Hepatitis B Virus (HBV) infection were studied and were categorized as: Group I - hepatosteatosis (>5%) and Group II - no steatosis (£5%). Anthropometric, histological, biochemical, virological, and metabolic determinants were compared. Logistic regression analysis was applied to identify variables that were independently associated with the presence of steatosis. Results: Of the 350 patients, 118 (33.7%) liver biopsies showed steatosis (Group I); 65 (55.1%) had mild (6 to <25%) and 53 (44.9%) had moderate to severe steatosis (325%). Patients in group I, compared with group II, were older (35.5 ± 10.5 vs 27.9 ± 14.0 years, P < 0.01), predominantly male (M: F, 10.8: 1 vs 4.8: 1, P = 0.035), obese (75.0% vs 23.4%, P < 0.01), with higher body mass index (25.2 ± 4.8 vs 20.4 ± 3.5, P < 0.01), with higher triglycerides (138.8 ± 62.1 vs 88.0 ± 27.9, P = 0.02), with higher cholesterol (171.9 ± 43.5 vs 139.3 ± 37.6, P = 0.017), and with higher serum insulin (13.1 ± 9.1 vs 9.1 ± 6.0, P < .027) levels. HBV DNA level was significantly lower in group I than group II; however, HBV genotype did not influence HS. By multivariate regression analysis, only high serum triglyceride level was independent parameter associated with HS. Conclusions: Steatosis is seen in one-third cases with HBV-related chronic liver disease and is associated with host metabolic factors, especially serum triglyceride levels, whereas HBV DNA level negatively correlated with HS.

Comparison of clinical, biochemical and histological features of alcoholic steatohepatitis and non-alcoholic steatohepatitis in Asian Indian patients.

Background: Alcoholic steatohepatitis (ASH) and non-alcoholic steatohepatitis (NASH) are significant forms of liver disease and may progress to end-stage liver disease, cirrhosis and potentially malignant complications. The most difficult aspect of establishing a diagnosis of NASH is distinguishing it from ASH. Laboratory markers such as AST, ALT and GGT lack sufficient sensitivity and specificity. Aim: To study the clinical, biochemical and histological differences between non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH). Materials and Methods: Sixty histologically confirmed cases of non-alcoholic steatohepatitis and 38 cases of alcoholic steatohepatitis were included in the study. A modified form of scoring system proposed by Yip and Burt was used to grade histological features of NASH and ASH. Results: Mean age was 42.85 ± 12.36 years in ASH group and 35.07 ± 8.06 years for NASH group. Male: Female ratio was 37:1 in ASH and 4:1 in NASH. The mean ALT (P = 0.012), SAP (P = 0.003), serum bilirubin (P = 0.001), AST/ALT ratio (P = 0.03), steatosis (P < 0.001), ballooning degeneration of hepatocytes (P < 0.001), portal inflammation (P < 0.001), Mallory hyaline (P = 0.001), ductular proliferation and fibrosis (P < 0.001) showed a significant difference between ASH and NASH cases. Discussion: Older age, male sex, larger derangement of serum biochemistry, high serum bilirubin, AST/ALT > 1, more ballooning degeneration, portal inflammation, Mallory's hyaline, hepatocytic and ductular cholestasis, ductular proliferation and higher stage of fibrosis favors a diagnosis of ASH. Younger age, high ALT, AST/ALT < 1, higher grade of steatosis and absence of extensive neutrophilic portal inflammation favors a diagnosis of NASH.

Predictors of histological activity and fibrosis in chronic Hepatitis C infection: A study from North India.

Background and Aims: The role of hepatitis C virus (HCV) genotypes in the severity of liver disease is still debatable and there is an occasional published report from India. The aim of this study is to assess the role of HCV genotypes in severity of liver disease in Indian patients. An attempt has also been made to perform a multivariate analysis to identify the predictors of severity of liver disease in chronic HCV infection. Materials and Methods: In this study, 31 newly diagnosed cases of chronic HCV infection over a period of two years were included. Age, sex and serum alanine transaminase (ALT) levels were recorded for each patient. HCV genotypes were identified using Line Probe assay (INNO-LiPA HCV II kit, Innogenetics, Belgium). Histological activity was graded and fibrosis was staged. Univariate and multivariate analysis was done to identify predictors of histological severity and fibrosis. Results: By univariate analysis, age of the patient, serum ALT levels and absence of genotype 3 (i.e., presence of HCV genotype other than genotype 3) showed association with histological activity score; whereas age and histological activity score showed association with fibrosis. However, on multivariate analysis, only serum ALT levels and absence of genotype 3 correlated well with activity score; while only activity score remained a significant predictor of stage of fibrosis. Conclusions: This study emphasizes the significant correlation of HCV genotype with severity of liver disease in chronic HCV infection. The stage of fibrosis showed correlation only with activity score as an independent factor. These results would further help in outlining algorithms for therapeutic stratification of patients with HCV infection.

Hepatic venous pressure gradient measurement: time to learn!

Portal hypertension is a clinical syndrome defined by a pathological increase in portal pressure. The development of cirrhosis of the liver is characterized by clinical manifestations related to portal hypertension like esophageal varices, ascites, bleeding, and encephalopathy. Direct measurement of portal pressure is invasive, inconvenient, and clinically impractical. Currently, the most commonly used parameter is the Hepatic Venous Pressure Gradient (HVPG), i.e., the difference between the wedged (WHVP) and the free hepatic venous pressures. HVPG represents the gradient between pressures in the portal vein and the intra-abdominal portion of inferior vena cava. When blood flow in a hepatic vein is stopped by a wedged catheter, the proximal static column of blood transmits the pressure from the preceding communicated vascular territory (hepatic sinusoids) to the catheter. Thus, WHVP reflects hepatic sinusoidal pressure and not the portal pressure itself. In the normal liver, due to pressure equilibration through interconnected sinusoids, wedged pressure is slightly lower than portal pressure, though this difference is clinically insignificant. In liver cirrhosis, the static column created by balloon inflation cannot be decompressed at the sinusoidal level due to disruption of the normal intersinusoidal communications; therefore, WHVP gives an accurate estimation of portal pressure in cirrhosis. The normal HVPG value is between 1 to 5 mmHg. Pressure higher than this defines the presence of portal hypertension, regardless of clinical evidence. HVPG >or= 10 mmHg (termed clinically significant portal hypertension) is predictive of the development of complications of cirrhosis, including death. HVPG above 12 mmHg is the threshold pressure for variceal rupture. The main advantages of HVPG are its simplicity, reproducibility, and safety. This review summarizes the technique of the HVPG measurement.

Distribution of hepatitis C virus genotypes in patients with chronic hepatitis C infection in India.

BACKGROUND & OBJECTIVES: Hepatitis C virus (HCV), an important cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, shows a considerable genetic heterogeneity among hepatitis C virus isolates from all over the world. At least six main groups of sequence variants are recognized. The natural history of disease and response to treatment may be related to the genotype of HCV in a particular patient. Antigenic differences between genotypes also have implications for optimal design of serological sequencing and confirmatory assays for HCV. The present study was undertaken with the objective to find out various genotypes of hepatitis C virus prevalent in Indian patients with chronic hepatitis C infection. METHODS: Thirty six consecutive newly diagnosed patients with chronic hepatitis C infection were included in the study. HCV RNA was extracted from the serum by standard guanidinium thiocyanate method. Following reverse transcription and amplification, the HCV genotypes were determined by line probe assay (INNO-LiPA HCV II). RESULTS: Of the 36 patients, genotype 3 was found in 24 (66.6%). Of these 24 patients, 3a was seen in 5 patients (13.8%), 3b in two (5.5%) and mixed subtype 3a and 3b in 17 patients (47.2%). Genotype 1 was found in 5 patients (13.8%), with 1b in 1 and 1a in rest four cases. Two patients (5.5%) were infected with genotype 2 (subtype 2a and mixed subtype 2a, 2b respectively). One (2.7%) was infected with genotype 4 (4a). Mixed genotype infection was found in 4 patients (11.1%). INTERPRETATION & CONCLUSION: The present findings showed that genotype 3 of hepatitis C virus was the most prevalent genotype in patients with chronic hepatitis C in this part of India.

Histological profile of liver disease in patients with dual hepatitis B and C virus infection.

There is limited information on the histological profile of chronic liver disease due to dual infection with hepatitis B virus and hepatitis C virus infection. Few studies have indicated higher histological activity with dual infection as compared to HBV and HCV infection present alone. This study aims at reviewing the histological profile of liver biopsies in the three groups. Liver biopsies of 25 patients serologically diagnosed as HBV and HCV dual infection (Group I), were compared with 25 age and sex matched cases of HBV infection (Group II) and HCV infection (Group III). RESULTS: Mean Histological Activity Score in group I was 8, which was higher than the scores of group II (6.2) and group III (7.3). The mean stage of fibrosis was also slightly higher in group I (2.3) as compared to group II (1.9) and group III (1.7). However, when stage 3 and 4 fibrosis (extensive fibrosis) were combined and compared with the number of patients with stage 1 and 2 fibrosis in each group, we found Group I (dual infection) had larger number of patients with extensive fibrosis (48%) than in Groups II and III (20% and 36% respectively). In addition, there was no significant difference in presence of features like fatty change, bile duct injury and lymphoid aggregates in the three groups. CONCLUSION: Patients with dual HBV and HCV infection are more likely to have an advanced stage of disease than those with a single infection, however there is no significant difference in histologic activity or any other histological parameter between these groups.