Radha Krishan Dhiman

Non‐cirrhotic portal fibrosis (idiopathic portal hypertension): Experience with 151 patients and a review of the literature

Background: Non‐cirrhotic portal fibrosis (NCPF), the equivalent of idiopathic portal hypertension in Japan and hepatoportal sclerosis in the United States of America, is a common cause of portal hypertension in India. The clinical features, portographic and histological findings, and management of 151 patients with non‐cirrhotic portal fibrosis are presented.

Prognostic Evaluation of Early Indicators in Fulminant Hepatic Failure by Multivariate Analysis

Viral hepatitis is the commonest cause offulminant hepatic failure (FHF) in developing countries.We evaluated the early indicators of prognosis in thesepatients by multivariate analysis. The records of 204 consecutive patients with acute liverfailure admitted with hepatic encephalopathy over fiveyears were studied. The etiology of these patientsincluded virus related in 186 (91.1%), drug induced in 15 (7.4%), Wilsons disease in one (0.5%),acute Budd-Chiari syndrome in one (0.5%), and malignantinfiltration in one (0.5%). Patients with FHFcomplicating viral hepatitis were analyzed by univariate and multivariate analysis. These patients werefurther subclassified depending upon the intervalbetween the onset of jaundice and the onset ofencephalopathy into hyperacute (HALF; interval 0-7days), acute (ALF; interval 8-28 days) and subacuteliver failure (SALF; interval 4-12 weeks). Sixty (32.3%)patients with viral hepatitis survived. Univariateanalysis showed that the interval between onset of encephalopathy and onset of jaundice, grade ofencephalopathy, raised intracranial pressure,prothrombin time, and serum bilirubin levels onadmission were related to outcome in these patients.Multivariate logistic regression analysis showed that thepresence of raised intracranial pressure at the time ofadmission, prothrombin time >100 sec on admission,age (>50 yr), and onset of encephalopathy seven days after onset of jaundice were associated withpoor prognosis. Forty seven (37.0%) of 129 patients withHALF survived compared with 9 (22.5%) of 40 with ALF and4 (21.1%) of 19 with SALF (P = NS). Raised intracranial pressure was more frequent in patients withHALF (48.8%) than in patients with ALF (32.5%) and SALF(15.8%; P = 0.01), while clinically detectable asciteswas more frequent in patients with SALF (78.9%) compared with HALF (19.7%) and ALF (37.5%; P< 0.0001). The factors adversely affecting theoutcome in our patients with FHF complicating viralhepatitis include presence of overt clinical features of raised ICP at the time of hospitalization,prothrombin time (>100 sec) on admission, age (>50yr), and onset of encephalopathy seven days after onsetof jaundice.

Figure connection test : a universal test for assessment of mental state

Abstract The number connection test (NCT), which assesses the extent of organic brain damage, has been used extensively to evaluate mental state in portasystemic encephalopathy, but has certain inherent limitations. It cannot be performed by illiterates and those unfamiliar with Roman alphanumeric notations. We, therefore, devised a figure connection test (FCT) based on the subjects identification of figures rather than alphabets or numerals. Four variations each of FCT‐A (A1‐A4) and FCT‐B (B1‐B4) employing different motifs were developed and compared with four variations each of NCT‐A (A1‐A4) and NCT‐B (B1‐B4) in groups of healthy volunteers with differing educational status. These volunteer groups were as follows: postgraduates 64; graduates 66; subgraduates 75; and illiterates 45. Significant differences in mean scores of various tests were observed between these normal groups. Control values of the tests for these groups have been standardized and can serve as nomograms. The effect of educational attainments on performance of FCT and other psychometric tests was analysed and trail‐making tests were validated for serial use.

APACHE II score is superior to SOFA, CTP and MELD in predicting the short‐term mortality in patients with acute‐on‐chronic liver failure (ACLF)

The aim of the study was to assess the performance of various prognostic scores including the acute physiology and chronic health evaluation (APACHE II), sequential organ failure assessment (SOFA), Child–Turcotte–Pugh (CTP) and model for end‐stage liver disease (MELD) scores in predicting short‐term mortality in patients with acute‐on‐chronic liver failure (ACLF).

Portal hemodynamics by duplex Doppler sonography in different grades of cirrhosis

Not much is known about the relationship betweenportal hemodynamics and the grades of cirrhosis. Usingpulsed Doppler ultrasonography, we studied portal veindiameter, portal flow velocity, and portal blood flow rate in 37 patients with livercirrhosis (11 Childs A, 13 Childs B, and 13 Childs C)and 10 healthy controls. There was no difference in themaximum inner diameter of the portal vein in cirrhotics and controls. However, there was a significantdecrease in the portal flow velocity in patients withChilds C cirrhosis, as compared to controls andpatients with Childs A and Childs B cirrhosis. The portal blood flow rate in Childs B and ChildsC cirrhosis was also significantly less as compared tocontrols and patients with Childs A cirrhosis. Patientswith ascites and encephalopathy had significantly lower portal flow velocities and blood flowrate as compared to those without ascites andencephalopathy, respectively. This study indicates thatportal flow significantly decreased in cirrhoticpatients with worsening Childs grade ofcirrhosis.

Pregnancy and Cirrhosis of the Liver

Summary: Pregnancy in patients with cirrhosis of the liver is uncommon. We reviewed 9 pregnancies in 7 patients with cirrhosis. One patient conceived within 1 month of diagnosis and in another the disease was diagnosed during the index pregnancy. Four patients has associated portal hypertension and 1 of them concieved after lienorenal shunt. Complications associated with these pregnancies were jaundice (1) jaundice plus ascites (2) and gastrointestinal bleeding (1). In 2 patients endoscopic sclerotherapy was done during the index pregnancy. The incidence of preterm delivery was 50% (4 of 8) and the majority (75%) occurred in pregnancies where associated complications were present. There was 1 maternal death in the postpartum period due to fulminant hepatic failure.

Correlation of 24-hr esophageal pH patterns with clinical features and endoscopy in gastroesophageal reflux disease

We performed 24-hr ambulatory esophageal pH monitoring in north Indian patients with gastroesophageal reflux disease (GERD) and correlated it with symptom severity and endoscopic abnormalities. Thirty-six consecutive patients with symptomatic GERD and 16 healthy volunteers underwent objective grading of clinical symptoms and endoscopic findings. Total, supine, and upright reflux periods as well as frequency and duration of reflux episodes were determined from the 24-hr pH-metry record using standard software. This was abnormal in 32 patients, who could be categorized into upright refluxers (31.2%), supine refluxers (34.4%), and combined refluxers (34.4%). Supine reflux and upright reflux were distinct entities that did not correlate with each other (r=0.22,P=NS). In upright refluxers, symptoms (P<0.02) and endoscopic abnormalities (P<0.005) were milder than in combined refluxers. Total duration of acid exposure correlated significantly with severity of symptoms (P<0.001) and endoscopic esophagitis (P<0.005). Patients with GERD had three distinct patterns of abnormal gastroesophageal reflux, with upright refluxers having milder disease and supine and combined refluxers having more severe disease. This may reflect differences in underlying mechanisms of reflux.

Radioisotope scintigraphy in the diagnosis of hepatic hydrothorax.

Background: Pleural effusion in cirrhotic patients (hepatic hydrothorax) may result from migration of ascitic fluid across defects in the diaphragm. Biochemical analysis of ascitic and pleural fluid provides only indirect information about the nature and origin of the effusion. The present study was performed in order to demonstrate the presence/absence of peritoneo–pleural communication by radioisotope imaging.

Elevation of interleukin‐18 in chronic hepatitis C: implications for hepatitis C virus pathogenesis

The outcome of hepatitis C virus (HCV) infection is determined by the interplay between the virus and the host immune response. Interleukin (IL)‐18, an interferon‐γ‐inducing factor, plays a critical role in the T helper type 1 (Th1) response required for host defence against viruses, and antibodies to IL‐18 have been found to prevent liver damage in a murine model. The present study was conducted to investigate the possible role of IL‐18 in the pathogenesis and persistence of HCV. IL‐18 levels were measured in sera of 50 patients at various stages of HCV infection (resolved, chronic and cirrhosis) and compared with those of normal controls. IL‐18 gene expression was studied in peripheral blood mononuclear cells (PBMC) from each group, and in liver biopsy tissue from patients with chronic hepatitis C. The mean levels of IL‐18 in sera were markedly elevated in patients with chronic hepatitis and cirrhosis, and were reduced in patients with resolved HCV infection. The serum IL‐18 concentrations were related to the Child–Pugh severity of liver disease in cirrhotic patients. There also existed a strong positive correlation of IL‐18 levels with histological activity score and necrosis. IL‐18 mRNA expression was significantly up‐regulated in the PBMC of cirrhotic patients when compared with other groups, while in the liver, higher levels of IL‐18 transcripts were expressed in patients with chronic hepatitis C. The results of our study indicate that IL‐18 levels reflect the severity and activity of HCV infection, and may contribute to the pathogenesis and progression of liver disease associated with HCV.

Intrahepatic portal venopathy and related disorders of the liver.

Intrahepatic portal venopathy leads to various entities that are important causes of portal hypertension. Noncirrhotic portal fibrosis (NCPF) occurs in the Indian subcontinent, whereas idiopathic portal hypertension (IPH) occurs in Japan although the pathogenesis and presentation of both are similar. NCPF presents mainly with upper gastrointestinal bleeding; IPH presents with massive splenomegaly. The liver functions are preserved. Wedged hepatic venous pressure is normal, but portal venous pressure is high indicating a presinusoidal block. Patients are best managed with endoscopic therapy or surgery, with better results than in patients with cirrhosis. Nodular regenerative hyperplasia is a histological diagnosis characterized by development of nodules in the liver due to uneven perfusion of the portal venous blood. These patients may develop portal hypertension and if they bleed would require treatment as in NCPF/IPH. Schistosomiasis produces portal hypertension by the development of fibrous tissue around the portal veins as a response to schistosome eggs. Gratifying results have been reported with praziquantel therapy. Rarely sarcoidosis and chronic biliary obstruction may also produce portal venopathy.