Role of stereotactic body radiation therapy in liver metastasis: A pilot study from tertiary cancer institute in India

Purpose: This trial studies the feasibility and potential utility of stereotactic body radiation therapy in patients with unresectable liver metastasis. Aims: (1) The aim of this study is to assess the local response of the liver lesions poststereotactic body radiation therapy regarding number and size of lesions and (2) to evaluate the toxicity to organ (s) at risk. Materials and Methods: A total of 15 patients were enrolled in this study from November 2014 to October 2015. The inclusion criteria for this study were patients having 1–3 liver metastasis from any solid tumor except germ cell tumor or lymphoma with no evidence of progressive disease (PD) outside the liver. A planning four dimensional-computed tomography (CT) scan was taken. Planning target volume was generated by giving margin of 5 mm. Dose prescribed was 36 Gy in 3#. Response was defined by CT abdomen done at 3 and 6 months poststereotactic body radiation therapy as per RECIST guideline (v1.1). Results: At 3 months poststereotactic body radiation therapy, five patients had partial response, five patients had stable disease, and five patients had PD as per RECIST criteria. Out of 20 assessable lesions, 16 were controlled at 3 months poststereotactic body radiation therapy. The actuarial local control rate was 86% at 3 months and 77% at 6 months poststereotactic body radiation therapy. The median progression free survival was 7 months. Two patients experienced Grade 2 gastric toxicity and one patient experienced Grade 2 small bowel toxicity. No cases of radiation-induced liver disease were observed. Conclusions: This trial examines the feasibility of stereotactic body radiotherapy to liver metastasis in the Indian scenario. It shows excellent tolerability and is a safe therapeutic option for inoperable patients, showing good local control

Treatment of chronic hepatitis C in end stage renal disease: experience at a tertiary care centre.

Introduction: Treatment of patients with chronic hepatitis C (CHC) is difficult in the setting of end stage renal disease (ESRD). The present study aimed to analyze the treatment outcome in patients with CHC and ESRD, being evaluated for kidney transplantation. Methods: Data of 65 patients of ESRD with CHC (males: 53, mean age: 39.2±14.4 years) was analysed retrospectively. Patients were treated with either pegylated or conventional interferon (IFN) without ribavirin. Treatment response was assessed for rapid virological response (RVR), early virological response (EVR), end of treatment response (ETR) and sustained virological response (SVR). Results: All patients were receiving hemodialysis (duration 1-60 months). Sixteen patients (25%) (genotype 1: 11, genotype 3: 4, genotype 2: 1) agreed for treatment (13 pegylated IFN and 3 conventional IFN). RVR was achieved in 7 patients (44%) and out of 11 patients (69%) who achieved EVR, ETR was achieved in 7 (44%) patients. Seven patients (44%) dropped out during treatment (2 because of side effects). SVR could be demonstrated in one of 7 patients who achieved ETR (6 patients were lost to follow up after ETR). Conclusions: In our experience, dropouts before, during and after treatment are a major problem in patients with CHC and ESRD. Of those who complete treatment, around half of them are able to achieve the end of treatment response.

Indocyanine green clearance test (using spectrophotometry) and its correlation with Model for End Stage Liver Disease (MELD) score in Indian patients with cirrhosis of liver.

Background: Child Turcotte Pugh (CTP) score and Model for End Stage Liver Disease (MELD) are used commonly to assess the prognosis of liver disease but the disadvantage of these static tests is their inability to identify the functional reserve of the liver. Among all quantitative liver function tests indocyanine green (ICG) clearance test is most widely used and has been used to determine operative risk before hepatectomy and to assess prognosis of patients with cirrhosis. Aim: To correlate indocyanine green (ICG) clearance test with MELD score in patients with cirrhosis of liver. Methods: Forty patients with cirrhosis of liver were included and divided into two groups according to their CTP scores. Group A had 20 patients with CTP class A and group B had 20 patients with CTP class B. After ICG injection, ICG retention at 15 minutes (ICGR15) and ICG clearance rate were calculated. Results: In group A, the mean ICGR15 was 32.86% + 6.4% while in group B it was 51.08% + 12.8% (p <0.001). ICG clearance rates were 4.3% + 2.8% and 3.5% + 3.8% per minute in group A and B respectively. MELD score had a strong positive correlation with ICGR15 but a negative correlation with ICG clearance rate. On ROC curve analysis, AUC for MELD was 0.805 vs. 0.88 for ICGR15 in assessing prognosis of patients with cirrhosis. The sensitivity and specificity of MELD score was 60% and 80% respectively while that of ICGR15 was 85% and 90% respectively. Conclusion: ICGR15 has a higher sensitivity and specificity than MELD score in assessing the prognosis of patients with cirrhosis of liver.

HBV specific T-cell responses in hepatitis B.

Background: Cellular immune responses seem to prevail in acute hepatitis, whereas chronically infected patients demonstrate generally suppressed cellular immune responses and significantly greater antibody responses. Aim: To study hepatitis B virus (HBV) specific T cell proliferative responses in HBV related liver diseases. Methods: We analyzed the T lymphocyte proliferative responses to the nonspecific mitogen phytohemagglutinin (PHA) and the HBV specific hepatitis B core antigen (HBcAg) by calculating T cell proliferation index in 10 acute viral hepatitis (AVH) patients, 19 chronic hepatitis B (CHB) patients, 10 HBV cirrhotics, 10 inactive carriers and 10 healthy controls using MTT assay. Results: The mean proliferation index (PI) to PHA was highest in healthy controls (133.2 + 58.1) and lowest in cirrhotics (44.1 + 46.9) with all other groups falling in between. On comparing the mean T cell responses to HBcAg, AVH patients had the highest mean response (186.48 + 116.37) followed by CHB (137.9 + 134.3), inactive carriers (63.2 + 41.2) and cirrhotics (55.5 + 42.7). Conclusions: Patients with AVH had the highest T cell response to HBcAg, which probably explains the clearance of virus in these patients, in contrast to patients with cirrhosis who had the lowest T cell response.

Therapy of nonalcoholic steatohepatitis (NASH) – antioxidants and cytoprotective agents.

Pathogenesis of nonalcoholic fatty liver disease (NAFLD) and its progressive form nonalcoholic steatohepatitis (NASH) is not completely understood. Because of the role of oxidative stress in the pathogenesis, antioxidants and cytoprotective agents have been used in the treatment of patients with NAFLD/NASH. Various antioxidants and cytoprotective agents used in these patients include Vitamin E, Vitamin C, Betaine, N- acetyl cysteine, silybin, lecithin, beta carotene, metadoxine, selenium and ursodeoxycholic acid (UDCA). Most of the data is available with vitamin E and UDCA, either in isolation or in combination with various agents. The available data on the use of various agents are either experimental or have small number of patients and randomized controlled trials with histological efficacy are sparse. More data is required before any conclusions are drawn regarding the use of anti oxidants and cytoprotective agents in patients NAFLD/NASH.

Nonalcoholic fatty liver disease in India – a lot done, yet more required.

Nonalcoholic fatty liver disease (NAFLD) is emerging as an important cause of liver disease in India. Epidemiological studies suggest prevalence of NAFLD in around 9% to 32% of general population in India with higher prevalence in those with overweight or obesity and those with diabetes or prediabetes. Clinicopathological studies show that NAFLD is an important cause of unexplained rise in hepatic transaminases, cryptogenic cirrhosis and cryptogenic hepatocellular carcinoma in Indian patients. There is high prevalence of insulin resistance and nearly half of Indian patients with NAFLD have evidence of full-blown metabolic syndrome. Though oxidative stress is involved in the pathogenesis of NAFLD/ nonalcoholic steatohepatitis, serum or liver iron and HFE gene mutations appear not to play a role in the pathogenesis of NAFLD in Indian patients. Imaging modalities are not useful in differentiating simple steatosis from NASH and liver biopsy may be useful in those with risk factors for significant liver disease. Pilot studies on treatment strategies have shown that weight reduction and exercise, ursodeoxycholic acid, metformin, vitamin E and pentoxyfylline are effective in normalizing transaminases and or in improving hepatic steatosis and inflammation in Indian patients with NAFLD. Randomized controlled treatment trials involving large number of patients with histological end point are required to assess the efficacy of different modalities. In conclusion, a lot has been done, yet more is required to understand various aspects of NAFLD in India.

Comparison of 7 staging systems in north Indian cohort of hepatocellular carcinoma.

Background & Aim: Many liver staging systems have been proposed for patients with hepatocellular carcinoma (HCC); however it is still controversial which staging system is best. The aim of this study was to compare the ability of 7 different staging systems in predicting survival in an Indian cohort of patients with HCC. Methods: In this prospective study, 101 HCC patients were diagnosed and stratified according to 7 different staging systems; along with analysis of independent predictors of survival and their correlation with it (Kaplan-Meier analysis). Results: CLIP, Tokyo score and BCLC staging system showed a significant difference in the probability of survival. All other staging systems failed to show a significant difference in survival. Age, portal vein thrombosis, serum bilirubin, MELD score showed a significant difference with survival in univariate analysis. However, serum bilirubin was the independent predictor of survival with a hazard ratio of 1.609 (95% CI 1.015-2.553, p= 0.043). Conclusion: The CLIP, Tokyo score and BCLC are the most useful staging systems in an Indian cohort.

Biphasic multidetector CT of primary hepatic lymphoma in a patient with HIV infection.

Primary hepatic lymphoma (PHL) is a rare condition. It is the most common hepatic neoplasm in patients with acquired immune deficiency syndrome (AIDS). We report a case of PHL in a patient with human immunodeficiency virus (HIV) infection and describe the imaging findings on biphasic multidetector CT (MDCT).

Insulin tolerance test is comparable to homeostasis model assessment for insulin resistance in patients with nonalcoholic fatty liver disease.

INTRODUCTION: Insulin resistance (IR) is common in patients with nonalcoholic fatty liver disease (NAFLD). We compared the performance of insulin tolerance test and the homeostasis model assessment (HOMA) for measuring IR in such patients. METHODS: In a prospective study, IR was determined using both insulin tolerance test and HOMA in 22 patients with NAFLD. Rate constant for insulin tolerance test (KITT) was calculated using the formula KITT (%/min) = 0.693/t(1/2), where t(1/2) was calculated from the slope of plasma glucose concentration during 3-15 minutes after administration of intravenous insulin. IR was assessed using HOMA as the product of fasting insulin (microU/L) and fasting plasma glucose (mmol/L) levels divided by 22.5. RESULTS: All the 22 patients had IR. Results of KITT and HOMA-IR for determining IR showed a fair correlation (r = 0.55; p = 0.03). CONCLUSIONS: Insulin tolerance test may be a useful method for assessing IR in patients with NAFLD.

Nonalcoholic fatty liver disease in India--is it different?

Nonalcoholic fatty liver disease (NAFLD) is an emerging clinical entity. There is limited data on NAFLD from India. The objective of this article was to review all the published literature on NAFLD from India. The epidemiological studies including prevalence ofNAFLD amongst special groups like in those with unexplained rise in transaminases, diabetes mellitus and cryptogenic cirrhosis, studies on pathogenesis including insulin resistance, iron abnormalities, and studies available for the treatment of such patients have been reviewed. In addition some of the differences between Indian patients and those from the West have been highlighted. Available literature show that majority of Indian patients with NAFLD have overweight or obesity as per Asian Pacific criteria even though they do not have the kind of morbid obesity as seen in patients from the West. Other differences between Indian patients and those from the West include less of metabolic syndrome including its components like diabetes mellitus and hypertension, less of iron abnormalities and HFE gene mutations and mild histological disease at presentation in Indian patients. More data is required to substantiate these findings and to prove if NAFLD patients in India are different at presentation.

Unconjugated hyperbilirubinemia in nonalcoholic steatohepatitis--is it Gilbert's syndrome?

BACKGROUND: Patients with nonalcoholic steatohepatitis (NASH) have normal liver function tests except for raised transaminases until they have progressed to cirrhosis of liver. The objective of this study was to evaluate patients of NASH for the presence of hyperbilirubinemia at presentation. METHOD: Sixty-seven patients of NASH were studied for the presence of hyperbilirubinemia at presentation. All patients were worked up for the presence of cirrhosis and hemolytic work up and fasting test were done in those found with unconjugated hyperbilirubinemia. RESULTS: Five out of 67 patients (7.5%) of NASH were found to have unconjugated hyperbilirubinemia. Though the fasting test was not positive, they all had a negative hemolytic workup and none of them had underlying cirrhosis. Clinical characteristics of patients with unconjugated hyperbilirubinemia were similar to those with normal serum bilirubin levels. CONCLUSION: Unconjugated hyperbilirubinemia in patients with NASH may suggest an associated Gilbert's syndrome.

Gastrointestinal tract infestation with strongyloides

Stercoralis is common in the tropical and subtropical areas of the world. In an immunocompetent person, disease is generally asymptomatic. However, it has the potential to cause serious life threatening disease in an immunocompromised patient. We report a 55 years old immunocompetent person who presented with malabsorption secondary to strongyloides stercoralis infestation. Unusual infestations like strongyloides should also be considered while investigating malabsorption

Is vaccination against hepatitis A virus required in patients with cirrhosis of the liver?

Hepatitis A virus (HAV) superinfection can cause decompensation in patients with chronic liver disease. The risk of HAV superinfection depends on the endemicity of HAV in that particular population. Recommendations of vaccination against HAV in patients with cirrhosis of the liver in India are lacking. Our aim was to assess the seroprevalence of anti-HAV antibodies in our population of patients with cirrhosis of the liver. In a retrospective analysis, the serum of 55 patients with cirrhosis of the liver was tested for total anti-HAV antibodies by ELISA. In the 35 patients who presented with acute decompensation, the serum was also analysed for IgM anti-HAV antibodies. Fifty-four of the 55 cirrhotics (99%) were positive for total anti-HAV antibodies. All 35 patients with decompensated liver disease were also positive for total anti-HAV antibodies, and none of them tested positive for IgM anti-HAV antibodies. Most of the patients with cirrhosis of the liver in the population studied were already exposed to HAV. Routine vaccination against HAV cannot be recommended in these patients.

Clinico-cytopathological spectrum of hepatocellular carcinoma, its correlation with serum alpha-fetoprotein level, and hepatitis B and C viral markers.

Fine-needle aspirationbiopsy (FNAB) is now widely accepted as a diagnostic modality for the treatment of hepatocellular carcinoma (HCC). The most common diagnostic problem in HCC is distinguishing it from a metastatic carcinoma. The literature from India on HCC is scanty. Hence, we studied the cytomorphological features of HCC and metastatic carcinoma. The study included 37 cases of space-occupying lesions (SOLs) of the liver as demonstrated by ultrasound or computed tomography (CT) scan. Cytomorphological features of these SOLs were analyzed in all subsequent to FNAB. Hepatitis B surface antigen (HBsAg), anti-hepatitis C virus antibody (anti-HCV) and alpha-fetoprotein (AFP) were determined in all the cases by enzyme-linked immunosorbent assay (ELISA). The cytopathological diagnosis was HCC in 22 and metastatic carcinoma of the liver in 15. The individual cytomorphological features and which helped to make a definite diagnosis of HCC were: a high nuclear cytoplasmic ratio (81.8%), predominantly trabecular pattern (63.6%) and atypical naked nuclei (100%). Other features were prominent multiple nucleoli (63.3%), hyperchromasia (100%) and moderate anisonucleosis (59%). AFP was elevated in 81.8% of the cases with a mean of 634.8+812.7 ng/ml. HBsAg by ELISA was found to be positive in 72.7% of cases while only 1 case (4.5%) was positive for anti-HCV. In 1 case (4.5%), there was dual infection due to hepatitis B virus (HBV) and HCV. No viral cause was found in 18.3% of cases.

Prevalence of obesity, diabetes mellitus and hyperlipidaemia in patients with cryptogenic liver cirrhosis.

Non-alcoholic steatohepatitis (NASH) is emerging as an important cause of cryptogenic cirrhosis. Obesity, diabetes mellitus and hyperlipidaemia are important risk factors for NASH. The presence of these risk factors in patients with cryptogenic cirrhosis may suggest NASH as an aetiology of cirrhosis in them. Twenty-five patients of cryptogenic cirrhosis were compared with 18 patients of hepatitis B virus and hepatitis C virus related cirrhosis and primary biliary cirrhosis for the presence of obesity, diabetes mellitus and hyperlipidaemia. Patients with cryptogenic cirrhosis were found to have a significantly higher body - mass index increased prevalence of diabetes mellitus and lower high-density lipoprotein compared to the controls. Increased body weight and diabetes mellitus may play a role in the causation of cirrhosis in patients with cryptogenic cirrhosis.