Seroprevalence of Hepatitis C Virus in Liver Disease Patients and Blood Donors from Northern India

Background: The molecular epidemiology of HCV and its association with liver diseases in North India is not well understood. Aim: To assess the incidence of HCV infection in blood donors and liver disease patients and the influence of HCV genotype on the severity of the liver disease. Methods: We screened 487 patients with acute viral hepatitis (AVH), 141 patients of fulminant hepatic failure(FHF), 1058 patients of chronic liver disease (CLD) (chronic hepatitis-468, cirrhosis-527, HCC-63), and 3504 voluntary blood donors for anti-HCV. Anti HCV positive patients were further subjected to HCV RNA testing followed by genotyping. Results: HCV infection was observed in 1.6%, 12.94%, 10.64%, 27.13%, 21.25% and 49.2% of blood donors, AVH,FHF, chronic hepatitis, cirrhosis and HCC patients respectively. Conclusion: Genotype 3 was found to be the major genotype. HCV genotype one infection was associated with advanced liver disease.

HEV-related Liver Disease in India : Why is the Disease Stormy?

Data on the viral load of HEV during pregnancy are limited. The study was designed to determine the viral load of HEV and its association with the disease severity in patients with ALF. A total HEV related 163 patients with ALF which included 105 pregnant, 46 non-pregnant women and girls, 12 men, and 730 patients with AVH which comprised of 220 pregnant women; 282 non-pregnant women and girls, and 228 men were included. Viral load was measured by real-time PCR. Comparison was made between the pregnant and non-pregnant women. HEV RNA was detectable in 265 patients (142 pregnant; 75 non-pregnant and 48 men) and 104 patients with ALF (64 pregnant, 34 non-pregnant and 6 men). The viral load of HEV in pregnant women with ALF and AVH was significantly higher 129,984.0±103,104.17 and 768.92±1,105.40 copies/ml, respectively compared to the non-pregnant women which was 189.2±225 and 12.73±7.8 copies/ml (P < 0.0001). The viral load of HEV was also significantly higher in the pregnant patients with ALF compared to the pregnant women with AVH and also men (P < 0.0001). High viral load of HEV during pregnancy could be one of the factors responsible for the severity of the infection during pregnancy.

Tuberculosis and liver disease: management issues.

Tuberculosis is one of the most common diseases in India and has attained epidemic proportions. Tuberculosis and liver are related in many ways. Liver disease can occur due to hepatic tuberculosis or the treatment with various anti-tubercular drugs may precipitate hepatic injury or patients with chronic liver disease may develop tuberculosis and pose special management problems. Tuberculosis per se can affect liver in three forms. The most common form is the diffuse hepatic involvement, seen along with pulmonary or miliary tuberculosis. The second is granulomatous hepatitis and the third, much rarer form presents as focal/local tuberculoma or abscess. Tubercular disease of liver occurring along with pulmonary involvement as in disseminated tuberculosis is treated with standard regimen for pulmonary tuberculosis. Granulomatous hepatitis and tubercular liver abscess are treated like any other extra-pulmonary tubercular lesions without any extra risk of hepatotoxicity by anti-tubercular drugs. Treatment of tuberculosis in patients who already have a chronic liver disease poses various clinical challenges. There is an increased risk of drug induced hepatitis in these patients and its implications are potentially more serious in these patients as their hepatic reserve is already depleted. However, hepatotoxic anti-tubercular drugs can be safely used in these patients if the number of drugs used is adjusted appropriately. Thus, the main principle is to closely monitor the patient for signs of worsening liver disease and to reduce the number of hepatotoxic drugs in the anti-tubercular regimen according to the severity of underlying liver disease.

Evaluation of adefovir & lamivudine in chronic hepatitis B: correlation with HBV viral kinetic, hepatic-necro inflammation & fibrosis.

Background & objectives: Chronic hepatitis B is an important cause of morbidity and mortality. We conducted a study comparing the efficacy of adefovir and lamivudine with respect to their impact on serum and hepatic viral DNA clearance, and improvement in hepatic necro-inflammatory score, in naive patients of chronic hepatitis B. Methods: This prospective randomized pilot study was conducted in Lok Nayak Hospital, New Delhi, involving 30 patients of chronic hepatitis B (both e antigen positive and negative); 15 were randomly selected to receive either adefovir or lamivudine for a period of 6 months. Quantification of serum and hepatic HBV DNA levels was done by real time PCR and liver biopsy was done at the beginning and end of 6 months. Results: Serum ALT was elevated to 2 or more times normalized in both the groups. In the adefovir group, two patients became HBeAg negative. In the lamivudine group, one patient became HBeAg negative. After therapy HBV DNA was negative in 26.7 per cent patients from adefovir group and 13.3 per cent patients from lamivudine group. Serum HBV DNA levels were correlated with the hepatic levels before therapy (r=0.843; P<0.001) and after therapy (r=0.713, P<0.001) showing strong correlation. There was a median reduction of 1.92 and 2.06 log copies per ml in serum HBV DNA load after adefovir and lamivudine therapy, respectively. The mean reduction in the histotogy activity index (HAI) score was 2 and 1.53, fibrosis score was 2.33 and 3.06 after adefovir and lamivudine therapy respectively. Interpretation & conclusions: Adefovir and lamivudine treatment caused biochemical and serological improvement when administered for about 6 months with significant reduction in HBV DNA, serum and hepatic viral load without completely clearing the virus from either serum or liver. It also helped in reduction of the necro-inflammatory and fibrosis score of patients with chronic hepatitis B. Our study also showed significant correlation between serum and hepatic HBV DNA levels both before and after therapy. There was not enough evidence to show therapeutic advantage of one drug over the other in any of the parameters measured.

Molecular analysis of swine hepatitis E virus from north India.

Background & objectives: Hepatitis E is the main cause of enterically transmitted non-A, non-B hepatitis in developing countries. In the developed countries such as the USA, Japan and Taiwan, the viruses infecting humans and swine share the same genotype with a high sequence similarity. Genotype 1 circulates in humans whereas genotype 4 in pigs in India. The present study was designed to investigate the presence of anti-HEV antibodies and HEV-RNA in swine population from north India, to investigate the genotype prevalent in it, and to compare it with other swine and human HEV strains from India. Methods: A total of 67 serum samples were collected from pigs of age period (1-6 months) from Indian Veterinary Research Institute (IVRI), Izatnagar, Bareily and subjected to anti-HEV IgG and HEV RNA detection. A phylogenetic tree was constructed using the neighbor-joining method and evaluated using the interior branch test method with MEGA 4 software. Results: Anti-HEV IgG and HEV RNA was found in 38.8 and 4.5 per cent of swine samples studied respectively. The above samples were observed to be of genotype 4e. The three new sequences had nucleotide similarity with other swine sequences in genotype 4 ranging from 80-98 per cent. Interpretation & conclusions: The three sequences observed in the present study showed nucleotide similarity with other swine sequences from southern and western India. The present study suggests that genotype 4 ‘e’ is prevalent in the north India.

Hepatic osteodystrophy.

Hepatic Osteodystrophy (HO) is a generic definition for the metabolic bone disease that may occur in individuals with chronic liver disease. Hepatic Osteodystrophy is an important but frequently overlooked complication, seen in chronic liver disease patients. This review article illustrates its significance, various causes and methods to diagnose this complication and recent advances and recommendations to treat Hepatic Osteodystrophy. Two distinct bone metabolic processes, osteoporosis (OP) and osteomalacia (OM) are combined together in various proportions in HO syndromes. It has been described in association with most types of chronic liver disease both cholestatic and non-cholestatic. Primary biliary cirrhosis (PBC) is the condition causing osteopenia more frequently, but other cholestatic liver diseases like primary sclerosing cholangitis (PSC), haemochromatosis and alcoholic liver disease are also frequently associated with this disorder. The pathogenesis of bone disease in both adults and children with chronic cholestasis is not completely understood. There has been considerable disagreement regarding the relative importance of osteomalacia versus osteoporosis as the factors leading to osteopenia of liver disease. It can significantly affect morbidity, and quality of life of these patients. Fractures are also associated with an excess mortality. Bone mineral density measurement is the best way to assess the presence and severity of osteopenia in CLD patients, while laboratory tests give important information about the metabolic status of the bone. Since advanced HO is difficult to treat and adversely affects both the quality of life and the long-term prognosis of patients with chronic liver disease, special care is required in order to prevent the development of clinical bone disease in individuals with advanced hepatic disease. Conclusion: Hepatic Osteodystrophy is under-recognized and less attended complication of CLD. Multiple factors contribute to the development of hepatic Osteodystrophy. Newer diagnostic modalities have improved the detection of HO and Vitamin D repletion, calcium supplementation and Bisphosphonates seem promising. The best course of management for these patients is to review the individual risk factors for osteoporosis, obtain a bone mass measurement, and prescribe age and disease-specific therapies.

Cystic ductal adenocarcinoma of pancreas: an unusual variant.

Cystic lesions of the pancreas are usually pseudocysts (90%); only 10% of them are cystic tumors. These cystic tumors constitute less than 10% of all pancreatic neoplasms, making them an extremely uncommon type of pancreatic malignancy. What is more important is that these tumors are very easily misdiagnosed as pseudocysts because their characteristics are very similar to those of the benign pseudocysts. This gains importance as the cystic tumors have a high cure rate and good prognosis if diagnosed and treated on time. Of all the cystic tumors, the most common are the benign serous cystadenomas, mucinous cystic tumors, intraductal papillary mucinous neoplasms etc. Ductal adenocarcinoma of pancreas presenting in cystic form is an uncommon type of cystic tumor, making it extremely rare among all pancreatic malignancies (solid or cystic). We present the following case report. The review of literature concerning the diagnosis and management has also been discussed.

Neuroendocrine tumors of the pancreas.

Pancreatic Neuroendocrine tumors (PNET) are rare tumors that require a high degree of suspicion for timely diagnosis. They are best divided into functional and nonfunctional varieties. Functional tumors often are symptom specific and are diagnosed at an earlier stage than nonfunctional tumors. The severity of symptoms and pace of disease should dictate therapy. Surgical extirpation remains the only curative modality for localized disease, but palliation of hormone-related symptoms can be achieved with different modalities (Management of hormonal Excess, biologic therapy, chemotherapy and biochemotherapy, local-regional therapy with hepatic arterial embolization).