Demographic profile, host, disease & viral predictive factors of response in patients with chronic hepatitis C virus infection at a tertiary care hospital in north India.

Background & objectives: Standard of care for chronic hepatitis C (CHC) in India is peginterferon and ribavirin (RBV). The response to treatment in real life stetting is unclear. The objectives of this study were to evaluate the demographic profile and assess the virological response and predictors of response in CHC patients. Methods: Consecutive patients with CHC were included in this study. Detailed clinical history, risk factors, and predictive factors of response were noted. Patients were treated with peginterferon α2b (1.5 μg/kg/wk) and RBV (12 mg/kg/day) for 6 to 18 months based on response. Results: A total of 211 patients were included in the analysis, mean age 40.6±12.3 yr, 144 (68%) were males and 71 (34%) had compensated cirrhosis. Commonest risk factor for acquiring CHC was previous transfusion and surgery (51%). Genotype 3 (72%) was most common followed by genotype 1 (23%). Overall sustained virologic response (SVR) was 64 per cent [95% CI 57.1%-70.4%]. The SVR was 66.5 per cent [95% CI 58.34-73.89%] for genotype 3 and 61.2 per cent [95% CI 46.23 to 74.80%] for genotype 1. Non-cirrhotics had better SVR rates compared to cirrhotics (76 vs 41%, P<0.001). On multivariate analysis, BMI ≥23 kg/m2, HOMA-IR ≥2, compliance (≤80%), and fibrosis >2 were predictors of low SVR. Interpretation & conclusions: Genotype 3 was the commonest HCV genotype. The commonest source of infection was previous transfusion and surgery. SVR rates for genotypes 3 were better than genotype 1 patients. Predictors of non-response were high BMI, insulin resistance, significant fibrosis and inadequate compliance.

Role of hepatitis B virus genotype D & its mutants in occult hepatitis B infection.

Background & objectives: Non-detection of hepatitis B virus (HBV) envelope protein (hepatitis B surface antigen, HBsAg) in a chronically HBV infected individual has been described as occult infection. One possible reason for this phenotype is alteration in large (L-HBsAg) to small (S-HBsAg) envelope protein ratio associated with reduced or non secretion of HBsAg. This results in quantitative levels of serum HBsAg below the detection limit of enzyme immunoassays. Genotype D of HBV has a characteristic 33 nucleotide (nt) deletion upstream of the pre-S2/S promoter. This deletion may reduce HBsAg secretion in occult infection patients infected with genotype D HBV. Additional deletions in the pre-S2/S promoter may further aggravate reduced HBsAg secretion in patients infected with genotype D HBV. Thus, the aim of the present study was to determine the role of genotype D specific 33nt deletion and additional pre-S2/S promoter deletions in causing reduced or no secretion of HBsAg, in occult infection. Since these deletions overlap virus polymerase, their effect on virus replication was also investigated. Methods: We examined the in vitro expression of HBsAg, ratio of cure and ‘e’ antigen (HBcAg/HBeAg), their secretion and virus replication, using overlength 1.3 mer/1.86 mer genotype A replicons, and genotype D replicons with and without additional pre-S2/S promoter deletions from cases of occult infection. Results: Genotype D replicon showed a decrease in HBsAg secretion compared to the wild-type genotype A. Genotype D replicons carrying additional pre-S2/S promoter deletions, showed further reduction in HBsAg secretion, demonstrated presence of intracellular HBcAg/HBeAg, virus replication intermediates and ‘e’ antigen secretion. Interpretation & conclusions: The characteristic 33 nt deletion of genotype D HBV reduces HBsAg secretion. Additional pre-S2/S promoter deletions may further diminish HBsAg secretion, leading to occult infection. Pre-S2/S promoter deletions do not affect HBV replication.

Rolling out the first batch of DM (Hepatology) fellows: Will it be considered as a red letter day in the history of Indian Gastroenterology.

Hepatology as a discipline is now well established. Most tertiary care centres in developed nations have hepatology as a distinct discipline. In India, PGIMER in Chandigarh and IPGMER at Kolkata have separate departments of hepatology. In India, a dedicated institute for heptobiliary sciences the ‘Institute of Liver and Biliary Sciences (ILBS)’ has been established in New Delhi. International journals with high impact factors namely ‘Hepatology’, ‘Journal of Hepatology’, ‘Liver International’ publish research work related exclusively to the subspeciality of Hepatology. India has many successful liver transplant centres in many regions. All the above events indicate a global explosion in knowledge of various liver diseases. In the past 3 decades, knowledge in liver diseases in India has also increased exponentially leading to identification of liver disorders predominantly seen in Indian subcontinent. Examples of such diseases would include vascular diseases of liver (NCPF, EHPVO, and HVOTO) hepatitis E virus associated liver problems, parasitic liver and biliary tract diseases. Over and above the burden of other global liver diseases such as alcoholic liver disease NAFLD, HBV & HCV associated liver disorders, drug induced liver injury (DILI) disorders are increasing in this country. By now, the in-depth understanding of etio-pathogenesis of these diseases coupled with novel diagnostic assays, and therapeutic interventions based on modern technologies in physics, biotechnology, bioinformatics and pharmacodynamics has resulted in creation of a the multidimensional subspeciality of hepatology. The subsequent creation of dedicated manpower to use and improve these aspects in hepatology is a natural event. Therefore, few tertiary care centre with adequate infrastructure in hepatology have already started (PGIMER, ILBS) separate training programs for hepatology. A few other centres are in the process of creating (CMC, Vellore: IPGMER, Kolkata) dedicated DM course in the discipline of hepatology. Indeed, the first batch of DM fellows in hepatology have already been trained, evaluated and have been certified as dedicated hepatologists in December 2010 at PGIMER, Chandigarh. This initiates the process of rolling out well trained doctors with DM qualification in hepatology resulting in creation of dedicated man power to resolve issues and improve understanding & therapy in liver disease in India. I think it is a welcome step and definite progress for the discipline, because, it is likely to improve care of patients with liver disease, understanding liver diseases specific for the Indian subcontinent (Tropical hepatology) and refining/modifying approaches to suit Indian patients. I hope that creation of such training centres for the subspeciality of hepatology will gradually get incorporated in many more tertiary care centers and contribute to manpower minfrastructure existing in this country.

Incidence of hepatocellular carcinoma among Indian patients with cirrhosis of liver: an experience from a tertiary care center in northern India.

BACKGROUND/AIM: Despite bearing the main burden of HCC, prospective studies from developing countries are lacking. This prospective observational study was designed to estimate the incidence of HCC among Indian patients with hepatic cirrhosis. METHODS: Between April 2001 and November 2004, we enrolled 301 patients with liver cirrhosis. Patients found to be free of HCC using baseline abdominal ultrasound, triple-phase computed tomography (TPCT) and serum alpha-fetoprotein (AFP) levels were followed up prospectively for detection of HCC using ultrasound and AFP every 6 months, and TPCT annually. RESULTS: Among the 194 patients (mean age [SD] 45.1 [+/-13.1] years; male:female 6.1:1.0) followed up, 154 had Child's A and 40 had Child's B disease. The causes of cirrhosis were: hepatitis B-71 (36.6%), hepatitis C-54 (27.8%), dual infection with hepatitis B and C-12 (6.2%) and others including autoimmune, alcoholic and cryptogenic cirrhosis 57 (29.4%). During a cumulative follow up period of 563.4 person-years, 9 cases of HCC were detected, with an incidence rate of 1.60 per 100 person-years. CONCLUSION: In our study, the incidence of HCC among patients with liver cirrhosis was intermediate, being lower than that in Japan but higher than that reported from Europe.

Hepatitis E virus: epidemiology, diagnosis, pathology and prevention.

HEV, a positive stranded RNA virus, is responsible for most of the epidemics of hepatitis in the developing world and is transmitted through contaminated water. It is the major aetiological agent for acute hepatitis and acute liver failure in endemic regions. It causes severe liver disease among pregnant females and patients with chronic liver disease. Serodiagnosis of HEV is now available and should be used routinely for diagnosis. The available evidence suggests that HEV may also be transmitted parenterally as well as vertically particularly in endemic areas. Experimental studies suggest that an HEV vaccine is a distinct possibility in the near future. In the absence of an effective vaccine, public health measures such as clean water supply, improved sanitation and public education are the major tools to prevent HEV epidemics in developing nations.

Molecular adsorbent and re-circulating system.

The molecular adsorbent recirculating system (MARS) is a non-biological artificial liver support system. Used for almost a decade, there are only two randomized controlled trials on the efficacy of MARS till date. A number of uncontrolled studies have documented a marked improvement in the biochemical parameters of patients after MARS. Although MARS seems to be an effective and promising tool in the management of liver failure, its cost needs to be reduced to enable it use in a member of indications.

Spectrum of hemostatic derangements, in Budd-Chiari syndrome.

BACKGROUND: Hemostatic abnormalities have been reported in various hepatocellular diseases. We evaluated the hemostatic functions in patients with Budd-Chiari syndrome. METHODS: Biochemical liver function tests, and measurement of prothrombin time, activated partial thromboplastin time, and plasma levels of anti-thrombin III (antigen) and activity of protein C were done in 36 patients with Budd-Chiari syndrome. RESULTS: Liver biochemistry was abnormal in 34 patients. Plasma prothrombin time and activated partial thromboplastin time were prolonged in 17 (47%) and 23 (64%) patients, respectively. Antithrombin III antigen levels and protein C activity were reduced in 15 (50%) and 25 (83%) patients, respectively, among the 30 patients studied. Albumin levels showed significant correlation with coagulation test results, levels of anti-thrombin-III, and protein C activity. CONCLUSION: Hepatic synthesis of coagulation factors and anticoagulants is reduced in Budd-Chiari syndrome; this may play a role in recurrence of thrombosis.

Post cholecystectomy hemobilia: transcatheter embolization of pseudoaneurysms with homemade steel coils.

Two patients presented with hemobilia, one and two months following cholecystectomy. Angiography demonstrated pseudoaneurysms arising form the gastroduodenal and right hepatic arteries. Percutaneous transcatheter embolization of the pseudoaneurysms was successfully performed in both patients using homemade steel coils.