Veena Malhotra

Profile, spectrum and significance of HBV genotypes in chronic liver disease patients in the Indian subcontinent

Background and Aim Certain hepatitis B virus (HBV) genotypes have been alleged to be associated with the development of cirrhosis and hepatocellular carcinoma (HCC), and the response to interferon therapy in Taiwanese patients. We undertook to study the prevalence and significance of HBV genotypes in the Indian subcontinent.

Beneficial effects of tumor necrosis factor-α inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis

BACKGROUND:Tumor necrosis factor-α (TNF-α) has been incriminated to play an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Pentoxifylline, a TNF-α inhibitor could prove useful in treating patients with NASH.METHODS:Eighteen patients (mean age, 34 ± 7.8 yr) with histologically proven NASH and with persistently elevated ALT (>1.5 times) were given pentoxifylline at a dosage of 400 mg t.i.d. for 6 months. No lipid-lowering agent or antioxidants were concurrently advised.RESULTS:Impaired fasting glycemia, impaired glucose tolerance, diabetes mellitus, and hypertriglyceridemia were noted in 6, 35, 17, and 53% of the patients, respectively.After 6 months of therapy, fatigue improved (55.6 vs 20%, P = 0.016), but serum triglyceride (182 ± 66 vs 160 ± 55 mg/dl, P = 0.397), cholesterol (173 ± 46 vs 162 ± 40 mg/dl, P = 0.440), and body mass index (BMI) (27.3 ± 3.1 vs 26 ± 3.1 kg/m2, P = 0.087) remained unchanged. Mean AST (66 ± 29 vs 33 ± 11 IU/l, p < 0.0001) and ALT (109 ± 44 vs 47 ± 20 IU/l, p < 0.0001) reduced significantly. ALT normalized in 23% at month 1 (P = 0.125), 35% at month 2 (P = 0.125), and 60% at month 6 (P = 0.008) of treatment. The insulin resistance index assessed by homeostatic metabolic assessment (HOMAIR) improved (5.1 ± 3.4 vs 2.6 ± 2, p = 0.046) and the serum TNF-α reduced significantly after therapy (22.15 ± 2.49 vs 17 ± 2.58 pg/ml, p = 0.011). The drug was well tolerated.CONCLUSIONS:In patients with NASH, pentoxifylline therapy effectively achieved significant clinical and biochemical improvement with reduction in HOMAIR. These benefits are possibly mediated through suppression of TNF-α.

Beneficial effects of pentoxifylline on hepatic steatosis, fibrosis and necroinflammation in patients with non‐alcoholic steatohepatitis

Background and Aim:  Inhibition of tumor necrosis factor (TNF)‐α is a logical approach to manage patients with non‐alcoholic steatohepatitis (NASH). Pentoxifylline reduces TNF‐α and alanine aminotransferase (ALT) levels in patients with NASH. The aim of the present paper was to study if pentoxifylline can improve histological injury in patients with NASH.

Profile of hepatocellular carcinoma in India: An insight into the possible etiologic associations

Several etiologic factors including hepatitis viruses, alcohol and aflatoxin have been implicated in the pathogenesis of hepatocellular carcinoma (HCC). There is, however, limited information from the Indian subcontinent.

Autoimmune hepatitis in the Indian subcontinent: 7 years experience.

Background: Autoimmune hepatitis (AIH) is presumed to be rare in India. The present prospective study was carried out to determine the prevalence, clinical, biochemical and histological profile of patients with AIH in India.

Efficacy of low-dose alpha interferon therapy in HBV-related chronic liver disease in Asian Indians: a randomized controlled trial

BACKGROUND/AIMS Interferon therapy has been shown to be effective in Western patients with chronic hepatitis due to hepatitis B viral infection, but not in Asian Chinese. Its efficacy in Asian Indian subjects with chronic HBV infection is not known. METHODS Forty-one patients with HBV-related chronic liver disease received randomly either: (a) recombinant alpha 2b interferon (n = 20) 3 MIU, subcutaneously, three times a week for 4 months, or (b) no treatment (n = 21). Patients were followed up for 12 months after completion of therapy. RESULTS In the interferon-treated group, complete response (loss of HBV-DNA and HBeAg) was significantly higher than spontaneous clearance in the control group (50% vs. 4.8% p < 0.05). Seroconversion to anti-HBe was seen in 35% of the treated and 4.8% of the control group (p < 0.05) at 4 months; it was noticeably higher in patients with chronic hepatitis than in those with cirrhosis. In the responders, alanine aminotransferase levels nearly normalized. One year after interferon therapy, HBeAg and HBV-DNA clearance was observed in 65% of patients, with HBsAg clearance in 15%. Reactivation was not seen in any patient. Side-effects were transient and minimal. CONCLUSION Low-dose recombinant alpha interferon therapy is quite effective and safe in Asian Indians with chronic liver disease due to hepatitis B infection.

Absence of hemochromatosis associated Cys282Tyr HFE gene mutation and low frequency of hemochromatosis phenotype in nonalcoholic chronic liver disease patients in India.

Background and Aim:  Hereditary hemochromatosis (HHC) is an autosomal recessive disorder causing primary iron overload syndrome and chronic liver disease (CLD). This genetic disease is commonly associated with C282Y mutation of the HFE gene, commonly seen in the Northern European population. Minor reports on HHC are available from Asia, however, so far no genetic study is available from India. We prospectively studied the prevalence of C282Y mutation in CLD patients and healthy subjects in a tertiary care referral center in India.

Primary prophylaxis of gastroesophageal variceal bleeding: consensus recommendations of the Asian Pacific Association for the Study of the Liver

The Asian Pacific Association for the Study of the Liver (APASL) set up a Working Party on Portal Hypertension in 2002, with a mandate to develop consensus guidelines on various clinical aspects of portal hypertension relevant to disease patterns and clinical practice in the Asia-Pacific region. Variceal bleeding is a consequence of portal hypertension, which, in turn, is the major complication of liver cirrhosis. Primary prophylaxis to prevent the first bleed from varices is one of the most important strategies for reducing the mortality in cirrhotic patients. Experts predominantly from the Asia-Pacific region were requested to identify the different aspects of primary prophylaxis and develop the consensus guidelines. The APASL Working Party on Portal Hypertension evaluated the various therapies that have been used for the prevention of first variceal bleeding. A 2-day meeting was held on January 12 and 13, 2007, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and were subsequently presented at the annual conference of the APASL at Kyoto, Japan, in March 2007.

A case of hepatocellular carcinoma associated with troublesome hypoglycemia: management by cytoreduction using percutaneous ethanol injection

Hypoglycemia is a well known paraneoplastic manifestation of hepatocellular carcinoma. However, hypoglycemia as the first presentation is extremely uncommon. We herein report a case of HCC presenting with severe, uncontrollable hypoglycemia that was managed with percutaneous ethanol injection therapy.

Low-dose recombinant interferon therapy in anti-HBe-positive chronic hepatitis B in Asian Indians

Approximately 15% of Indian patients with hepatitis B virus (HBV)‐related chronic liver disease (CLD) have infection with precore mutant forms. These patients are likely to have an aggressive course. There are equivocal reports of success with interferon therapy of mutant infection in the West. This therapy has not been evaluated in precore mutant‐related CLD in Asian Indians. Eighteen patients (mean age 38.2 ± 12 years, M: F: 17: 1) with biopsy proven CLD and precore mutant HBV infection (hepatitis B surface antigen (HBsAg) positive, hepatitis B e antigen (HBeAg) negative, anti‐HBe positive, HBV‐DNA positive) were included. Interferon alpha 2b was given at 3 mIU on alternate days for 4 months. Serology, determination of HBV‐DNA (both by dot‐blot hybridization and polymerase chain reaction) and liver biopsy were repeated after completion of the therapy. Response to interferon therapy was defined as loss of HBV‐DNA by dot‐blot hybridization. Thirteen (72.2%) patients responded to the treatment (responders). Mean alanine aminotransferase levels (83 ± 12 vs 55 ± 29 IU/L, P < 0.01) and the histological activity index (15 ± 1.4 vs 12 ± 1.3, P < 0.01) significantly decreased in the responders compared with initial values. Serum albumin levels also improved at the end of the therapy (3.5 ± 0.4 g/dL vs 3.8 ± 0.4 g/dL, P= 0.07). During follow up, seven of the 13 (54%) responders relapsed; cirrhotics relapsed more often than chronic hepatitis patients (P < 0.05). All 18 patients, however, continued to be HBV‐DNA positive at the end of follow up. This study concluded that: