Guptan Rc

Prospective randomized trial of endoscopic sclerotherapy versus variceal band ligation for esophageal varices: influence on gastropathy, gastric varices and variceal recurrence

BACKGROUND/AIMS Endoscopic variceal ligation and endoscopic sclerotherapy are both recommended for the prevention of variceal rebleeding. To compare their efficacy, their influence on gastric varices and the development of portal gastropathy, 95 patients with variceal bleeding were studied. METHODS The patients were randomized to receive weekly endoscopic sclerotherapy using alcohol (n=48) or endoscopic variceal ligation (n=47). The endoscopic sclerotherapy and endoscopic variceal ligation groups were comparable in etiology, severity of liver disease and grade of varices. RESULTS In the arrest of acute bleed, endoscopic sclerotherapy and endoscopic variceal ligation were comparable (86% vs. 80%, p=ns). Endoscopic variceal ligation as compared to endoscopic sclerotherapy, obliterated esophageal varices in fewer sessions (4.1+/-1.2 vs. 5.2+/-1.8, p<0.01) and a shorter time (4.4+/-1.3 vs. 6.9+/-3.4 wk, p<0.01). Three (6.4%) patients bled after endoscopic variceal ligation and 10 (20.8%) after endoscopic sclerotherapy (p<0.05). The actuarial percentage of variceal recurrence during a follow-up of 8.5+/-4.4 months, was higher after endoscopic variceal ligation than endoscopic sclerotherapy (28.7% vs 7.5%, p<0.05). Esophageal stricture formation after endoscopic sclerotherapy occurred in five (10.4%) patients, but in none after endoscopic variceal ligation. Significantly more patients developed gastropathy after endoscopic sclerotherapy than ligation (20.5% vs. 2.3%; p=0.02). Endoscopic sclerotherapy (52%) and endoscopic variceal ligation (59%) were equally effective in obliterating the lesser curve gastric varices. Six patients died: three in each group. CONCLUSIONS (i) Endoscopic sclerotherapy and endoscopic variceal ligation were equally effective in controlling acute bleed; (ii) endoscopic ligation achieved variceal obliteration faster and in fewer treatment sessions; (iii) endoscopic variceal ligation had a significantly lower rate of development of portal gastropathy and rebleeding, (iv) while both techniques influenced gastric varices equally, there was significantly higher esophageal variceal recurrence after endoscopic variceal ligation than sclerotherapy.

Beneficial effects of lamivudine in hepatitis B virus-related decompensated cirrhosis

BACKGROUND/AIMS HBV-related chronic liver disease patients often present with hepatic decompensation and are not eligible for interferon therapy. Whether long-term lamivudine is effective in these patients was prospectively evaluated. METHODS Eighteen patients with HBV-related decompensated cirrhosis, all with quantitative DNA +ve and 10 HBeAg +ve, were given lamivudine 150 mg/d. RESULTS Each patient received at least 9 months (mean 17.9) of lamivudine. Three HBeAg+ve patients (30%) seroconverted to anti-HBe and one lost HBsAg during the follow-up. An improvement from baseline in the aspartate aminotransferase (130 vs. 72 IU/l, p<0.04); alanine aminotransferase (111 vs. 58 IU/l, p<0.01) and Child-Pugh score (8.3 vs 6.7, p<0.013) was seen. Lamivudine had no significant side-effects. HBV DNA became undetectable in all patients by 8 weeks of therapy. In three (17%) patients, HBV DNA again became positive at 9, 9 and 27 months. YMDD mutant was, however, detected in only one (6%). A significant reduction was noted in the morbidity and hospitalizations for complications of liver disease before and after starting lamivudine (1.5+/-0.7 vs. 0.6+/-0.7, p<0.002). CONCLUSIONS In decompensated HBV-related cirrhosis, lamivudine: i) is effective in suppressing HBV DNA and seroconversion to anti-HBe (30%), ii) can achieve significant improvement in clinical and biochemical status of liver functions.

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.

Higher efficacy of sequential therapy with interferon-alpha and lamivudine combination compared to lamivudine monotherapy in HBeAg positive chronic hepatitis B patients.

BACKGROUND:Monotherapy with interferon (IFN) or lamivudine is effective in a limited proportion of chronic hepatitis B (CHB) patients. A sequential combination may have better therapeutic effects by sustained viral suppression combined with immunomodulation.AIM:To compare the efficacy of sequential lamivudine and IFN therapy versus lamivudine monotherapy in HBeAg positive CHB patients.PATIENTS AND METHODS:Seventy-five treatment naïve HBeAg positive patients with histologically proven CHB and alanine aminotransferase (ALT) >1.5 × ULN received lamivudine 100 mg per day for 52 wks with IFN 5 MIU per day added for 16 wks after the first 8 wks (group A, n = 38; age 30 ± 12 yr; M:F = 35:3) or lamivudine 100 mg per day for 52 wks (group B, n = 37; age 30 ± 16 yr; M:F = 31:6). Biochemical and virologic responses were assessed at weeks 52 and 76 and analysis was done on intention-to-treat. Serial samples were studied for the emergence of lamivudine-resistant YM552I/VDD mutations by direct sequencing.RESULTS:At week 52, HBeAg loss occurred in 15 (39.5%) in group A and 14 (37.8%) in group B (p = 1.00). HBeAg loss, anti-HBe appearance, and undetectable DNA levels were seen in 26.3% and 13.5% (p = 0.249), respectively. Nine of 10 (90%) patients in group A and 1 of 5 (20%) in group B maintained the response through week 76 (p = 0.017). At week 76, 5 additional patients in group A and 3 in group B further achieved the primary end point and the overall HBeAg loss was observed in 44.7% and 18.9% (p = 0.025) and HBeAg loss, anti-HBe appearance, and undetectable hepatitis B virus (HBV) DNA levels in 36.8% and 10.8% in group A and group B, respectively (p = 0.026). At week 76, undetectable HBV DNA was seen in 39.5% and 16.2% in groups A and B, respectively (p = 0.039). Normal ALT was seen in 47.7% and 40.5% at week 52 (p = 0.489) and ALT was normal in 39.5% and 13.5% at week 76 (p = 0.018) in groups A and B, respectively. YM552I/VDD-resistant mutants emerged in 6 of 38 (15.5%) patients in group A, and 3 of 37 (8.1%) in group B (p = ns). The rate of histological improvement was comparable in the two groups.CONCLUSIONS:Our results demonstrate that sequential therapy is superior to lamivudine monotherapy in achieving sustained seroconversion, ALT normalization, and HBV DNA loss. Compared to 80% with sequential therapy, only 20% Indian patients with CHB did not relapse after stopping lamivudine monotherapy.

Alpha-interferon therapy in chronic hepatitis due to active dual infection with hepatitis B and C viruses

Background : Nearly 14% of non‐alcoholic chronic liver disease in India is related to hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection. There are no clear data available from the literature on the therapeutic management of these patients who often suffer an unfavourable course.

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.

Histological spectrum of chronic hepatitis in precore mutants and wild-type hepatitis B virus infection.

This study compares the histology of liver biopsies in precore mutant (PCM) and wild-type hepatitis B virus (HBV) infection. Thirty cases of PCM and 60 cases of wild-type HBV infection were included. Patients were diagnosed on the basis of serological profile and HBV DNA assessment. Liver biopsies in each case were assessed for histological activity and stage of fibrosis using a modification of Knodells scoring system. There was no statistically significant (P=0.14) difference in histological activity in the two groups. The difference in stage of fibrosis in the two groups was statistically significant (P=0.001). Quantitative estimation of viral load did not show any correlation with liver histology. PCM HBV showed greater stage of fibrosis compared with wild-type infection, and this may be related to disease progression and lack of response to therapy.

Immunogenicity and reactogenicity of a combined high dose hepatitis A and hepatitis B vaccine, compared to that of Twinrix™ in healthy Indian children

BACKGROUND AND AIMS Hepatitis A virus (HAV) and hepatitis B virus (HBV) are vaccine preventable important childhood acquired infectious diseases in developing countries. In the changing epidemiology of HAV, the utility of such a vaccine in India needs urgent attention. Further, the efficacy of two versus three dose schedule needs to be assessed to improve compliance. SUBJECTS AND METHODS One hundred healthy school children, aged 1-15 years were recruited in a randomised open study to receive either vaccination schedule: Group I: combined high-dose hepatitis A and B vaccine to be administered on a 0, 6 month schedule intramuscularly; Group II: to be administered on 0, 1, 6 month Twinrix (GlaxoSmithKline Biologicals, Rixensart, Belgium) schedule intramuscularly. The seroconversion (> or =1MIU/ml for anti-HBs antibodies and > or =33MIU/ml for anti-HAV antibodies) and seroprotection (anti-HBs > or =10MIU/ml after the third dose of vaccine) rates were determined at months 1, 2, and 7. RESULTS The mean age and gender was similar between groups: 7.9+/-2.6 years (range 3-15 years). At month 7 all subjects (100%) in both groups were seropositive for anti-HAV antibodies, Group I had higher anti-HAV titres at months 1 or 2 compared to Group II (P=0.025, P=0.040). Group II developed higher seroprotection rates (month 2, P=0.002, month 6, P=0.003) compared to Group I and higher titres (month 2, P=0.001, month 6 P=0.001) compared to Group I. At month 7, the geometric mean titres (GMTs) were comparable between groups and seroprotection reached 100% in both the groups. The incidence of any symptom per dose analysis reported during a 4-day follow-up period was significantly higher in Group I, 53% (52/98) of the documented doses compared to 37% (54/146) in Group II (P=0.018). CONCLUSION Twinrix vaccine is safe and highly immunogenic in Indian children. Further study of the high dose vaccine would determine if its two dose regimen is a feasible advantage.

Efficacy of granulocyte-macrophage colony-stimulating factor or lamivudine combination with recombinant interferon in non-responders to interferon in hepatitis B virus-related chronic liver disease patients.

Abstract Background and Aims : Non‐response to interferon (IFN) monotherapy is a major therapeutic problem in the management of chronic hepatitis B infection. The efficacy of combination therapy to enhance the immunomodulatory effect of IFN by combining granulocyte‐macrophage colony‐stimulating factor (GMCSF) or decreasing viral load by adding an antiviral agent such as lamivudine was evaluated prospectively.