Experience with concomitant ultrasound-guided foam sclerotherapy and endovenous laser treatment in chronic venous disorder and its influence on Health Related Quality of Life: interim analysis of more than 1000 consecutive procedures.

AIM: The aim of this paper was to evaluate the efficacy of the concomitant use of endovenous laser treatment (ELT) and ultrasound-guided foam sclerotherapy (USGFS) in the management of chronic venous disorder and to objectively analyze the influence of the combination therapy on the Health Related Quality of Life (HRQL) of the treated patients. METHODS: In this prospective series, 1 114 varicose veins in 924 consecutive subjects were treated either with a 980 nm (7-15W) or a 1320 nm (3-10W) endovenous laser. INCLUSION CRITERIA: informed consent, clinical, etiologic, anatomical, and pathophysiological (CEAP) clinical class >or=2, and an accessible vein. EXCLUSION CRITERIA: coagulation disorder, pregnancy, lactation, current thrombosis, systemic disease, poor general health, or allergy to sodium tetradecyl sulfate (STS). ELT was performed on refluxing saphenous truncal and non-saphenous veins, including incompetent perforators. USGFS was utilized to treat selective refluxing, symptomatic varicose tributaries that were not amenable to ELT alone. The Venous Dysfunction Score (VDS) and Health Related Quality of Life (HRQL) were assessed. All of the patients were strictly monitored and had Duplex ultrasound scanning to evaluate for deep vein thrombosis (DVT) at 24-72 hours. Thorough Duplex scanning was done at 1 week, 1 month, 3 months, 6 months, 12 months, and 24 months. RESULTS: At 1 month, there was continued reflux (> 0.5 seconds) in 26 SFJs (3.0%, N=824) and 4 SPJ s (2.5%, N=155) and at 3 months in 15 SFJs (1.8%), 5 SPJ s (3.7%). At 6 months, reflux was present in 10 SFJs (1.2%) and 4 SPJs (2.5%). At a mean of 12+/-10 months of post-treatment follow-up, 4 SFJ (1.9%, N=207) and 1 SPJ (1.9%, N=52) had reflux. Overall, there was elimination of reflux in 98% of junctions. The posterior accessory saphenous veins (PAV: N=117) had 100 % elimination of reflux at 1 month, a result that remained unchanged for more than a year (P<0.001). Similarly, anterior accessory saphenous veins (AAV: N=56), cranial, caudal, or thigh, extensions of the small saphenous vein (CESSV: N=31), and non-saphenous veins and incompetent perforators (NSV, IP: N=31) all had sustained and statistically significant response (P<0.001). Sequentially assessed VDS showed significant improvement (P<0.001). The Aberdeen Varicose Vein Questionnaire (AVVQ) revealed significant improvement in HRQL at 1-2 year (P<0.001). Failed ELT attempts occurred in six cases due to vein spasm (N=4, 0.36%) or fiber/laser machine malfunction (N=2, 0.18%). These veins were successfully treated with ultrasound-guided foam sclerotherapy. Thirty-two patients (2.9%) complained of a small area of numbness at one month. There was complete resolution in 6 (18.8%) of the patients by 6 months. There were four cases of a localized cellulitis at laser venous access sites. These resolved uneventfully with oral antibiotics. There were also two skin reactions, with localized urticaria, due to dressing tape. These required no additional treatment. There were two cases of superficial phlebitis that resolved with continued compression and NSAIDs. There was one asymptomatic popliteal DVT and one uncomplicated superficial skin burn that both resolved uneventfully with no treatment other than observation. No pulmonary embolism (PE), thrombophlebitis, or visual disturbance occurred. CONCLUSIONS: Ultrasound-guided foam sclerotherapy given concomitantly with ELT is safe and highly efficacious in the management of GSV, SSV reflux and in their tributaries or in non-saphenous veins. CVD patients treated with combination therapy given in this manner demonstrated significant improvement in their HRQL.

Role of HBV genotype in predicting response to lamivudine therapy in patients with chronic hepatitis B.

BACKGROUND: Predictors of response of chronic hepatitis B (CHB) to lamivudine therapy need better definition. Whether hepatitis B virus (HBV) genotypes could serve as such a predictor has not been well studied. AIM: To study the association of HBV genotypes with the outcome of lamivudine treatment in patients with CHB. METHODS: Seventy-six patients with CHB (45 HBeAg +ve) received lamivudine 100 mg/day, orally for 12 mo. Infecting HBV genotypes were determined in pre-treatment specimens using restriction fragment length polymorphism. End-of-treatment response (ETR) and sustained viral response (SVR) were defined as undetectable HBV DNA (< 0.5 pg/mL) at 12 and 18 months, respectively. RESULTS: ETR was observed in 26 (34%) and SVR in 11 (14%) patients receiving lamivudine. The pre-treatment characteristics of the responders and non-responders were comparable. Genotypes A and D were observed in 28 (37%) and 48 (63%) patients, respectively. The frequency of genotypes A and D was comparable between responders (28.6% vs. 37.5%) and non-responders (71.4% vs. 62.5%), respectively (p=ns). Of the 26 responders, SVR could be evaluated in 20 subjects; 9 (45%) relapsed and 11 achieved SVR. Patients with genotype D achieved higher SVR rate than genotype A (10 of 48, 28.8% vs. 1 of 28, 3.5% p =0.0359). CONCLUSIONS: Forty-five percent of Indian patients with CHB who achieve ETR relapse, and SVR to lamivudine therapy is achieved in 14%. Patients with genotype D achieve higher SVR rate than with genotype A.

Identification of a novel surface mutant of hepatitis B virus in a seronegative chronic liver disease patient.

Hepatitis B virus (HBV) with mutations in the envelope proteins can emerge during natural infections, vaccinations or interferon therapy and appears occasionally to escape virus elimination or detection. The implications of such mutations at the molecular level are often obscure. We report the identification of a new surface mutant of HBV. This mutant was identified, and isolated from a chronic liver disease patient, negative for HBsAg as well as other serological markers but positive for HBV DNA. Several mutations were observed in the surface antigen gene out of which a Thr118-Ala118 change was predicted to have a destabilizing effect on the structural integrity of the 'a' determinant and also alter the antigenicity profile of the mutant HBsAg. Besides a RNA hairpin loop was predicted for the transcript generated by the small surface protein of this mutant, which could have an inhibitory effect at the translational level. These observations thus indicate that mutations in the surface gene could lead to a considerable decrease or complete absence of properly folded surface antigen which in turn could explain the absence of reactive HBsAg in the serum of the patient.

Prevalence of hepatitis GB virus C/hepatitis G virus infection in blood donors in India.

BACKGROUND: Hepatitis GBV-C/HGV is a newly described RNA virus with a parenteral route of transmission. It has been implicated in fulminant hepatitis and chronic viral hepatitis. We undertook to study the prevalence of GBV-C/HGV infection in blood donors of a tertiary care hospital in India. METHOD: Serum of 221 consecutive blood donors was tested for HBsAg, anti-HCV by EIA and HGV RNA by RT-PCR. Two sets of primers; one from the 5'non-coding region and other from NS5a region of the HGV genome, were used for amplification. RESULTS: Prevalence of HGV RNA was found to be very low in healthy blood donors. Only two of the 221 (0.9%) donors were found to be HGV RNA positive. HBsAg and AntiHCV were found to be present in 5.43% (12/221) and 1.31% (3/221) respectively. Dual infection was seen in two of the 221 (0.9%) patients; one patient had HBsAg and HGV RNA positivity, while the other, had HBsAg and AntiHCV positivity. CONCLUSION: GBV-C/HGV is an uncommon infection in healthy blood donors in India, especially when compared to the prevalence of HBV and HCV infection. It is therefore unlikely to be an important cause of transfusion associated hepatitis in India.

Increased frequency of gallstones in cirrhotic and non-cirrhotic portal hypertension.

BACKGROUND: The prevalence of gallstones is high in cirrhotics compared with the general population. It is not clear whether cirrhosis per se or presence of portal hypertension influences this increased frequency. MATERIAL AND METHODS: Six hundred and fifteen patients with portal hypertension; 412 cirrhosis (69 alcoholic and 343 non-alcoholic), 88 non-cirrhotic portal fibrosis (NCPF) and 115 extrahepatic portal vein obstruction (EHPVO) were prospectively studied by using real time ultrasound to investigate the prevalence of gallstones in comparison to a matched healthy population. RESULTS: Gallstones were observed in 44 (7.2%) portal hypertension patients compared with 19 (3.1%) controls (p < 0.01), the risk ratio was 2.41 (CI=1.35-4.35, OR 95%). The prevalence of gallstones was 6.8% in cirrhosis, 10.2% in NCPF and 4.3% in EHPVO patients. The overall prevalence was similar in cirrhosis and non-cirrhotics (6.8% vs 6.6%). Gallstones were slightly more common in alcoholic than non-alcoholic cirrhotics (8.3% vs. 6.0%), patients with Child's C than A and B disease (8.2% vs. 5.4%), the differences were however, not significant. Portal pressure as assessed by intravariceal pressure estimation (n=102) was comparable in patients with cirrhosis, NCPF and EHPVO. CONCLUSIONS: (i) Gallstones are more than two times common in portal hypertension patients compared to the control population, and (ii) since gall stones are equally common in cirrhotic and non-cirrhotic portal hypertension; a role of portal hypertension per se in the genesis of gallstones needs to be considered.

Clinical implications of viral activity in dual infection with hepatitis B and C in chronic liver disease.

BACKGROUND: There is limited information on the clinical and biochemical profile of chronic liver disease due to dual infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. There are variable reports on the severity of liver disease in dual infections. This is important, from clinical and therapeutic point of view. The present study analyzes liver disease in dual infections as compared to HBV and HCV infection present alone. MATERIAL AND METHODS: Out of 186 histologically proven non-alcoholic chronic liver disease patients, 30 (16.1%) were serologically diagnosed to be HBV and HCV dual infection (Group A, n=30). The clinical profile of these patients was compared with consecutively seen HBV related (Group B, n=30) and HCV related chronic liver disease (Group C, n=30) patients. Patients with dual infection were further grouped based on predominant HBV or HCV viral activity. RESULTS: Patients with dual infection were younger than those with chronic HCV infection (38.4 +/- 14.4 vs. 45.9 +/- 14.7 years, p < 0.05); with male predominance (p=0.06). Patients with chronic HCV infection more often presented with low-grade fever than dual infection group (60% vs. 30%, p < 0.05). Ascites and variceal bleeding were common presentations of HBV related cirrhosis. Patients with dual infection had significantly more deranged liver functions. The duration of illness was shorter in these patients compared with chronic HCV (2.9 +/- 1.6 vs. 7.3 +/- 1.4 year, p < 0.05). When patients with dual infection were subgrouped on HBV DNA and HCV RNA positivity, there was a tendency for increased biochemical derangement with active HBV infectionity. CONCLUSIONS: Our results highlight the fact that patients with HBV and HCV dual infection related chronic liver disease have a more aggressive course. There is a tendency for a more severe liver disease when HBV is active in the dual infection group.

Low prevalence of hepatitis C viral infection in patients with non-alcoholic chronic liver disease in India.

To investigate the prevalence and profile of chronic liver disease due to hepatitis B (HBV) and C (HCV) infection in patients with non-alcoholic chronic liver disease in North India, 148 biopsy proven patients (73 with a history of transfusion and 75 non-transfused) were studied. Detection of hepatitis B included HBsAg, AntiHBc, and HBV DNA testing. Presence of HCV infection was investigated by EIA using second generation tests and confirmed by RIBA III and HCV RNA testing. Eighty three (56.1%) patients had cirrhosis related to hepatitis B, 13 (15.7%) of them had precore (HBeAg -ve, HBVDNA +ve) and 11 (13%) had surface (HBsAg-ve, IgM antiHBc-ve, HBVDNA +ve) mutation. Antibodies to HCV were found in 16 (10.8%) patients. Dual infection with HBV and HCV was seen in 20 (13.5%) patients. Twenty nine (19.5%) patients, had cryptogenic cirrhosis as none of the markers for HBV or HCV infection was positive. In conclusion, our results demonstrate that HBV was the most prevalent viral infection associated with chronic liver disease patients in North India. Prevalence of HCV infection was low. Studies to detect HBV mutants and other viruses should be done in patients with suspected cryptogenic cirrhosis of the liver.

Prevalence of hepatitis B infection within family contacts of chronic liver disease patients--does HBeAg positivity really matter?

BACKGROUND: The risk of infectivity is known to be high in contacts of HBeAg positive chronically infected patient. We investigated and compared the frequency and significance of transmission of HBV infection from chronic liver disease patients (CLD) with HBeAg or anti-HBe and HBV DNA positive status. MATERIAL AND METHODS: Four hundred and seventy nine contacts [first degree blood relatives (n=278), second degree contacts (n=139) and sexual contacts (n=62)] of 92 HBV-related, liver biopsy proven, CLD patients were studied. Three hundred and seventy three belonged to 65 index patients with HBsAg+ve, HBeAg+ve, HBV DNA+ve, HBV DNA+ve infection and 106 belonged to 27 index patients with (HBsAg+ve, HBeAg-ve, anti-HBe+ve, HBV DNA+ve infection). One hundred and seventy six family members, age and sex matched, belonging to 38 healthy individuals, with no history of liver disease or HBV positivity, served as controls. Viral serology and quantitative DNA estimation was done in index patients. RESULTS: Forty nine of 65 (75.4%) families of HBeAg+ve and 63% families of HBeAg-ve index patients had one or more family member exposed to HBV (positive family, p=ns). The chronic HBV infection (HBsAg+ve) and past-exposure (only IgG anti-HBc+ve) rates in the contacts of HBeAg+ve and HBeAg-ve index patients were 17.4% and 19.8% (p=ns), and 31% and 14.2% respectively, both being significantly higher (P < 0.01) than the prevalence rates in the control group (chronic HBV infection 2.3%, past-exposure 10.2%). Overall, 48.5% and 34% (p < 0.05) of contacts in the HBeAg+ve and HBeAg-ve groups had markers of HBV infection. The quantitative HBV DNA levels were comparable between HBeAg+ve and HBeAg-ve index patients (1712 +/- 356 pg/ml vs 1802 +/- 812 pg/ml). First degree relatives had higher chronic HBV infection rates than second degree contacts (29% vs. 0%, p < 0.05). The duration of symptomatic illness of HBeAg+ve index patients was longer than HBeAg-ve (p < 0.05). A significant proportion of HBsAg+ve first degree relatives of HBeAg+ve (33%) and HBeAg-ve (40%) patients, had evidence of CLD. CONCLUSIONS: (i) The frequency of transmission of HBV infection is nearly similar in contacts of HBeAg+ve and HBeAg-ve infected patients, more so in first degree relatives, (ii) these observations make family contacts a very high risk group, requiring priority screening and vaccination against HBV.

High seroprevalence and clinical significance of hepatitis B and C infection in hospitalized patients with alcoholic cirrhosis.

OBJECTIVES: Patients with alcoholic cirrhosis (AC) are frequently infected with hepatotropic viruses which could alter the clinical spectrum of the disease. We studied the seroprevalence of hepatitis B (HBV) and hepatitis C virus (HCV) and their impact on the clinical profile of patients with AC. METHODS: Two hundred and ten hospitalized patients of AC were studied and screened for markers of HBV and HCV infection. Clinical, biochemical and virological correlation was done. RESULTS: One hundred and forty (66.6%) patients had no viral infection Group I, 50 (23.8%) were positive for HBsAg Group II and 20 (9.5%) for anti-HCV Group III. All patients were males with comparable ages (43.9 years, 44 years and 45.9 years respectively). The amount of alcohol consumed by patients in Group III (130 +/- 115 g/d) was significantly less than Group II (204 +/- 130 g/d, P < 0.05) and Group I (281 +/- 188 g/d, p < 0.001). The duration of alcohol abuse was shorter in Group II and III, although not statistically significant. Presentation as jaundice was common in Group II and III (p < 0.05). The AST and ALT values (IU/L) were significantly higher in Group II (239 +/- 351, 197 +/- 266) and III (157 +/- 170, 86 +/- 52) than Group I (89 +/- 78, 66 +/- 54) (P < 0.05). The serum alkaline phosphatase (IU/L) was higher in Group III (349 +/- 223) as compared to Group II (263 +/- 186) and Group I (162 +/- 62) (P < 0.05). There was however, no difference in Child's grade or the discriminant function between the three groups of patients. CONCLUSIONS: (i) One-third of the hospitalized patients with AC are infected with HBV or HCV infection, (ii) these infections hasten clinical presentation of patients with alcoholic liver disease, with lesser amount of alcohol consumption and (iii) jaundice, raised ALT/AST and alkaline phosphatase are more common with superadded viral infection.

Restless legs syndrome in patients with chronic venous disorders: an untold story.

OBJECTIVES: To prospectively study the profile of restless leg syndrome (RLS) in patients presenting to a phlebology practice. METHODS: The study uses prospective questionnaire and clinical observation study. In all, 174 consecutive patients and 174 matched controls were evaluated in detail. The diagnosis of restless legs syndrome (RLS) was established by the International RLS study group (IRLSSG) criteria. Detailed clinical, systemic and Duplex ultrasound evaluations were done to establish the presence of chronic venous disorders (CVD) (reflux > 0.5 s on augmentation manoeuvers and revised clinical, aetiological, anatomical and pathological [CEAP] criteria). RESULTS: Of the 174 consecutive subjects studied (22M: 152F), 63 (36%) had evidence of RLS compared with only 34 of 174 of the controls (19%, P < 0.05). Sixty-two (98%) of these RLS-positive study subjects were subsequently diagnosed with CVD. In comparison, 31 (91%) of the RLS-positive control subjects (n = 34) were found to have CVD. This prevalence of CVD was comparable with RLS-positive study subjects, but was significantly higher than the prevalence in CVD in RLS-negative controls (P < 0.01). Only three (9%) of the controls had RLS without CVD. RLS-positive subjects were typically women above the age of 40 years (P < 0.01 vs. men, P < 0.01 vs. below 40 years). A significant difference in clinical presentation in the study subjects was the high prevalence of leg cramps in the RLS-positive subjects (P < 0.01). None of the patients with RLS in this series gave history of anaemia, chronic renal failure or an established psychiatric or neurological disease as found pathognomic for RLS by others. CONCLUSIONS: RLS appears to be a common overlapping clinical syndrome in patients with CVD. Prospective blinded therapeutic trials are planned to study the influence of definitive treatments for CVD on sequential RLS scores.

Low Prevalence of Hepatitis C Virus Genotype -1b in Chronic Liver Disease Patients in India.

BACKGROUND: The Hepatitis C Virus (HCV) genome shows significant heterogeneity due to a high rate of mutatio; this has a potential bearing on the outcome of interferon therapy. Genotype-1b is known to be less responsive to interferon. We studied the spectrum of HCV genotypes in chronic liver disease (CLD) patients in India. MATERIAL AND METHODS: HCV RNA was extracted from the serum of 44 randomly selected cases of HCV-related CLD, proven by liver biopsy, (mean age of patients 40±15 yr., cirrhotic: 32%) and RT PCR was carried out. The amplicon of 240 bp (second nested PCR) was hybridized to the probes (type specific) coated on to a nitrocellulose membrane. Following this, streptavidin, labeled with alkaline phosphatase, was added to bind with biotinylated hybrid, which with chromogen type-specific band formation resulted. Patients were classified on the occurrence of one (Group I), two (Group II) or multiple genotypes (Group III). RESULTS: Genotypes 1 and 3 were the commonest genotypes, followed by type 2 and the rare genotype 4b in a lone patient. Genotype 1 was seen in 39% (1a 23%, and 1b 16%) while genotype 3 in 45% (3a 23% and 3b 7%) patients. Eighty percent (35 of 44) patients had the single genotype (Group I, mean age 46 ± 8 yr.), 14% had two genotypes (Group II, mean age 36 ± 16 yr.) and the remaining (Group III, mean age 22 ± 9 yr.) had multiple genotypes. Serum ALT levels in these three groups of patients were 117 ± 92, 85 ± 45 and 49 ± 7 IU/L respectively. CONCLUSIONS: Genotypes 1 and 3 are common in India, with subtype 1b not so common,A unique genotype 4 b was detected in one patient,Indian patients have the possibility of good antiviral response to interferon therapy in chronic HCV infection.

Low Specificity of the Third Generation Elisa for HCV Detection in Voluntary Blood Donors in India.

OBJECTIVE: Third generation anti-HCV ELISA is currently recommended for the diagnosis of HCV infection. We determined its specificity in voluntary blood donors (VBDs) and patients with chronic liver disease (CLD) in relation to confirmatory line immunoassay (LIA) and reverse transcription polymerase chain reaction (RT-PCR). MATERIAL AND METHODS: 1926 serum samples of VBDs and 16 HCV related CLD patients were screened by ELISA. An optical density/cut-off ratio (OCR) of >1 was taken as positive for anti-HCV antibodies. Samples were confirmed by LIA and HCV-RNA detection by RT-PCR. Interpretation of LIA was done as: indeterminate, reactive or non-reactive. Every 50th VBD sample, negative for anti-HCV by LIA was subjected to LIA and RT-PCR to rule out false negativity of ELISA. RESULTS: Anti-HCV was positive in 34 (1.76%) VBDs and all the CLD patients. Only one (2.9%) VBD was reactive by LIA and 6 (17.6%) were HCV-RNA positive. Serum samples from VBDs with OCR >3 were significantly more often (p<0.05) PCR positive than those with an OCR of >3. In the CLD patients, specimens even with OCR between 1-3 were reactive by PCR. All ELISA negative samples were non-reactive by LIA and PCR. CONCLUSIONS: (i) There is a high false positivity of the third generation ELISA for the diagnosis of HCV infection in VBDs, (ii) Higher OCR should be used for improving the specificity of ELISA in VBDs, (iii) VBDs with an OCR of >3 should be subjected to HCV-RNA determination.

Enhanced immunogenicity of recombinant hepatitis B vaccine in exposed family contacts of chronic liver disease patients.

Close family contacts of hepatitis B virus (HBV)-related chronic liver disease patients have a high risk of exposure to HBV. Variable responses to vaccination have been reported in family contacts, especially in previously exposed contacts (IgG antiHBc-positive). Seventy-nine healthy family contacts, who were HBsAg-negative with normal alanine amino-transferase level and no evidence of liver disease, were vaccinated using a recombinant HBV vaccine, irrespective of past exposure status. A significantly higher number of previously exposed subjects (n = 25; Group I) developed early seroprotective anti-HBs titers with 2 initial doses of vaccine compared to the unexposed contacts (Group II; n = 54) (64% vs. 33%, respectively; P < 0.05). However, the responses were comparable on completion of the schedule (96% vs. 94%, respectively). HBV DNA was detected in 11 of 25 (44%) exposed and none of the unexposed contacts at baseline. Post-vaccination, 3 of 11 (27%) subjects became HBV DNA-negative and remained negative for the next 12 months. These results suggest that exposed family contacts achieve efficient seroprotection after HBV vaccination, irrespective of the IgG anti-HBc status. The response to vaccination resembles an anamnestic reaction and possibly demonstrates a therapeutic effect.

Dietary and nutritional abnormalities in alcoholic liver disease: a comparison with chronic alcoholics without liver disease.

OBJECTIVE: To document the profile and role of malnutrition in alcoholic hepatitis, compared with chronic alcoholics and nonalcoholic chronic liver disease. METHODS: To this end, we studied 67 patients with alcoholic liver disease (ALD) (group I), 52 chronic alcoholics without histological evidence of liver disease (group II), 44 nonalcoholic cirrhotics (group III), and 52 healthy controls (group IV). Alcoholic and nonalcoholic calories were calculated and percentage dietary and nutritional deficiencies computed. Anthropometric indices, nitrogen balance, and immune status of the patients were assessed. RESULTS: Alcohol constituted about 48% of daily caloric intake in patients with ALD. The percentage mean intake of carbohydrate, protein, and energy was decreased in all three study groups compared with controls. The deficiencies were more pronounced in patients with severe than with moderate ALD. These deficiencies were more severe in the group III patients. Whereas body fat stores were maintained in groups I and II, reduction in lean body mass and serum transferrin was significant in patients in groups I and III. In group II patients compared to group I patients, the body mass index (19.9 +/- 4.0 vs. 22.3 +/- 3.4) and triceps skinfold thickness (6.1 +/- 4.8 vs. 10.2 +/- 5.6 mm) were significantly lower. CONCLUSIONS: 1) protein energy malnutrition is common in both alcoholic and nonalcoholic cirrhotics, but is more pronounced in the latter; 2) the degree and profile of malnutrition in chronic alcoholics and in alcoholic cirrhotics are comparable; 3) based on our results, we hypothesize that malnutrition may not play a primary role in the pathogenesis of ALD.

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 antige (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: 1. Interferon therapy is beneficial, albeit to a limited extent, in HBV precore mutant-related chronic liver disease in Asian Indians. 2. It is ineffective in eliminating the mutant HBV infection, which explains the high relapse rate. 3. Prolonged low-dose interferon therapy alone or in combination with newer nucleoside analogues should be evaluated in these patients.

Frequency and clinical profile of precore and surface hepatitis B mutants in Asian-Indian patients with chronic liver disease.

BACKGROUND: Infection due to hepatitis B virus (HBV) could be due to wild or mutant (precore or surface) viruses. The prevalence and clinical profile of different viral forms in patients with chronic liver disease has not been established. METHODS: One hundred and twenty patients with histologically proven HBV-related chronic liver disease were studied. Patients with dual infection with HCV/HDV/HIV, past history of interferon therapy, or autoimmune hepatitis were excluded. Eighteen (15.5%) patients had the precore mutation (HBsAg +ve, HBeAg -ve/anti-HBe +ve, HBV DNA +ve), and 13 (10.8%) had the surface gene mutations (HBsAg -ve, HBeAg -ve, IgG anti-HBc, and HBV DNA +ve). The remaining 89 (74.2%) patients were infected with wild type HBV. The course of all patients with mutant forms and 41 of those with the wild type form was followed for a mean (+/- SD) of 4.4 +/- 2.4 yr. RESULTS: Compared with wild-type-infected patients, those with surface mutation were younger (39.9 +/- 14 vs. 30.1 +/- 12.4 yr, p < 0.05). Patients with precore mutations had a shorter illness than those with surface mutant (p < 0.01) and wild forms (p < 0.05). Histologically, patients with precore type had more active liver disease than wild type (39% vs. 15%, p < 0.05). Patients with precore mutations were always symptomatic, often presenting with ascites (67%) and jaundice (55%). Patients with surface mutant forms often presented with quiescent cirrhosis (77%) or cirrhosis with hepatoma (15%). CONCLUSIONS: One-fourth of HBV-related chronic liver disease in Asian Indians is attributable to mutant HBV forms. The presence of variant viruses alters the natural history of the disease, with the precore variance having a more aggressive course and the surface mutant, a more quiescent but unfavorable course, compared with the wild type.

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. METHODS: Fourteen consecutive cases of biopsy-proven chronic liver disease fulfilling the following criteria were included: Child's A or B liver disease, hepatitis B surface antigen positive, HBV-DNA positive, antibody to HCV positive and HCV-RNA positive. Seven patients had chronic liver disease (group I), while the remaining seven patients (group II) had additional disorders (non-Hodgkin's lymphoma (two), acute leukaemia (two), thalassaemia (two), chronic renal failure (one). Interferon alpha-2b (IFN) was given in a dose of 6 MIU thrice weekly for 6 months. Complete response was defined as loss of HBV-DNA and HCV-RNA at 6 months and sustained response (SR) as the sustained loss of HBV-DNA and HCV-RNA for more than 6 months during the follow-up period. RESULTS: At the end of 6 months, alanine aminotransferase (ALT) levels remained unchanged (120 +/- 40 vs 136 +/- 64 IU/L), but six of the seven (86%) patients in group I lost HBV-DNA. All three hepatitis Be antigen (HBeAg)-positive patients lost HBeAg with an early flare of ALT (at 45 +/- 12 therapy days). Two of these patients (29%) lost HCV-RNA. Thus, SR was seen in 29%, while HBV-DNA loss was found in 100% during the follow-up period. In group II patients, there was a significant decrease in ALT (308 +/- 14 vs 65 +/- 25 IU/L, P < 0.001), but only three (43%) patients lost HBV-DNA and two (29%) lost HCV-RNA. One patient with acute leukaemia and another with renal failure had a complete response to IFN, but none of the lymphoma patients showed any antiviral response. CONCLUSIONS: In chronic hepatitis due to dual infection with HBV and HCV, interferon therapy is: (i) safe; (ii) effective (more so in clearing HBV); (iii) often associated with early ALT flare; and (iv) may be less effective if non-Hodgkin's lymphoma is present.