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S K Sarin

Publications and source records attributed to S K Sarin.

At least 19 recordsLinked to original sources
PubMed2002

Non-cirrhotic portal fibrosis: current concepts and management.

Non-cirrhotic portal hypertension (NCPH) comprises diseases having an increase in portal pressure (PP) due to intraheptic or prehepatic lesions, in the absence of cirrhosis. The lesions are generally vascular, either in the portal vein, its branches or in the perisinusoidal area. Because the wedged hepatic venous pressure is near normal, measurement of intravariceal or intrasplenic pressure is needed to assess PP. The majority of diseases included in the category of NCPH are well-characterized disease entities where portal hypertension (PHT) is a late manifestation and, hence, these are not discussed. Two diseases that present only with features of PHT and are common in developing countries are non-cirrhotic portal fibrosis (NCPF) and extrahepatic portal vein obstruction (EHPVO). Non-cirrhotic portal fibrosis is a syndrome of obscure etiology, characterized by 'obliterative portovenopathy' leading to PHT, massive splenomegaly and well-tolerated episodes of variceal bleeding in young adults from low socioeconomic backgrounds, having near normal hepatic functions. In some parts of the world, NCPF is called idiopathic portal hypertension (IPH) or 'hepatoportal sclerosis'. Because 85-95% of patients with NCPF and EHPVO present with variceal bleeding, treatment involves management with endoscopic sclerotherapy (EST) or variceal ligation (EVL). These therapies are effective in approximately 90-95% of patients. Gastric varices are another common cause of upper gastrointestinal bleeding in these patients and these can be managed with cyanoacrylate glue injection or surgery. Other indications for surgery include failure of EST/EVL, and symptomatic hypersplenism. The prognosis of patients with NCPF is good and 5 years survival in patients in whom variceal bleeding can be controlled has been reported to be approximately 95-100%.

Diagnosis, Differential↗
PubMed2002

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.

Adult↗
PubMed2002

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.

Adult↗
PubMed2001

Gastric varices and portal hypertensive gastropathy.

Gastric varices and portal hypertensive gastropathy (PHG) are an important complication of both generalized and segmental portal hypertension. The natural history and risk factors for bleed from GV are not extensively studied as that for esophageal varices. Recently, effective therapy for gastric variceal bleed in form of tissue adhesives, balloon-occluded retrograde transvenous obliteration of gastric varices (BRTO) has been developed. Further advances are still needed regarding natural history, risk factors, bleeding, and mechanism of GV rupture.

Catheterization↗
PubMed2001

Base-pair alterations in the epsilon-lower stem due to a novel double substitution in the precore gene of HBV-e negative variant were recovered by secondary mutations.

The HBe negative phenotype, a natural precore mutant (G1896A/G1897A) of HBV with aborted HBeAg expression is known to cause chronic hepatitis. The destabilized C : G base-pairing in the lower stem of epsilon-hairpin due to G1896A substitution is reportedly compensated by a second C1858T mutation and suggested to play an important role in enhanced selection of the HBe negative variant. We undertook to investigate presence of such compensatory mutations at other positions by analyzing epsilon-sequences (nts. 1847-1907) as well as to look for their effect(s), if any, on the consensus sequence of the overlapping core-initiator of HBe negative HBV variants in CLD patients. Three of the 5 HBe negative patients had classical G1896A mutation having a second compensatory mutation at nt. 1858. One patient showed an additional G1897A substitution, presenting as a novel precore stop codon mutation (UGG-->UAA), followed by a compensatory mutation at position 1857. In the third patient, a G1899A substitution was seen which compensated the impaired U at position 1855. Other substitution and deletion mutations were also observed in the remaining epsilon-hairpin, which however, did not produce any compensatory mutation. Further, all the precore variants showed a conserved G at position 1904, important for the optimal context of their core-initiator which however, remained impaired with A (nt. 1850). Our results suggest that the nts. 1851-1859 and nts. 1895-1904 in the lower stem, and restoration of authentic base-pairings therein, maintain the structural integrity and stability of the epsilon-hairpin. This may have a role in the enhanced selection of the HBe negative variants and persistence of HBV infection in chronic liver disease patients.

Base Pairing↗
PubMed2001

Coagulation profile and platelet function in patients with extrahepatic portal vein obstruction and non-cirrhotic portal fibrosis.

BACKGROUND AND AIMS: Coagulation disorders commonly develop in patients with cirrhosis of the liver. They have also been reported in patients with non-cirrhotic portal fibrosis (NCPF) and extra-hepatic portal venous obstruction (EHPVO); the two conditions with portal hypertension and near-normal liver functions. The spectrum and prevalence of coagulation abnormalities and their association with the pathogenesis of these diseases and with hypersplenism was prospectively studied. METHODS: Eighteen EHPVO patients that included an equal number of NCPF patients and 20 healthy controls were prospectively studied. The coagulation parameters assessed included: international normalized ratio, partial thromboplastin time, and fibrinogen and fibrinogen degradation products. Platelet aggregation and malondialdehyde levels were measured. RESULTS: Both EHPVO (83%) and NCPF (78%) patients had a significantly prolonged international normalized ratio and a decrease in fibrinogen and platelet aggregation. The EHPVO patients had a significant prolongation in partial thromboplastin time (67% patients), with increased levels of fibrinogen degradation product levels occurring in all patients; these were normal in NCPF patients. Platelet malondialdehyde levels were normal in both groups. Hypersplenism was present in four EHPVO and seven NCPF patients. It did not significantly influence the coagulation profile in either NCPF or EHPVO patients. CONCLUSIONS: Coagulation anomalies are common and significant in both NCPF and EHPVO patients, suggestive of a mild disseminated intravascular coagulation disorder. These imbalances could be caused by chronic subclinical endotoxemia and cytokine activation after the initial portal thromboembolic event. The persistence of these abnormalities in adolescent patients indicates an ongoing coagulation derangement.

Adolescent↗
PubMed2001

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

BACKGROUND: 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. METHODS: Seventy-four consecutive cases of HCC were studied. A detailed history, tests for hepatitis B virus (HBV; HBsAg, HBeAg, anti-HBe, IgG anti-HBc, anti-HBs and HBV-DNA), hepatitis C virus (HCV; anti-HCV and HCV-RNA) infection, liver histopathology and HBV-DNA integration by using Southern blot hybridization were studied. A p53 gene mutation was also studied by using PCR and single-strand conformation polymorphism. RESULTS: Hepatocellular carcinoma patients were predominantly males (mean age 49.5 +/- 14.0 years). Portal hypertension and cirrhosis were seen in 56 (76%) patients, more often (P < 0.05) in viral marker positive cases. Forty-five percent of patients had features of hepatic decompensation at presentation. Evidence of HBV infection was present in 53 (71%) patients. Twenty-six (49%) of these patients had either HBeAg + ve, HBV-DNA + ve (n = 12), or HBsAg - ve, HBV-DNA + ve (n = 14) forms of HBV infection. Hepatitis B virus DNA integration in the liver tissue was seen in 10 of 17 (59%) patients. Infection with HCV alone was detected in three (4%) and dual HBV and HCV infection in six (8%) patients. A majority (78.5%) of the chronic alcoholics had associated viral infection. The etiology of HCC remained undetermined in 15 (20%) patients. The p53 gene mutations were detected only in three of 21 (14%) liver tissues. Aflatoxin toxicity, oral contraceptive use or metabolic disorder were not seen. CONCLUSIONS: In India: (i) HBV infection is the predominant factor for the development of HCC, often related to mutant forms of HBV; (ii) a majority of the HCC patients have overt cirrhosis of the liver; and (iii) HCV and alcohol per se are uncommonly associated.

Aflatoxin B1↗
PubMed2001

Portal biliopathy.

In patients with portal hypertension, particularly with extrahepatic portal vein obstruction, portal biliopathy producing biliary ductal and gallbladder wall abnormalities are common. Portal cavernoma formation, choledochal varices and ischemic injury of the bile duct have been implicated as causes of these morphological alterations. While a majority of the patients are asymptomatic, some present with a raised alkaline phosphatase level, abdominal pain, fever and cholangitis. Choledocholithiasis may develop as a complication and manifest as obstructive jaundice with or without cholangitis. Endoscopic sphincterotomy and stone extraction can effectively treat cholangitis when jaundice is associated with common bile duct stone(s). Definitive decompressive shunt surgery is sometimes required when biliary obstruction is recurrent and progressive.

Algorithms↗
PubMed2001

Safety of an ofloxacin-based antitubercular regimen for the treatment of tuberculosis in patients with underlying chronic liver disease: a preliminary report.

BACKGROUND AND AIMS: Hepatotoxicity is a major side-effect of antitubercular drugs (ATD). As these drugs are metabolized in the liver, there is a theoretical risk of increased hepatotoxicity in patients with underlying chronic liver disease (CLD). Ofloxacin has antitubercular activity and has exclusive renal clearance. The aim was to study the efficacy and safety of an ofloxacin-based antitubercular regimen for treating tuberculosis in patients with underlying CLD. METHODS: Thirty-one cases were randomly assigned to two drug regimens using WHO dosage schedules: (i) regimen A (n = 15): isoniazid, rifampicin and ethambutol for 2 months, followed by isoniazid and rifampicin for a further 7 months; and (ii) regimen B (n = 16): isoniazid, pyrazinamide, ethambutol and ofloxacin for 2 months, followed by isoniazid, ethambutol and ofloxacin for a further 10 months. Hepatotoxicity was diagnosed if alanine aminotransferase/aspartate aminotransferase increased > fivefold from the baseline or to > 400 IU/L, or if bilirubin increased by > 2.5 mg/dL from the baseline. RESULTS: The response to ATD was achieved in all the patients who completed the therapy. Four (26.6%) patients on regimen A developed hepatotoxicity as compared to none on regimen B (P = 0.043). None of these patients could be restarted on ATD using the same regimen A because of the persistently deranged liver functions. CONCLUSIONS: In patients with tuberculosis who have underlying CLD: (i) an ofloxacin-based antitubercular regimen without rifampicin is as effective as a rifampicin-based regimen; and (ii) a combination of isoniazid with rifampicin is more hepatotoxic than a combination with ofloxacin and pyrazinamide.

Adolescent↗
PubMed2001

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. METHODS: Consecutive patients with chronic liver disease suspected to be AIH, were screened for antinuclear antibodies (ANA), antismooth muscle antibodies (ASMA), antimitochondrial antibody (AMA), and anti-liver kidney microsomal antibodies (anti-LKM-1). Serum protein electrophoresis and liver biopsy were done. Autoimmune hepatitis was diagnosed according to the International Autoimmune Hepatitis Group criteria. RESULTS: Fifty of 1358 (3.43%) patients with chronic liver disease were diagnosed as autoimmune liver disease; 39 with AIH, two with overlap syndrome, five with primary sclerosing cholangitis, and four with primary biliary cirrhosis. Twenty-nine patients were categorized as definite AIH and 10 as probable AIH. Autoimmune hepatitis was common in females (males : females 1:3), with a mean age of 31 +/- 17 years. Patients often presented with fatigue, jaundice and anorexia. Skin lesions (58%), joint symptoms (30%), and menstrual abnormalities (26%) were not uncommon. Mildly elevated alkaline phosphatase and hyper gamma globulinemia were seen in 78 and 91% patients, respectively. Eighty percent of patients were type I AIH, while 20% of cases remained unclassified. Histopathological changes included piecemeal necrosis (100%), plasma cell infiltration (91%), rosette formation (82%), and cirrhosis (76%). Overall mortality was 25% during a mean follow up of 15.7 +/- 17.0 months. CONCLUSIONS: Our results clearly demonstrate that: (i) AIH is not uncommon in India; and (ii) while the profile and spectrum of AIH resembles that seen in the West, Indian patients present late, often in a cirrhotic state.

Adolescent↗
PubMed2001

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.

Adolescent↗
PubMed2000

P53 tumor suppressor gene mutations in hepatocellular carcinoma patients in India.

BACKGROUND: Specific mutations of the p53 tumor suppressor gene in hepatocellular carcinoma (HCC) have been reported from several parts of the world, but to the authors' knowledge to date the status of this gene has not been studied in HCC patients in India, where HCC is one of the major cancers and the frequency of chronic hepatitis B virus (HBV) as well as hepatitis C virus (HCV) infection and exposure to dietary aflatoxin B(1) is very high. The most frequent mutation of the p53 gene in HCC is an AGG(Arg) to AGT(Ser) missense mutation at codon 249 of exon 7. METHODS: Liver biopsy specimens from 21 HCC patients and 10 healthy controls were obtained through surgery or by needle biopsy technique. Phenol-chloroform-extracted DNA specimens were employed for the detection of HBV infection and p53 gene mutations. Nucleotide mutations of exons 4-9 of the p53 gene were analyzed by polymerase chain reaction (PCR), single strand confirmation polymorphism, and direct sequencing. Third-generation sandwich enzyme-linked immunosorbent assay (ELISA) was used for the serologic detection of HBV and HCV infection. RESULTS: Analysis of exons 4-9 of the p53 gene revealed only 3 mutations (3 of 21 specimens, 14.28%; 95% confidence interval, -0.7-29.3), 2 mutations at codon 249 showing G-->T transversions, and 1 mutation (4.7%) at codon 250 with a C-->T transition. The base substitutions at the third base of codon 249 resulted in a missense mutation leading to a change in amino acid from arginine to serine whereas at codon 250 it caused a change from proline to serine. Dot blot hybridization and PCR for HBV DNA from HCCs revealed 58.8% (10 of 17 specimens) and 90. 47% (19 of 21 specimens), positivity, respectively. ELISA for hepatitis B virus surface antigen in serum showed a positivity of 71. 42% (15 of 21 specimens), but there was only 40% positivity (8 of 20 specimens) for hepatitis B virus envelope antigen whereas 6 of 17 patients (35.29%) showed the presence of antibodies against hepatitis B virus envelope protein. No patient was found to be positive for the HCV antibody. CONCLUSIONS: The very low frequency of p53 mutations and the extremely high frequency of HBV infection (> 90%) in HCC indicate that the mutations in the p53 gene frequently found in HCC reported from different endemic areas of the world may not play a direct role in the development of HCC in India. HBV infection and, possibly, exposure to the dietary aflatoxin B(1) appear to play major roles in the molecular pathogenesis of HCC in India.

Adolescent↗
PubMed2000

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.

Administration, Oral↗
PubMed2000

Beneficial influence of an indigenous low-iron diet on serum indicators of iron status in patients with chronic liver disease.

The main Fe storage organ in the body is the liver. In patients with chronic liver disease, secondary Fe overload is common. Phlebotomy, often used in the West to reduce Fe overload to improve the efficacy of interferon therapy, is not socially acceptable in India. We assessed the efficacy of a low-Fe diet in reducing serum Fe levels. Nineteen patients with hepatitis B- and C-related chronic liver disease, ten with normal (< 25 mumol/l) baseline serum Fe levels (group A) and nine with high (> 25 mumol/l) serum Fe levels (group B) were included. All the subjects were advised to eat a low-Fe diet. The daily Fe intake was reduced approximately 50% by consumption of the rice-based diet. Haemoglobin, serum Fe, transferrin saturation index (TSI), ferritin and alanine transaminase (EC 2.6.1.2) levels were studied at 1 and 4 months. Dietary Fe intake and body weight were closely monitored. All patients complied with the dietary regimen and at 4 months significant (P < 0.001) reductions from baseline were seen in serum Fe (20 (SD 3) v. 12 (SD 4) mumol/l group A; 30 (SD 3) v. 19 (SD 7) mumol/l group B) and TSI (38 (SD 8) v. 23 (SD 9)% group A; 53 (SD 15) v. 34 (SD 13)%, group B) in both the groups, albeit earlier in group B subjects. Serum ferritin levels, however, reduced only in group A (112 (SD 62) v. 43 (SD 25) ng/ml, P < 0.05) and not in group B. Non-significant reductions in haemoglobin levels were seen in both groups. Alanine transaminase levels reduced significantly (P < 0.05) in both the groups (95 (SD 49) v. 44 (SD 25) IU/l, group A; 82 (SD 16) v. 51 (SD 14) IU/l group B). Thus, a low-Fe diet results in significant reductions in serum Fe and TSI levels, irrespective of baseline Fe levels. This diet should be evaluated to improve the efficacy of interferon therapy in patients with hepatitis B- and C-related chronic liver disease.

Adult↗
PubMed2000

The natural history of portal hypertensive gastropathy: influence of variceal eradication.

OBJECTIVE: The natural history and likelihood of bleeding from portal hypertensive gastropathy (PHG) present in patients with portal hypertension before endoscopic variceal obliteration may differ from that in patients who develop PHG during or after variceal eradication. METHODS: A total of 967 variceal bleeders who had achieved variceal eradication by endoscopic sclerotherapy in the recent past were prospectively studied. In all, 88 (9.1%) patients (cirrhosis in 54, noncirrhotic portal fibrosis in 18, and extrahepatic portal vein obstruction in 16) had distinct mucosal lesions. PHG alone was present in 78, PHG with gastric antral vascular ectasia (GAVE) in eight, and GAVE alone in two patients. PHG was graded as mild or severe and according to whether present before (group A) or after endoscopic intervention (group B). Patients underwent regular endoscopy at follow-up to see if the PHG was transitory (disappearing within 3 months), persistent (no change), or progressive. Bleeding from PHG lesions was defined as acute or chronic. RESULTS: Twenty-two (26%) patients had PHG before (group A) and 64 (74%) developed PHG after variceal eradication (group B). During a mean follow-up of 25.1 +/- 14.2 months, PHG lesions disappeared in group A in only two patients (9%), but in group B in 28 (44%) patients (p < 0.05). PHG lesions more often progressed in the former as compared to the latter (18% vs 9.4%, p = NS). The incidence of bleeding was higher in group A than group B (32% vs 4.7%, p < 0.02). Bleeding from PHG occurred in 10 patients (11.6%); seven of them were from group A, and all had either progressive (n = 3) or persistent (n = 4) lesions. CONCLUSIONS: PHG developing after variceal eradication is often transitory and less severe. If PHG is pre-existing, endoscopic therapy for varices could worsen the PHG, with a likelihood of bleeding. Such patients may be benefited by concomitant beta-blocker therapy.

Adolescent↗