Association of pro-inflammatory cytokines, adipokines & oxidative stress with insulin resistance & non-alcoholic fatty liver disease.

Background & objectives: The cytokines, adipokines, and oxidative stress have been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD); however, such data remain scarce in India. The present study evaluated pro-inflammatory cytokines, adipokines, and markers of oxidative stress in patients with non-alcoholic fatty liver disease (NAFLD), and their association with degree of adiposity, insulin resistance and markers of disease severity. Methods: The present prospective cross-sectional pilot study included 79 subjects; 34 NAFLD, 22 chronic hepatitis B (CH-B) and 23 healthy controls (HC). The parameters studied were adiponectin, leptin, tumour necrosis factor α (TNFα), interleukin-1 and 6 (IL-1, IL-6), and systemic markers of oxidative stress. Results: The mean body mass index (kg/m2) in NAFLD patients, CHB, and HC were 26.4±3.7, 21.3±2.3, and 22.3±2.7, respectively. The median serum levels of all pro-inflammatory cytokines were significantly higher (P<0.001) in NAFLD compared to control groups. Compared to HC, levels of adiponectin and leptin were significantly (P<0.05, P<0.01) reduced in both NAFLD and CHB. IL-6 showed marked and selective increase only in NAFLD patients. The levels of IL-6 were significantly (P<0.02) higher in NAFLD patients with advanced histology grade and correlated with IR (r=0.42, P=0.02). In a sub-group, markers of oxidative stress were significantly higher, and that of antioxidant potential were significantly lower among NAFLD patients compared to control subjects. Interpretation & conclusions: Patients with NAFLD revealed significantly elevated levels of pro-inflammatory cytokines, increased oxidative stress, and a significant association of IL-6 with IR and advanced histopathology.

Prevalence, severity, and risk factors of symptomatic gastroesophageal reflux disease among employees of a large hospital in Northern India.

Background and aims Gastroesophageal reflux disease (GERD) is considered to be a common and chronic gastrointestinal disorder. The prevalence of GERD is believed to be less in Asia than in Western countries. Population-based data on GERD are lacking from India. The present study aimed at determining the prevalence of GERD symptoms in an adult Indian community and the potential risk factors associated with GERD. Methods The study population consisted of all the employees of All India Institute of Medical Sciences, New Delhi. An interview-based observational study was done on the basis of an earlier validated questionnaire. The subjects were asked about the frequency and severity of heartburn and/or regurgitation experienced by them in the previous year. These symptoms were then scored from 0 to 18. Subjects with a score of at least 4 were considered to have symptomatic GERD. Association of GERD with factors like age, sex, BMI, Kuppuswamy social class index, smoking, alcohol, NSAID use, and comorbid illness was analyzed. Results A total of 4079 employees were interviewed in person on a 29-item questionnaire from June 2003 to January 2005. Of the 4039 eligible subjects, 653 (16.2%) had GERD; 3.6% had heartburn on daily basis and 5.9% on a weekly basis. The corresponding prevalences for regurgitation were 3.3% and 5.0%, respectively. One hundred and eight of 4039 (2.7%) had severe GERD symptoms. Higher BMI (OR=1.90, 95% CI: 1.4–2.6 for BMI ≥25), current smoking (OR=1.48, 95% CI: 1.19–1.83), asthma (OR=3.13, CI: 2.06–4.76) and hypertension (OR=1.71, 95% CI: 1.16–2.50) were associated with the presence of GERD symptoms. Conclusions Prevalence of GERD in an urban adult population from northern India is 16.2% which is similar to other industrialized countries. Higher body mass index, current smoking, and presence of asthma or hypertension predisposes to GERD in our population.

Alcoholic liver disease and antioxidants.

One of the major mechanisms postulated in production of liver injury in alcoholics is the oxidant stress, which is produced by an imbalance between the pro-oxidants and anti-oxidants. The major sources of oxidants are the enzyme systems which metabolize ethanol and the enzyme systems operating in the inflammatory cells. Further, alcohol, either directly or by means of associated malnutrition also leads to deficiency of anti-oxidants which tips the balance towards oxidative stress. We have also discussed the various anti-oxidants that have been used in alcoholic liver disease and their effect on liver necroinflammation and survival in these patients.

Have hematopoietic growth factors made an impact on the management of liver disease?

It is clear that the major indication for the use of hematopoietic growth factors in hepatology is to counteract the adverse effects of interferons (neutropenia and thrombocytopenia) and ribavirin (hemolytic anaemia) during the treatment of hepatitis C infection. This is important because the probability of SVR depends on proper adherence to therapy (at least 80% of the requisite dose maintained for at least 80% of the requisite duration) and proper adherence can only be achieved if the side effects are reduced to a minimum. Even though the studies have demonstrated beyond doubt that the use of hematopoietic growth factors does indeed reduce the incidence and severity of these adverse effects and helps the patients to complete the course of therapy, the data on improvement of SVR is still limited. There is only one study of darbepoetin and filgrastim showing the beneficial effect on SVR. Even among the hematological side effects, possibly the only significant effect which limits the use of optimal HCV therapy is the hemolytic anaemia induced by ribavirin. The other two main side effects, i.e. neutropenia and thrombocytopenia are not clinically problematic. The use of such growth factors would be particularly effective if patients who have advanced liver disease or cirrhosis are able to receive adequate anti-viral therapy as has been demonstrated in the study of eltrombopag among HCV cirrhotics. Apart from this, other indications of G-CSF or GM-CSF use are still in the experimental stage. So, as of now, apart from erythropoietic factors, the role played by other hematopoietic growth factors in hepatology is limited. But future research, especially in the areas of immunotherapy of liver cancers and stem cell therapy for endstage liver disease, is surely going to give these factors their due place in hepatology.

Acral and palmo-plantar hyperpigmentation in a patient with disseminated hepatocellular carcinoma.

Capecitabine (5-fluorouracil prodrug) is being evaluated for the management of hepatocellular carcinoma, and is associated with a peculiar skin reaction called hand and foot syndrome (HFS). We describe one patient with HCC and drug-induced HFS.

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.

Celiac disease: variations of presentations in adults.

BACKGROUND: Patients with celiac disease, who remain undiagnosed or asymptomatic in childhood, may present in adulthood with either typical or atypical features. METHODS: In a retrospective analysis, we reviewed the case records of 45 consecutive patients with celiac disease diagnosed in adulthood. The diagnosis of celiac disease was made on the basis of the modified European Society of Pediatric Gastroenterology, Hepatology and Nutrition criteria. The modes of presentation, clinical manifestations, endoscopic features and histological features were analyzed. RESULTS: The mean age of these patients at diagnosis was 28.7 (11.2) years. The median duration of symptoms before diagnosis was 2.5 years (range: 6 months to 40 years). Chronic diarrhea was the presenting manifestation in 20 (44%) patients only. Twenty-two (49%) patients were referred to us by hematologists, endocrinologists or gynecologists for evaluation of refractory anemia in 10 (2.2%), short stature in 6 (13.3%), metabolic bone disease in 2 (4.4%) and secondary infertility or delayed menarche in 4 (8.8%). Intestinal mucosal folds were scalloped in 31 (69%), attenuated in 34 (76%) and normal looking in 11 (24%) of them. Mild, moderate and severe villous abnormalities on intestinal mucosal biopsies were present in 10 (22.2%), 15 (33.3%) and 19 (42.2%) patients, respectively. CONCLUSIONS: More than half of adult patients with celiac disease present with atypical manifestations. A high index of suspicion is required for diagnosing variant forms of celiac disease in adults.

Profile of fatal visceral leishmaniasis at an Indian tertiary care center.

Visceral leishmaniasis is a highly morbid and incapacitating infection, which usually presents with prolonged fever, weight loss and hepato-splenomegaly. Despite the availability of effective treatment, the disease can have a high mortality even at referral centers. A case series of fatal visceral leishmaniasis, encountered during a prospective, two year period is presented. All the patients died due to multisystem organ failure. However, delayed diagnosis due to atypical manifestations was an important factor contributing to the fatal outcome of the patients. Instead of relying solely on the classical clinical features of visceral leishmaniasis, simple laboratory findings like pancytopenia, altered albumin/globulin ratio and appositive aldehyde and rK 39 dipstick tests can help in making an early diagnosis even in atypical cases, thereby reducing the mortality of visceral leishmaniasis.

Corrosive-like strictures caused by ingestion of aluminium phosphide.

Aluminium phosphide ingestion is a major cause of poisoning-related mortality in tropical countries. Local oesophageal complications due to aluminium phosphide have been reported to occur rarely. We describe 3 patients who survived the intake of aluminium phosphide tablets and developed oesophageal strictures.

Viral hepatitis in India.

Viral hepatitis is a major public health problem in India, which is hyperendemic for HAV and HEV. Seroprevalence studies reveal that 90%-100% of the population acquires anti-HAV antibody and becomes immune by adolescence. Many epidemics of HEV have been reported from India. HAV related liver disease is uncommon in India and occurs mainly in children. HEV is also the major cause of sporadic adult acute viral hepatitis and ALF. Pregnant women and patients with CLD constitute the high risk groups to contract HEV infection, and HEV-induced mortality among them is substantial, which underlines the need for preventive measures for such groups. Children with HAV and HEV coinfection are prone to develop ALF. India has intermediate HBV endemicity, with a carrier frequency of 2%-4%. HBV is the major cause of CLD and HCC. Chronic HBV infection in India is acquired in childhood, presumably before 5 years of age, through horizontal transmission. Vertical transmission of HBV in India is considered to be infrequent. Inclusion of HBV vaccination in the expanded programme of immunization is essential to reduce the HBV carrier frequency and disease burden. HBV genotypes A and D are prevalent in India, which are similar to the HBV genotypes in the West. HCV infection in India has a population prevalence of around 1%, and occurs predominantly through transfusion and the use of unsterile glass syringes. HCV genotypes 3 and 2 are prevalent in 60%-80% of the population and they respond well to a combination of interferon and ribavirin. About 10%-15% of CLD and HCC are associated with HCV infection in India. HCV infection is also a major cause of post-transfusion hepatitis. HDV infection is infrequent in India and is present about 5%-10% of patients with HBV-related liver disease. HCC appears to be less common in India than would be expected from the prevalence rates of HBV and HCV. The high disease burden of viral hepatitis and related CLD in India, calls for the setting up of a hepatitis registry and formulation of government-supported prevention and control strategies.

Vitamin E-based therapy is effective in ameliorating transaminasemia in nonalcoholic fatty liver disease.

BACKGROUND: Comparative trials of ursodeoxycholic acid (UDCA), vitamin E and weight management programs among patients with nonalcoholic fatty liver disease (NAFLD) are lacking. AIM: To find an effective single agent or combination of agents for management of NAFLD. METHODS: In this retrospective study, consecutive patient with histologically confirmed NAFLD with raised ALT were included. The patients received either weight management (exercise and therapeutic lifestyle changes [TLC] diet with a target to reduce body weight 10% in 6 months) (group I) ; weight management + UDCA (300 mg BID) (group II); or weight management + UDCA + vitamin E (400 mg OD) (group III). Outcome measure was normalization of ALT. RESULTS: 42 patients (18, 12 and 12 in groups I, II and III, respectively) were included between 1996 and 2004. All patients in group III normalized their ALT levels, which was significantly higher than numbers in group I (8/18) and group II (5/12); (p=0.003). Post treatment ALT was significantly lower in group III (28.6 [9.3]) as compared to group I (59.3 [32.2]) and group II (49.0[31.8]); (p=0.01). Type of therapy received was the only factor predictive of ALT normalization. CONCLUSION: Combination regimen containing vitamin E appears to be effective in normalizing ALT among NAFLD patients.