Norethisterone Related Drug Induced Liver Injury: A Series of 3 Cases.

Drug induced liver injury (DILI) is uncommon and severe forms are associated with significant morbidity and mortality. Female sex hormones (estrogens and progestogens) related DILI generally occur with estrogen component. Progesterone component related DILI are infrequently reported. Norethisterone is commonly used drug in gynecologic practice to prevent excess per vaginal bleeding. We report 3 cases of Norethisterone related DILI manifesting as significant rise of transaminases. All of these patients took Norethisterone for prolonged periods and improved completely after withdrawal of drug.

Yield of endoscopic ultrasound-guided fine needle aspiration for subcentimetric lymph nodes: A comparison to larger nodes.

BACKGROUND AND OBJECTIVES: Subcentimetric (defined as <1 cm at short axis) lymph nodes are considered benign and there is limited literature on the results of fine needle aspiration (FNA) of these nodes. METHODS: Endoscopic ultrasound (EUS) guided FNA was done on 189 lymph nodes in 166 patients with pyrexia of unknown origin (n = 113) or malignancy (n = 53). Subcentimetric lymph nodes (Group A) were compared to nodes with short axis diameter ≥1 cm (Group B). Data are shown as number, percentage, and median (25-75 interquartile range). RESULTS: There was no significant difference between Group A and Group B regarding site of lymph nodes (mediastinal in 73.6 and 72.5%, abdominal in 26.3 vs. 27.4%), number of slides (median 14 vs. 15), needle passes (median 2), and needle used (22 G needle in 85.5% vs. 69.9%). Group A had significantly lesser long axis diameter (1.5 [1.2-2] vs. 2.1 [1.6-2.9] cm) and short axis diameter (0.7 [0.6-0.8) vs. 1.4 [1.1-1.6] cm). A diagnosis (pathologic or reactive) could not be made in 2 (2.6%) and 11 (9.7%) lymph nodes in Group A and Group B, respectively (P = 0.078), due to inadequate material. Respective diagnoses in Group A and Group B were reactive lymphadenopathy (51.3% vs. 18.5%, P = 0.000), granulomatous lymphadenopathy (34.2% vs. 53%, P = 0.011), and malignancy (11.8% vs. 18.5%, P = 0.231). The lymph nodes with granulomatous and malignant change were significantly larger and had higher chances of having sharply demarcated borders as compared to reactive nodes. CONCLUSION: EUS-guided FNA of subcentimetric lymph nodes have comparable results to larger nodes. Almost half of the subcentimetric lymph nodes are pathologic.

Efficacy and safety of sofosbuvir-based regimens in chronic hepatitis C patients on dialysis.

INTRODUCTION: Patients with end-stage renal disease (ESRD) have poor treatment tolerance and outcome to interferon-based regimens. Sofosbuvir-based regimens have improved treatment success in chronic hepatitis C. There is limited data in ESRD patients as sofosbuvir is excreted by the kidney. Several small studies have shown good results. METHODS: Sixteen consecutive patients of ESRD (on dialysis) and chronic hepatitis C were treated with sofosbuvir-based regimens as they were prospective kidney transplantation recipients, at a tertiary care center in north India. Sofosbuvir was given 400 mg on alternate days. Data is shown as number, mean (SD), and median (range). RESULTS: Sixteen patients (12 males) aged 45±12 years received sofosbuvir-based treatment. These patients were on hemodialysis from 10 (2-48) months. Eleven of these patients had genotype 1, four had genotype 3, and one had genotype 4 infection; baseline RNA was 7 (5-8) log. The following treatment regimens were used: sofosbuvir, ribavirin, and low dose peginterferon (n = 8; 6 genotype 1 and one each had genotype 3 and 4); sofosbuvir and daclatasvir (n = 7); sofosbuvir, ribavirin, and daclatasvir (n = 1). Ten patients achieved end of treatment response and 8 (80%) of these achieved sustained virological response at 12 weeks (SVR12); six are on treatment. Two patients with genotype one (including one with cirrhosis) had relapse. Seven patients needed blood transfusion; interferon was stopped in one due to thrombocytopenia. Fatigue was present in 4 patients. CONCLUSION: Sofosbuvir-based regimens can be used in ESRD patients on dialysis with good efficacy.

Endoscopic ultrasound characteristics of tubercular lymphadenopathy in comparison to reactive lymph nodes.

AIM: Tuberculosis is a common disease in India with significant morbidity and mortality. Limited data is available on the description of tubercular lymphadenopathy on endoscopic ultrasound. METHODS: Retrospective data of 116 lymph nodes in 113 patients was evaluated at a tertiary care center. Lymphadenopathy in the mediastinum and abdomen were included. The study was aimed at identifying the endoscopic ultrasound (EUS) features of tubercular lymphadenopathy and comparing them with reactive lymphadenopathy in patients with pyrexia of unknown origin. RESULTS: The following features were suggestive of tubercular lymphadenopathy (n = 55) as compared to reactive lymphadenopathy (n = 61): hypoechoic echotexture (94.5% vs. 75.4%, p 0.004), patchy anechoic/hypoechoic areas (30.2% vs. 0%, p = 0.000), calcification (24.5% vs. 0%, p = 0.000), sharply demarcated borders (34.5% vs. 9.8%, p = 0.001), pus like material on aspirate (18.2% vs. 0%, p 0.000), and conglomeration of lymph nodes (10.9% vs. 0%, p = 0.009). The tubercular lymph nodes were significantly larger than reactive nodes at long axis and short axis diameter (2.4 ± 1.1 vs. 1.6 ± 0.6 cm, p < 0.001 and 1.5 ± 0.7 vs. 0.9 ± 0.3 cm, p = 0.001 respectively). On cytopathological examination, presence of necrosis (92.7% vs. 0%, p = 0.000) and granulomas (78.1% vs. 0%, p = 0.000) favored tubercular as compared to reactive lymphadenopathy. CONCLUSION: EUS features like hypoechoic echotexture, patchy anechoic/hypoechoic areas, calcification, sharply demarcated borders, conglomeration, purulent aspirate, larger size, and cytopathological presence of necrosis/granulomas are suggestive of tubercular as compared to reactive lymphadenopathy.

Portal vein thrombosis.

Portal vein thrombosis is an important cause of portal hypertension. PVT occurs in association with cirrhosis or as a result of malignant invasion by hepatocellular carcinoma or even in the absence of associated liver disease. With the current research into its genesis, majority now have an underlying prothrombotic state detectable. Endothelial activation and stagnant portal blood flow also contribute to formation of the thrombus. Acute non-cirrhotic PVT, chronic PVT (EHPVO), and portal vein thrombosis in cirrhosis are the three main variants of portal vein thrombosis with varying etiological factors and variability in presentation and management. Procoagulant state should be actively investigated. Anticoagulation is the mainstay of therapy for acute non-cirrhotic PVT, with supporting evidence for its use in cirrhotic population as well. Chronic PVT (EHPVO) on the other hand requires the management of portal hypertension as such and with role for anticoagulation in the setting of underlying prothrombotic state, however data is awaited in those with no underlying prothrombotic states. TIPS and liver transplant may be feasible even in the setting of PVT however proper selection of candidates and type of surgery is warranted. Thrombolysis and thrombectomy have some role. TARE is a new modality for management of HCC with portal vein invasion.

Outcomes of immunosuppressant therapy with lower dose of antithymocyte globulin and cyclosporine in aplastic anemia.

OBJECTIVE: Immunosuppressant therapy (IST) with antithymocyte globulin (ATG) and cyclosporine is an established treatment option for patients with aplastic anemia (AA), who are not eligible for allogeneic stem cell transplantation. However, data on the dose of ATG and its efficacy from the developing countries is minimal. METHODS: We performed a retrospective analysis of all AA patients (age >12 years), treated with equine ATG and cyclosporine from a single center in India. Patients who received or were eligible for stem cell transplantation were excluded. The overall response rate (ORR) to IST was calculated at 3 and 6 months. We also determined the influence of using a lower dose of Atgam ATG (25 mg/kg/day × 4 days) and compared its efficacy against the standard dose of locally manufactured Thymogam ATG (40 mg/kg/day × 4 days). Factors influencing the ORR were analyzed using Fisher's exact test with a significant P < 0.05. RESULTS: Thirty-nine patients with AA treated with ATG and cyclosporine were studied. Median age was 31 years with a male:female ratio of 0.85:1. The ORR was 58% at 3 months, 77% at 6 months and was similar with lower dose Atgam and standard dose Thymogam. On multivariate analysis of ORR at 6 months, the interval between the onset of symptoms to the initiation of therapy was close to attaining statistical significance (odds ratio 23.53, P value 0.053) while the other variables did not attain significance. CONCLUSIONS: IST with equine ATG in a lower dose (25 mg/kg/day × 4 days) and cyclosporine is a feasible and effective treatment option for AA in resource-constrained settings.

Pregnancy with portal hypertension.

Even though pregnancy is rare with cirrhosis and advanced liver disease, but it may co-exist in the setting of non-cirrhotic portal hypertension as liver function is preserved but whenever encountered together is a complex clinical dilemma. Pregnancy in a patient with portal hypertension presents a special challenge to the obstetrician as so-called physiological hemodynamic changes associated with pregnancy, needed for meeting demands of the growing fetus, worsen the portal hypertension thereby putting mother at risk of potentially life-threatening complications like variceal hemorrhage. Risks of variceal bleed and hepatic decompensation increase many fold during pregnancy. Optimal management revolves round managing the portal hypertension and its complications. Thus management of such cases requires multi-speciality approach involving obstetricians experienced in dealing with high risk cases, hepatologists, anesthetists and neonatologists. With advancement in medical field, pregnancy is not contra-indicated in these women, as was previously believed. This article focuses on the different aspects of pregnancy with portal hypertension with special emphasis on specific cause wise treatment options to decrease the variceal bleed and hepatic decompensation. Based on extensive review of literature, management from pre-conceptional period to postpartum is outlined in order to have optimal maternal and perinatal outcomes.