Clinician's dilemma: Naproxen-induced liver injury

Naproxen is a widely used nonsteroidal anti-inflammatory drug (NSAID) in pediatric population, used for mild-to-moderate pains, arthritis, and other immune-mediated disorders. It rarely causes clinically apparent liver injury in the adult population taking high doses of the drug over a prolonged period and is reported even rarer in pediatric population. We present a case of drug-induced liver injury (DILI) in a 13-year-old girl taking naproxen in therapeutic doses for juvenile rheumatoid arthritis. There was a complete recovery of liver function following discontinuation of naproxen therapy.

Thrombocytopenia in Children: A Large Prospective Study on Clinical Manifestations, Seasonal Variation, Etiology, and Outcome

Aim: To study the clinico-etiological profile of children with thrombocytopenia. Methods: This prospective hospital-based study included all children (<18 years) with thrombocytopenia at the time of hospitalization and/or thrombocytopenia during the course of their hospital stay. A detailed history was recorded and appropriate laboratory investigations were carried out. Results: The study group comprised 246 children (mean age, 9.29 years; median age, 10 years) with male to female ratio of 1.5:1. Nearly 45% of children were above 10 years of age. Trends of admissions showed that the majority of children with thrombocytopenia (n = 115) got hospitalized during the rainy season, followed by summer (n = 84). Fever (72.8%), pallor (52.8%), bleeding manifestations (22%), lymphadenopathy (20.3%), and splenomegaly (20.3%) were common clinical features. Petechiae was the most common bleeding manifestation (63%). Septicemia (24%) was the most common etiology, followed by megaloblastic anemia (14.6%), undiagnosed fever (10.2%), local infection (9.3%), hepatitis (6.5%), and scrub typhus (6.1%). About nine children died. All those who died had septicemia and multi-organ dysfunction (MOD). On logistic regression analysis, age >10 years, presence of bleeding, arthralgia, rash, pallor, gastrointestinal (GI) symptoms, hematological disorders, and malignancy were associated with severe thrombocytopenia. Conclusion: Thrombocytopenia is a common hematological observation. This study revealed seasonal variation in the occurrence of thrombocytopenia in children, with the maximum number of cases in the rainy season. Septicemia is the commonest etiology. The majority of children with thrombocytopenia have no bleeding manifestations. Age >10 years, presence of bleeding, arthralgia, rash, pallor, GI symptoms, hematological disorders, and malignancy are associated with severe thrombocytopenia.

A pilot study on area under curve of mycophenolic acid as a guide for its optimal use in renal transplant recipients.

Background & objectives: The immunosuppressants administered to renal transplant subjects are usually monitored therapeutically to prevent graft rejection and drug toxicity. Mycophenolic acid (MPA) is an immunosuppressant. The present prospective study was undertaken to establish the utility of plasma level monitoring of MPA and to correlate it with clinical outcomes in renal transplant receipients. Methods: MPA plasma level at 2, 4 and 9 h and the area under concentration-time curve (AUC) were estimated using high performance liquid chromatography in 24 renal transplant recipients receiving immunosuppressant MPA plus tacrolimus and steroid. Results: There was wide inter-individual variation in MPA plasma level and the AUC. The incidences of gastrointestinal adverse drug events (diarrhoea and acidity) were significantly more in the high MPA AUC patients. Though biopsy proven acute rejection was not found, of the six subjects with lower MPA AUC (<30 mg.h/l), three were clinically diagnosed to develop tacrolimus nephrotoxicity. The Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) scores represented better health related quality of life in lower MPA AUC than in the higher MPA AUC (>60 mg.h/l). Interpretation & conclusions: The present findings suggest the MPA AUC of 30 - 60 mg.h/l in the maintenance stage of renal transplant patients to have optimum clinical benefit and relegated adverse events profile indicating the usefulness of AUC of MPA with limited sampling strategy in optimizing its use.

The quality of life of women volunteering as live-related kidney donors in India.

Background. Women outnumber men 6:1 as live-related donors in our renal transplant programme. Women donors in developing regions are often illiterate and unemployed. This study was done to assess the change in quality of life of women who donate kidneys. Methods. We prospectively studied 73 consecutive women volunteering as live-related kidney donors over a 6-month period using the World Health Organization Quality of Life Brief (WHO QoL Bref) Questionnaire and Hospital Anxiety and Depression Scale (HADS). Each woman was interviewed 2 weeks before and 6 months after kidney donation. Results. There was a significant improvement in all the domains, namely physical (p=0.0001), psychological (p<0.0001), social relationship (p=0.037) and environment (p<0.0001) of the WHO QoL Bref questionnaire. Donors who were mothers had a greater improvement in all 4 domains than donors with other relationships. There was a significant decrease in the depression score (p<0.0001), but no change in the anxiety scores (p=0.065) following kidney donation. All donors would donate again, if possible. Conclusion. In live-related women kidney donors, quality of life improves and depression scores decline after kidney donation.

The first successful simultaneous pancreas-kidney transplant in India.

Insulin-dependent diabetes mellitus is associated with renal failure, diabetic retinopathy, neuropathy and vasculopathy. We report the first successful simultaneous pancreas-kidney transplant in India in a young diabetic with renal failure. The dual transplant has cured his diabetes and renal failure and has had a beneficial effect on his neuropathy, retinopathy and quality of life. Obstacles to dual transplant in India include a lack of suitable recipients and a cadaver donor programme that is still in its infancy.

Primary malignant fibrous histiocytoma of the greater omentum.

Primary malignant mesenchymal tumours of the greater omentum are rare. We report a 40-year old man with a painless abdominal lump of two months duration. At laparotomy, the mass was found to be arising from the greater omentum. A near-total omentectomy was done. Histological examination of the resected tumour revealed features consistent with malignant fibrous histiocytoma.

Pneumocystis carinii pneumonia: role of high resolution computed tomography.

Pneumocystis carinii (PC) is a common opportunistic infection in renal transplant recipients and requires an early diagnosis for its successful treatment. For its definitive diagnosis PC needs to be demonstrated in bronchoalveolar lavage (BAL) fluid. At times BAL may not be possible or get delayed. In such conditions typical appearances seen on high resolution CT of the chest help in early diagnosis of PC pneumonia (PCP). This easily performed procedure helped in early diagnosis of PCP in two patients.

Results of renal transplantation on conventional immunosuppression in second decade in India: a single centre experience.

BACKGROUND: In-spite of many renal transplant (RT) centres in the country, there is paucity of data on the survival results in India. Furthermore, there is hardly any data of results in second decade. In this study we present the results of RT in second decade at our centre. METHODS: RT at our hospital is being done since 1972. First eight years saw occasional RT and complete data is not available in these patients. So, we have excluded these patients from the study. We have included rest all 144 patients who had RT between Jan. 1981 to Dec. 1989, so as to have at least 10 years of follow-up or more. All these patients were on conventional immunosuppression. RESULTS: Of the 144 patients, 126 (87.5%) were males and the mean age was 29.5 +/- 8.5 years (range 14-54). Basic disease was presumed chronic glomenulonephritis (CGN) in 79.9%, vesicouretenic reflux (VUR) in 8% and diabetic nephropathy in 1.4% patients. Mean number of haemodialysis (HD) and blood transfusion before RT were 44 +/- 24.7 and 8.9 +/- 4.7 (range 0-25), respectively. Mean donor age was 40.9 +/- 10.1 year (range 18-62). HLA matching was haploidentical in 74.5% cases, HLA identical in 3% cases and 11.5% were less than two-antigen match. Of the 63% patients, who had at least one acute rejection (AR) during their follow-up, 78.8% cases had this AR within first three months after the renal transplant. During 10 years of follow up, 65 patients died (23 with normal graft function and 42 with chronic rejection) and 17 lost to follow-up. Eight patients lost their graft but were surviving at 10 years and 54 had functioning graft till the time of analysis. With mean follow-up of 83.9 +/- 61.2 (range 1-216) months, 10-year actuarial patients and graft survival was 53% and 47%, respectively. Graft half-life in these patients is 92 months. In multivariate analysis of the donor age, number of blood transfusion (BT), degree of HLA matching and AR, only AR was found to be statistically correlated with the graft outcome (p=0.004). CONCLUSION: Our study concludes that in our set-up during eighties, on conventional immunosuppression, actuarial patient and graft survival at 10 year is 53% and 47%, respectively with graft half-life being 92 months. Only acute rejection has been found to affect the graft outcome in these patients.

Influence of HLA compatibility on renal graft survival using live unrelated & cadaver donors in India.

BACKGROUND & OBJECTIVES: Living unrelated donor (LURD) renal transplantation has shown a rising trend over the last 5 yr at our center following the passing of The Transplantation of Human Organs Act by the Government of India in 1994. In this paper, the results of LURD and cadaver (CAD) donor renal transplantation are compared. We have also looked into factors that have a bearing on graft survival such as the extent of HLA mismatch (MM), infections, acute rejections (AR), donor age and sex. METHODS: A total of 42 LURD and 25 CAD renal transplants performed between March 1994 and February 1999 has been included in the study. HLA typing, panel reactive antibody (PRA) screening and T and B cell cross match assay were performed by the complement dependent cytotoxicity (CDC) method for all patients. RESULTS: The graft survival rates were generally higher in the LURD category as compared to the CAD group and were significant at 6 month period (90 vs 56%, P = 0.002). A follow up of the patients up to 60 months revealed a matching effect since the 3, 4 allele MM group had better survival rates as compared to the 5, 6 MM group. Twenty six of the 67 recipients (39%) experienced episodes of acute rejection (AR). Patients with 3, 4 MM had fewer such episodes than those with 5, 6 allele MM (P < 0.05). Of the 32 deaths, 20 were those with a functional kidney, of which 15 were caused by severe infections. INTERPRETATION & CONCLUSION: Better HLA matching ensures fewer episodes of rejection and better long term graft survival in comparison to the poorly matched grafts. The graft survival for LURD recipients was appreciably higher than that of CAD recipients.

Embryonal sarcoma of the liver mimicking a hydatid cyst in an adult.

Undifferentiated (embryonal) sarcoma of the Liver is a rare malignant mesenchymal tumour. This presents predominantly in late childhood. It carries a dismal prognosis. Surgical resection with or without adjuvant therapy remains the mainstay of treatment. The present report describes a sixteen year old girl who presented with a large hepatic mass mimicking a hydatid cyst: clinically, radiologically and on serology.

Recurrent abscess at site of laparoscopic cholecystectomy port due to spilled gallstones.

Spillage of gallstones is common during laparoscopic cholecystectomy and may lead to intra-abdominal abscesses and sinus formation. We describe two patients with recurrent abscess at the site of epigastric port due to presence of large spilled stone in the parietes following laparoscopic cholecystectomy. Removal of the stone led to resolution of symptoms.

Impact of hepatitis C virus infection on renal transplant outcome in India--a single centre study.

BACKGROUND: Hepatitis C virus (HCV) infection is currently the main cause of hepatotropic viral infection in renal transplant (RT) recipient throughout the world. Contrary reports are available as regard graft and patient survival and liver disease outcome in these patients. From India, outcome of HCV positive patients following RT has not been documented. Herewith, we present results of RT in HCV positive patients at our centre. METHODS: Study design was prospective case control with primary end point being graft and patient survival and the exposure being HCV infection. Between June 1995 till February 1998, 128 patients had RT at our hospital, of which, 37 (28.9%) were anti-HCV positive at the time of RT. All the patients were on triple immunosuppressive therapy. As a policy of unit, none of the donor had HBV and/or HCV infection. Anti-HCV positive patients formed the subjects (Gr. I), while anti-HCV negative patients severed as control (Gr. II). Anti HCV was done using 3rd generation ELISA tests kit. HCV-RNA could not be done due to non-availability. None of the positive patient was treated with anti-viral therapy. Acute rejection, serious infections, patient and graft survival and outcome of liver disease was compared in these patients. RESULTS: Mean age of the patients, number of males, number of pre-RT haemodialysis and blood transfusion, donor age and HLA-mismatch were comparable in both the groups. Mean follow-up in Gr. I was 28 +/- 9.4 months and in Gr. II 31.4 +/- 7.6 months. At the end of this follow-up, acute rejection was seen in 43% and 33.3% patient in Gr. I and II respectively. In Gr. I, serious infections were seen in 30% while the same in Gr. II was 11.8% (p < 0.01). There was no difference in graft survival in Gr. I and II (72% and 66%) and the patient survival were also similar (72% and 66%). Of the deaths in Gr. I, 80% died of sepsis and 20% died of liver cell failure related to one each of hepatitis B and hepatitis E. Of the deaths in Gr. II, 65% died of sepsis and 17% died of hepatic cell failure. But, there was no difference in causes of deaths in these two groups. In both the groups, none of liver related death was due to isolated HCV infection. There was no effect of donor age, HLA mismatch, number of haemodialysis and pre-RT blood transfusion on the survival of graft as well as patient. CONCLUSION: In conclusion, HCV infection is major problem in RT with us. In a short follow-up of nearly 30 months, graft and patient survival is same in HCV positive and negative patients. However, serious infections are significantly more common in HCV positive patients.

Post transplant diabetes mellitus in live related renal allograft recipients: a single centre experience.

The incidence of post-transplant diabetes mellitus (PTDM) was evaluated in 250 patients who underwent live-related renal transplantation at our hospital between 1978 and 1992. Twelve (4.8%) patients developed PTDM requiring drug therapy. PTDM occurred in 4 of 197 (2%) patients on conventional prednisolone-azathioprine immunosuppression as compared to 8 of 53 (15.1%) patients receiving cyclosporine in addition (triple-therapy). Three patients (25%) developed PTDM during or immediately following anti-rejection therapy with intravenous methylprednisolone. Eight patients (66.6%) developed PTDM within six months of transplantation. Majority of our patients (66.6%) could be managed successfully with oral hypoglycemic agents. Two patients (16.6%) showed spontaneous resolution of hyperglycemia within six months of onset of PTDM. Eleven patients (91.6%) were symptomatic for their hyperglycemia with two patients presenting as 'pseudorejection' and one with diabetic ketoacidosis. Females were more predisposed to develop PTDM in our study (10% vs. 4.1%). HLA-B15 and DR 3 were the commonest phenotypes in our PTDM patients. No other known predisposing or triggering factors associated with PTDM were found in our patients. The current study suggests, that addition of cyclosporine to the conventional immunosuppression in live-related renal allograft recipients has contributed to an increased incidence of post-transplant diabetes mellitus. Close and regular blood sugar monitoring is thus recommended in post-transplant patients especially those on triple drug immunosuppression.

The quality of life in successful live-related renal allograft recipients in India.

BACKGROUND. The high cost of maintenance of haemodialysis makes most patients in India and elsewhere opt for a renal transplant. The degree of rehabilitation can best be assessed by evaluating the quality of life in successful recipients. METHODS. We studied vocational rehabilitation, social relations, sexual and married life, psychological status and life satisfaction in 51 successful live-related renal allograft recipients using Schwab's depressive scale, Bigot's life satisfaction index and the Kamofsky physical scale. RESULTS. Eight-four per cent of our patients had returned to their original jobs. Ninety-eight per cent of patients had a Kamofsky scale of 90-100 and 81% were leading a normal married life. Ninety-four per cent of them led an active social life. CONCLUSION. Successful live-related renal transplantation is associated with a good quality of life and should be the treatment of choice for patients with end-stage renal disease.

Spontaneous rupture of spleen in viral hepatitis A.

A twenty-five year old man presented with history of fever, malaise and jaundice and developed a spontaneous rupture of the spleen during hospital admission. Investigations revealed deranged liver function tests and positive serology for hepatitis A.