Successful hepatorenal transplantation in hereditary amyloidosis caused by a frame-shift mutation in fibrinogen Aalpha-chain gene.

Hereditary systemic amyloidosis comprises several autosomal dominant diseases caused by mutations in a number of plasma proteins, including the fibrinogen Aalpha-chain. Four mutations in the fibrinogen Aalpha-chain that are able to induce amyloidosis have been identified so far, the most common being the Glu526Val mutation. We have observed a family in which the father and his son reached end-stage renal failure because of renal amyloidosis induced by a frame-shift mutation in the fibrinogen Aalpha-chain gene producing a novel amyloid protein. Two kidney transplantations in the father and one in the son resulted in fast graft loss caused by recurrence of amyloid deposition. We then performed hepatorenal transplantation in the son. Three years later, liver and kidney functions are normal without recurrence of amyloid deposition. This case, together with three others with the Glu526Val mutation in the extensive literature, suggests that liver transplantation can cure hereditary fibrinogen amyloidosis, whatever the mutation may be.

Is the management of hepatitis C patients appropriate? A population-based study.

BACKGROUND: In order for hepatitis C patients to receive antiviral treatment, they must reach medical care. AIM: To assess the proportion of patients reaching medical care after hepatitis C diagnosis in a general population (1 006 171 inhabitants) in France. METHODS: Between 1994 and 1999, 1508 cases were diagnosed, of which 1251 were eligible for the study. RESULTS: Two-hundred and two patients did not have any medical care; among them, 55.4% had normal alanine transferase, 58.4% had risk factors related to lifestyle and 22.8% were alcoholics. Amongst the 1049 other patients, 41.6% had a liver biopsy, 25.0% were treated. Treatment was more often carried out in males than in females (OR: 1.59; P = 0.001), and in patients under 65 than in older patients (OR: 2.22; P < 0.008). Among non-treatment reasons, alcoholism (P = 0.001), drug-addiction (P = 0.04) and escaping monitoring (P = 0.04) were more frequent in males than in females, whereas normal alanine transferase was more frequent in females than in males (P = 0.004). Amongst 278 patients with a Metavir score >A1F1, 71 (25.5%) did not undergo treatment. CONCLUSION: In a general population, one patient in six did not receive on-going health care; a quarter of patients with a Metavir score >A1F1 did not receive any treatment. These results showed insufficient clinical management, which could compromise the effectiveness of treatment in general population.

[Cutaneous complications following liver transplantation: epidemiologic and clinical study in 86 patients]. / Manifestations dermatologiques chez les transplantés hépatiques.

INTRODUCTION: Organ transplanted patients exhibit cutaneous lesions caused by immunosuppressive treatment and/or immunosuppression itself. Several selected studies concerning kidney transplants have been reported, but few concerning liver transplants. We report a retrospective study of skin diseases after liver transplantation. PATIENTS AND METHOD: This study was carried out on liver transplanted patients at the University hospital in Besançon since 1986. Eighty six patients were examined between January 1997 and May 1998. Standardized data obtained at the clinical examination and from past history were compiled concerning cutaneous side effects of immunosuppressive treatments as well as infectious and tumoral skin lesions. RESULTS: Cutaneous side effects related to immunosuppressive treatments: 46.5p. 100 of patients exhibited hypertrichosis, 18.5p. 100 gingival hyperplasia, 8.2p. 100 acne, 23.2p. 100 skin atrophy, 13.9p. 100 senile purpura and 17.4p. 100 sebaceous hyperplasia. Infectious diseases were 2 erysipelas, 2 folliculitis, 29 p. 100 of common fungal infections, 13.9p. 100 of mucocutaneous herpes simplex infections, 3p. 100 of zoster, 38.3p. 100 of cutaneous warts (24.4p. 100 of common warts and 7p. 100 of condylomata). Tumoral skin lesions were 17.4p. 100 of actinic keratoses, 13.9p. 100 of skin cancer (7 squamous and 11 basal cell carcinoma). A correlation was shown between time past graft and the occurrence of skin cancer, between actinic keratoses and skin cancer and between common warts and squamous cell carcinoma. DISCUSSION: We have demonstrated that drug induced skin disorders, infections and tumoral skin diseases were similar and as frequent in liver as in kidney transplanted patients. However, a lower frequency of warts was observed in liver transplanted patients as well as a higher frequency of basal cell carcinoma, compared with squamous cell carcinoma. This ratio is reversed in kidney grafted patients. These results suggest that immunosuppression is lower in liver transplanted patients with possible age involvement.

[The hepatopulmonary syndrome]. / Le syndrome hépatopulmonaire.

DEFINITION: The hepatopulmonary syndrome (HPS) associates a chronic hepatic affection, hypoxemia < 70 mm Hg and pulmonary vasodilatation. PHYSIOPATHOLOGY: The mechanisms leading to pulmonary vasodilatation are complex and unclear. There appears to be an imbalance between the vasodilatating and vasoconstricting mediators. Nitrogen monoxide and endotheline-1 are well known. Hypoxia can be explained by the association of heterogenic ventilation-perfusion, shunts (rare), and a default in "diffusion-perfusion". CLINICAL ASPECTS: In a hypoxic patient, platypnoea and orthodeoxia are characteristic of HPS. Stellar angioma associated with digital hippocratism and signs of portal hypertension are usually present. TO PERMIT DIAGNOSIS: The air of blood gases, followed by 100% O2, standing and reclining, must be measured in all cirrhotic patients to detect hypoxemia. Contract sonography is the key diagnostic examination. Pulmonary perfusion scintigraphy establishes prognosis. Pulmonary angiography differentiates two groups of patients and, for type II patients, embolization therapy can be proposed. Preliminary data indicate that densitometry, conducted in rigorous conditions, can show pulmonary vasodilatation. Its interest must be confirmed by further studies on larger cohorts of patients. THERAPEUTIC POSSIBILITIES: The only efficient treatment of HPS is hepatic transplant (HT). The placing of an intra-hepatic portal systemic shunt can be proposed while waiting for HT, or in certain patients not requiring HT. No medical treatment has demonstrated its efficacy, but better knowledge of the physio-pathologic mechanisms should improve this situation in the future.

Interferon alpha therapy in haemophilic patients with chronic hepatitis C: a French multicentre pilot study of 58 patients.

BACKGROUND AND OBJECTIVES: Information about the long-term efficacy of interferon alpha (interferon-alpha) in haemophilic patients with chronic hepatitis not co-infected with the human immunodeficiency virus (HIV-1) is still limited. Previous studies seemed to indicate a low rate of response. The aim of this study was to evaluate the safety and long-term efficacy of interferon treatment in multi-transfused haemophiliacs. METHODS: Fifty-eight haemophiliacs were scheduled to receive 3 MU of interferon-alpha 2b three times a week for 12 months. The patients were followed up for at least 24 months post-treatment. Response was assessed by measurements of serum hepatitis C virus (HCV) RNA. RESULTS: Twenty-four patients (41.4%) dropped out. Except for seven patients, the symptoms that led to interrupting interferon treatment would probably not have resulted in the same decision in non-haemophilic patients. One patient developed an inhibitor to the deficient clotting factor without haemorrhagic consequences. In an intent to treat, the sustained virological response rate was 14%. However, when considering only the 34 patients who received the full treatment, HCV-RNA was cleared in eight patients (23%). CONCLUSIONS: This study suggests that multi-transfused haemophiliacs with chronic hepatitis not co-infected with HIV-1 respond to prolonged treatment with interferon-alpha in a similar proportion to that observed in non-haemophiliacs. There was a high rate of patients who did not complete the interferon-alpha treatment, and this seems to be characteristic of this patient population.

Pattern of chromosomal imbalances in non-B virus related hepatocellular carcinoma detected by comparative genomic hybridization.

Only limited data are available on comparative genomic hybridization (CGH) in hepatocellular carcinoma (HCC). They concern mainly B virus related HCC. Therefore, we used CGH to detect chromosomal imbalances in 16 non-B virus related HCC in alcoholic cirrhosis in 7 cases (HA1 to HA7), in C virus cirrhosis in 7 cases (HC1 to HC7), in non-cirrhotic liver in 2 cases (NC1, NC2), and in 9 non-malignant cirrhotic tissues. The most frequent imbalances in HCC were gains of whole chromosomes or chromosomal regions 7 or 7q (10/16, 62%), 1q (9/16, 56%), 5 or 5q (9/16, 56%), 8q (8/16, 50%), 6p (6/16, 37%), 15q (5/16, 31%), 20 or 20q (5/16, 31%), and losses of 17p (6/16, 37%), and 8p (5/16, 31%). High-level gains were identified in HCC on 1q (2/16), 3q (1/16), 7q (1/16), and 8q (3/16). No chromosomal imbalances were detected in any of the cirrhotic tissues. Most of the gains, losses, and amplifications detected in this CGH study corresponded well to those identified in previous studies, except for gains of whole chromosome 5 or 7 and/or of chromosome arms 5q or 7q and losses on 4q. Our results suggest that other chromosomal regions are involved in hepatocarcinogenesis.

Caffeine metabolism before and after liver transplantation.

AIM: To study drug metabolism in patients before and after liver transplantation using caffeine as a probe drug. Forty-five patients undergoing liver transplantation for various liver diseases and who had well documented dossiers were selected for the study. Before the liver transplantation and 1 month, 1 year, and 6 years after liver transplantation, they were given 200 mg of caffeine by the oral route in the morning after voiding their bladder. Twenty-four-hour urine samples were collected and caffeine and metabolites were determined by HPLC: 1-methylurate (1U), 1-methylxanthine (1X), 1.7-dimethylurate (17U), 1.7-dimethylxanthine (17X), 7-methylxanthine (7X), 3-methylxanthine (3X), 1.3-dimethylurate (13U), 3.7-dimethylxanthine (37X), 1.3-dimethylxanthine (13X), 1.3.7-trimethylxanthine = caffeine (137X). Indices of enzyme activities were calculated from the following urinary elimination ratios: (AFMU+1U+1X)/17U for CYP1A2, 17U/17X for CYP2A6, 1U/1X for xanthine oxidase (XO), AFMU/(AFMU+1U+1X) for N-acetyltransferase (NAT-2). RESULTS: Compared with results obtained in a group of 70 healthy subjects, caffeine metabolism before liver transplantation was deeply depressed with a decreased elimination rate in the case of all metabolites and a decreased CYP1A2 activity. Caffeine metabolism began to return to the control values one month after transplantation. One year and 6 years after liver transplantation, quantitatively, the metabolism of caffeine was stable and not different from control, but with qualitative modifications. CYP1A2 activity was decreased with reduced urinary elimination rates of 1X and 17X. XO and CYP2A6 activities and 1U and 17U urinary elimination rates were increased. Immunosuppressive treatment was possibly responsible for the metabolic pathway changes. Almost the same modifications were observed in 9 patients after bone marrow transplantation who had been treated with the same immunosuppressive drugs, cyclosporine and azathioprine. During severe rejection phases in 6 of the liver transplant patients, caffeine metabolism was progressively decreased when the usual liver function tests showed moderate but uniform changes. CONCLUSION: Despite an apparent normal drug-metabolic function, immunosuppressive treatment induces stable variations in drugmetabolic pathways after liver transplantation which can be detected from the changes in caffeine metabolism.

Treatment of mild chronic hepatitis C with interferon alpha-2b: results of a multi-centre randomized study in 80 patients.

OBJECTIVE: The natural history of mild chronic hepatitis C is not well-known and the benefit of treating this form of the disease is not well-defined. We conducted a pilot study to answer this question. DESIGN: Mild chronic hepatitis C was defined by positivity for anti-HCV antibodies, detectable serum HCV RNA by PCR, and a Knodell score < or = 5 on a liver biopsy performed within the previous 6 months. Eighty patients from six centres were randomized into two groups receiving interferon alpha-2b, 3 MU three times a week for 6 months (group 1, n = 39) or no treatment (group 2, n = 41). Sustained response was defined by the loss of detectable serum HCV RNA at 6 months after therapy. RESULTS: The two groups were not different at entry with respect to age, sex ratio, source of infection, disease duration, genotype, viral load and Knodell score. One patient (group 1) was excluded from the study, while two patients in group 1 (5%) and seven in group 2 (17.1 %) did not complete the trial. A sustained response was observed in seven patients (18%) in group 1 versus none in group 2 (P < 0.01). The difference in mean Knodell score remained non-statistically significant between the two groups at the end of the study. Reduction or interruption of interferon was necessary in eight patients (24.2%). CONCLUSIONS: This first randomized controlled study in mild chronic hepatitis C shows a proportion of sustained responders to interferon alpha-2b similar to that observed in active chronic hepatitis C.

Caffeine metabolism in a group of 67 patients with primary biliary cirrhosis.

OBJECTIVE: To evaluate the polygenic regulated caffeine metabolism in a group of 67 patients with a documented primary biliary cirrhosis (PBC) classified according to the histologic stage proposed by Scheuer. METHODS: Over a 14-year period, drug liver metabolism, using caffeine as a probe drug, has been systematically carried out in addition to the usual clinical, histological and biochemical investigations performed in patients with PBC. The "Caffeine test" consisted of a 200 mg caffeine oral intake. Urines were collected over 24 hours: caffeine (137X), 1-7-dimethylxanthine (17X), 1-3-dimethylxanthine (13X), 1-3-dimethylurate (13U), 3-7-dimethylxanthine (37X), 1-7-dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U), 7-methylxanthine (7X), 3-methylxanthine (3X), and 5-acetylamino-6-formylamino-3-methyluracyl (AFMU) were analyzed by high performance liquid chromatography (HPLC). Total and individual metabolite urinary elimination rates were expressed in micromol/24 hours. Enzyme activities were evaluated from the following urinary metabolite ratios: (AFMU+1U+1X)/17U for CYP1A2, 17U/17X for CYP2A6, AFMU/(AFMU+U+ 1X) for NAT-2, 1U/1X for XO. RESULTS: Compared to healthy subjects, patients with PBC presented a reduced metabolism of caffeine due to a decreased CYP1A2 activity, all the more important since the patients had an advanced histological stage. This picture was nearly identical to the observed picture in chronic liver diseases from various origins. PBC affected the various metabolic pathways of caffeine in a differential manner. CYP1A2 activity was decreased but XO and mainly CYP2A6 activities were increased as shown by the raised urinary ratio 17U/total metabolite elimination. In contrast to the described loss of bimodality of the NAT-2 index distribution in patients with alcoholic cirrhosis, we found a clear-cut, bimodal distribution in patients with PBC, without a high incidence of slow acetylator status. CONCLUSION: Metabolism of caffeine is strongly and differentially disturbed in patients with PBC and apparently not exactly in the same way as that in alcoholic cirrhosis which is more often taken as an index of chronic liver disease. This suggests the need for caution with medicines whose metabolism is under polygenic regulation. Because of the relationships between caffeine metabolism modifications and histological stages, the caffeine test might be used along with the usual tests to safely follow-up the evolution of the disease.

Relationship between the severity of alcoholic liver cirrhosis and the metabolism of caffeine in 226 patients.

OBJECTIVES: To evaluate the polygenic regulated caffeine metabolism in a group of 226 patients with liver alcoholic cirrhosis classified according to the Child score. METHODS: Over a 14-year period an hepatic function test, using caffeine as probe drug, has been systematically associated to the usual clinical and biochemical investigations performed in patients with liver alcoholic cirrhosis. "Caffeine test" consisted in a 200 mg caffeine oral intake. Urines were collected over 24 hours: caffeine (137X), 1-7 dimethylxanthine (17X), 1-3 dimethylxanthine (13X), 1-3 dimethylurate (13U), 3-7 dimethylxanthine (37X), 1-7 dimethylurate (17U), 1-methylxanthine (1X), 1-methylurate (1U), 7-methylxanthine (7X), 3-methylxanthine (3X), and 5-acetylamino-6-formylamino-3-methyluracyl (AFMU) were analyzed by high performance liquid chromatography (HPLC). Total and individual metabolite urinary elimination rates were expressed in micromol/24 hours. Enzyme activities were evaluated from the following urinary metabolites ratios: (AFMU+1U+1X)/17U for CYPIA2, 17U/17X for CYP2A6, AFMU/(AFMU+ 1U+1X) for NAT-2, 1U/1X for XO. RESULTS: Compared to healthy subjects, whatever the Child score, caffeine metabolism was reduced by half in patients with alcoholic cirrhosis. The main cause was the decreased CYP1A2 activity. On the other hand, XO and CYP2A6 activities were increased and NAT-2 activity remained unchanged in slow acetylators (SA) and decreased in rapid acetylators (RA) Child B and C. Bimodality of NAT-2 distribution was unclear, but a right assignment of RA and SA phenotype in cirrhotic patients, confirmed by comparison with genotype, was obtained, using the antimode value of NAT-2 distribution used in healthy subjects. At last, there was an interindividual variability in caffeine metabolism as great as in the usual laboratory parameters. CONCLUSION: Metabolism of caffeine is decreased in patients with alcoholic liver cirrhosis. This decrease paralleled the modifications of the usual laboratory tests and does not bring additional information on the severity of the disease. But the equilibrium between the various metabolic pathways of caffeine is impaired. Beyond the changes of a specific enzymatic activity, this must be taken into account particularly for drugs whose metabolism is of the polygenic regulation type.

[Organized hepatitis C screening. Results and cost of a one-year campaign in a pilot area]. / Dépistage organisé de l'hépatite virale C. Résultats et coût d'un an de campagne dans un département pilote.

OBJECTIVES: The management and monitoring process and the efficiency of targeted hepatitis C screening in the French health care system are not known. We assessed the main results and the cost of the program established in the Doubs area, where organized screening was integrated into the activities of voluntary physicians. METHODS: All biological laboratories in the area, 23% of the private general practitioners, 42% of occupational physicians, one prison health service and one health centre agreed to participate. Screening was targeted to the following risk factors: transfusion before 1991, intravenous drug use, tattooing and household contact. The prescription form specified the indication and allowed free testing. RESULTS: Among the volunteers, 58% of the general practitioners, 63% of the occupational physicians and 50% of the laboratories prescribed at least one screening test. In one year, 948 serologies were prescribed, mainly for tattooing (45%) or transfusion (28%). Only 83% of the tests were performed, with patient observance depending on age, indication and the place of prescription. Thirty-one patients were positive (4%). The cost of the campaign was 10 994 F per screened case. CONCLUSION: Mobilizing health professionals for organized screening is difficult which affects the efficiency of strategies.

A twenty-year history of alveolar echinococcosis: analysis of a series of 117 patients from eastern France.

OBJECTIVES: Alveolar echinococcosis of the liver is a very rare and severe parasitic disease due to the growth of the larva of Echinococcus multilocularis. The aim of this paper was to describe a 20-year study of the epidemiological, clinical and therapeutic aspects of alveolar echinococcosis in eastern France. DESIGN: One hundred and seventeen consecutive cases, diagnosed and followed in our liver unit, were studied from 1972 to 1993. METHODS: Data from 85 patients followed since 1983 (period B) were compared to data from a first series of 32 patients (period A) collected from 1972 to 1982; 1983 was chosen as the cut-off year because of the numerous changes that occurred in the diagnosis, follow-up and treatment of the disease at this time, in particular the introduction of parasitostatic benzimidazoles. RESULTS: The results of patient follow-up were evaluated in December 1997. The cumulative prevalence was 2.5 per 100,000 persons in period A whereas it reached 6.6 per 100,000 in period B. The annual incidence in period B was 7.3 on average, compared with 2.7 in period A. Twenty-nine per cent of patients from period B were asymptomatic at the time of diagnosis compared with 10% in period A. This change was correlated with less advanced liver lesions, and was related to the extensive use of abdominal ultrasound, and from 1987, serological screening. Curative resections were performed in 24% of the cases in period B versus only 3% in period A. From 1986, liver transplantations were performed in eight patients from period A and 13 patients from period B. In period B, palliative surgery was frequently replaced by radiological non-operative procedures to treat abscesses and jaundice. From 1982, 73 patients received benzimidazoles for a period of time ranging from 4 to 138 months. Stabilization of the lesions was observed in two-thirds of the patients. Episodes of jaundice or digestive haemorrhage due to portal hypertension were 31.5 and 11 times less frequent respectively in patients from period B compared with period A. Actuarial survival at 5 years improved from 67% in period A to 88% in period B in patients of similar age. CONCLUSIONS: Radical changes in the diagnosis and the management of alveolar echinococcosis have occurred during the last decade. Together they have contributed to an improvement in the status of the patients affected by this very severe parasitic disease.

Caffeine metabolism differences in acute hepatitis of viral and drug origin.

The 24-h urinary excretion rate of caffeine metabolites following 200 mg caffeine intake has been proved to be a valuable safe quantitative test of liver function. The pathological mechanism of acute hepatitis of viral and drug origin is different. In both diseases, the patient's caffeine metabolic capacity during the acute and the recovery period was compared. In the acute period, in both diseases, the strongly reduced metabolism of caffeine paralleled the variations of the usual biochemical tests. During the recovery period, in viral hepatitis, caffeine metabolism and biochemical tests returned to the normal values. In drug-induced hepatitis during the recovery period, caffeine metabolism remained severely impaired at a time when biochemical tests were back to the control levels. This discrepancy might be due to the histological or molecular toxic effects of the drug(s), irrespective of cytolysis. After drug-induced hepatitis, a caffeine test might be used to check the total recovery or to choose an adapted dosage of medicines.

[Strategies of hepatitis C screening in general practice. Results of a two-center randomized trial]. / Stratégies de dépistage de l'hépatite virale C en Médecine générale. Résultats d'un essai randomisé bicentrique.

OBJECTIVES: To improve the detection of patients infected with hepatitis C virus. METHODS: A study was undertaken in the general medicine setting in two hepatitis C networks. General practitioners volunteered and received training on hepatitis C, then were randomly assigned to one of two screening strategies: group 1: general practitioners prescribed hepatitis C virus testing if the risk factors for HCV hepatitis C virus infection were identified during questioning of patients, group 2: general practitioners were helped in their screening approach by posters and leaflets on the risk factors of hepatitis C virus, available in the waiting room. RESULTS: A total of 184 general practitioners enrolled 90 from group 1 and 94 from group 2. During a 15-month-period, 617 serologies were prescribed, 323 by general practitioners in group 1 (in patients who were an average of 40 year-old) and 294 in group 2 (in patients who were an average of 44 year-old); 489 serologies (79.3%) were actually performed (261 and 228 respectively) and 25 (5.1%) tested positive (15 and 10 respectively). The number of prescribed, performed, and positive serologies did not differ from one group to the other. The motive for hepatitis C virus screening was similar in both groups and included a history of transfusion in 27% of cases, intravenous drug use in 6%, increased ALT or symptoms compatible with hepatitis in 13%, nosocomial exposure in 22%. Risk factors in the 25 patients who were hepatitis C virus positive were drug use (44%), history of transfusion before 1991 (16%), elevated ALT or symptoms (12%), others (28%). CONCLUSION: This study comparing screening strategies in general medicine, resulted in the diagnosis of hepatitis C virus infection in 5% of tested patients, regardless of the strategy. However, the fewer serologies prescribed by general practitioners (an average of 3 tests in a 15-month-period) suggests a low rate of identified risk factors in general practice, and emphasizes that other types of screening procedures should be implemented and evaluated.

Primary disease recurrence after liver transplantation for alveolar echinococcosis: long-term evaluation in 15 patients.

Between 1986 and 1991, 21 patients received liver grafts in our center for incurable alveolar echinococcosis (AE). The aim of this study was to analyze the long-term results in 15 of these 21 patients who survived more than 1 year after undergoing a liver transplantation (LT). The follow-up, mainly aimed at the diagnosis of recurrence, consisted of repeated radiological and specific immunological investigations. The role of pre- and post-LT benzimidazole (BZM) therapy was also evaluated. Among the 15 patients, 8 patients had a palliative LT related to previously known pulmonary AE metastases and/or inextirpable abdominal parasitic foci. In the 7 remaining patients, LT was considered curative. In June 1998, the mean follow-up duration was 96 months (range: 28-138 months). Five late deaths occurred, 2 of them were directly related to residual AE. A reinfection of the graft was observed in 4 patients. Preoperative BZM therapy seemed useful in preventing or delaying the parasitic recurrence. Post-LT BZM was able to stabilize and even to reduce residual AE. The anti-Em2 enzyme-linked immunosorbent assay (ELISA), which is the standard test used in patient follow-up after partial liver resection for AE, did not appear useful in detecting recurrence here; however, an ELISA, using a crude heterologous antigen (Echinococcus granulosus) allowed early diagnosis of residual AE. In conclusion, primary disease recurrence is not rare after LT for AE. Immunosuppressive therapy may favor larval growth in extrahepatic sites; therefore, an extensive extrahepatic radiological check-up has to be performed before LT. BZM therapy seems to stabilize residual foci. Anti-Eg immunoglobulin G (IgG) follow-up is the most useful test for early diagnosis of parasite recurrence.