Challenges in the diagnosis and treatment of pure non-gestational uterine choriocarcinoma in a child: a case report.

BACKGROUND: Diagnosing non-gestational uterine choriocarcinoma in children is challenging because of its rarity and nonspecific imaging findings. Herein, we report a case of non-gestational uterine choriocarcinoma in a child, which was unexpectedly found during exploratory laparotomy and confirmed by histopathological findings. However, the tumor did not respond to chemotherapy. CASE PRESENTATION: A 4-year-old Indonesian female patient was brought into the emergency unit with chief complaint of vaginal bleeding. She had suffered from vaginal spotting 4 months before being admitted to the hospital. Physical examination revealed a distended abdomen in the left lumbar region and a palpable fixed mass with a smooth surface. Abdominal computed tomography scans revealed a large mass (10 × 6 × 12 cm) with fluid density and calcification. Thus, we suspected left ovarian teratoma. The patient's luteinizing hormone, follicle-stimulating hormone, and lactate dehydrogenase levels were 25.2 mIU/ml, 0.1 mIU/ml, and 406 U/l, respectively. According to the clinical and radiological findings, we decided to perform an exploratory laparotomy and found a tumor originating from the uterus, not the ovarium. We did not observe liver nodules and any enlargement of abdominal lymph nodes. Subsequently, we performed hysterectomy. The histopathological findings supported the diagnosis of choriocarcinoma. The patient was discharged uneventfully on postoperative day 5. Thereafter, the patient underwent nine cycles of chemotherapy, including carboplatin (600 mg/m2 IV), etoposide (120 mg/m2 IV), and bleomycin (15 mg/m2 IV). However, on the basis of the clinical findings of a palpable mass and partial intestinal obstruction, the tumor relapsed soon after the ninth cycle of chemotherapy. Currently, the patient is undergoing chemotherapy again. CONCLUSIONS: Although pure non-gestational uterine choriocarcinoma is rare, it should be considered as one of the differential diagnoses for intraabdominal tumors in a child, so as to better guide and counsel families regarding the surgical plan and prognosis, respectively. In the present case, the patient's response to chemotherapy was poor, implying that the treatment of non-gestational choriocarcinoma is still challenging, particularly in the pediatric population.

Regulatory T Cells but Not Tumour-Infiltrating Lymphocytes Correlate with Tumour Invasion Depth in Basal Cell Carcinoma.

Basal cell carcinoma (BCC) is the most common skin malignancy worldwide. Current evidence suggests tumour-infiltrating lymphocytes (TILs) may influence the clinical outcomes of patients with BCC. The present study aimed to profile the infiltrative characteristics of stromal TILs and regulatory T cells (Treg cells) in the tumour centre (TC), tumour periphery (TP), and normal adjacent tissue (NAT) of BCC. A total of 111 samples from 43 cutaneous BCC cases were examined for TIL (CD3+) and Treg cell (FOXP3+/CD3+) expression using immunohistochemical techniques. The correlations of Treg cells with TILs, invasion depth, and tumour morphological risk were analysed. We identified a high mean proportion of Treg cells within the tumour (TC = 46.9%, TP = 56.1%, NAT = 51.8%) despite a relatively low median of TILs (TC = 12.7%, TP = 10.3%, NAT = 3.6%), supporting the classification of BCC as a cold tumour. A significant positive correlation was observed between the proportion of Treg cells and sTILs (ρ = 0.325, p < 0.001), suggesting a predominant role of TILs in the infiltration of Treg cells. An inverse correlation discovered between Treg cells and tumour invasion depth (r = −0.36, p = 0.017) might indicate Treg cells' anti-tumour capacity in BCC.

Lag time, high-risk histopathological features, metastasis, and survival interrelation in retinoblastoma: a perspective from lower-middle income country.

AIM: To investigate the impact of lag time to metastasis and survival rates among patients with retinoblastoma. METHODS: This retrospective study was conducted with 52 patients from the Department of Ophthalmology and the Department of Pediatrics of Dr. Sardjito General Hospital, between 1st January 2014 and 31st December 2020. Lag time was defined as the time delay between the first sign of retinoblastoma to the diagnosis of retinoblastoma. The subjects with lag time > one year were included in the case group, while the subjects with lag time < one year were included in the control group. RESULTS: The lag time was significantly correlated with American Joint Committee on Cancer and Intraocular Classification of Retinoblastoma staging of retinoblastoma (P=0.005 and P=0.006, respectively). The lag time was also significantly correlated with both metastasis event [odds ratio (OR): 5.06, 95%Cl: 1.56-16.44, P=0.006] and mortality (OR: 4.54, 95%Cl: 1.37-15.07, P=0.011). The follow-up was continued for 32 subjects for 3y after initial diagnoses. Survival analysis revealed a significant difference among these two groups (P=0.021). Furthermore, lag time was significantly correlated with survival of retinoblastoma (r=-0.53, P=0.046). CONCLUSION: The study highlights the importance of lag time between the onset of first symptoms and the time of retinoblastoma diagnosis which significantly contribute to metastasis and mortality of patients with retinoblastoma. Examinations for the early detection of retinoblastoma should be performed for individuals at-risk to minimize lag time and improve the outcomes.

Keloid-like Pilomatricoma of the Auricle: A Case Report and Review of Literature.

Pilomatricoma is a rare benign skin adnexal tumor arising from hair matrix cells. It usually manifests as a firm-to-hard, well-circumscribed, nontender nodule often mistaken as a dermoid cyst. However, its clinical presentation has been reported to mimic keloid. In addition, although it occurs most frequently in the head and neck area, pilomatricoma is rarely reported on the auricle. Herein, we reported a case of pilomatricoma occurring on the posterior part of a 9-year-old girl's auricle. Unlike classic pilomatricoma, the tumor closely resembled a keloid. Nevertheless, histological examination following excision of the tumor revealed a dermal tumor arranged in solid nests consisting of basaloid and ghost cells along with foreign body reaction, calcification, and ossification, confirming the diagnosis of pilomatricoma. The rarity, atypical clinical presentation, and unique location of this tumor contributed to the misdiagnosis of this case. Therefore, we reviewed previous cases of pilomatricoma of the auricle reported in the literature to provide a comprehensive understanding of this rare entity.

The frequency and clinicopathological significance of NRAS mutations in primary cutaneous nodular melanoma in Indonesia.

BACKGROUND: Melanoma is a lethal skin malignancy with a high risk of metastasis, which prompts a need for research on treatment targets and prognostic factors. Recent studies show that the presence of neuroblastoma RAS viral oncogene homolog (NRAS) mutation can influence cell growth in melanomas. The NRAS mutation, which stimulates the mitogen-activated protein kinase (MAPK) signaling pathway, is associated with a lower survival rate. However, evidence from Indonesia population is still very rare. Further understanding of the role of NRAS mutations in Indonesian melanoma cases will be crucial in developing new management strategies for melanoma patients with NRAS mutations. AIMS: To explore the frequency of NRAS mutations and their clinicopathological associations in patients with primary nodular cutaneous melanoma in Central Java and Yogyakarta, Indonesia. METHODS AND RESULTS: Fifty-one paraffin-embedded tissue samples were collected from primary nodular skin melanoma cases between 2011 and 2019 from the two largest referral hospitals in Yogyakarta and Central Java, Indonesia. The NRAS mutation status was evaluated using qualitative real-time polymerase chain reaction (qRT-PCR). The association of NRAS mutation was analyzed with the following: age, gender, location, lymph node metastasis, ulceration, mitotic index, tumor-infiltrating lymphocytes (TILs), necrosis, tumor thickness, lymphovascular invasion (LVI), and tumor size. NRAS mutations were detected in 10 (19.6%) samples and predominantly observed (60%) in exon 2 (G12). These mutations were significantly correlated with lymph node metastases (p = .000); however, they were not associated with other variables analyzed in this study. CONCLUSIONS: The prevalence of NRAS mutations in primary nodular cutaneous melanoma cases from Indonesia is consistent with previous studies and is significantly associated with increased lymph node metastases. However, the predominant mutation detected in exon 2 (G12) is different from previous studies conducted in other countries. This suggests that melanoma cases in Javanese people have different characteristics from other ethnicities.

Potential prognostic value of PD-L1 and NKG2A expression in Indonesian patients with skin nodular melanoma.

OBJECTIVE: Biomarker mRNA levels have been suggested to be predictors of patient survival and therapy response in melanoma cases. This study aimed to investigate the correlations between the mRNA expression levels of PD-L1 and NKG2A in melanoma tissue with clinicopathologic characteristics and survival in Indonesian primary nodular melanoma patients. RESULTS: Thirty-one tissue samples were obtained; two were excluded from survival analysis due to Breslow depth of less than 4 mm. The median survival of upregulated and normoregulated PD-L1-patients were 15.800 ± 2.345 and 28.945 ± 4.126 months, respectively. However, this difference was not significant statistically (p = 0.086). Upregulated and normoregulated NKG2A patients differed very little in median survival time (25.943 ± 7.415 vs 26.470 ± 3.854 months; p = 0.981). Expression of PD-L1 and NKG2A were strongly correlated (rs: 0.787, p < 0.001). No clinicopathologic associations with PD-L1 and NKG2A mRNA levels were observed. These results suggest that PD-L1 may have potential as a prognostic factor. Although an unlikely prognostic factor, NKG2A may become an adjunct target for therapy. The strong correlation between PD-L1 and NKG2A suggests that anti-PD-1 and anti-NKG2A agents could be effective in patients with PD-L1 upregulation. The mRNA levels of these two genes may help direct choice of immunotherapy and predict patient outcomes.

Xanthogranulomatous Pyelonephritis with Pyonephrosis and Renal Abscess in a Young Adult: A Consequence of Neglected Urinary Tract Infection Leading to Nephrectomy.

Xanthogranulomatous pyelonephritis (XGP) is a rare form of chronic pyelonephritis, which is challenging to diagnose because its clinical presentation mimics other entities and is commonly associated with a history of urinary tract obstruction. We report a case of XGP in a young adult without nephrolithiasis and urinary tract obstruction. A 23-year-old woman presented with intermittent abdominal pain in the right upper quadrant persisting for the last ten months. The pain was dull, poorly localized, and started spreading to the right back, right shoulder, and right thigh in the last three months. Other complaints included fever, chills, pain during urination, and nausea. The patient had a history of infrequent urination, recurrent urinary tract infections (UTIs), and a low fluid intake. A physical examination revealed that the patient had right upper quadrant abdominal tenderness and right costovertebral angle tenderness. Laboratory findings showed leukocytosis and neutrophilia. The radiological examination revealed a round mass in the superior pole of the right kidney with mixed cystic and solid components, and a well-defined margin. It further enlarged from 4.5 cm to 10.6 cm in diameter in three months. The urologist performed a total right nephrectomy. The histopathological examination showed XGP with renal abscess. Proteus mirabilis was identified from the pus specimen culture. XGP should be considered in the diagnosis of patients having chronic UTI presented with or without the findings of urinary tract obstruction.

Histopathological findings for prediction of liver cirrhosis and survival in biliary atresia patients after Kasai procedure.

BACKGROUND: Without early recognition and Kasai procedure, biliary atresia (BA) results in liver cirrhosis and leads to either transplantation or death at a young age. We aimed to characterize the liver histopathological findings for prediction of cirrhosis and survival in BA patients after Kasai surgery. METHODS: We retrospectively reviewed all histopathological results for BA patients who underwent liver biopsy during Kasai surgery from August 2012 to December 2018 in Dr. Sardjito Hospital, Yogyakarta, Indonesia. RESULTS: Fifty infants with BA were ascertained in our study, of whom 27 were males and 23 were females. The median age of Kasai procedure was 102.5 days (interquartile range (IQR), 75.75-142.25 days). There were 33 (66%) and 17 (34%) BA patients with and without liver cirrhosis, respectively, while the overall survival was 52%. The patients with a severe bile duct proliferation, severe cholestasis, and severe portal inflammation have a higher risk by 27-, 22-, and 19.3-fold, respectively, to develop liver cirrhosis compared with patients with a moderate/mild bile duct proliferation, moderate/mild/without cholestasis, and moderate/mild portal inflammation, respectively (p = 3.6 × 10- 6, 5.6 × 10- 4, and 1.6 × 10- 3, respectively), while the giant cell transformation was not associate with the development of liver cirrhosis (p = 0.77). The bile duct proliferation was strongly correlated with cholestasis and portal inflammation (p = 7.3 × 10- 5 and 2 × 10- 4, respectively), and cholestasis was also significantly correlated with portal inflammation (p = 0.016). Interestingly, the age at Kasai procedure was strongly associated with the development of liver cirrhosis (p = 0.02), but not with the patients' survival (p = 0.33), while the degree of fibrosis and cholestasis were significantly correlated with the patients' survival, with HR of 3.9 (95% CI = 1.7-9.0; p = 0.017) and 3.1 (95% CI = 1.4-7.0; p = 0.016), respectively. CONCLUSIONS: Histopathological findings of bile duct proliferation, cholestasis, and portal inflammation can predict the liver cirrhosis development in patients with BA. Furthermore, degree of fibrosis and cholestasis affect the patients' survival following the Kasai operation.

Mutational heterogeneity between different regional tumour grades of clear cell renal cell carcinoma.

Only a limited number of studies have explored the possible associations between tumour grade and mutated genes in clear cell renal cell carcinoma (ccRCC), and we set out to investigate this further using a multiple sampling and next generation sequencing (NGS) approach in a series of ccRCCs. Multiple regions were sampled from formalin-fixated paraffin-embedded ccRCC tumour blocks from seven patients. In 27 samples from six patients, we performed targeted NGS using a custom 42-gene panel based on the most frequently mutated genes in ccRCC reported in public databases. In four samples from the seventh patient, we performed whole exome sequencing (WES) and array comparative genomic hybridisation for detection of copy number variants (CNVs). Mutated genes and the tumour grades of the samples in which they had been identified were compared both within and between all individual tumours. CNVs were compared across all samples from patient 7. We identified clear genetic heterogeneity within and across tumours, but VHL mutations were seen in all patients. Looking across all samples, we identified eleven genes that were only mutated in samples with one particular tumour grade. However, these genes were never mutated in all samples with that tumour grade. Increasing chromosomal instability corresponded with increasing tumour grade, but we observed minimal association between tumour grade and total mutational load in the WES data. Our study confirms the genetic heterogeneity and tumour grade heterogeneity of ccRCC. Although a relatively small number of samples was analysed, genes were identified that could potentially be specific, though insensitive, markers of higher ccRCC tumour grades.

BRAF V600 mutation profiling in primary skin nodular melanoma in Indonesia: an analysis using high resolution pyrosequencing.

OBJECTIVE: We aimed to investigate the prevalence and type of BRAF V600 mutations and the associations with clinicopathological variables in primary skin nodular melanoma cases in Yogyakarta and Central Java, Indonesia using pyrosequencing. RESULTS: BRAF V600 mutations of the V600E type were found in 21 (53.85%) specimens. The variant allele frequencies (VAFs) ranged from 5.07 to 94.70%, averaging 29.05%. However, most cases had low VAFs, with 13 (61.9%) specimens below 20% and 4 (19.05%) below 10%.

Primary Chordoma of the Nasopharynx: A Rare Case Report and Review of the Literatures.

Primary chordoma of the nasopharynx is an extremely rare malignant tumor of notochordal origin in the extra-osseous axial skeleton. It presents as a soft tissue mass without involvement of the skull base bone (clivus) and may mimic other lesions of the nasopharynx. A 26-year-old male patient is presented with nasal obstruction and congestion for the last 3 years. Physical and radiological examination revealed a mass in the naso-oropharyngeal region. It was suspected to be a cystic mass or abscess on radiological imaging. However, histopathological examination revealed a chordoma. We review all 20 cases of primary nasopharyngeal chordoma reported previously in the literature. Nasopharyngeal chordoma should be considered in the differential diagnosis of nasopharyngeal mass due to its unspecific appearance on clinical and radiology examination.

Tissue P16 is Associated with Smoking Status among Indonesian Nasopharyngeal Carcinoma Subjects.

Background: Nasopharyngeal carcinoma (NPC) is a malignancy with high incidence in Southern China and South-East Asia. NPC incidence among males in Indonesia is estimated around 8.3/100,000 populations. Tobacco smoking is a common risk factor for cancer, including NPC. P16 is one of the key proteins related to the activation of apoptotic pathways, that commonly change during carcinogenesis. Carcinogenesis is often related to environmental exposure, including tobacco smoke. Objective: To analyze the association between P16 protein and smoking status among NPC subjects in Indonesia. Methods: Forty formalin fixed-paraffin embedded NPC tissue samples of known smoking status (20 smokers, 20 non-smokers) were collected from the Department of Anatomical Pathology, Dr. Sardjito Hospital, Yogyakarta. P16 was detected by immunohistochemistry staining. German semi-quantitative scoring system was applied to the P16 staining. Expression index with the score of 0 to 3 was classified as negative staining, meanwhile 4 to 12 was classified as positive staining. The association between P16 (score) and smoking status among NPC patients was analyzed using Fischer exact test. One-sided p ≤ 0.05 was considered as statistically significant. Results: All samples were Javanese males, with age range 25-76 years old. P16 positive staining among smokers was 5% (1/20), while among non-smokers was 40% (8/20). P16 among smokers was significantly lower than non-smokers patients (p=0.010). No difference was found between quantity of smoke and P16 score. Conclusion : A significant association between P16 and smoking status in Indonesian NPC patients has been revealed. The result of this study may be used to improve prevention and management of NPC cases related to smoking habit in Indonesia.

Low BRAF V600 mutation prevalence in primary skin nodular melanoma in Indonesia: a real-time PCR detection among Javanese patients.

BACKGROUND: Cutaneous melanoma is a rare, aggressive skin malignancy with a high mortality rate. Although only contributing 7.6% of the cases worldwide, Asia is responsible for 18.6% of deaths from cutaneous melanoma. BRAF V600 mutation presents a potential prognostic predictor in melanoma. Unfortunately, studies on that mutation in melanoma, particularly nodular subtype, in Indonesia are still scarce. This research aimed to investigate the prevalence of BRAF V600 mutation in primary skin nodular melanoma in Yogyakarta and Central Java, Indonesia. Its association with clinicopathological parameters was also analyzed. METHODS: Forty paraffin-embedded tissue samples from primary skin nodular melanoma cases in 2011-2018 were collected from the two biggest referral hospitals in Yogyakarta and Central Java, Indonesia. The BRAF V600 mutation status was assessed using qualitative real-time PCR and its associations with age, sex, anatomic location, lymph node metastasis, tumor thickness, ulceration, mitotic index, necrosis, lymphovascular invasion, and tumor-infiltrating lymphocytes were analyzed. RESULTS: BRAF V600 mutations were found in 4 (10%) samples. These mutations were significantly associated with the central (non-extremity) region (p = 0.013) and presence of lymphovascular invasion (p = 0.005). However, it was not associated with any other variables analyzed in this study. CONCLUSION: The prevalence of BRAF V600 mutation in Indonesian primary skin nodular melanoma cases is low and significantly associated with anatomic location and lymphovascular invasion. It is lower than prevalences in other Asian populations as well as in Caucasian populations and suggests that melanoma cases in Javanese people may have distinct clinicopathological characteristics from other Asian ethnicities.

Profile of Mutations in the Reverse Transcriptase and Overlapping Surface Genes of Hepatitis B Virus (HBV) in Treatment-Naïve Indonesian HBV Carriers.

Mutations in the reverse transcriptase (RT) region of the hepatitis B virus (HBV) genome are an important factor in low therapeutic effectiveness. Nonetheless, the prevalence of these mutations in HBV strains isolated previously in Indonesia has not been systematically examined. Therefore, in this study, we investigated the profile of mutations in the RT region and the associations of these mutations with amino acid changes in the surface protein in the virus of treatment-naïve Indonesian HBV carriers. Overall, 96 sequences of the full-length Indonesian HBV genomes (genotype B, n = 54; genotype C, n = 42) were retrieved from the National Center for Biotechnology Information. Naturally occurring primary and/or compensatory drug resistance mutations were found in 6/54 (11.1%) genotype B strains and in 1/42 (2.4%) genotype C strains. The potential mutations underlying resistance to a nucleos(t)ide analog and/or pretreatment mutations were more frequent in both genotypes but more frequent in genotype C strains than in genotype B strains. The A-B interdomain region in the RT gene was more frequently mutated in genotype C than in genotype B (3.51 ± 2.53 vs. 1.08 ± 1.52, P ＜ 0.001). Knowledge about the mutational profiles of the RT gene and changes in the surface protein may help clinicians to select the most appropriate antiviral drug and vaccination or HBV immunoglobulin regimen for management of HBV infection in Indonesia.

A deep-sequencing method detects drug-resistant mutations in the hepatitis B virus in Indonesians.

OBJECTIVE: The long-term administration of a nucleos(t)ide analogue (NA) for the treatment of chronic hepatitis B may encourage the emergence of viral mutations associated with drug resistance. Minor populations of viruses may exist before treatment, but are difficult to detect because of technological limitations. Identifying minor viral quasispecies should be useful in the clinical management of hepatitis B virus (HBV) infection. METHODS: Six treatment-naïve Indonesian patients with chronic HBV infection participated in this study. The polymerase region of the HBV genome, including regions with known drug-resistant mutations, was subjected to capillary sequencing and MiSeq sequencing (Illumina). Mutations were analyzed with Genomics Workbench software version 6.0.1 (CLC bio). RESULTS: The mean mapping reads for the six samples was 745,654, and the mean number of amplified fragments ranged from 17,926 to 25,336 DNA reads. Several known drug-resistant mutations in the reverse transcriptase region were identified in all patients, although the frequencies were low (0.12-1.06%). The proportions of the total number of reads containing mutations I169L/M, S202R, M204I/L or N236S were >1.0%. CONCLUSION: Several known NA-resistant mutations were detected in treatment-naïve patients in Indonesia using deep sequencing. Careful management of such patients is essential to prevent drug-resistant mutations from spreading to other patients.

Mutational diversity of NS5A and NS3 during triple therapy (telaprevir, pegylated-interferon-α 2b and ribavirin) for genotype 1b chronic hepatitis C: The Kobe Hepatitis Therapeutic Group.

Telaprevir, a non-structural (NS)3/4A protease inhibitor, is a direct-acting antiviral drug that inhibits viral replication. Triple therapy with telaprevir, pegylated interferon, and ribavirin is a standard therapeutic regimen for patients with genotype 1b chronic hepatitis C virus (HCV) infection and a high viral load. Several factors, including mutations in the NS5A gene, are important predictors of the efficacy of interferon therapy. In this study, we examined the mutational diversity of NS5A and its impact on the efficacy of triple therapy. We enrolled patients with genotype 1b chronic HCV infection and a high viral load (31 males/17 females; mean age, 57.6 years), who were treated with triple therapy. This study was conducted at Kobe University Hospital and at three affiliated hospitals in Hyogo prefecture, Japan, between November 2011 and June 2013. A sustained viral response after 12 weeks (SVR12) was achieved in 37/48 patients (77%). Based on intent-to-treat analysis, SVR12 was significantly greater in patients with the major allele than in those with the minor allele for the IL28B single nucleotide polymorphism (SNP; 88 vs. 56%; P<0.05). The prevalence of the V2334I mutation in NS5A was significantly higher in patients who achieved SVR12, while that of G2356E was significantly higher in patients who did not achieve SVR12 (P<0.05). Mutations in the NS3 region that are thought to confer resistance to telaprevir were detected in 3/27 patients who achieved SVR12 (Val36, n=3) and in 5/10 patients who did not achieve SVR12 (Val36, n=4; Thr54, n=1). In conclusion, the IL28B SNP and mutations in the NS5A region were associated with the therapeutic response to triple therapy. Half of the patients who did not achieve SVR12 had mutations conferring resistance to telaprevir. However, pre-existing mutations in NS3 did not affect the efficacy of triple therapy.

Hepatitis B and C virus infection among hemodialysis patients in Yogyakarta, Indonesia: Prevalence and molecular evidence for nosocomial transmission.

Hemodialysis patients are at an increased risk of acquiring hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. However, the prevalence of hepatitis viral infection and its genotype distribution among hemodialysis patients in Indonesia are unclear. In order to investigate these issues and the possibility of nosocomial transmission, 161 hemodialysis patients and 35 staff members at one of the hemodialysis unit in Yogyakarta, Indonesia, were tested for serological and virological markers of both viruses. HBV surface antigen (HBsAg) was detected in 18 patients (11.2%) and in two staff members (5.7%). Anti-HCV was detected in 130 patients (80.7%) but not in any staff members. Occult HBV and HCV infection were detected in 21 (14.7%) and 4 (12.9%) patients, respectively. The overall prevalence rates of HBV and HCV infection among patients were 24.2% and 83.2%, respectively. HCV infection was independently associated with hemodialysis duration and the number of blood transfusions. Phylogenetic analysis revealed that 23 of 39 tested HBV strains (59%) were genotype B, 11 (28.2%) were genotype C, and 5 (12.8%) were genotype A. HCV genotype 1a was dominant (95%) among 100 tested HCV strains. Nosocomial transmission was suspected because the genotype distribution differed from that of the general population in Indonesia, and because the viral genomes of several strains were identical. These findings suggest that HBV and HCV infection is common among hemodialysis patients in Yogyakarta, and probably occurs through nosocomial infection. Implementation of strict infection-control programs is necessary in hemodialysis units in Indonesia.

GB virus C infection in Indonesian HIV-positive patients.

GB virus C (GBV-C), a human virus of the Flaviviridae family that is structurally and epidemiologically closest to hepatitis C virus (HCV), has been reported to confer beneficial outcomes in HIV-positive patients. However, the prevalence of GBV-C in HIV-positive individuals in Indonesia is unknown. Since GBV-C is more prevalent in anti-HCV positive patients than in anti-HCV negative subjects, transmission of GBV-C and HCV could be by the same method. This study examined the prevalence and molecular characteristics of GBV-C infection in HIV patients in Yogyakarta, Indonesia. The prevalence of GBV-C among HIV patients (n = 125, median age 31 years) based on the 5'UTR region was 111/125 (88.8%), including 39/48 (81.3%) and 72/77 (93.5%) HIV-infected patients with and without HCV infection, respectively. GBV-C isolates were of genotype 2a, 3 and 6 in 58.3%, 12.6% and 28.4% of patients, respectively. Patients with genotype 3 were significantly younger than those with genotypes 2a or 6 (P = 0.001 and P = 0.012, respectively). Genotypes 3 and 6 were significantly associated with injection drug use (P = 0.004 and P = 0.002, respectively) and HCV co-infection (P < 0.001 for both genotypes), indicating a shared transmission route with HCV. In conclusion, the prevalence of GBV-C among HIV-positive patients in Indonesia is high, and three genotypes were detected, namely genotype 2a, 3 and 6.

Quantification of pregenomic RNA and covalently closed circular DNA in hepatitis B virus-related hepatocellular carcinoma.

Pregenomic RNA (pgRNA) is generated from covalently closed circular DNA (cccDNA) and plays important roles in viral genome amplification and replication. Hepatic pgRNA and cccDNA expression levels indicate viral persistence and replication activity. This study was aimed to measure hepatic pgRNA and cccDNA expression levels in various states of hepatitis B virus (HBV) infection. Thirty-eight hepatocellular carcinoma (HCC) patients, including 14 positive for hepatitis B surface antigen (HBsAg) and 24 negative for HBsAg but positive for anti-hepatitis B core (anti-HBc) antibody, were enrolled in this study. In HBsAg-negative but anti-HBc-positive group, HBV-DNA was detected in 20 of 24 (83%) noncancerous liver tissues for at least two genomic regions based on polymerase chain reaction (PCR) analysis. pgRNA and cccDNA expression levels in occult HBV-infected patients were significantly lower than those in HBsAg-positive patients (P < 0.001). pgRNA and cccDNA in cancerous tissues were also detected without significant difference from those in noncancerous tissues. In conclusion, cccDNA and pgRNA are detected and represented HBV replication not only in noncancerous but also in cancerous liver tissues. In addition, the replication is shown in not only patients with HBsAg-positive but also occult HBV-infected patients, suggesting the contribution to HCC development.

Clinical and virological characteristics of hepatitis B or C virus co-infection with HIV in Indonesian patients.

Hepatitis virus-related liver disease increases substantially the mortality rate of patients with HIV on highly active antiretroviral therapy (HAART). Therefore, early diagnosis of hepatitis B virus (HBV) and hepatitis C virus (HCV) is important. However, the prevalence of HBV and HCV infection in Indonesian patients infected with HIV is unknown. Therefore, this study examined the molecular and clinical characteristics of HBV and HCV in 126 patients infected with HIV, mostly on HAART, at Dr. Sardjito Hospital, Yogyakarta, Indonesia. The rates of triple infection, HIV/HCV co-infection, HIV/HBV co-infection, and mono-infection were 4.8%, 34.1%, 3.2%, and 57.9%, respectively. Seven HCV genotypes were detected, with genotypes 1a, 1b, 1c, 3a, 3k, 4a, and 6n found in 23 (52%), 1 (2%), 4 (9%), 5 (11%), 7 (16%), 3 (6%), and 1 (2%) patients, respectively, indicating multiple modes of transmission. HBV-DNA was detected in 2/10 patients with hepatitis B surface antigen; both patients were HAART naive. Univariate analysis revealed that male sex, higher education level, injection drug use, sexual contact, alanine aminotransferase ≥40 IU/L, and aspartate aminotransferase-to-platelet ratio index > 0.5 were associated with HCV co-infection. In multivariate analysis, injection drug use (OR: 26.52; 95% CI: 3.52-199.54) and alanine aminotransferase ≥40 IU/L (OR: 6.36; 95% CI: 1.23-32.89) were independently associated with HCV co-infection. HCV co-infection was common among Indonesian patients infected with HIV, particularly among injecting drug users, and was a risk factor for disease progression of HIV.