PCNA-associated factor (KIAA0101/PCLAF) overexpression and gene copy number alterations in hepatocellular carcinoma tissues.

BACKGROUND: PCNA-associated factor, the protein encoded by the KIAA0101/PCLAF gene, is a cell-cycle regulated oncoprotein that regulates DNA synthesis, maintenance of DNA methylation, and DNA-damage bypass, through the interaction with the human sliding clamp PCNA. KIAA0101/PCLAF is overexpressed in various cancers, including hepatocellular carcinoma (HCC). However, it remains unknown whether KIAA0101/PCLAF overexpression is coupled to gene amplification in HCC. METHODS: KIAA0101/PCLAF mRNA expression levels were assessed by quantitative real-time PCR (qRT-PCR) in 40 pairs of snap-frozen HCC and matched-non-cancerous tissues. KIAA0101/PCLAF gene copy numbers were evaluated by droplet digital PCR (ddPCR) in 36 pairs of the tissues, and protein expression was detected by immunohistochemistry (IHC) in 81 pairs of formalin-fixed paraffin-embedded (FFPE) tissues. The KIAA0101/PCLAF gene copy number alteration and RNA expression was compared by Spearman correlation. The relationships between KIAA0101 protein expression and other clinicopathological parameters, including Ki-67, p53, and HBsAg protein expression in HCC tissues, were evaluated using Chi-square test. RESULTS: Our results demonstrated that KIAA0101/PCLAF mRNA levels were significantly higher in HCC than in the matched-non-cancerous tissues (p < 0.0001). The high KIAA0101/PCLAF mRNA levels in HCC were associated with poor patient survival. The KIAA0101/PCLAF gene was not amplified in HCC, and KIAA0101/PCLAF gene copy numbers were not associated with KIAA0101/PCLAF transcript levels. KIAA0101 protein was overexpressed in the majority of HCC tissues (77.8%) but was not detectable in matched-non-cancerous tissues. Significant correlations between the expression of KIAA0101 protein in HCC tissues and p53 tumor suppressor protein (p = 0.002) and Ki-67 proliferation marker protein (p = 0.017) were found. However, KIAA0101 protein levels in HCC tissues were not correlated with patient age, tumor size, serum AFP level, or the HBsAg expression. CONCLUSIONS: KIAA0101/PCLAF mRNA and protein overexpression is frequently observed in HCC but without concurrent KIAA0101/PCLAF gene amplification. Significant correlations between the expression of KIAA0101 protein and p53 and Ki-67 proteins were observed in this study. Thus, detection of KIAA0101/PCLAF mRNA/protein might be used, along with the detection of p53 and Ki-67 proteins, as potential biomarkers to select candidate patients for further studies of novel HCC treatment related to these targets.

A Surviving Child from Acute Liver Failure after an Ingestion of Cassia occidentalis Seeds.

Cassia occidentalis toxicity is thought to be uncommon; however, several cases have been described with acute hepatomyoencephalopathy with a high-mortality rate. We report a previously healthy, 2-year-old girl who developed acute liver failure after fresh seed ingestion. Without a specific antidote, we decided to implement supportive measures and medications including lactulose, sodium benzoate and N-acetylcysteine. The patient also experienced with cardiogenic shock and transient distal renal tubular acidosis, which were all spontaneously resolved. The liver chemistries returned to normal 3 months after the ingestion, without receiving liver assisted device or liver transplantation.

Late allograft fibrosis in pediatric liver transplant recipients: Assessed by histology and transient elastography.

Late allograft fibrosis in LT recipients can cause graft dysfunction and may result in re-transplantation. TE is a non-invasive tool for the assessment of liver fibrosis. We aimed to evaluate the prevalence of allograft fibrosis in pediatric LT recipients, identify factors associated with allograft fibrosis, and determine the diagnostic value of TE, compared to histology. All children who underwent LT for ≥3 years were included. TE was performed for LSM in all patients. LSM of ≥7.5 kPa was considered as abnormal and suggestive of allograft fibrosis. Percutaneous liver biopsy was performed when patients had abnormal LSM and/or abnormal LFTs. Histological fibrosis was diagnosed when METAVIR score ≥F1 or LAF scores ≥1. TE was performed in 43 patients and 14 (32.5%) had abnormal LSM suggestive of allograft fibrosis. Histological fibrosis was identified in 10 of the 15 patients (66.7%) who underwent percutaneous liver biopsy and associated findings included chronic active HBV infection (n = 3), and late acute rejection (n = 3). Multivariate analysis showed that graft age was significantly associated with allograft fibrosis (OR = 1.22, 95% CI: 1.05-1.41, P = 0.01). In conclusion, late allograft fibrosis is common in children undergoing LT for ≥3 years and associated with graft age. HBV infection and late acute rejection are common associated findings. Abnormal TE and/or LFTs may guide physicians to consider liver biopsy for the detection of late allograft fibrosis in LT children.

Isolated IgG4-related sclerosing cholangitis misdiagnosed as malignancy in an area with endemic cholangiocarcinoma: a case report.

BACKGROUND: The most common cause of perihilar obstruction is cholangiocarcinoma, especially in Thailand. Benign perihilar stricture represents less than 20% of cases. IgG4-related disease and IgG4-related sclerosing cholangitis, however, have been receiving increased recognition. Isolated IgG4-related sclerosing cholangitis is less common. The preoperative diagnosis of IgG4-related sclerosing cholangitis without pancreatic involvement is very difficult because the clinical presentation and preoperative evaluation are extremely difficult to distinguish from perihilar cholangiocarcinoma. CASE PRESENTATION: We report the case of a 56-year-old man who presented with obstructive jaundice with preoperative imaging showing proximal common bile duct obstruction. He underwent right lobe liver hepatectomy with extrahepatic bile duct resection and regional lymph node dissection due to high suspicion of malignancy. The pathological report showed severe acute and chronic inflammation of the bile duct with morphology and immunohistochemistry suggestive of IgG4-related sclerosing cholangitis. CONCLUSIONS: IgG4-related sclerosing cholangitis with perihilar obstruction should be considered even in areas where cholangiocarcinoma is endemic.

Human epidermal growth-factor receptor 2 overexpression in gastric carcinoma in Thai patients.

OBJECTIVE: To determine human epidermal growth-factor receptor 2 (HER2) protein-overexpression frequency and the concordance rate between immunohistochemistry and fluorescence in situ hybridization techniques in gastric carcinoma. MATERIAL AND METHOD: A retrospective analysis of gastric adenocarcinomas obtained from 224 adult patients between January 2000 and December 2008 were performed. The paraffin-embedded tissues were sliced into 4-microm-thick sections and analyzed for HER2 protein expression levels by immunohistochemistry (IHC) using an automated slide-staining IHC system. Breast carcinoma tissues were included in every staining batch as positive control. In order to detect and quantify amplification of the HER2, the authors performed fluorescence in situ hybridization (FISH) using PathVysion HER2 DNA Probe Kit. The IHC results were independently recorded by two pathologists using the standard HER2 scoring system for gastric carcinoma. FISH results were interpreted using standard guideline as employed in breast carcinoma. The two-tailed-Fisher's exact test was used to assess the concordance between IHC and FISH results. RESULTS: HER2 protein overexpression level was identified in 9% (20 in 224 cases) of the gastric tumors; 80% of which were well or moderately differentiated and of the intestinal or mixed type. However HER2-overexpressing tumors comprised only 16% of the intestinal/mixed-type or well/moderately differentiated tumors. There was no signal obtained from 29 specimens from FISH studies. Thus, the overall results of IHC and FISH methods were concordant in 88% (171 out of 195, p < 0.001). CONCLUSION: There is a significant concordance rate between IHC and FISH in gastric carcinoma. The present study is the first HER2 study of such carcinoma in Thai patients.

Large Mammary Paget Disease without Underlying Breast Carcinoma.

Mammary Paget disease is an uncommon type of breast cancer. Redness, scaling, and thickness involving the nipple and areola are common clinical symptoms. Invasive breast cancer was found in nearly 90% of these patients. Only a few cases of mammary Paget disease with no underlying cancer have been described, with a better prognosis. Treatment options include wide excision or mastectomy. However, if the lesion is very extensive, breast reconstruction may be required. We reported a rare case of extensive Paget disease in a 65-year-old woman who had a 7-year history of a 14 × 19 cm progressively enlarging erythematous scaling lesion that covered her entire left breast. No evidence of related malignancy or metastatic lesion was seen. A left mastectomy with sentinel lymph node biopsy and immediate pedicled transverse rectus abdominis myocutaneous flap reconstruction was chosen. There is uncertainty about axillary node metastasis since multiple enlarged and palpable left axillary lymph nodes were seen. She had axillary lymph node dissection instead. A histological examination confirmed the diagnosis of Paget disease of the nipple in the absence of underlying breast cancer and there was no evidence of axillary lymph node metastasis. This article emphasizes the need to pay close attention to diagnosis, progression, and treatment of the disease.

Prognostic value of ABCG2 in moderately and poorly differentiated intrahepatic cholangiocarcinoma.

AIMS: Intrahepatic cholangiocarcinoma (ICC) is a primary hepatic malignancy derived from cholangiocytes. The survival rate of ICC patients is very low, and conventional chemotherapy is not effective in prolonging long-term survival. Adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporters mediate the transport of various substances in several cellular processes. The expression of ABCB1, ABCC1 and ABCG2 has been implicated in multidrug resistance and poor prognosis in several types of cancer. The aim of this study was to examine their expression in normal cholangiocytes and ICC tissues. METHODS AND RESULTS: Immunohistochemistry was employed to evaluate the expression of these transporters in 60 cases of ICC with respect to clinicopathological features and patient outcome. The proportions of cases with loss of ABCB1, ABCC1 and ABCG2 expression were 93.3%, 68.3% and 50%, respectively. Only the loss of ABCG2 was related to a worse prognosis (P = 0.031), and was associated with lymph node involvement (P = 0.003) and higher tumour grade (P = 0.028). Furthermore, multivariate analysis showed that the loss of ABCG2 expression was an independent prognostic factor in patients with moderately or poorly differentiated ICC (P = 0.02). CONCLUSIONS: These results suggest that ABCG2 may be involved in cholangiocarcinogenesis; the loss of its expression may enhance tumour progression and contribute to aggressive growth of ICC.

Long-term outcome of living donor liver transplantation in a Thai boy with hereditary tyrosinemia type I: a case report.

UNLABELLED: Hereditary tyrosinemia type I (HT-I) is an autosomal recessive inborn error of tyrosine metabolism, caused by mutation(s) in the gene encoding for fumarylacetoacetate hydrolase (FAH) enzyme. The authors report a Thai boy who presented at two months of age with liver failure. HT-I was diagnosed based on the presence of succinylacetone in urine and homozygous R237X mutations of FAH gene. He was started on tyrosine and phenylalanine restricted diet immediately. Due to a limitation of 2-(2-nitro-4-trifluoromethyl benzoyl)-1,3-cyclohexanedione (NTBC) therapy in Thailand, it was commenced at eight months old and used as a bridging therapy before liver transplantation. He had a good response to NTBC therapy with an improvement in liver chemistries and synthetic functions. Subsequently, living donor liver transplantation (LDLT) was performed at 15 months old Long-term follow-up for 6.3 years following LDLT revealed normal growth, good school performance, normal liver, renal tubular, and glomerular functions, and without urinary excretion of succinylacetone. CONCLUSION: Liver transplantation is a promising treatment for patients with HT-1 when NTBC is unavailable, resulting in a good long-term outcome.

Surgical management of Brunner's gland hamartoma causing upper GI hemorrhage: report of two cases and literature review.

Brunner's gland hamartomas are uncommon benign tumor of the duodenum. Most lesions are small and asymptomatic. Occasionally, those lesions may be large and manifest as a rare cause of upper GI hemorrhage or duodenal obstruction. The authors report here two cases of Brunner's gland hamartoma presenting with upper GI hemorrhage that were not amenable to endoscopic polypectomy thus requiring surgical resection. The literature on Brunner's gland hamartoma was reviewed.

The prognostic significance of microvessel density in intrahepatic cholangiocarcinoma.

OBJECTIVE: Intrahepatic cholangiocarcinoma (IHCC) is the second most common primary cancer of the liver Tumor angiogenesis seem to play an important role in tumor growth and prognosis of cancer patients. The purpose of the present study was to determine the prognostic value of tumor microvessel density (MVD) in patients with IHCC. MATERIAL AND METHOD: Clinicopathological prognostic factors, recurrence rate, and survival in 22 patients with IHCC who underwent liver resection for IHCC were reviewed. Tumor MVD was estimated using immunohistochemical methods. Overall probabilities of recurrence and survival were estimated using Kaplan-Meier methods. Prognostic significance ofMVD and other factors was tested using Cox proportional hazards regression. RESULTS: There was no significant association between any clinicopathologic factors (age, sex, tumor markers, and pathologic factors including MVD) and time-to-tumor recurrence. The only prognostic factor associated with survival was tumor stage. MVD was neither a significant survival predictor nor a predictor of tumor recurrence. CONCLUSION: The only factor associated with poor prognosis in patients with IHCC in the present study was higher tumor stage. MVD was not a significant prognostic factor in patients with IHCC.

Hepatocellular adenoma: a case report.

A case of hepatocellular adenoma (HCA) was described in a 26-year-old woman, who was a potential kidney donor for her father and denied taking the oral contraceptive pill. A hypervascular mass of 4.1 cm in largest dimension was detected in the liver segment V by computerized tomography and magnetic resonance imaging (MRI). The normal levels of liver enzymes, negative serum markers for hepatitis viruses, and non-elevated alpha- fetoprotein level were detected. The wedge resection of segment V was done with an uneventful clinical course. In Western countries, HCAs are known to occur in women in their reproductive periods. It may not be associated with oral contraceptive. Molecular biological studies disclosed three variants of HCAs, i.e., I) with mutation of HNF 1-alpha gene, II) with mutation of beta-catenin gene, and III) no mutation of the two genes. Histological correlations with the three variants as recommended by the Bordeaux group in 2007 could not be accomplished in the present study due to overlapping histological features between the variants I and III. The etiological factors of HCA are known to relate to the contraceptive pill usage in female and the anabolic-androgenic-steroid administration in male. In Thailand, the occurrence of HCA is expected to be only 0.3% of cases with hepatocellular carcinoma.

Double check up of malignancy biopsy specimens for patient safety.

BACKGROUND: The diagnostic of malignancy in biopsy specimens is very important because it guides to selected treatment option and prognostic prediction. However biopsy specimens usually have small pieces leading to variations of the interpretation by anatomical pathologists. OBJECTIVE: To detect and correct the errors or the significant discrepancies in the diagnosis of biopsy specimens before sign-out and to determine the frequency of anatomic pathology significant discrepancies. DESIGN: The application of the mutually agreed work instructions (record) for the detection of errors or the significant discrepancies and their process of sign-out. The record of biopsy specimen that received a secondary check (1959 cases, 2005-2007) was analyzed. RESULTS: After a secondary check, 53 cases of non-malignancy for any reason by a second pathologist were included. However when using our definition on significant discrepancies, only 37 cases were considered. Another seven cases with the opinions with malignancy that were of different cell types that do harm to the patients were added. Therefore, 44 cases (2.25%) had truly significant discrepancies. CONCLUSION: The truly significant discrepancy frequency was 2.25% during the process of pre-sign-out secondary check of malignancy of biopsy specimens. The project has been applied as a routine daily work. It can be an innovative safety program for patient in Thailand.

Gastrointestinal stromal tumors (GISTs): a pathology view point.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. Most gastrointestinal soft tissue neoplasms, previously classified as leiomyomas, schwannomas, leiomyoblastomas, or leiomyosarcomas, are now classified as GISTs based on histology, immunohistochemistry, and molecular study. They originate from the stem cells that differentiate toward the pacemaker cell (Interstitial cell of Cajal). Prognostic factors have been identified for GISTs and include tumor size and mitotic rate. Surgery is the standard treatment for resectable GISTs. Metastatic and inoperable GISTs should be considered the medication with tyrosine kinase inhibitor (imatinib mesylate), which inhibits the c-kit receptor. The role of the pathologist in the differential diagnosis of GISTs, as well as in the assessment of the malignant potential of the tumors, is becoming increasingly important in influencing decisions regarding clinical management of GISTs. The present paper reviews the literature of GISTs and emphasizes on the field of the pathologist's work.

Revision of gastrointestinal mesenchymal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal (GI) tract. The advent of target therapy (imatinib mesylate) for GISTs increases the importance of pathologic diagnosis. The previous diagnosis with smooth muscle tumor (leiomyoma or leiomyosarcoma) and nerve sheath tumor (schwannoma) become GISTs after the study with CD117 immunohistochemistry accompanying conventional histologic study in many series. OBJECTIVE: To identify the incidence of GISTs in the patients who were previously diagnosed with smooth muscle or nerve sheath tumors. The histology and immunoreactivity of both newly found and previously diagnosed with GISTs are also studied MATERIAL AND METHOD: A retrospective database identified all patients seen from 1998 to 2006. Patients with mesenchymal tumors of the GI tract and intraabdominal extragastrointestinal tract were selected, 53 cases in total. Clinical and pathological data, treatment, and outcome were analyzed RESULTS: After revision, the total number of GISTs is 42 cases. There were 33 cases previously diagnosed with leiomyosarcoma that became the diagnosis with GISTs (31 cases or 93.9%), due to CD117 positivity. Most of GISTs cases had spindle cell type (26 cases, 61.9%) and only the colon and omentum had predominant mixed cell type. CONCLUSION: GISTs are the most common mesenchymal neoplasm of the stomach and small intestine and are relatively less frequent at other gastrointestinal sites. An increasing awareness of their histologic, immunophenotypic, and molecular features coupled with an evolving understanding of their histogenesis is facilitating our ability to identify these tumors.

Vascular pythiosis of carotid artery with meningitis and cerebral septic emboli: A case report and literature review.

Vascular Pythiosis caused by Pythium insiodiosum rarely involves carotid artery. A case of concealed ruptured pseudoaneurysm of the carotid artery with neck abscesses, and cerebral septic emboli is described. Patient presented with large pulsatile neck mass that failed to response to surgery, antifungals and immunotherapeutic vaccine. Residual unresectable disease leads to death in the patient. Pythiosis should be considered as a differential diagnosis of head and neck infection.

Reduced HBV cccDNA and HBsAg in HBV-associated hepatocellular carcinoma tissues.

Approximately 50% of hepatocellular carcinoma (HCC) is attributable to chronic infection with hepatitis B virus (HBV). Serum hepatitis B surface antigen (HBsAg) is an important diagnostic marker of HBV infection, whereas intrahepatic HBV covalently closed circular DNA (cccDNA) is a surrogate marker of HBV persistence. This study aimed to investigate relationships between serum HBsAg, intrahepatic HBsAg, and intrahepatic cccDNA in HBV-associated HCC. Intrahepatic HBsAg was determined by immunohistochemistry in matched non-cancerous and HCC tissues from 88 patients; 56 patients (63.64%) were serum HBsAg positive. In serum HBsAg-positive group, intrahepatic HBsAg was positive staining in 73.2% of non-cancerous tissues, but only in 10.7% of HCC tissues. Significant correlation between serum HBsAg and intrahepatic HBsAg was observed in non-cancerous tissues (p < 0.001), but not in HCC tissues (p = 0.415). Absolute quantification of intrahepatic cccDNA was performed by droplet digital PCR in tissues from 30 patients; 18 patients (60%) were serum HBsAg positive. In serum HBsAg-positive group, intrahepatic cccDNA was detected in 66.66% of non-cancerous tissues, but only in 5.55% of HCC tissue; intrahepatic cccDNA levels in non-cancerous tissues were significantly higher than those in HCC tissues (p < 0.001), and correlated with serum HBsAg (p < 0.01). Significant correlations between intrahepatic HBsAg and intrahepatic cccDNA were found in both non-cancerous tissues (p < 0.01) and HCC tissues (p < 0.05). We concluded that HBV cccDNA and intrahepatic HBsAg in HBV-associated HCC tissues were significantly reduced, as compared with matched non-cancerous tissues. This warrants further investigation into the impacts and the cause(s) of cccDNA reduction in HBV-associated HCC tissues, which might yield novel immune-related therapy for HBV-associated HCC.

Combined hepatocellular and cholangiocarcinoma: CT findings with emphasis on multiphasic helical CT.

OBJECTIVE: To describe CT findings of patients with combined hepatocellular carcinoma and cholangiocarcinoma (HCC-CC) in correlation with clinical data and histopathological results. MATERIAL AND METHOD: Ten from 31 cases whose CT study was available were reviewed retrospectively in the aspect of imaging findings, clinical data, and pathological results. RESULTS: Most of the tumors were hypodense solitary mass with gradually enhanced after contrast administration. Bile duct dilatation was observed in two cases. The overall CT findings were more similar to CC rather than HCC despite the pathological result showing predominant HCC component. Serum alpha-fetoprotein level was normal or mildly elevated while an elevated concentration of carbohydrate antigen 19-9 was observed. Hepatitis profiles showed positive to hepatitis B virus infection in four cases and hepatitis C virus infection in one case. CONCLUSION: The diagnosis of combined HCC-CC should be considered if the tumor has similar findings to CC without bile duct dilatation on cirrhotic liver and the patient has normal or low rising of the AFP level with or without elevated CA 19-9 level. In non-cirrhotic liver, the finding is non-specific.

Dysplastic nodules and small primary carcinoma of the liver: a study detecting the early morphological changes during hepatocarcinogenesis.

OBJECTIVE: Detect the early histological changes relating to human hepatocarcinogenesis in three nodular hepatocellular lesions. MATERIAL AND METHOD: Three cases of dysplastic nodules and one of small hepatocellular carcinoma were obtained from the authors' surgical-pathology file during 2000-2005 for a histopathological study in relevance to the early changes during hepatocarcinogenesis by employing hematoxylin and eosin stain, as well as some immunohistochemical staining. RESULTS: One nodular hepatocellular lesion, diagnosed as a complex lesion of focal nodular hyperplasia contained a microscopic focus (1.5 mm in diameter) of combined hepatocellular and cholangiocarcinoma. CONCLUSION: The small dysplastic hepatocytes subjected to neoplastic transformation combined hepatocellular and cholangiocarcinoma and are the precursorial cells of hepatocellular carcinoma. Chronic viral hepatitis B or C, aflatoxin B, and nitrosamine(s), as well as some nodular hepatocellular lesions share distinct roles in the complex process of hepatocarcinogenesis pertaining to this Southeast Asian country.

Fluorescence in situ hybridization method in isolated single nuclei extracted from paraffin-embedded hepatocellular carcinoma tissues.

BACKGROUND: Genetic analysis using the fluorescence in situ hybridization (FISH) method applied to intact tissue sections of formalin-fixed paraffin embedded (FFPE) tissue is well known to be relatively difficult. The frequent technical problems include unsuccessful hybridization as a result of poor probe penetration, excessive probe requirement, excessive background, auto-fluorescence, and overlapping or incomplete nuclei. These problems lead to absence or insufficiency of fluorescent signals, resulting in an inaccurate analysis. Formalin-fixed paraffin embedded tissue can be analyzed either as intact tissue sections or as a suspension of disaggregated, but intact, nuclei. Intact tissue sections have the advantage of preserved tissue architecture and morphology but have the intrinsic disadvantage of poor probe penetration, overlapping or incomplete nuclei and auto-fluorescence, accordingly reducing the accuracy of fluorescent signals evaluation. OBJECTIVE: To present the effective FISH method applied to isolated of single nuclei and the procedures for isolation of a single nuclei from formalin-fixed paraffin embedded tissues of hepatocellular carcinoma. MATERIAL AND METHOD: Ten paraffin-embedded blocks of hepatocellular carcinoma tissues from the department of pathology, Ramathibodi hospital, Thailand were studied. Isolated single nuclei were extracted from 10-microm sections of paraffin-embedded blocks of hepatocellular carcinoma tissue and hybridized with alpha-satellite centromeric DNA enumeration probes for chromosomes X (CEP X, spectrum green) and satellite III for chromosomes Y (CEP Y spectrum orange). The signal of at least, 200 interphase nuclei were counted from each specimen. RESULTS: The efficacy of this method has been evaluated in 10 formalin-fixed paraffin embedded tissue of hepatocellular carcinoma. The results showed bright, planar and an easy to score signal. CONCLUSION: FISH procedure described here is particularly suitable for retrospective studies of genetic aberration applied to formalin-fixed paraffin embedded tissues.

Combined liver-kidney transplantation in a patient with acute liver failure coexisting with acute renal failure.

Acute renal failure (ARF) is common among patients with liver failure awaiting liver transplantation due to the increased waiting time for available liver grafts and extended survival from improved intensive care. The role of combined liver and kidney transplantation (LKT) in this situation is quite controversial. A case of acute liver failure (ALF) complicated with ARF is reported. Non-A, non-B hepatitis was the cause of ALF. He had hemodialysis for one month before transplantation. Combined LKT was performed because of prolonged pre-transplant hemodialysis and the potential of irreversible renal failure. Severe impairment of both native kidneys was confirmed by renal scan at 6 months after transplantation. Combined LKT may be needed for patients with acute liver failure complicated with prolonged acute renal failure.