Diagnostic problems in nodular regenerative hyperplasia (nodular transformation) of the liver. Review of the literature and report of two cases.

Nodular regenerative hyperplasia (NRH) is a rare lesion of the liver associated with portal hypertension in more than half of patients. We present two cases demonstrating complications and diagnostic problems of NRH and review the pathogenesis, clinical, radiologic, and pathologic features of 240 cases in the literature. Patient 1 died from variceal bleeding as a complication of NRH. Patient 2 presented with ascites. Sonographic, computed-tomographic and magnetic resonance findings did not differ from liver cirrhosis. Three needle biopsies showed nonspecific reactive hepatitis. Wedge liver biopsy provided the correct diagnosis of NRH and a shunt operation was performed. Non-Hodgkin's lymphoma (centroblastic type) was diagnosed three years after NRH. At present there is no clinical or radiologic evidence of progression of NRH in this patient. The diagnosis of NRH cannot be made without histologic examination. Correct diagnosis is difficult in percutaneous needle biopsy. Therefore, laparoscopically guided liver biopsy or wedge biopsy is often necessary for diagnosis. NRH should be included in the differential diagnosis of portal hypertension. Portal diversion can be considered.     

Impact of hepatitis B virus (HBV) X gene integration in liver tissue on hepatocellular carcinoma development in serologically HBV-negative chronic hepatitis C patients

BACKGROUND/AIMS: We analyzed hepatitis B virus (HBV) X gene integration in hepatocytes of HBV-negative, chronic hepatitis C (CH-C) patients with mild fibrosis, and prospectively followed these patients for the development of hepatocellular carcinoma (HCC). METHODS: The study included 39 HBV-negative CH-C patients with mild fibrosis. HBV-X integration was determined by Alu-PCR analysis of liver specimens obtained by fine-needle biopsy. RESULTS: Integration of HBV-X gene sequence into liver genome occurred in 9 of the 39 patients. Six of the 39 patients developed HCC during the 12-year follow-up period. No significant difference was found in the incidence of HCC between patients with and without HBV-X integration. However, the two patients with HBV-X integration who developed HCC did not have cirrhosis at the time when HCC was diagnosed, whereas the four patients without HBV-X integration who developed HCC did have cirrhosis. CONCLUSIONS: Our findings suggest that HBV-X integration detected at the mild fibrosis stage might not indicate a high risk for HCC. HBV-X integration may be associated with HCC development in the absence of cirrhosis. However, we did not find evidence that HBV-X integration directly plays a role in hepatocarcinogenesis in CH-C patients. Further studies will be needed to clarify this point.     

Useful detection of CD147 （EMMPRIN） for pathological diagnosis of early hepatocellular carcinoma in needle biopsy samples

AIM To make clear whether CD147 (EMMPRIN)expression in pathological tumor samples with a fineneedle aspiration biopsy is useful for pathological diagnosis of early hepatocellular carcinoma (HCC).METHODS Twenty-two patients (15 men and 7 women;median age 68 years, range 56-81 years) underwent a liver tissue biopsy in order to make a diagnosis of HCC.Paraffin-embedded liver biopsy tissue samples from 22 patients were stained with anti-CD147 antibody,murine monoclonal antibody 12C3 (MAb12C3) for immunohistochemical analysis. An immunohistochemical analysis of CD147 was performed and the degree of staining compared between tumor and non-tumor tissue. In addition, the degree of staining within tumor tissue was compared according to a number of clinicopathological variables.RESULTS The degree of staining of CD147 was significantly higher in tumor tissues than non-tumor tissues, even in tumors less than 15 mm in diameter.The expression of this protein was significantly elevated in HCC tissue specimens from patients with a low value of serum AST and γ-GTP.CONCLUSION CD147 serves potentially as a pathological target for cancer detection of early HCC.     

Increasing sensitivity of morphological diagnosis in hepatocellular carcinoma (HCC) by combination of cytological and fine-needle histological examination after ultrasound guided fine needle biopsy

Increasing sensitivity of morphological diagnosis by combination of cytological and fine-needle histological examination after ultrasound guided fine needle biopsy in hepatocellular carcinoma (HCC). AIM: We investigated the factors which may affect the sensitivity of morphological diagnostics (cytology and fine-needle histology) in HCC after ultrasound guided biopsy. METHOD: In 62 patients, an ultrasound guided cytological (n = 62) and fine-needle histological (n = 45) biopsy was performed. In addition, the smears were investigated by cytophotometry (n = 62). RESULTS: Considering each method separately, the sensitivity of both cytological and histological diagnostics was about 80%. The sensitivity could be raised to 89% by combining the two methods. In seven patients, the HCC could not be primarily confirmed morphologically. In nine patients, the result of histological and cytological investigation was not congruent. With regard to the size of the biopsied lesion, tumor stage, cytophotometric finding and survival these 16 patients (group A) were compared with the 46 patients in whom the HCC could be primarily confirmed morphologically (group B). The statistical analysis did reveal a significantly lower percentage of tumors with diploid or tetraploid (euploid) cells in group B. Euploid tumors were significantly more highly differentiated. In patients with euploid tumors, the sensitivity of the cytological investigation was 67% and respectively 75% of the histological investigation. The sensitivity could be raised to 82% in this population by combining the two investigations. On the other hand in aneuploid tumors, the sensitivity could only be increased from 93% and 88% respectively to 97% by combining cytology and fine-needle histology. SUMMARY: Our investigations show that the sensitivity of morphological diagnostics can be raised especially in the highly differentiated HCC with a physiological DNA content by combination of cytological and fine-needle histological investigations.     

Diagnostik und Früherkennung des hepatozellul?ren Karzinoms

The diagnosis of hepatocellular carcinoma (HCC) in patients without liver cirrhosis is based on histopathological and immunohistological findings. When liver cirrhosis is present HCC can be diagnosed based on typical contrast dynamics in cross-sectional imaging. In contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) HCC shows enrichment of contrast agent in the arterial phase and a typical wash out in the portal venous or late phase. Therapeutic options and prognosis depend on tumor stage at the time of diagnosis. Patients with a higher risk of developing HCC, such as patients with chronic liver diseases with advanced fibrosis or cirrhosis or those with chronic hepatitis B (delta) and C virus infections should be enrolled in surveillance programs. Non-alcoholic steatohepatitis (NASH) was recently recognized as an risk factor for HCC development. Already in precirrhotic stages, surveillance should be performed by conventional ultrasound examination every 6 months. As very small hepatic masses <1?cm do not correlate with HCC in most cases, follow-up examinations should be performed promptly. Regular surveillance examinations can significantly reduce HCC-related mortality.     

Portal vein thrombosis complicating hepatocellular carcinoma. Value of ultrasound-guided fine-needle biopsy of the thrombus in the therapeutic management

Abstract: During a 4-year period portal vein thrombosis was diagnosed in 20 Child class A patients with cirrhosis by means of ultrasound and ultrasound-Doppler study. Seventeen of them showed single or multiple focal liver lesions diagnosed as hepatocellular carcinoma by ultrasound-guided fine-needle biopsy and the remaining three a coarse liver echo-pattern without focal lesions. One patient was found to have developed portal vein thrombosis after the fifth ethanol injection of a single hepatocellular carcinoma lesion 17 mm in diameter. Ultrasound-guided fine-needle biopsy of the thrombus was performed on all the patients: portal vein thrombosis was neoplastic in 13 cases and non-neoplastic in seven cases (five patients with a single lesion; one with two lesions; one with coarse liver echo-pattern). Among the five patients with a single lesion, one had already been treated by percutaneous ethanol injection therapy. There were no complications related to the biopsy procedures. The diagnosis of non-neoplastic thrombosis allowed five new patients to be recruited for percutaneous ethanol injection treatment and allowed it to continue in the patient with portal vein thrombosis occurring after the fifth ethanol injection. The routine use of ultrasound-guided fine-needle biopsy of portal vein thrombosis yields an accurate diagnosis of the nature of the thrombus and can improve the selection for percutaneous ethanol injection treatment of patients with cirrhosis with hepatocellular carcinoma lesions.     

TIPS for patients with early HCC: A bridge to liver transplantation

Portal hypertension (PHT) and hepatocellular carcinoma (HCC) are complications of cirrhosis which often coexist, rending the management more complex. HCC is generally considered as a contraindication for transjugular intrahepatic portosystemic shunt (TIPS). We studied the outcome of 8 patients treated by TIPS after HCC diagnosis between 2010 and 2020. TIPS wasn't associated with worsening of liver function or tumor spreading and all patients underwent liver transplantation. TIPS should be considered in case of HCC, especially for variceal bleeding or as a bridge to HCC treatments that are discarded due to PHT levels/ascites by improving liver function before liver transplantation.     

Focal hepatic lesions. Their diagnosis by fine-needle (25 G) aspiration puncture]

151 patients with focal lesions of the liver underwent percutaneous fine-needle aspiration biopsy under ultrasonographic control. We used 25 G needles, the thinnest available. Aspiration biopsy was performed on malignant disease in 122 cases, and on benign disease in 29 cases. There were 3 false negatives diagnosis and 2 minor complications. The overall accuracy of the cytologic evaluations was 91.2%, with a sensitivity of 89.1% and specificity of 100%. Guided percutaneous fine-needle aspiration biopsy is recommended for a morphological diagnosis of focal liver lesions, because of its simplicity, safety and high degree of correct diagnosis.     

肝硬化的诊断和评估

肝硬化是各种慢性肝病的终末阶段,如何早期诊断肝硬化及对肝硬化进行分期并进行有效病情评估,在临床工作中尤为重要。介绍了肝脏穿刺病理学检查、血清学检查及影像学检查在肝硬化的临床诊断中的应用,以及肝脏储备功能评估、并发症评估和预后评估的研究进展。指出随着分子生物学及影像学诊断技术的发展,必将大力提高无创诊断的准确性和特异性,并深入完善疾病的评估体系。     

Role of liver biopsy in hepatocellular carcinoma

The role of liver biopsy in the diagnosis of hepatocellular carcinoma(HCC) has been challenged over time by the ability of imaging techniques to characterize liver lesions in patients with known cirrhosis. In fact, in the diagnostic algorithm for this tumor, histology is currently relegated to controversial cases.Furthermore, the risk of complications, such as tumor seeding and bleeding, as well as inadequate sampling have further limited the use of liver biopsy for HCC management. However, there is growing evidence of prognostic and therapeutic information available from microscopic and molecular analysis of HCC and, as the information content of the tissue sample increases, the advantages of liver biopsy might modify the current risk/benefit ratio. We herein review the role and potentiality of liver biopsy in the diagnosis and management of HCC. As the potentiality of precision medicine comes to the management of HCC, it will be crucial to have rapid pathways to define prognosis, and even treatment, by identifying the patients who could most benefit from target-driven therapies. All of the above reasons suggest that the current role of liver biopsy in the management of HCC needs substantial reconsideration.     

Direct invasion to the colon by hepatocellular carcinoma： Report of two cases

Although hepatocellular carcinoma （HCC） is a common tumor, direct invasion of the gastrointestinal tract by HCC is uncommon. Recently, we encountered two cases of HCC with direct invasion to the colon. The first patient was a 79-year-old man who underwent transarterial chemo-embolization （TACE） for HCC 1.5 years prior to admission to our hospital. Computed tomography （CT） showed a 7.5-cm liver tumor directly invading the transverse colon. Partial resection of the liver and transverse colon was performed. The patient survived 6 mo after surgery, but died of recurrent HCC. The second patient was a 69-year-old man who underwent TACE and ablation for HCC 2 years and 7 months prior to being admitted to our hospital for melena and abdominal distension. CT revealed a 6-cm liver tumor with direct invasion to the colon. The patient underwent partial resection of the liver and right hemicolectomy. The patient recovered from the surgery. But, unfortunately, he died of liver failure due to liver cirrhosis one month later. Although the prognosis of HCC that has invaded the colon is generally poor due to the advanced stage of the disease, surgical resection may be a favorable treatment option in patients with a good general condition.     

Comparison of liver biopsy and noninvasive methods for diagnosis of hepatocellular carcinoma.

BACKGROUND & AIMS: Current management guidelines for hepatocellular carcinoma (HCC) do not require biopsy to prove the diagnosis. We evaluated our experience of patients with liver disease and hepatic lesions suspicious for HCC who underwent both fine-needle aspiration and core biopsy and correlated the results with those from commonly used noninvasive approaches. METHODS: We retrospectively reviewed the outcomes of a series of patients undergoing biopsy because of a suspicion of HCC and compared sensitivity, specificity, and predictive value of biopsy with existing noninvasive methods for diagnosing HCC. RESULTS: HCC was diagnosed by biopsy in 74 (63%) of 118 cases, and an additional 10 were found to have HCC on follow-up. Patients with positive biopsy results had significantly higher serum alpha-fetoprotein levels (median, 57 vs 12; P = .014) than those with negative biopsies, although these 2 groups were otherwise similar with regard to tests of liver function, lesion size on imaging, and Child-Pugh class. No patient developed evidence of tumor spread along the needle track after biopsy. We compared the diagnosis of HCC by biopsy with noninvasive diagnostic criteria advocated by the European Association for the Study of the Liver and those used by the United Network for Organ Sharing. Compared with criteria of the European Association for the Study of the Liver and the United Network for Organ Sharing, biopsy had greater sensitivity, specificity, and predictive value. CONCLUSIONS: We recommend a greater role for image-guided biopsy of lesions greater than 1 cm clinically suspicious for HCC to allow adequate treatment planning because the risks of biopsy appear small and the potential benefits significant. Obtaining material for both cytologic and histologic examination at biopsy maximizes the diagnostic yield.     

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (FNA) of liver lesions.

BACKGROUND: Endoscopic ultrasonography (EUS) is not traditionally thought to be clinically applicable in liver imaging. EUS-guided fine-needle aspiration of the liver has not been well described. METHODS: A prospective study was conducted in which 574 consecutive patients with a history or suspicion of gastrointestinal or pulmonary malignant tumor undergoing upper EUS examinations underwent EUS evaluation of the liver. Fourteen (2.4%) patients were found to have focal liver lesions and underwent EUS-guided fine-needle aspiration. RESULTS: The median largest diameter of the liver lesions was 1.1 cm (range 0.8 to 5.2 cm). The mean number of passes was 2.0 (range 1 to 5 passes). All fine-needle passes yielded an adequate specimen. One of the 14 patients underwent EUS-guided fine-needle aspiration of 2 liver lesions. Fourteen of the 15 liver lesions sampled by means of EUS-guided fine-needle aspiration were malignant and one was benign. Before EUS, computed tomography (CT) depicted liver lesions in only 3 of 14 (21%) patients. Seven of 14 patients had a known cancer diagnosis. For the other 7, the initial diagnosis of cancer was made by means of EUS-guided fine-needle aspiration of the liver. There were no immediate or late complications. CONCLUSIONS: EUS can detect small focal liver lesions that are not detected at CT. Findings of EUS-guided fine-needle aspiration can confirm a cytologic diagnosis of liver metastasis and establish a definitive M stage that may change clinical management.     

Differenzialtherapie von Lebertumoren

Focal nodular hyperplasia is a polyclonal hyperplasia of liver cells as a result of locally enhanced blood flow because of vessel malformations. Only symptomatic FNH is an indication for resection or enucleation. In contrast to FNH growth of adenoma is dependent on sexual hormones. Solitary HNFα-inactivated and inflammatory adenomas larger than 5 cm should be removed because of risk of tumor rupture or bleeding, while β-catenin mutated adenomas should be surgically removed at any stage because of risk of malignant transformation. The prognosis of patients with HCC is dependent on the tumor stage, but also on the liver function. Resection is the treatment of choice for HCC in patients without liver cirrhosis. Patients with liver cirrhosis and early HCC without extrahepatic metastasis can be successfully treated by liver transplantation. If transplantation is not possible these tumors should be removed by local percutaneous ablation. Transarterial chemoembolization is an effective treatment for more advanced HCC in patients with good liver function. Studies showed that the multikinase inhibitor sorafenib significantly improves survival of patients with advanced or metastatic HCC in child A cirrhosis. The only curative option for patients with intrahepatic cholangiocarcinomas is surgical resection. Patients with unresectable cholangiocarcinomas should be treated with a chemotherapy consisting of Gemcitabine-Cisplatin-combination.     

Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma

This study prospectively evaluates the accuracy of contrast-enhanced ultrasound (CEUS) and dynamic magnetic resonance imaging (MRI) for the diagnosis of nodules 20 mm or smaller detected during ultrasound (US) surveillance. We included 89 patients with cirrhosis [median age, 65 years; male 53, hepatitis C virus 68, Child-Pugh A 80] without prior hepatocellular carcinoma (HCC) in whom US detected a small solitary nodule (mean diameter, 14 mm). Hepatic MRI, CEUS, and fine-needle biopsy (gold standard) (FNB) were performed at baseline. Non-HCC cases were followed (median 23 months) by CEUS/3 months and MRI/6 months. FNB was repeated up to 3 times and on detection of change in aspect/size. Intense arterial contrast uptake followed by washout in the delayed/venous phase was registered as conclusive for HCC. Final diagnoses were: HCC (n = 60), cholangiocarcinoma (n = 1), and benign lesions (regenerative/dysplastic nodule, hemangioma, focal nodular hyperplasia) (n = 28). Sex, cirrhosis cause, liver function, and alpha-fetoprotein (AFP) levels were similar between HCC and non-HCC groups. HCC patients were older and their nodules significantly larger (P < 0.0001). First biopsy was positive in 42 of 60 HCC patients. Sensitivity, specificity, and positive and negative predictive values of conclusive profile were 61.7%, 96.6%, 97.4%, and 54.9%, for MRI, 51.7%, 93.1%, 93.9%, and 50.9%, for CEUS. Values for coincidental conclusive findings in both techniques were 33.3%, 100%, 100%, and 42%. Thus, diagnosis of HCC 20 mm or smaller can be established without a positive biopsy if both CEUS and MRI are conclusive. However, sensitivity of these noninvasive criteria is 33% and, as occurs with biopsy, absence of a conclusive pattern does not rule out malignancy. These results validate the American Association for the Study of Liver Disease (AASLD) guidelines.     

Comparative study of the data of fine-needle aspiration biopsy and echographic aspects of hepatic tumors as a function of the circumstances of discovery. Apropos of 206 patients

This study was carried out in order to compare the accuracy of ultrasound and ultrasonically guided fine-needle aspiration biopsy in screening for tumoral hepatic syndrome in 206 patients. According to their different clinical presentations, patients were divided into 4 groups: 1: Documented cancer, 2: Hepatic cirrhosis, 3: Fortuitous ultrasonic detection, 4: Clinical hepatic tumor. Cytologic findings were divided into 4 types: benign, primary malignant tumor, secondary malignant tumor (with or without etiologic orientation) non significant result. The ultrasonic and cytologic results were retrospectively compared to definitive diagnosis which was known in 199 patients. No early or delayed complications related to fine-needle aspiration biopsy were recorded. Ultrasonic imaging globally suggested the final diagnosis in 116 patients (diagnostic precision: 58.2 percent) while the cytologic result corresponded to final diagnosis in 183 patients (diagnostic precision: 92.5 percent). Improved results by fine-needle aspiration biopsy with regard to ultrasound was recorded in each group, particularly in group 3; its diagnostic sensitivity was 92 percent for malignant lesions with 100 percent specificity and an excellent value in discriminating between their primitive or secondary nature. Fine-needle aspiration biopsy gave an exact etiologic orientation in half of cases with metastasis and helped to discover the primitive tumor in some patients when this was not known previously. We conclude that fine-needle aspiration biopsy is a simple, moderately invasive and accurate procedure in the diagnosis of hepatic lesions. As ultrasound alone is not suggestive, especially in the case of a fortuitous ultrasonic detection, fine-needle aspiration biopsy improves diagnostic precision.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical features in hepatocellular carcinoma and the impact of autopsy on diagnosis. A study of 530 cases from a low-endemicity area

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) had been one of the malignancies with the highest reported increase of incidence in Sweden, but during the late 20-year period the incidence has been decreasing. The aims of our study were to state the impact of autopsy on diagnosis and to identify clinical characteristics in HCC. METHODOLOGY: This retrospective study was performed in G?teborg, Sweden and included all cases with a diagnosis of liver cancer from a period with a high autopsy frequency (1958-1979). The cases were reevaluated histopathologically and the autopsy records as well as the case files were scrutinized. RESULTS: The majority (63%) of the 530 biopsy verified cases of HCC were diagnosed unexpectedly at autopsy. Cirrhosis of the liver could be established in 71% of the cases, but was diagnosed or at least clinically suspected before the diagnosis of the tumor only in a minority (19%) of all HCC patients. At presentation, malaise (85%), weight loss (78%), anorexia (67%) and hepatomegaly (84%) were common. The median survival time from diagnosis was one month. In most cases (92%) the cause of death was either directly or indirectly related to HCC and/or underlying liver disease such as advanced tumor disease, hepatic failure and gastrointestinal bleeding. Spontaneous rupture of HCC was the cause of death in 17 cases (3%) CONCLUSIONS: In an unselected population in a low incidence area of HCC, most patients have clinically unknown cirrhosis of the liver and present with vague general paramalignant symptoms. HCC has an extremely poor prognosis. Since HCC, in a majority of cases, remains undiagnosed before death, the autopsy has great impact on the diagnosis. This should be considered in interpretation of results from epidemiological studies.     

Development from simple steatosis to liver cirrhosis and hepatocellular carcinoma: a 27-year follow-up case

Nonalcoholic fatty liver disease (NAFLD) is classified as nonalcoholic steatohepatitis (NASH) or simple steatosis (SS) according to histological findings. It is well recognized that NASH may develop into cirrhosis and hepatocellular carcinoma (HCC), both with unfavorable prognoses. Although the outlook of SS is reported to be better than that of NASH, the long-term prognosis of SS remains unclear. Here, we report the case of a patient who was diagnosed as having SS by a first liver biopsy, and later developed into cirrhosis and HCC over a period of 27 years. In 1980, a 42-year-old Japanese man was admitted because of abnormal liver function tests. He had no history of alcohol intake and was negative for hepatitis virus markers and autoantibodies. A liver biopsy specimen showed macrovesicular steatosis without ballooned hepatocytes, Mallory hyaline, lobular inflammation, or perisinusoidal/perivenular fibrosis, confirming the diagnosis of SS. The patient’s serum aminotransferase levels did not normalize despite repeated dietary instruction, and in 2001, liver histology demonstrated cirrhosis with mild steatosis and hepatocyte ballooning, leading to the diagnosis of NASH-related cirrhosis. HCC appeared in 2007. Overall, this patient progressed to cirrhosis and HCC in 20 and 27 years, respectively, following initial diagnosis. Platelet counts and degree of steatosis, as assessed by periodic ultrasonography, were seen to gradually reduce with progression of fibrosis. This case demonstrates that even a diagnosis of SS does not guarantee non-progression to cirrhosis and HCC, and careful follow-up is needed not only in patients with NASH, but also in those with SS.     

Characterization of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis

Background

The incidence of hepatocellular carcinoma (HCC) has increased significantly in United States over the last few decades in parallel with the epidemic of nonalcoholic fatty liver disease (NAFLD). Limited data suggests that HCC could arise in steatotic liver without the presence of cirrhosis. The present study was conducted to characterize patients with NAFLD presenting with HCC in non-cirrhotic liver (NCL) compared to the NAFLD- HCC patients in association with cirrhotic liver (CL).

Methods

A retrospective analysis of all patients diagnosed with HCC and NAFLD diagnosis seen at our institution between 2003 and 2012 was done. The patients were characterized based on demographic and clinical variables as well as histological and tumor features. Comparisons between the NCL and CL groups were done using analysis of variance (ANOVA) or the non-parametric Kruskal–Wallis tests and Pearson's chi-square tests or Fisher's Exact tests as appropriate. P value of <0.05 was considered statistically significant.

Results

Thirty-six patients with NAFLD and HCC in NCL (HCC-NCL group) were identified and compared to 47 patients with NAFLD-HCC and Liver Cirrhosis (HCC-LC group). Liver fibrosis was not present in 55.9 % of patients in the HCC-NCL group (F0), stage 1 was present in 17.6 %, stage 2 in 8.8 % and stage 3 in 17.6 %. Lobular inflammation was present in 63.6 % of non-cirrhotic patients. Patients in the HCC-NCL were older (67.5 ± 12.3 vs. 62.7 ± 8.1 years), and less likely to be obese (52 % vs. 83 %) or have type 2 diabetes (38 % vs. 83 %), with p value <0.05 for all. More importantly, compared with the HCC-CL group, those in the HCC-NCL group were more likely to present with a single nodule (80.6 % vs. 52.2 %), larger nodule size (>5 cm) (77.8 % vs. 10.6 %), and receive hepatic resection as the modality of HCC treatment (66.7 % vs. 17 %); and were less likely to receive loco-regional therapy (22.3 % vs. 61.7 %) or orthotopic liver transplantation (OLT) (0 % vs. 72.3 %), with p value <0.001 for all. Furthermore, 86 % of patients without cirrhosis had HCC recurrence compared to only 14 % in patients with cirrhosis (p < 0.001). Unadjusted analysis indicates that non-cirrhotics had worse survival with mortality rate of 47 % vs. 28 % in CL group (p = 0.03); however this difference in survival between two groups was not significant after adjusting for age or OLT (p > 0.05).

Conclusion

Patients with HCC in the absence of liver cirrhosis are more likely to present at an older age with larger tumor and have higher rates of tumor recurrence. Studies to assess the cost-effectiveness of HCC surveillance in this group should be conducted.

     

Risk factors for hepatocellular carcinoma in cirrhosis due to nonalcoholic fatty liver disease: A multicenter,case-control study

AIM To identify risk factors associated with hepatocellular carcinoma(HCC), describe tumor characteristics and treatments pursed for a cohort of individuals with nonalcoholic steatohepatitis(NASH) cirrhosis. METHODS We conducted a retrospective case-control study of a well-characterized cohort of patients among five liver transplant centers with NASH cirrhosis with(cases) and without HCC(controls).RESULTS Ninety-four cases and 150 controls were included. Cases were significantly more likely to be male than controls(67% vs 45%, P 0.001) and of older age(61.9 years vs 58 years, P = 0.002). In addition, cases were more likely to have had complications of end stage liver disease(83% vs 71%, P = 0.032). On multivariate analysis, the strongest association with the presence of HCC were male gender(OR 4.3, 95%CI: 1.83-10.3, P = 0.001) and age(OR = 1.082, 95%CI: 1.03-1.13, P = 0.001). Hispanic ethnicity was associated with a decreased prevalence of HCC(OR = 0.3, 95%CI: 0.09-0.994, P = 0.048). HCC was predominantly in the form of a single lesion with regional lymph node(s) and distant metastasis in only 2.6% and 6.3%, respectively. Fifty-nine point three percent of individuals with HCC underwent locoregional therapy and 61.5% underwent liver transplantation for HCC. CONCLUSION Male gender, increased age and non-Hispanic ethnicity are associated with HCC in NASH cirrhosis. NASH cirrhosis associated HCC in this cohort was characterized by early stage disease at diagnosis and treatment with locoregional therapy and transplant.