Clinico-histological and molecular features of hepatocellular carcinoma from nonalcoholic fatty liver disease

Patients with nonalcoholic fatty liver disease (NAFLD) continue to increase with the epidemics of obesity, and NAFLD is estimated to become the most prevalent etiology of hepatocellular carcinoma (HCC). Recently, NAFLD-HCC has been recognized to have clinico-histologically and molecularly distinct features from those from other etiologies, including a lower incidence rate of HCC and less therapeutic efficacy to immune checkpoint inhibitors (ICIs). Consistent with the clinical observations that up to 50% of NAFLD-HCC occurs in the absence of cirrhosis, the imbalance of pro- and antitumorigenic hepatic stellate cells termed as myHSC and cyHSC can contribute to the creation of an HCC-prone hepatic environment, independent of the absolute fibrosis abundance. Immune deregulations by accumulated metabolites in NAFLD-affected livers, such as a fatty-acid-induced loss of cytotoxic CD4 T cells serving for immune surveillance and “auto-aggressive” CXCR6+ CD8 T cells, may promote hepatocarcinogenesis and diminish therapeutic response to ICIs. Steatohepatitic HCC (SH-HCC), characterized by the presence of fat accumulation in tumor cells, ballooned tumor cells, Mallory–Denk body, interstitial fibrosis, and intratumor immune cell infiltration, may represent a metabolic reprogramming for adapting to a lipid-rich tumor microenvironment by downregulating CPT2 and leveraging its intermediates as an “oncometabolite.” Genome-wide analyses suggested that SH-HCC may be more responsive to ICIs given its mutual exclusiveness with β-catenin mutation/activation that promotes immune evasion. Thus, further understanding of NAFLD-specific hepatocarcinogenesis and HCC would enable us to improve the current daily practice and eventually the prognoses of patients with NAFLD.     

Immunotherapy for nonalcoholic fatty liver disease-related hepatocellular carcinoma: Lights and shadows

About one-fourth of adults globally suffer from nonalcoholic fatty liver disease (NAFLD), which is becoming a leading cause of chronic liver disease worldwide. Its prevalence has rapidly increased in recent years, and is projected to increase even more. NAFLD is a leading cause of hepatocellular carcinoma (HCC), the sixth-most prevalent cancer worldwide and the fourth most common cause of cancer-related death. Although the molecular basis of HCC onset in NAFLD is not completely known, inflammation is a key player. The tumor microenvironment (TME) is heterogeneous in patients with HCC, and is characterized by complex interactions between immune system cells, tumor cells and other stromal and resident liver cells. The etiology of liver disease plays a role in controlling the TME and modulating the immune response. Markers of immune suppression in the TME are associated with a poor prognosis in several solid tumors. Immunotherapy with immune checkpoint inhibitors (ICIs) has become the main option for treating cancers, including HCC. However, meta-analyses have shown that patients with NAFLD-related HCC are less likely to benefit from therapy based on ICIs alone. Conversely, the addition of an angiogenesis inhibitor showed better results regarding the objective response rate and progression-free survival. Adjunctive diagnostic and therapeutic strategies, such as the application of novel biomarkers and the modulation of gut microbiota, should be considered in the future to guide personalized medicine and improve the response to ICIs in patients with NAFLD-related HCC.     

TERT promoter mutations and chromosome 8p loss are characteristic of nonalcoholic fatty liver disease‐related hepatocellular carcinoma

The number of patients with nonalcoholic fatty liver disease (NAFLD)‐related hepatocellular carcinoma (HCC) is increasing. To understand the molecular features of the tumor phenotype, we aimed to clarify the overall landscape of genetic aberrations accumulated in NAFLD‐related HCC. Of 247 HCC patients who underwent hepatectomy during 2010 to 2014 at a single center in Japan, 10 were diagnosed with NAFLD‐HCC based on strict clinical and pathologic criteria. We analyzed the genetic aberrations of 11 NAFLD‐HCC tumor samples from these 10 patients by whole‐exome sequencing, targeted sequencing of the selected genes, and copy number variation studies. Whole‐exome sequencing revealed a mean somatic mutation rate of 1.86 per megabase, and 12 genes were recurrently mutated in NAFLD‐HCCs. Targeted sequencing of the 26 selected genes (12 recurrently mutated genes in whole‐exome sequencing and 14 representative HCC‐associated genes) revealed that TERT promoter mutations occurred in 9 of 11 HCCs (82%), followed by CTNNB1 (45%) and TP53 (36%) mutations. Array‐based copy number variation studies identified recurrent gains at 1q and 8q, and recurrent losses at 1p, 4q, 6q, 8p, 13q, 16p, 17p, and 18q. Notably, chromosome 8p loss occurred in all of the NAFLD‐HCC samples. The current study provided the characteristics of genetic aberrations in NAFLD‐HCC and suggested that TERT promoter mutations and chromosome 8p loss mainly contribute to NAFLD‐related liver carcinogenesis.     

铁超载对高脂饮食 诱导的非酒精性脂肪肝病大鼠脂代谢的影响

目的：探讨铁超载对非酒精性脂肪肝病（NAFLD）模型大鼠脂代谢的影响。方法：48只雄性SD大鼠随机分成空白对照组（基础饲料）、高铁组（含1% FeSO₄的基础饲料）、高脂组（高脂饲料）、高脂低铁组（含0.5% FeSO₄的高脂饲料）、高脂高铁组（含1% FeSO₄的高脂饲料）。干预20周后,称取大鼠体质量;肝脏油红O染色观察肝脏脂质堆积情况;测定肝脏内甘油三酯（TG）含量;实时荧光定量PCR（qPCR）和Western blot分别检测大鼠肝脏中脂肪酸合成酶（FAS）、肉碱酰基转位酶Ⅰ（CPT1）的mRNA和蛋白表达水平。结果：与对照组比较,高脂膳食20周使大鼠体质量、肝脏TG含量均明显增加（P均 < 0.05）,并促进TG在肝脏的沉积;且FAS的mRNA和蛋白水平均增加,CPT1的mRNA和蛋白水平均降低（P均 < 0.05）。与高脂组比较,高脂高铁组大鼠肝脏TG含量明显增加（P < 0.05）;FAS的mRNA和蛋白水平均显著增加,CPT1的mRNA和蛋白水平均降低（P均 < 0.05）。结论：铁超载能够促进NAFLD大鼠肝脏脂质堆积,加重脂代谢紊乱,促进NAFLD病程进展。     

Gut microbiome in non-alcoholic fatty liver disease associated hepatocellular carcinoma: Current knowledge and potential for therapeutics

Metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) are rising in incidence and are an increasingly common cause of cirrhosis and hepatocellular carcinoma (HCC). The gut microbiome is closely connected to the liver via the portal vein, and has recently been identified as a predictor of liver disease state. Studies in NAFLD, cirrhosis and HCC have identified certain microbial signatures associated with these diseases, with the disease-associated microbiome changes collectively referred to as dysbiosis. The pathophysiologic underpinnings of these observations are an area of ongoing investigation, with current evidence demonstrating that the gut microbiome can influence liver disease and carcinogenesis via effects on intestinal permeability (leaky gut) and activation of the innate immune system. In the innate immune system, pathogen recognition receptors (Toll like receptors) on resident liver cells and macrophages cause liver inflammation, fibrosis, hepatocyte proliferation and reduced antitumor immunity, leading to chronic liver disease and carcinogenesis. Dysbiosis-associated changes include increase in secondary bile acids and reduced expression of FXR (nuclear receptor), which have also been associated with deleterious effects on lipid and carbohydrate metabolism associated with progressive liver disease. Longitudinal experimental and clinical studies are needed in different populations to examine these questions further. The role of therapeutics that modulate the microbiome is an emerging field with experimental studies showing the potential of diet, probiotics, fecal microbiota transplantation and prebiotics in improving liver disease in experimental models. Clinical studies are ongoing with preliminary evidence showing improvement in liver enzymes and steatosis. The microbial profile is different in responders to cancer immunotherapy including liver cancer, but whether or not manipulation of the microbiome can be utilized to affect response is being investigated.     

Role of caveolin‐1 in hepatocellular carcinoma arising from non‐alcoholic fatty liver disease

The molecular features of hepatocellular carcinoma arising from non‐alcoholic fatty liver disease (NAFLD‐HCC) are not well known. In this study, we investigated the mechanism by which NAFLD‐HCC survives in a fat‐rich environment. We found that caveolin (CAV)‐1 was overexpressed in clinical specimens from NAFLD‐HCC patients. HepG2, HLE, and HuH‐7 HCC cell lines showed decreased proliferation in the presence of the saturated fatty acids palmitic acid and stearic acid, although only HLE cells expressed high levels of CAV‐1. HLE cells treated with oleic acid (OA) showed robust proliferation, whereas CAV‐null HepG2 cells showed reduced proliferation and increased apoptosis. CAV‐1 knockdown in HLE cells attenuated the OA‐induced increase in proliferation and enhanced apoptosis. Liquid chromatography–tandem mass spectrometry analysis revealed that the levels of OA‐containing ceramide, a pro‐apoptotic factor, were higher in HepG2 and CAV‐1‐deficient HLE cells than in HLE cells, suggesting that CAV‐1 inhibits apoptosis by decreasing the level of OA‐containing ceramide. These results indicate that CAV‐1 is important for NAFLD‐HCC survival in fatty acid‐rich environments and is a potential therapeutic target.     

Increased risk of colorectal polyps in patients with non-alcoholic fatty liver disease undergoing liver transplant evaluation

Background

Screening colonoscopy is a standard part of the liver transplant (LT) evaluation process. We aimed to evaluate the yield of screening colonoscopy and determine whether non-alcoholic fatty liver disease (NAFLD) was associated with an increased risk of colorectal neoplasia.

Methods

We retrospectively assessed all patients who completed LT evaluation at our center between 1/2008-12/2012. Patients <50 years old and those without records of screening colonoscopy, or with greater than average colon cancer risk were excluded.

Results

A total of 1,102 patients were evaluated, 591 met inclusion criteria and were analyzed. The mean age was 60 years, 67% were male, 12% had NAFLD and 88% had other forms of chronic liver disease. Overall, 42% of patients had a polyp found on colonoscopy: 23% with adenomas, 14% with hyperplastic polyps and with 1% inflammatory polyps. In the final multivariable model controlling for age, NAFLD [odds ratio (OR) 2.41, P=0.001] and a history of significant alcohol use (OR 1.69, P=0.004) were predictive of finding a polyp on colonoscopy. In addition, NAFLD (OR 1.95, P=0.02), significant alcohol use (OR 1.70, P=0.01) and CTP class C (OR 0.57, P=0.02) were associated with adenoma, controlling for age.

Conclusions

Screening colonoscopy in patients awaiting LT yields a high rate of polyp (43%) and adenoma (22%) detection, perhaps preventing the accelerated progression to carcinoma that can occur in immunosuppressed post-LT patients. Patients with NAFLD may be at a ~2 fold higher risk of adenomas and should be carefully evaluated prior to LT.     

Association between nonalcoholic fatty liver disease and colorectal adenoma: a systemic review and meta-analysis

Background

Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome (MetS) and the most common chronic liver disease worldwide. The association between NAFLD and colorectal adenoma has been investigated in multiples studies but the results have been conflicting. We performed a systematic review and meta-analysis to evaluate this in asymptomatic patients who underwent screening colonoscopy.

Methods

We searched the literatures of all languages from PubMed, EMBASE and the Cochrane library from January 1, 1980 through July 15, 2014. Combined and subgroup analyses stratified by study designs, study locations, characteristics of adenoma (location, size, number, and advanced adenoma) were performed.

Results

Four cross-sectional and one cohort studies with a total of 6,263 subjects were included in the meta-analysis. NAFLD was significantly associated with colorectal adenoma [pooled odds ratio (OR) 1.74, 95% confidence interval (CI): 1.53-1.97]. The association was more significant in Asian population (pooled OR =1.77, 95% CI: 1.52-2.05, n=3 studies), compared to European/North American population (pooled OR =1.42, 95% CI: 0.75-2.67, n=2 studies). NAFLD was significantly associated with the number of colorectal adenoma (pooled OR =1.78, 95% CI: 1.10-2.86, n=2 studies), but not the location, size, or presence of advanced adenoma.

Conclusions

Our results suggest NAFLD is significantly associated with the presence of colorectal adenoma in asymptomatic patients undergoing screening colonoscopy. This finding provides additional risk stratifications for applying colorectal cancer (CRC) screening strategies. However, more studies of western population are needed to further investigate the ethnic disparity.     

Screening strategies for colorectal cancer among patients with nonalcoholic fatty liver disease and family history

Patients with nonalcoholic fatty liver disease (NAFLD) and family history of colorectal cancer (CRC) are at higher risks but how they should be screened remains uncertain. Hence, we evaluated the cost‐effectiveness of CRC screening among patients with NAFLD and family history by different strategies. A hypothetical population of 100,000 subjects aged 40–75 years receive: (i) yearly fecal immunochemical test (FIT) at 50 years; (ii) flexible sigmoidoscopy (FS) every 5 years at 50 years; (iii) colonoscopy 10 yearly at 50 years; (iv) colonoscopy 10 yearly at 50 years among those with family history/NAFLD and yearly FIT at 50 years among those without; (v) colonoscopy 10 yearly at 40 years among those with family history/NAFLD and yearly FIT at 50 years among those without and (vi) colonoscopy 10 yearly at 40 years among those with family history/NAFLD and colonoscopy 10 yearly at 50 years among those without. The incremental cost‐effectiveness ratio (ICER) was studied by Markov modeling. It was found that colonoscopy, FS and FIT reduced incidence of CRC by 49.5, 26.3 and 23.6%, respectively. Using strategies 4, 5 and 6, the corresponding reduction in CRC incidence was 29.9, 30.9 and 69.3% for family history, and 33.2, 34.7 and 69.8% for NAFLD. Compared with no screening, strategies 4 (US$1,018/life‐year saved) and 5 (US$7,485) for family history offered the lowest ICER, whilst strategy 4 (US$5,877) for NAFLD was the most cost‐effective. These findings were robust when assessed with a wide range of deterministic sensitivity analyses around the base case. These indicated that screening patients with family history or NAFLD by colonoscopy at 50 years was economically favorable.     

p27癌基因蛋白在肝癌和癌旁肝组织中表达的意义研究

目的 应用新近发现的ｐ２７癌基因蛋白单克隆抗体探讨其在肝癌组织中表达的意义。方法 用２７蛋白单克隆抗体对１００例肝癌和癌旁肝组织标本进行免疫组化（Ｓ－Ｐ法）染色。结果 （１）ｐ２７在正常肝组织阳性表达率为８３．３％（５／６）,癌旁肝炎组织为８４．２％（３２／３８）,癌旁肝硬化为５９．７％;癌旁肝组织异型增生为５５．９％（１９／３４）,肝癌为３８．０％。（２）ｐ２７蛋白在小梁型肝癌,高分化肝癌和无转     

miR-34a及其下游基因在铁超载大鼠非酒精性脂肪肝发生过程中的作用

目的：探讨miR-34a及其下游基因在铁超载大鼠非酒精性脂肪肝（NAFLD）发生过程中的作用。方法：将36只5周龄雄性SD大鼠随机分为对照组（基础饲料）、高铁组（含1% FeSO₄的基础饲料）、高脂组（脂肪供能比为35%的高脂饲料）和高脂高铁组（含1% FeSO₄的高脂饲料）。干预12周后,称取大鼠体质量;肝脏油红O染色观察大鼠肝脏中脂质堆积程度;测定大鼠血清中丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）含量;实时荧光定量PCR（qPCR）检测大鼠肝脏中miR-34a、沉默信息调节因子1（SIRT1）及过氧化物酶体增殖物激活受体α（PPARα）的mRNA表达水平,并用Western blot方法检测SIRT1和PPARα的蛋白表达水平。结果：与对照组相比,高脂组和高脂高铁组大鼠体质量、血清ALT及miR-34a表达水平均显著增加（P均 < 0.05）,SIRT1及其下游PPARα的mRNA和蛋白表达水平均降低（P均 < 0.05）,肝脏脂质堆积程度加重;与高脂组比较,高脂高铁组SIRT1和PPARα的mRNA和蛋白表达水平均显著降低（P均 < 0.05）。结论：高脂高铁联合作用,可进一步激活miR-34a的表达,进而抑制其下游基因的表达,从而加重NAFLD大鼠肝脏脂代谢紊乱。     

Tumor size of hepatocellular carcinoma in noncirrhotic liver: A controversial predictive factor for outcome after resection

Background

Hepatocellular carcinoma in noncirrhotic liver (NC-HCC) presents usually with large size, which is seen as a contraindication to liver transplantation (LT) or even resection. The objective of our single-center study was to identify prognostic factors following resection of large NC-HCCs and to subsequently devise a treatment strategy (including LT) in selected patients.

Methods

From 2000 to 2010, 89 patients who had hepatic resection for NC-HCC (large ≥8 cm in 52) were analyzed with regard to pathological findings, postoperative and long-term outcome.

Results

Five patients died postoperatively. After a mean follow-up of 35 ± 30 months, NC-HCC recurred in 36 patients (26/47 survivors in group 8 cm+, 10/37 in group 8 cm−; p = 0.007). Five-year overall (OS) and disease-free survival (DFS) rates were significantly worse for group 8 cm+ (43.4% vs. 89.2% and 39.3% vs. 60.7% for group 8 cm−, p < 0.05). Seven patients underwent re-hepatectomy and/or LT for isolated intrahepatic recurrence, with 5-year DFS of 57.1%. In a multivariate analysis, the factors associated with poor OS and DFS were vascular invasion and tumor size ≥8 cm in the overall population and vascular invasion, fibrosis and satellite nodules in group 8 cm+. Adjuvant transarterial chemotherapy was a protective factor in group 8 cm+. In 22 isolated NC-HCC cases with no vascular invasion or fibrosis, tumor size had no impact on five-year DFS (85%).

Conclusions

Although patients with NC-HCC ≥8 cm had a poorer prognosis, the absence of vascular invasion or fibrosis was associated with excellent survival, regardless of the tumor size. In recurrent patients, aggressive treatment (including LT) can be considered.     

铁超载对非酒精性脂肪肝病HepG2细胞模型中Hepcidin和 Fpn-1的影响

目的：探讨铁超载对非酒精性脂肪肝病（NAFLD）HepG2细胞模型中铁代谢指标Hepcidin和Fpn-1的影响。方法：采用四甲基噻唑蓝（MTT）法分别检测浓度均为0.062 5、0.125、0.25、0.5、1.0、2.0 mmol/L的油酸（OA）和硫酸亚铁铵[Fe（NH₄）₂·（SO₄）₂·6H₂O,下称Fe]对HepG2细胞活力的影响,确定OA和Fe联合给药浓度。采用0.5 mmol/L OA联合不同浓度（0、0.125、0.25、0.5 mmol/L）的Fe诱导HepG2细胞建立NAFLD 细胞模型,并设阴性对照组（未经药物处理的细胞）和0.5 mmol/L Fe单独处理组为对照,测定细胞内甘油三酯（TG）和铁蛋白（Fn）含量。采用实时荧光定量PCR（qPCR）法和Western blot法测定细胞中铁调素（Hepcidin）、膜铁转运蛋白（Fpn-1） mRNA和蛋白的表达。结果：与阴性对照组相比,0.5 mmol/L的OA,0.125、0.25、0.5 mmol/L的Fe对细胞存活率无明显影响（P > 0.05）。与对照组和0.5 mmol/L OA组相比,0.5 mmol/L OA与各浓度Fe联合作用时,随着铁浓度增大,细胞内的TG和铁蛋白（Fn）含量逐渐增加,差异具有统计学意义（P < 0.05）。与对照组和0.5 mmol/L OA组相比,0.5 mmol/L OA联合不同浓度Fe处理后Hepcidin的mRNA和蛋白表达均明显下降（P < 0.05）;0.5 mmol/L OA联合不同浓度Fe处理后Fpn-1 mRNA的表达均明显上调（P < 0.05）;与对照组相比,0.5 mmol/L Fe组、0.5 mmol/L OA联合0.25、0.5 mmol/L Fe组Fpn-1蛋白水平明显降低（P < 0.05）。结论：0.5 mmol/L OA联合不同浓度Fe处理时可引起细胞发生脂质沉积,使体内正常铁代谢发生紊乱,Hepcidin的mRNA和蛋白表达均明显下降,Fpn-1 mRNA表达上调而蛋白表达下降,进一步加重NAFLD的进展。     

Outcomes of hepatectomy for noncirrhotic hepatocellular carcinoma: A systematic review

BackgroundNoncirrhotic hepatocellular carcinoma (HCC) is rare. The aim of this study was to evaluate the published evidence for hepatectomy in patients with noncirrhotic HCC.MethodsA literature search was conducted in PubMed database for eligible studies from the time of inception to March 2014. Comparisons of surgical outcomes for noncirrhotic and cirrhotic HCC were pooled and analyzed by meta-analytical techniques.ResultsThirty-one observational studies comprising a total of 3771 patients who underwent hepatectomy for noncirrhotic HCC were reviewed. The median postoperative morbidity was 29.5% (range, 8.3–55.5%) and mean mortality was 2.7% (range, 0–6.5%). Median 5-year overall and disease free survival was 47.9% (range, 26–81%) and 38.0% (range, 24.0–58.4%) respectively. In comparative studies, both the 5-year disease free (odds ratio (OR): 0.61, 95% confidence interval (95% CI): 0.51–0.72; P < 0.001) and overall survival (OR: 0.61, 95% CI: 0.42–0.90; P = 0.01) in the noncirrhotic group were significantly better than those in the cirrhotic group.ConclusionsHepatectomy for noncirrhotic HCC carries low perioperative morbidity and mortality and offers favorable long-term outcomes.     

Long-term surgical outcomes of Non alcoholic fatty liver disease associated hepatocellular carcinoma

BackgroundThe global burden of non-alcoholic fatty liver disease (NAFLD) and NAFLD-associated hepatocellular carcinoma (HCC) is steadily rising. We pursued to investigate the results after liver resection for NAFLD-HCC versus hepatitis B virus (HBV)-HCC exploiting Kaplan Meier method, log-rank test and uni/multivariate analysis with the logistic regression models”.MethodsPatients who underwent liver resection for HCC between January 2004 and December 2018 were included. The outcomes of NAFLD-associated HCC were analyzed.ResultsThe prevalence of NAFLD-associated HCC was 8.4%. A significant number of NAFLD patients had no cirrhosis (21 patients; 38.8%). Although NAFLD patients had a significantly better 5-year survival (P = 0.033), NAFLD was not significantly associated with overall survival in multivariate analysis (P = 0.287). However, survival after 5 years declined in NAFLD patients and was similar to HBV. NAFLD was protective against systemic recurrence compared with HBV (P = 0.018), and this was confirmed in multivariate analysis (P = 0.044). Five-year systemic recurrence (P = 0.044) was significantly lower in NAFLD patients and decreased with time from surgery. Multivariate analysis revealed that anatomical liver resection was independently associated with decreased recurrence in NAFLD patients (HR = 0.337; P = 0.033).ConclusionOverall survival is similar between NAFLD-associated HCC and HBV-associated HCC. Despite there being no significant difference between liver function tests, type of surgery performed, liver cirrhosis, size of tumor, number of tumors, pathological factors like satellite nodules and Edmonson Steiner staging, NAFLD-associated HCC shows lower systemic recurrence compared to HBV-associated HCC.     

超声造影在局灶性脂肪肝与肝脏良性肿瘤鉴别诊断中的应用价值

目的:探讨超声造影在局灶性脂肪肝与肝脏良性肿瘤鉴别诊断中的应用价值.方法:收集在我院手术或行肝脏穿刺组织病理检查确诊的肝脏良性肿瘤及局灶性脂肪肝共患者156例(156个主要病灶),均有完整病史、常规超声、超声造影检查,病理结果,回顾性分析超声及超声造影检查结果.结果:超声造影检查对局灶性脂肪肝与肝脏良性肿瘤诊断的灵敏度为82.61%、特异度为92.73%、阳性预测值为82.61%、诊断准确率为89.74%,明显高于常规超声检查的63.04%、82.73%、60.42%、76.92%,比较差异有统计学意义(P<0.05);局灶性脂肪肝的46个病灶表现为与肝组织同步增强及消退,肝血管瘤、肝脏腺瘤、肝局限性结节增生在动脉相、门脉相时表现各有不同.结论:超声造影用于局灶性脂肪肝及肝脏良性肿瘤诊断时灵敏度及特异度均明显高于常规超声检查,可根据动脉相及门脉相的表现对局灶性脂肪肝与肝脏良性肿瘤进行鉴别诊断.     

Primary carcinoma of the liver: diagnosis, prognosis, and management

Hepatoma accounts for less than 2% of all cancer death in this country, but it is responsible for 10-20% lethal malignancy in Asia and Africa. There are racial differences in its clinical manifestation, association with cirrhosis and/or hepatitis viral infection, pattern of spread, and prognosis. Mass screening program in China using alpha-fetal protein test has detected earlier cases, improved resectability and cure rate. About 10-15% of the patients in this country had surgical treatment. For patients with locally advanced and unresectable carcinoma, regional therapies such as infusion chemotherapy (IA hepatic or IV portal), ligation of hepatic artery, radiotherapy (external or internal), immunotherapy, either singularly or in various combinations have been tried. Despite the availability of Adriamycin and newer combinations of chemotherapeutic agents, patients with disseminated disease rarely respond. Other than earlier diagnosis, search for more effective drugs and multinodal approaches should be continued.