Relationship between liver histopathological changes and HBs Ag in 111 patients treated by long-term hemodialysis

ABSTRACT— We studied liver biopsies performed between January 1972 and June 1980 in 111 patients receiving regular dialysis treatment. Biopsies were performed either because of suspected liver disease (61 patients) or routinely during abdominal surgery or kidney transplantation (50 patients). Repeat biopsies were done in 14 cases. Hepatitis B virus markers, assayed every 3 months during the observation period, were detected at some time in 71 patients (64%); 51 remained persistently positive. Histological examination showed normal liver in 39 cases, lobular hepatitis in 15, chronic persistent hepatitis in 36 and chronic active hepatitis in 21. All patients with chronic active hepatitis were chronic HBsAg carriers, and repeated biopsies showed aggravation only in these patients. The course was remarkably asymptomatic, with lesions leading to fibrosis despite the lack of histopathological patterns of severe necrosis and/or inflammation, which were conspicuously absent in this series.     

Fibrosis progression rates between chronic hepatitis B and C patients with elevated alanine aminotransferase levels

BACKGROUND: We evaluated the annual rate of fibrosis progression in chronic hepatitis B and C patients with elevated alanine aminotransferase (ALT) levels. METHODS: Forty-nine chronic hepatitis B patients and 21 chronic hepatitis C patients, each of whom had undergone two or more liver biopsies at an interval of more than 1 year, were enrolled in this retrospective clinical research protocol. The annual rate of fibrosis progression was calculated by dividing the change in fibrosis stage between the first and second liver biopsies by the interval in years between them. RESULTS: The median interval in chronic hepatitis B and C was 3.4 (first and third quartiles, 1.8-4.7) and 3.2 (2.1-6.5) years, respectively. Overall, the mean fibrosis progression rate was 0.21 +/- 0.31 (mean +/- SD) fibrosis units (FU) per year in 49 patients with chronic hepatitis B, and 0.13 +/- 0.18 FU/year in 21 patients with chronic hepatitis C. The ALT level was an independent variable correlating with fibrosis progression. In patients whose median ALT level was 70 IU/l or more, the mean fibrosis progression rate was 0.28 +/- 0.32 FU/year in 36 patients with chronic hepatitis B, and 0.22 +/- 0.23 FU/year in eight patients with chronic hepatitis C. CONCLUSION: This paired-biopsy study of untreated chronic hepatitis B or C demonstrated that fibrosis progression occurred largely in patients with continuously elevated ALT levels even over a relatively short period, and that liver fibrosis might progress by one stage within an average of 4-5 years of follow-up in patients with elevated ALT of 70 IU/l or more.     

Histomorphological characteristics of liver tissue in patients with chronic viral hepatitis

OBJECTIVE : Chronic viral hepatitis and cirrhosis caused by hepatitis B virus (HBV), hepatitis C virus (HBC) or both constitute the majority of cases of liver diseases in China. Pathologists often need to differentiate between the morphological features of HBV and HCV. The aim of this study was to explore the differences in inflammatory activity, fibrosis and morphological characteristics in various types of chronic viral hepatitis. METHODS : Inflammatory activity and degree of fibrosis in liver biopsies taken from 224 patients with chronic hepatitis were determined according to the Diagnostic Criteria of Chronic Hepatitis, China, 1995. Each of hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and the hepatitis C virus nuclear core protein (CP₁₀) were detected on paraffin sections of the biopsies by using immunohistochemical methods. Patients were divided into HBV, HCV and HBV + HCV infection groups and the differences among these groups were assessed on the basis of histopathological characteristics including inflammatory activity, fibrosis, steatosis, intrahepatic cholestasis, Councilman bodies and ground‐glass hepatocytes. RESULTS : The HCV infection group had more severe inflammatory activity, fibrosis and intrahepatic cholestasis than did the HBV infection group. The degree of inflammatory activity and fibrosis in the HBV + HCV infection group was moderate, but the degree of intrahepatic cholestasis was the most severe of the three study groups. Ground‐glass hepatocytes were only noted in HBV‐infected specimens. There was no difference in the occurrences of steatosis and Councilman bodies among the three study groups. CONCLUSIONS : The degree of inflammatory activity and fibrosis induced by HCV in hepatocytes is more severe than that induced by HBV. The histological changes observed in liver infected by both HBV and HCV are no more severe than those observed in liver infected with either HBV or HCV. Intrahepatic cholestasis may play an important role in aggravating damage to hepatocytes.     

血清胆碱酯酶与慢性乙型肝炎和肝硬化患者临床及病理的关系

目的 探讨血清胆碱酯酶(ChE)与慢性肝病患者的临床及病理的关系。方法随机选择105例慢性肝病患者，检测血清ChE活性，并行肝组织病理检查。结果肝病程度越重，ChE活性值降低愈明显，两者呈明显的负相关。肝组织炎症活动度及纤维化程度越高，血清ChE活性值降低愈明显，与病理损害程度呈明显的负相关关系。结论血清ChE可用于慢性肝病病情严重程度及预后的判断，血清ChE是观察慢性肝炎患者肝组织炎症及纤维化变化的较敏感指标。     

Liver damage in Italian patients with hereditary hemochromatosis is highly influenced by hepatitis B and C virus infection

We evaluated the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in 78 Italian patients with hereditary hemochromatosis as well as the relation between HCV antibody (anti-HCV) status, hepatitis B surface antigen (HBsAg) and liver histology. None of the patients had been transfused or ever consumed more than 60 g of alcohol per day. Eighteen showed histological signs of chronic hepatitis, active cirrhosis was present in 12, chronic active hepatitis in 4 and chronic persistent hepatitis in 2. Liver fibrosis or cirrhosis without inflammatory activity was observed in 31 subjects, whereas liver histology was normal except for iron overload in 18. The prevalence of HBsAg in the whole series was 5% and of anti-HCV was 20.5%. The prevalence of HBsAg and anti-HCV was significantly higher in the chronic hepatitis group than in the fibrosis/cirrhosis (p = 0.01) and the normal groups (p < 0.01). Fourteen of 18 hereditary hemochromatosis patients with chronic hepatitis were HBsAg (4) or anti-HCV (10) positive and all the latter subgroup had HCV-RNA in their serum as shown by the polymerase chain reaction. Although most of the patients with associated chronic hepatitis had cirrhosis, their serum ferritin levels and amount of mobilizable iron were significantly lower than those of the fibrosis/cirrhosis group (p < 0.01). This indicates that hepatitis viral infection acts synergistically with iron in accelerating the development of liver damage.     

不同中医证型慢性乙型肝炎轻度患者肝组织病理研究

目的：研究不同中医证型的慢性乙型肝炎（CHB）轻度患者肝组织病理特点,并探讨其临床意义。方法：将310例CHB轻度患者进行中医辨证分型,采用Menshini法1秒钟经皮肝穿取肝组织进行炎症和纤维化程度判断,并与车祸死亡正常人作对照,同时荧光定量PCR法检测患者血清HBVDNA水平。结果：①肝组织炎症≥G2、肝纤维化≥S2等级的患者年龄明显高于肝组织炎症〈G2、肝纤维化〈S2等级的年龄;②各中医证型患者肝组织炎症级别≥G2的比率明显高于正常组,但证型间比较差异均无显著性意义;③各中医证型患者肝组织纤维化程度≥S2的比率明显高于正常组,但证型间比较仅肝肾阴虚和脾肾阳虚两型明显高于肝郁脾虚和湿热中阻型;④各中医证型间HBVDNA水平比较,肝肾阴虚和脾肾阳虚两证型明显低于肝郁脾虚型,其他证型之间差异无显著性意义。结论：CHB轻度患者至少有1／3的患者需要抗病毒治疗,而且年龄越大越有必要;在控制肝脏炎症方面,辨证治疗应多加倡导,在抗纤维化治疗方面应重视补肾法研究。     

Relationship between liver histopathological changes and HBsAg in 111 patients treated by long-term hemodialysis

We studied liver biopsies performed between January 1972 and June 1980 in 111 patients receiving regular dialysis treatment. Biopsies were performed either because of suspected liver disease (61 patients) or routinely during abdominal surgery or kidney transplantation (50 patients). Repeat biopsies were done in 14 cases. Hepatitis B virus markers, assayed every 3 months during the observation period, were detected at some time in 71 patients (64%); 51 remained persistently positive. Histological examination showed normal liver in 39 cases, lobular hepatitis in 15, chronic persistent hepatitis in 36 and chronic active hepatitis in 21. All patients with chronic active hepatitis were chronic HBsAg carriers, and repeated biopsies showed aggravation only in these patients. The course was remarkably asymptomatic, with lesions leading to fibrosis despite the lack of histopathological patterns of severe necrosis and/or inflammation, which were conspicuously absent in this series.     

Histological evolution of chronic hepatitis C. Factors related to progression

We have evaluated the histological progression of liver disease in 29 untreated patients with chronic hepatitis C. All patients were positive to antibodies to hepatitis C virus by ELISA2 and RIBA2. Two liver biopsies were carried out for each patient, with an interval ranging between 12 and 126 months (mean 50.2±30.7). In all cases the usual histological classification was applied and the histological activity index scoring system according to Knodell et al. was determined. Fifteen cases worsened (51.7%), 12 cases showed no histological changes (41.4%) and two patients improved (6.9%). Cirrhosis was found in five patients (18.5%) in the second liver biopsy. Epidemiological, clinical, biochemical and histological parameters were compared between the group without histological progression and the group with impairment in liver histology. Factors related to histological worsening were: more advanced age (p=0.002), high levels of aspartate aminotransferase (p=0.04), high global histological activity index (p=0.03) and piecemeal necrosis and bridging necrosis scores (p=0.02) at first biopsy. The histological activity index can be applied to assess the natural history of chronic viral hepatitis, and is a good tool to evaluate the prognosis. Thus chronic hepatitis C virus infection is a histologically progressive disease in at least half the cases.     

慢性肝炎肝组织病理改变与血清总胆汁酸关系探讨

目的 研究空腹血清总胆汁酸(TBA)与血清纤维化指标的关系，阐明其临床意义。方法 收集慢性肝病患者73例，肝组织活检当天行血清TBA及HA检测，并分析其相关性。结果 慢性肝炎患者TBA水平与正常值相比明显升高，与肝组织炎症活动(G)、纤维化程度(S)及血清纤维化指标(HA)呈正相关，相关系数r分别为0．515、0．430、0．687。结论 TBA是反映肝脏炎性活动及肝纤维化的较敏感指标。     

AAR和APRI对成年慢性丙型肝炎患者肝纤维化的诊断价值

目的探讨AST／ALT比值（AST／AL Tratio,AAR）和AST／PLT比值指数（AST／PLT ratio index。APRI）对成年慢性丙型肝炎（丙肝）患者肝纤维化的诊断价值。方法选择98例成年慢性丙肝患者进行回顾性分析。对所有患者进行肝脏穿刺活体组织检查以确定肝纤维化分期,比较分析AAR和APRI与肝纤维化分期的关系。结果AAR只在S0期与S1～S4期患者之间差异有统计学意义（P〈0．05）,在S0～S1期与S2～S4期、S0～S2期与S3～S4期、S0～S3期与S4期患者之间差异无统计学意义（P均〉0．05）;APRI在SO期与S1～S4期、S0—S1期与S2～S4期、S0～S2期与S3～S4期、S0～S3期与S4期患者之间差异均有统计学意义（P〈0．05）。受试者工作特征曲线分析显示,AAR诊断s1期、S2～S3期和S4期的曲线下面积均〈0．7,而APRI均〉0.7。APRI诊断S1期、S2～S3期和S4期的诊断界值分别为0．150、0．195和0．245。结论对于成年慢性丙肝患者肝纤维化分期的判定,APRI比AAR更具有参考价值,APRI可以用于S1期、S2～S3期和S4期的诊断。     

Impact of interferon-alpha therapy on liver fibrosis progression in patients with HBeAg-negative chronic hepatitis B

The possible effect of interferon-alpha (IFNa) on liver fibrosis progression has not been adequately studied in chronic hepatitis B. We evaluated 147 patients with HBeAg-negative chronic hepatitis B who had > or =2 liver biopsies and had been treated with IFNa (n = 120) or had remained untreated (n = 27). The median interval between the two biopsies was 24 (12-160) months. All biopsies were scored blindly by a single liver histopathologist according to the classification of Ishak et al. (J Hepatol 1995; 22: 696-699). IFNa induced sustained biochemical response in 30, initial response and subsequent relapse in 57 and no response in 33 patients. Fibrosis improved in 17.5% of treated (sustained responders: 40%, relapsers: 9%, nonresponders: 12%) and 4% of untreated patients and worsened in 34% (sustained responders: 7%, relapsers: 40%, nonresponders: 48%) and 70% of cases, respectively (P = 0.002). The annual rate of fibrosis progression was worse in the untreated (0.427 +/- 0.119) than in treated patients (0.067 +/- 0.052, P = 0.001). However, the fibrosis progression rate in the untreated patients was not significantly different than the net fibrosis progression rate (after subtraction of IFNa duration) in nonresponders or relapsers. In multivariate analysis, worse fibrosis progression rate was associated with older age (P = 0.010), worse baseline grading score (P < 0.001), lower baseline fibrosis (P = 0.035) and the type of response to IFNa (P = 0.032). In conclusion, in HBeAg-negative chronic hepatitis B, IFNa significantly reduces the rate of fibrosis progression, but such an effect is mainly observed in patients with sustained biochemical responses. In relapsers and nonresponders, fibrosis benefit equals the treatment period. The strongest factor associated with fibrosis progression is the change in necroinflammatory activity.     

Is determination of serum N-terminal procollagen type III peptide (sPIIIP) a marker of hepatic fibrosis?

Serum N-terminal procollagen type III peptide (sPIIIP) levels were evaluated in 58 patients affected by chronic liver disease, in order to assess the usefulness of sPIIIP as a marker of hepatic fibrosis. In 45 patients sPIIIP was also correlated to liver histology; biopsies were scored by two of the authors, without knowledge of diagnosis. Compared to normal controls, sPIIIP concentration was found to be significantly elevated in chronic active hepatitis (CAH) and in cirrhosis, but not in fatty liver. Patients affected by chronic persistent hepatitis (CPH) had values of sPIIIP higher than normal in four of 11 cases considered. A close correlation was found between sPIIIP values and histological parameters of inflammation, necrosis, and degeneration, while the relationship between sPIIIP levels and fibrosis was weaker. These data suggest that sPIIIP determination may reflect the extent of inflammatory changes in the liver; but it cannot be considered a reliable index of hepatic fibrosis.     

Diabetes mellitus in chronic hepatitis B and C: prevalence and potential association with the extent of liver fibrosis

Diabetes mellitus has been reported to have an increased prevalence and to be associated with more severe fibrosis in patients with chronic hepatitis C. We evaluated the prevalence of diabetes mellitus in patients with chronic hepatitis B or C as well as the possible association between presence of diabetes and extent of liver fibrosis. In total, 434 consecutive patients with histologically documented hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (n = 174) or chronic hepatitis C (n = 260) were studied. The relationships of diabetes and epidemiological, somatomorphic, laboratory and histological patient characteristics were evaluated. Liver histological lesions were blindly evaluated according to the Ishak's classification. Diabetes was present in 58 (13%) patients, without any difference between those with chronic hepatitis B (14%) or C (13%). Diabetes was observed significantly less frequently in patients with fibrosis score 0-2 (7.7%) than 3-4 (10.4%) than 5-6 (29.2%) (P < 0.001). The presence of diabetes was independently associated with higher gamma-glutamyl-transpeptidase (GGT) levels and more severe fibrosis or presence of cirrhosis (P < 0.001) as well as with presence of hepatic steatosis and increased serum triglycerides levels (P < 0.02). In the noncirrhotic patients, diabetes was significantly associated with older age and higher GGT levels, but not with the extent of fibrosis. In conclusion, diabetes mellitus is observed in more than 10% of patients with either HBeAg-negative chronic hepatitis B or chronic hepatitis C. The presence of diabetes is strongly associated with more severe liver fibrosis, but such an association may be related to the high prevalence of diabetes in patients with cirrhosis.     

Histopathological aspects of viral hepatitis

SUMMARY. The main method of classification of chronic viral hepatitis is now by cause, and the old histology-based classification is no longer considered appropriate. However, liver biopsy remains an important part of patient assessment and, in the context of clinical trials, biopsy findings are often scored in a semiquantitative manner. The concepts of grading and staging, borrowed from tumour pathology, have been introduced, representing the severity of the necroinflammatory lesion and the extent of its structural consequences respectively. The pathology of the individual forms of viral hepatitis A to G shows more similarities than differences. However, some pathological features are commonly associated with specific viruses. The combination of portal lymphoid follicles, bile duct damage, lobular activity and steatosis give chronic hepatitis C a characteristic histological profile. Very similar appearances have been noted in the limited number of biopsies so far reported from patients with known combined hepatitis C and G virus infection.     

171例慢性乙型肝炎病毒感染者临床与肝组织病理分析

目的:观察171例HBV DNA阳性的慢性乙型肝炎病毒(HBV)感染者临床检测指标与肝脏组织病理的关系.方法:将171例患者分为4组,A组丙氨酸氨基转移酶(ALT)≤0.5 ×ULN(正常值上限),B组0.5 ×ULN＜ALT≤1×ULN,C组1×ULN＜ ALT≤2×ULN,D组2×ULN＜ ALT≤5 × ULN,观察各组患者肝脏炎症分级(G)和纤维化分期(S)的差异,进一步分析各组炎症分级和纤维化分期与其他肝脏生化学指标如天门冬氨酸氨基转移酶(AST)、血小板(PLT).及肝纤维化模型(APRI,以AST/PLT比值的统计量作为数字化模型)的关系.结果:A组25％患者肝组织炎症为G2,B组和C组分别有16.4％、49.2％患者肝组织炎症分级为G2～G3,不同ALT组间肝组织炎症分级的差异有显著性意义(P＜0.05),随着ALT水平升高,肝组织G2～G3检出比例增加;171例患者不同肝组织炎症分级组,球蛋白(Glo)、AST、γ-谷氨酰转肽酶(GGT)、PLT、APRI的差异均有显著性意义(P＜0.05);不同肝组织纤维化分期组,年龄、HBeAg状态、白蛋白(Alb)、AST、GGT、PLT、HBV DNA、APRI的差异均有显著性意义(P＜0.05),其中随着纤维化程度进展,AST、APRI值逐渐升高,Alb、PLT逐渐下降.结论:HBV DNA阳性的慢性HBV感染者,即使ALT正常,仍有不同程度的肝组织炎症和纤维化改变,需综合观察年龄、AST、GGT、APRI、HBeAg状态和HBV DNA水平,必要时建议患者行肝脏穿刺病理检查,以准确了解肝脏疾病进展.     

Cyclooxygenase-2 expression in chronic hepatitis C and the effect of interferon alpha treatment

BACKGROUND AND AIM: Cyclooxygenase-2 (COX-2), a target of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), is upregulated in chronic hepatitis B and may have a role in hepatocellular carcinoma. Little is known about the expression of COX-2 in chronic hepatitis C (HCV) infection. The aim the present study was to evaluate the extent of COX-2 expression in liver biopsies in patients with HCV infection and to determine the effect of treatment with interferon alpha (IFN). METHODS: Percutaneous liver biopsy specimens were retrieved. Following formalin fixation and paraffin embedding, the biopsies were histologically evaluated for inflammation and fibrosis. The extent of COX-2 expression was measured by the avidin biotin immunohistochemical technique using a monoclonal COX-2 antibody. The extent of COX-2 expression was graded according to the number of hepatocytes expressing COX-2. Data were analyzed using Student's t-test. RESULTS: Liver biopsies from 10 patients before and after treatment with IFN were obtained and compared with nine normal liver biopsies. All of the liver biopsies showed some COX-2 expression. COX-2 expression was confined to hepatocytes and bile duct epithelium and was not detected in vascular endothelium or inflammatory cells. The extent of COX-2 expression was greater in hepatitis C infected liver biopsies than in normal biopsies. Following treatment with IFN, there was a greater than threefold reduction in COX-2 expression (P < 0.01). This result was independent of the sustained virological response. CONCLUSION: In this small pilot study we have shown that COX-2 is overexpressed in liver biopsies infected with HCV and COX-2 expression is reduced following treatment with IFN.     

Histological progression during short-term follow-up of patients with chronic hepatitis C virus infection

Assessment of prognosis from hepatitis requires liver histology. When the fibrosis stage is known, and if the fibrosis progression rate can be established, time to development of cirrhosis can be calculated. The fibrosis progression rate can be calculated from a single biopsy when duration of infection prior to biopsy is known. Sequential biopsies can also be examined. In this work, we studied histological activity and fibrosis stage in liver biopsies of 157 hepatitis C virus (HCV)-infected patients, including 92 for whom the approximate duration of infection was known. The mean fibrosis progression rate was 0.09 units per year, and was not influenced by mode of infection or viral genotype. Forty-six patients who had very mild histological changes in the initial biopsy underwent repeat biopsy 2 years later (with no intervening anti-viral treatment). Comparison of paired biopsies confirmed a tendency to histological progression and increasing hepatic fibrosis (mean, 0.15 fibrosis units per year). A normal baseline alanine aminotransferase (ALT) value was associated with slow fibrosis progression before baseline biopsy and between biopsies. These data do not differ from published cross-sectional and longitudinal studies, and suggest that histological progression will be observed during follow-up of most patients, including those with mild histological changes at time of initial assessment.     

Histological improvement of chronic hepatitis B,and non-A,non-B with interferon treatment: Application of a numerical scoring system for evaluating sequential morphologic changes

In order to assess the sequential changes of liver pathology after interferon therapy, 70 liver biopsy specimens, collected from 23 HBeAg-positive patients with chronic hepatitis B and 12 patients with chronic non-A, non-B hepatitis, were studied using a numerical scoring system proposed by Knodell et al. The biopsy specimens were obtained immediately prior to the administration of interferon and within one week following the termination of interferon therapy. Three patients with chronic hepaitits B were negative for DNA-polymerase (DNA-P) prior to the interferon administration. Ten patients (50%) lost DNA-P activity. HBeAg became negative in 8 patients (34.8%), of whom 2 seroconverted to anti-HBe. Serum alanine aminotransferase levels normalized in 9 patients with chronic hepatitis B, and non-A, non-B hepatitis. The total Histological Activity Index (HAI) scores in both patients with chronic hepatitis B, and non-A, non-B decreased significantly (P<0.001 and P<0.005, respectively) after interferon treatment. There was also a significant improvement (0.02<P<0.001) in each histological category except for fibrosis. When the changes of the HAI scores in patients with chronic hepatitis B were correlated to the outcome in the DNA-P and HBeAg/anti-HBe system after treatment, the histological improvement did not significantly correlate to the outcome of these serological parameters.     

庚型肝炎患者肝组织中HGV表达的免疫组化研究

目的探讨庚型肝炎病毒（ＨＧＶ）在庚型肝炎肝组织中的表达状况与临床意义．方法应用免疫组织化学ＰＡＰ方法以鼠抗ＨＧＶＮＳ５单克隆抗体对庚型肝炎患者２０例（急性肝炎２例，慢性肝炎８例，肝硬变１０例，血清ＨＧＶＲＮＡ皆阳性）肝组织中ＨＧＶ抗原进行检测．结果庚型肝炎患者２０例中，８例（４０％）肝组织中检出ＨＧＶ抗原；不同病期检出率分别为：急性肝炎０／２（０％），慢性肝炎２／８（２５％），肝硬变６／１０（６０％），各组间差异无显著意义；阳性信号位于肝细胞胞质；阳性细胞可位于炎症坏死灶周围；抗原阳性与阴性组间肝组织炎症活动度及血清谷丙转氨酶水平无明显差别，但阳性组纤维化指数较高．结论ＨＧＶ感染及其在肝组织中表达可能与肝组织纤维化有一定关系     

Liver protocollagen proline hydroxylase in human liver diseases and experimental liver fibrosis.

Liver protocallagen proline hydroxylase activity (PPH activity) was determined in patients with various liver diseases, CCl4-induced liver fibrosis rats and cholin deficiency (tcd) fatty liver rats. The following results were obtained: Liver PPH activity in patients with chronic hepatitis was higher than that in patients with acute hepatitis, while the activity in patients with liver cirrhosis was much higher than that in patients with chronic hepatitis. The activity was higher in patients with chronic active hepatitis than in those with chronic inactive hepatitis. Patients with active and progressive liver cirrhosis were found to have an especially high PPH activity, in whom the activity reflected well the degree of liver fibrosis. Even though fibrosis in persistent hepatitis was almost negligible or slight, the degree of liver PPH activity in persistent hepatitis was similar to that in liver cirrhosis. Liver PPH activities in CCl4-induced liver fibrosis rats and CD fatty liver rats elevated proportionally to the lapse of time. Whilst liver PPH activity in rats of CD fatty liver without fibrosis in 23 to 31 weeks after the start of the experiment was slightly lower than that in rats of CD fatty liver with fibrosis. But liver PPH activity of the former was considerably higher than that of control rats.