An unusual hyperplastic hepatocellular nodule in a patient with hepatitis C virus-related liver cirrhosis

Recent advances in diagnostic imaging techniques have increased the likelihood of detecting novel nodular lesions of the liver. We report here a case of unusual hyperplastic hepatocellular tumor found in a 70-yr-old woman with hepatitis C virus-related cirrhosis. A mass was incidentally detected in the right lobe by abdominal ultrasonography and confirmed by computed axial tomography (CT). Magnetic resonance imaging demonstrated that the tumor had hyperintense signal with a small hypointense region in the center and a thin, hypointense rim on T1-weighted image and a hypointense signal on T2-weighted image. CT during hepatic arteriography showed that the tumor was hypodense with a central hyperdense region, whereas CT during arterial portography revealed that the tumor was isodense and surrounded by a thin circular hypodense band with a central hypodense region. These radiographic findings suggested a diagnosis of dysplastic nodule with malignant foci of hepatocellular carcinoma. The patient underwent tumor resection. Macroscopically, the tumor, 45 x 45 x 30 mm in size, was encapsulated and had a central stellate-like scar with radiating septa. Histological examination showed a hyperplastic hepatocellular tumor without cellular, nuclear or structural atypia. The central fibrous scar contained abundant small, artery-like and vein-like vessels, whereas there were no normal portal triads but rather several portal tract-like structures lacking bile ducts in the parenchyma of the tumor. Some of the portal tract-like structures were composed of artery-like and vein-like vessels, and the others possessed vein-like vessels only. There were no bile ducts in the tumor. The nontumorous liver tissue had evidence of macronodular cirrhosis. Finally, this tumor was regarded as an unusual type of hyperplastic hepatocellular nodule encountered in cirrhotic liver, characterized by the presence of central stellate-like fibrosis and the lack of bile ducts. Although the pathogenesis of the hyperplastic lesion is unclear, it may represent a focal regenerative hepatocellular response to localized circulatory disorder.     

Incidence and risk factors for hepatocellular carcinoma in 967 patients with cirrhosis

PURPOSE: To determine the incidence of hepatocellular carcinoma in cirrhosis and to examine the influence of age and sex, and the contribution of etiological factors. METHODS: 967 patients with liver cirrhosis and free of hepatocellular carcinoma were enrolled in this longitudinal, retrospective and observational study. Monitoring for hepatocellular carcinoma was scheduled at 3- to 6-month intervals. The mean (+/-SD) length of follow-up was 60.3+/-51.7 months (range 6 258). RESULTS: During the observation period, hepatocellular carcinoma developed in 64 patients. The calculated annual incidence was 2.1%. The probability of being free of liver cancer was 92% at 5 years, 80% at 10 years, and 69% at 15 years. Age was the only independent risk factor for the development of malignancy in the multivariate analysis. There were no differences according to male sex, alcohol abuse, and chronic hepatitis B and C virus infection. CONCLUSIONS: The annual incidence of hepatocellular carcinoma was 2.1%. These results, although confirming that age is a risk factor for hepatocellular carcinoma in cirrhosis, indicate that alcohol abuse, male sex, and concurrent hepatitis B and C virus infection do not involve a higher risk of developing liver cancer.     

Outcome of hepatitis C patients with and without hepatocellular carcinoma undergoing liver transplant

OBJECTIVE: Hepatitis C virus (HCV) infection is associated with development of hepatocellular carcinoma (HCC). The aim of this study was to examine clinical characteristics and outcome of patients with HCV with or without HCC undergoing liver transplant. METHODS: We reviewed the charts of all 55 patients transplanted between November 1990 and December 1996 for HCV cirrhosis with HCC and compared them with a control group of HCV patients without HCC. Patients with a history of alcohol abuse or HBsAg positivity were excluded. There were 37 men and 18 women, with a mean age of 57.6 yr (range, 19-70 yr) in the HCC group. RESULTS: There was no significant difference between the HCC and nonHCC groups regarding Child's class or United Network for Organ Sharing (UNOS) status at the time of transplant. Twenty-six (45%) patients were diagnosed or suspected of having HCC before transplant. Twenty-five patients (45.5%) had a single focus of HCC. Fourteen percent (seven of 50) of the patients with HCC had been treated with interferon, whereas 12% (six of 52) of patients in the nonHCC group had received interferon. Duration of interferon therapy ranged from 1 to 9 months. All interferon treatment occurred within 5 yr of transplant. A history of intravenous drug use or transfusion was identified in 37 (67%) of HCC patients. Thirty-two patients (58%) without HCC had a parenteral exposure. There was no significant difference in patient or graft survival rates between the patients with and without HCC. CONCLUSION: Approximately one-half of HCC was not detected before liver transplant. There was no significant difference in the mode of transmission, clinical status at the time of transplant, or outcome between the HCV patients with and without HCC.     

Surgical therapy for hepatocellular carcinoma with liver cirrhosis

Approximately 80% of hepatocellular carcinoma (HCC) patients in Japan have associated liver cirrhosis, which increases the difficulty of surgical treatment. Liver dysfunction associated with liver cirrhosis is one of the most important predictive prognostic factors for HCC patients. Percutaneous ethanol injection therapy (PEIT) is useful for patients with small HCC or with poor hepatic functional reserve. Transcatheter arterial chemoembolization (TACE) is also useful both for patients with unresectable HCC and patients with multiple intrahepatic recurrence. Liver resection, however, lead to better outcome than other treatments when liver function is maintained after surgery. To determine operative procedures, it is important to evaluate the exact function of remnant liver, based on the preoperative liver function test and the evaluation of tumor character. For advanced HCC patients with vascular invasion, non-surgical treatments such as PEIT or TACE are not indicated, and surgical intervention can be an effective modality to improve their survival. Improvements of surgical technique and perioperative management have decreased fatal complications at a major liver resection and allowed us to carry out liver resection on patients with advanced HCC.     

Past exposure to hepatitis B virus as a risk factor for hepatocellular carcinoma in patients with chronic liver disease

Maltitol is a disaccharide alcohol that is produced by hydrogenation of maltose and exhibits resistance to intestinal disaccharidases. We demonstrated previously that maltitol stimulated transepithelial diffusional calcium transfer in the ileum, accompanied by an elevation of intestinal calcium absorption as well as calcium retention in the body. In this study we examined whether the maltitol-induced increase in the diffusional transfer of intestinal calcium absorption leads to an alteration of the physical properties of bones in the weanling rats which exhibit the maximal level of intestinal active calcium absorption. Rat pups were removed from dams at 24 d of age and were fed the diets containing either maltose (control) or maltitol and a requisite amount of calcium (0.52%) for 21 d. Balance studies performed during the final 5-d period showed that maltitol-fed rats had greater calcium retention and calcium absorption. The breaking force of femoral bones was 13% greater in the rats fed the maltitol diet than in controls. The calcium content and dry weight of both femurs and tibias, as well as the bone mineral density of tibias, were elevated in the rats fed the maltitol diet. In a separate experiment, gastric intubation of maltitol-containing diet increased the serum calcium concentration in the portal vein at 2 and 4 h compared to controls. These results indicate that the maltitol-induced increase in the intestinal calcium absorption through paracellular pathway leads to enhancement of the calcium content and the breaking strength in the bone of weanling rats.     

Prevention of hepatitis B and C virus infection for prevention of cirrhosis and hepatocellular carcinoma

In Taiwan, cirrhosis and hepatocellular carcinoma (HCC) have been common in medical practice since the 1960s. In 1969, Taiwan was shown to be a hyperendemic area of hepatitis B virus (HBV) infection with a high rate of hepatitis B surface antigen (HBsAg) positivity, 19% of the population being infected before the fourth decade of life. There is evidence indicating that more than 80% of chronic hepatitis, cirrhosis and HCC are the sequelae of chronic HBV infection. In 1984, after 3 years of preparation, a programme to control cirrhosis and HCC began. All neonates born to HBsAg+ mothers were given Pasteur plasma-derived vaccine 5 micrograms i.m. at 1, 5 and 9 weeks with a booster at 12 months. In 1986, all neonates were included in this programme. In addition, beginning in 1987, all non-vaccinated preschool children were also immunized and susceptible medical personnel and people from HBsAg+ households were recommended to receive the vaccine. Using data obtained from the 7-year evaluation study on the efficacy of this vaccine and some historical data, the HBsAg positivity rate in people born in the first few years after 1986 was estimated to be 2.6%. This rate is expected to decrease to 0.2% in those born after around 1990. In July 1992, an anti-hepatitis C virus (HCV) test was included in blood donor screening tests. This was followed by a decrease in the incidence of post-transfusion hepatitis (PTH) from 13 to 2.5% and there have been no anti-HCV+ PTH cases since. However, without immunization, the prevalence of HBsAg decreased among children in Taipei in 1989. This coincided with the widespread use of disposable syringes and needles and an improvement in the sterilization of medical instruments. Therefore, it is likely that HCV infection may also decrease as a result of these practices. Through the use of immunization and improved medical procedures, chronic hepatitis, cirrhosis and HCC may decrease in Taiwan by around 95%.     

Cytomegalovirus viremia: risk factor for allograft cirrhosis after liver transplantation for hepatitis C

BACKGROUND: Despite recent advances in diagnosis and treatment, cytomegalovirus (CMV) infection continues to be a common cause of morbidity in liver transplant (LT) recipients. Because CMV infection suppresses cell-mediated immunity, which seems to be important in neutralizing hepatitis C virus (HCV) infection, we assessed the impact of CMV infection on histopathological HCV recurrence after LT. METHODS: The study group was comprised of 43 consecutive LT recipients with at least 6 months of histologic follow-up. Group 1 consisted of the 8 patients who developed CMV viremia after LT; group 2 comprised the 35 patients without CMV viremia. There was no significant difference with regard to age, initial immunosuppression, incidence of rejection, distribution of HCV genotypes, or mean follow-up between the groups. Semiquantitative histopathologic assessment of allograft hepatitis was performed using the Knodell's score. RESULTS: The mean total Knodell score of the final allograft biopsy was significantly greater in group 1 patients (P=0.016), with most of the difference due to periportal/bridging necrosis (P=0.009) and lobular activity subitem (P=0.01) scores. Half of the CMV viremic patients eventually developed allograft cirrhosis as compared with 11% of the CMV-negative patients (P=0.027). Accordingly, the cirrhosis-free actuarial survival by Kaplan-Meier estimates was significantly diminished in the CMV viremic patients. Glycoprotein B genotype analysis of CMV isolates revealed no significant differences between patients who did and those who did not develop allograft cirrhosis. CONCLUSIONS: After LT for chronic HCV, patients who develop CMV viremia incur a significantly greater risk of severe HCV recurrence.     

Prognostic factors after hepatic resection for hepatocellular carcinoma associated with Child-Turcotte class B and C cirrhosis

OBJECTIVE: To evaluate prognostic factors after resection of hepatocellular carcinoma (HCC) in patients with Child-Turcotte class B and C cirrhosis. SUMMARY BACKGROUND DATA: Although hepatic resection remains the mainstay in the treatment of HCC and can be performed with low morbidity and mortality rates in patients without cirrhosis, its role is poorly defined for patients with severe cirrhosis. METHODS: From 1986 to 1996, partial hepatectomy was performed for HCC in 63 patients with Child-Turcotte class B (n = 46) and C (n = 17) cirrhosis. There were 46 men and 17 women, with an average age of 61.2 years (range 35 to 79 years). Associated conditions were diabetes mellitus in 45, esophageal varices in 32, severe hypersplenism in 26, cholelithiasis in 13, gastroduodenal ulcer in 6, and hiatal hernia, gastric lymphoma, splenic abscess, and pancreatic cyst each in 1. Concomitant surgical procedures were performed for most of these conditions. RESULTS: Major complications occurred in 17 patients (27%), six (9.5%) of whom died within 1 month after surgery. The overall in-hospital death rate was 14.3%. Liver failure and intraabdominal sepsis were mostly fatal complications. The overall and disease-free survival rates, respectively, were 70.2% and 64.5% at 1 year, 43.5% and 23.8% at 3 years, and 21.4% and 14.9% at 5 years. Multivariate analysis with the Cox regression model revealed that favorable factors for survival were Child class B, no transcatheter arterial embolization before surgery, young age, and low alanine aminotransferase (ALT) level before surgery. CONCLUSIONS: Hepatic resection can provide a favorable result in young patients with HCC complicating Child class B cirrhosis with low hepatitis activity, but transcatheter arterial embolization before surgery should be avoided in such patients.     

Patients with ultrasonic coarse-nodular cirrhosis who are anti-hepatitis C virus-positive are at high risk for hepatocellular carcinoma

BACKGROUND: The relationship between echosonographic patterns of patients with cirrhosis who are antihepatitis C virus (HCV)-positive, the DNA synthesis of hepatocytes, and the risk for HCC were studied. METHODS: Thirty-eight patients with anti-C-100 antibody-positive and Child's grade A posthepatitic cirrhosis were studied. DNA synthesis activity was measured by a bromodeoxyuridine (BrdU, a thymidine analogue)-labeling index (LI), using the BrdU-anti-BrdU in vitro method, and the patients were followed prospectively by frequent liver ultrasonography for 3 years. The ultrasound patterns were classified into fine, coarse, and coarse-nodular (CN) patterns, and the reproducibility of the classification in practical use also was confirmed. RESULTS: Of the 21 patients with high DNA synthesizing cirrhosis (BrdU LI > or = 1.5%), 10 (48%) showed coarse-nodular, 5 (24%) coarse, and 6 (29%) fine pattern in ultrasonography. Conversely, of the 17 patients with low DNA synthesizing LC (BrdU LI < 1.5%), only 1 (6%) showed coarse-nodular, 2 (12%) coarse, and 14 (82%) fine pattern. A significant relationship was found between the two groups of BrdU LI and ultrasound imaging patterns (P < 0.05). The incidence of CN pattern was significantly higher (P < 0.01) in the high DNA synthesizing group than in low DNA synthesizing group. Of the 11 patients with CN pattern by ultrasound imaging, 10 (91%) were in the high DNA synthesizing group, and 9 (82%) developed HCC during the follow-up period, compared with 3 of 7 (43%) with coarse, and only one of 20 (5%) with fine pattern developed HCC. The incidence of HCC was significantly higher (P < 0.01) in patients with a CN cirrhosis pattern than in those with a fine pattern. CONCLUSIONS: In patients with cirrhosis who are anti-HCV-positive, the CN pattern by ultrasound imaging indicates increased DNA synthesis of hepatocytes and a high risk for developing HCC.     

Cathepsin D serum mass concentrations in patients with hepatocellular carcinoma and/or liver cirrhosis

Cathepsin D serum mass concentrations were determined by enzyme immunoassay in patients with hepatocellular carcinoma (n = 51) and/or liver cirrhosis (n = 92) or benign steatosis (n = 16) and correlated with some biochemical and clinical properties of these diseases. Increased cathepsin D serum mass concentrations (P < 0.001) were observed in all these groups of patients as compared to normal subjects (n = 98). However, patients with steatosis had serum mass concentrations of this enzyme significantly lower (mean 2-3 fold) than those measured in cancer patients (P < 0.05) or cirrhotic patients (P < 0.001). Interestingly, significantly higher cathepsin D serum mass concentrations (mean + 62%) (P < 0.006) were determined in the cirrhosis group as compared to cancer patients. No correlation between cathepsin D and a number of clinical and biochemical properties examined, namely, alpha-foetoprotein, number of neoplastic lesions and tumour size in cancer patients or, Child-Pugh grade of severity of cirrhosis and other enzymes of liver function tests in the cirrhotic group was found. The present data and those from other studies which indicate that cathepsin D may be involved in carcinogenesis suggest that this enzyme may be potentially useful as an additional biochemical marker to identify cirrhotic patients who may develop precancerous hepatic nodules.     

Osteodystrophy in patients with chronic hepatitis and liver cirrhosis

Bone mineral density (BMD) of the lumber vertebrae and factors related to bone metabolism were determined in patients with chronic viral hepatitis and patients with liver cirrhosis to clarify correlations between hepatic dysfunction, considered to be one of the causes of hepatic osteodystrophy, and decrease in bone mass. BMD of the second to fourth lumbar vertebrae was determined with a Lunar (Madison, WI, USA) DPX, a dual-energy X-ray absorptiometry diagnostic system. BMD was significantly lowest in patients with liver cirrhosis, followed by patients with chronic hepatitis, and healthy subjects, in this order. There was a significantly positive but weak correlation between albumin and BMD. Levels of 25(OH)D and 1,25(OH)2D were significantly lower in patients with liver cirrhosis than in those with chronic hepatitis. BMD and vitamin D were decreased in all patients whose cholinesterase (ChE) was below 0.3 delta pH. Urinary pyridinoline (Upyr) was significantly higher in the patients with liver cirrhosis, in whom bone mass was decreased, than in the patients with chronic hepatitis, whereas serum osteocalcin levels were distributed in the upper normal range in patients with chronic hepatitis and those with liver cirrhosis. There was a positive correlation between 25(OH)D and serum osteocalcin levels in patients with liver cirrhosis. These results indicate that osteogenesis is decreased and suggest that the decrease in BMD which occurs in viral liver cirrhosis, probably related to decreased, bone formation and slight promotion of bone resorption, reflects deranged hepatic function. This is the first report of Upyr and urinary deoxypyridinoline (UDpyr) determination in patients with liver cirrhosis and patients with chronic hepatitis. The negative correlation of Upyr and UDpyr with ChE is a novel finding.     

The incidence of hepatocellular carcinoma in patients with chronic hepatitis C after interferon treatment

To determine whether serum hepatitis C virus (HCV) RNA disappearance after interferon (IFN) treatment prevents development of hepatocellular carcinoma (HCC), we evaluated retrospectively the incidence of HCC in patients with chronic hepatitis C. A total of 213 patients were monitored for more than 6 months after completion of IFN treatment. Sixty-three of the 213 patients (29.6%) achieved a complete response (CR) to treatment and 150 (70.4%) had no response (NR). HCC developed in 12 (5.6%), all of whom were NR. Logistic analysis showed age, alpha -fetoprotein, and staging of histological finding before IFN treatment were independent factors to development of HCC. The fact that there was no HCC development from CR provides a basis for IFN treatment in chronic HCV infection.     

Liver cell dysplasia in liver cirrhosis and hepatocellular carcinoma

The aim of the study was to assess the incidence of both types of liver cell dysplasia and concomitance with cirrhosis, hepatocellular carcinoma (HCC) and positive reaction for HBsAg in the autopsy material and an attempt to determine a relationship between these two types of liver cell dysplasia and hepatocellular carcinoma. Autopsy material included 102 cases of hepatocellular carcinoma, 101 cases of hepatocirrhosis without accompanying cancer and 106 control cases. Histological specimens stained with HE were analyzed for the presence of large liver cell dysplasia (LLCD) according to Anthony et al., small liver cell dysplasia (SLCD) according to Watanabe et al., the presence of macroregenerative nodules (< 8 mm) and antigen HBs (stained with orcein according to Shikata). The detected LLCD were also assessed semiquantitatively taking into account the number of dysplastic areas in a given case. Statistical significance of the results was tested with the chi square test. LLCD was most frequently detected in HCC with concomitant cirrhosis (55.3%), then in cirrhosis without HCC (40.6%), and in HCC without cirrhosis only in 12.5%. LLCD was found significantly more frequently (p < 0.05) in cirrhosis with HCC than in cirrhosis without HCC. Antigen HBs was found in 25.6% of cirrhoses and/or HCC. No significant differences in the presence of HBsAg were seen between the analyzed groups. The incidence of LLCD and HBsAg in controls was significantly lower than in other groups. A mean age at death in case of cirrhosis with HCC subdivided into that with or without LLCD was not significantly different, whereas in case with cirrhosis with LLCD age at death was 10.8 years higher (the difference statistically significant). Analysis of material with respect to gender revealed a high proportion of men in case of HCC with concomitant cirrhosis but without LLCD (13:1). A strong relationship was seen between the presence of positive reaction for HBsAg and LLCD (p < 0.001). Also the intensity of LLCD positively correlated with the presence of HBsAg. Furthermore, a positive correlation was seen between the presence of LLCD and macronodular cirrhosis (posthepatitic). The present findings suggest a closer relation between HBV infection and LLCD than between cirrhosis or HCC and LLCD. Also morphological patterns of LLCD foci do not confirm the hypothesis of some investigators about the precancerous character of these lesions. In the whole current material only seven cases of SLCD were detected. They were all present in cirrhotic livers with concomitant HCC. Both the morphological pattern of these lesions and their sometimes discerned close spatial relation with HCC foci indicate that SLCD is an alternative way of HCC development.     

Laparoscopic prediction of hepatocellular carcinoma in cirrhosis patients

Previously, laparoscopic studies have not been successful in predicting the occurrence of small hepatocellular carcinoma because cirrhotic patients had not been separated into groups of those who developed small hepatocellular carcinoma under 3 cm in diameter, and those who did not. Retrospective examination with better separation of the two groups gave improved results. Of the 26 laparoscopic findings, only the presence of large complex regenerative nodules was closely associated with the occurrence of subclinical small hepatocellular carcinoma. The study of other cirrhotic patients with and without large complex regenerative nodules gave a cumulative hepatocellular carcinoma occurrence rate of 73% for patients who had these nodules by the third year after laparoscopy. In contrast, the rate for patients without such nodules was 6%, showing a significant difference (P < 0.05) between the two groups. We concluded that the laparoscopic finding of large complex regenerative nodules of liver cirrhosis can be used to predict the occurrence, or a complication, of subclinical small hepatocellular carcinoma.     

Treatment of hepatocellular carcinoma associated with cirrhosis in the era of liver transplantation

PURPOSE: To review the treatment of cirrhotic patients with hepatocellular carcinoma in the era of liver transplantation and to determine the most appropriate approach to the treatment of patients at different stages of disease. DATA SOURCES: A MEDLINE search of English-language articles published between 1981 and 1997 and the clinical experience of the Mount Sinai Liver Transplant Program. STUDY SELECTION: Selected studies were 1) original articles reporting results of resection and transplantation in the treatment of hepatocellular carcinoma in cirrhotic patients and 2) initial reports from major transplantation centers of multimethod therapies combining chemotherapy with transplantation. DATA EXTRACTION: Study designs were assessed with careful attention to methods and aims. Relevant data on patient population, tumor stage distribution, treatment, survival, and rate of recurrent disease were extracted and analyzed. DATA SYNTHESIS: Options for the treatment of hepatocellular carcinoma in cirrhotic patients vary according to tumor stage and severity of underlying liver disease. Resection remains an important method primarily in eastern countries, where the screening of high-risk populations has been associated with early detection of small asymptomatic lesions. Long-term survival after resection, however, is low. In western countries, liver transplantation is becoming the treatment of choice in patients with advanced cirrhosis and small, unresectable lesions; resection is reserved for cirrhotic patients with small, peripheral lesions and preserved hepatic function. Minimally invasive procedures (such as percutaneous ethanol injection and transarterial chemoembolization) have been developed to treat unresectable tumors. Transarterial chemoembolization may also be effective in patients with advanced cirrhosis and unresectable lesions who are awaiting transplantation. CONCLUSIONS: The efficacy of liver transplantation for hepatocellular carcinoma has been proven mainly in patients with advanced cirrhosis and small lesions. Future studies may clarify the role of approaches combining neoadjuvant chemotherapy with transplantation for large (stage III) tumors.     

Seroprevalence of hepatitis B and C viral markers in patients with primary hepatocellular carcinoma in Singapore

This paper reviews studies on the basic principles of biostimulation of wound healing by various low-energy lasers. It looks at the mechanism of action of biostimulation as well as the laser's effect on cell proliferation, collagen synthesis, and would healing.     

Anti-HCV in patients without risk factors for hepatitis C. Prospective study in 200 patients

Using a second generation enzyme immunoassay (ELISA) for the detection of antibodies against Hepatitis C virus (HCV), we investigated the frequency of antibodies anti-HCV and the Alanine Aminotransferase (ALT) plasma levels of 200 patients without history of viral hepatitis, liver diseases, blood transfusions, intravenous drugs abuse, homosexuality, hemodialysis, infection by Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), nor workers of health services. There plasma samples (1.5%), were positives for antibodies anti-HCV, all of these samples were confirmed by RIBA (Recombinant Immunoblot Assay). In these three patients, the ALT plasma level were more than two folds the normal upper limit, another six patients had high ALT levels but less than one fold the normal upper limit. None of the infected patients had any clues that suggested the possible way of infection in the clinic history. We concluded that the incidence of Hepatitis C in the studied patients is 1.5% and that the ALT levels could be used to identify Hepatitis C infection.     

An autopsy case of primary squamous cell carcinoma of the liver associated with hepatitis C virus antibody positive liver cirrhosis

An increase in potassium (K) intake may lower blood pressure (BP), but inconsistent results have been obtained in clinical trials. We studied the effects of K supplementation in hypertensive patients with monitoring of home and ambulatory BP. Fifty-five patients with essential hypertension (26 men, 29 women, 36-77 years old) participated in this study. A 4-week K supplementation period and 4-week control period were assigned in a randomized crossover manner. During the K period, the subjects were given 64 mmol/day of K as slow-release KCl tablets. Office, home, and 24-h BP, as well as serum and urinary electrolytes, were measured at the end of each period. In the control period, office, home, and 24-h BP were 151 +/- 2/88 +/- 1 (mean +/- SE), 138 +/- 1/83 +/- 1, and 137 +/- 1/81 +/- 1 mm Hg, respectively. Serum K increased from 4.15 +/- 0.04 to 4.42 +/- 0.05 mmol/L, and urinary K increased from 54 +/- 2 to 96 +/- 3 mmol/day with the K supplementation. Office, home, and 24-h BP were significantly lower in the K period than in the control period, although the differences were small (2.7 +/- 1.1/1.4 +/- 0.6, 3.6 +/- 0.9/1.7 +/- 0.5, 3.4 +/- 1.0/1.2 +/- 0.5 mm Hg, respectively). Changes in home and 24-h systolic BP with K supplementation were highly significant (P < .001), compared with office BP (P < .05). The change in 24-h systolic BP was correlated negatively with baseline BP and urinary Na/K ratio, and positively with baseline urinary K excretion. The changes in daytime and nighttime BP were comparable. These results indicate that increasing K intake lowers BP in hypertensive subjects, especially in those with higher BP and lower K intake. Our study supports the usefulness of K supplementation in the treatment of hypertension, although its antihypertensive effect may be small.